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BMD,DEXA, Osteoporosis, FRAX, Osteopenia, Cost effective, Drug treatment, Hip fractures, T-score.
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OsteoporosisMore questions than answers
Vinod Naneria
Consultant orthopaedic surgeon
Choithram Hospital amp Research Centre
Indore India
Osteoporosis - Definition
bull A conference was organized on osteoporosis in Rome on 22nd ndash 25th June1992 by WHO partnering with the International Osteoporosis Foundation a nonprofit organization with a corporate advisory board that currently consists of 31 drug and medical-equipment companies
Acknowledgements
bull This meeting was organized by the WHO Collaborating Centre for Metabolic Bone Disease Sheffield England the world health organization and the European Foundation for Osteoporosis and Bone Disease with financial support from the Rorer Foundation Sandoz Pharmaceuticals and Smith Kline Beecham
The Study Group gratefully acknowledges the contribution made to the meeting By Professor G Mazzuoli Umberto I Polyclinic Rome Italy
WHO technical services 843 - 1994
Osteoporosis - Definition
bull The World Health Organization defines osteoporosis as a progressive systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture WHO technical services 843 - 1994
Normal bone T-score better than -1 Osteopenia T-score between -1 and -25 Osteoporosis T-score less than -25 Established osteoporosis Presence of a non-traumatic fracture
A disease created
bull In a single conference one disease mdash osteoporosis mdash had been expanded from an elderly person with a fracture to anyone who had a -25 T-score And another condition Osteopenia was created
The Definition
bull In classic 1968 monograph Wilson and Jungner defined for the World Health Organization (WHO) principles intended to serve as the basis for recommending or planning screening for early detection of a disease
bull Can osteoporosis fall in the category of a disease
WHO principles for recommending or planning screening for early detection of a disease
bull The condition should be an important health problem Yes
bull There should be an accepted treatment for patients with recognized disease +-
bull Facilities for diagnosis and treatment should be available No
bull There should be a recognizable latent or early symptomatic stage Silent Thief
bull There should be a suitable test or examination
WHO principles hellip disease
bull The test should be acceptable to the population What choice
bull The natural history of the condition including development from latent to declared disease should be adequately understood
Not understood well
bull There should be an agreed policy on whom to treat as patients No agreed policy
bull The cost of case-finding should be economically balanced in relation to possible expenditure as a whole
Not cost effectivebull Case-finding should be a continuing process and not a
once and for all project Case finding is once for all
Bad medicine osteoporosisbull Osteoporosis is not a disease but a risk factor
for fracture particularly of the hip bull Age over 80 is by far the single greatest risk bull It is an assumption that ldquotreatmentrdquo exists bull Limited evidence of the effectiveness of
bisphosphonates in the primary prevention of hip fracture in people with no history of fracture
bull Secondary prevention the small reduction in hip facture is again in highly selected elderly populations
Des Spence general practitioner Glasgow BMJ 2010340c643
Front line review ndash bad medicine
bull The term osteoporosis is an age dependent concept primary prevention is questionable in all but the most frail and ldquoosteopeniardquo should be struck from the medical lexicon
bull Research carries the scars of big pharma with relative risk reductions non-clinical outcomes and composite end points
Des Spence general practitioner Glasgow BMJ 2010340c643
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Osteoporosis - Definition
bull A conference was organized on osteoporosis in Rome on 22nd ndash 25th June1992 by WHO partnering with the International Osteoporosis Foundation a nonprofit organization with a corporate advisory board that currently consists of 31 drug and medical-equipment companies
Acknowledgements
bull This meeting was organized by the WHO Collaborating Centre for Metabolic Bone Disease Sheffield England the world health organization and the European Foundation for Osteoporosis and Bone Disease with financial support from the Rorer Foundation Sandoz Pharmaceuticals and Smith Kline Beecham
The Study Group gratefully acknowledges the contribution made to the meeting By Professor G Mazzuoli Umberto I Polyclinic Rome Italy
WHO technical services 843 - 1994
Osteoporosis - Definition
bull The World Health Organization defines osteoporosis as a progressive systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture WHO technical services 843 - 1994
Normal bone T-score better than -1 Osteopenia T-score between -1 and -25 Osteoporosis T-score less than -25 Established osteoporosis Presence of a non-traumatic fracture
A disease created
bull In a single conference one disease mdash osteoporosis mdash had been expanded from an elderly person with a fracture to anyone who had a -25 T-score And another condition Osteopenia was created
The Definition
bull In classic 1968 monograph Wilson and Jungner defined for the World Health Organization (WHO) principles intended to serve as the basis for recommending or planning screening for early detection of a disease
bull Can osteoporosis fall in the category of a disease
WHO principles for recommending or planning screening for early detection of a disease
bull The condition should be an important health problem Yes
bull There should be an accepted treatment for patients with recognized disease +-
bull Facilities for diagnosis and treatment should be available No
bull There should be a recognizable latent or early symptomatic stage Silent Thief
bull There should be a suitable test or examination
WHO principles hellip disease
bull The test should be acceptable to the population What choice
bull The natural history of the condition including development from latent to declared disease should be adequately understood
Not understood well
bull There should be an agreed policy on whom to treat as patients No agreed policy
bull The cost of case-finding should be economically balanced in relation to possible expenditure as a whole
Not cost effectivebull Case-finding should be a continuing process and not a
once and for all project Case finding is once for all
Bad medicine osteoporosisbull Osteoporosis is not a disease but a risk factor
for fracture particularly of the hip bull Age over 80 is by far the single greatest risk bull It is an assumption that ldquotreatmentrdquo exists bull Limited evidence of the effectiveness of
bisphosphonates in the primary prevention of hip fracture in people with no history of fracture
bull Secondary prevention the small reduction in hip facture is again in highly selected elderly populations
Des Spence general practitioner Glasgow BMJ 2010340c643
Front line review ndash bad medicine
bull The term osteoporosis is an age dependent concept primary prevention is questionable in all but the most frail and ldquoosteopeniardquo should be struck from the medical lexicon
bull Research carries the scars of big pharma with relative risk reductions non-clinical outcomes and composite end points
Des Spence general practitioner Glasgow BMJ 2010340c643
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Acknowledgements
bull This meeting was organized by the WHO Collaborating Centre for Metabolic Bone Disease Sheffield England the world health organization and the European Foundation for Osteoporosis and Bone Disease with financial support from the Rorer Foundation Sandoz Pharmaceuticals and Smith Kline Beecham
The Study Group gratefully acknowledges the contribution made to the meeting By Professor G Mazzuoli Umberto I Polyclinic Rome Italy
WHO technical services 843 - 1994
Osteoporosis - Definition
bull The World Health Organization defines osteoporosis as a progressive systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture WHO technical services 843 - 1994
Normal bone T-score better than -1 Osteopenia T-score between -1 and -25 Osteoporosis T-score less than -25 Established osteoporosis Presence of a non-traumatic fracture
A disease created
bull In a single conference one disease mdash osteoporosis mdash had been expanded from an elderly person with a fracture to anyone who had a -25 T-score And another condition Osteopenia was created
The Definition
bull In classic 1968 monograph Wilson and Jungner defined for the World Health Organization (WHO) principles intended to serve as the basis for recommending or planning screening for early detection of a disease
bull Can osteoporosis fall in the category of a disease
WHO principles for recommending or planning screening for early detection of a disease
bull The condition should be an important health problem Yes
bull There should be an accepted treatment for patients with recognized disease +-
bull Facilities for diagnosis and treatment should be available No
bull There should be a recognizable latent or early symptomatic stage Silent Thief
bull There should be a suitable test or examination
WHO principles hellip disease
bull The test should be acceptable to the population What choice
bull The natural history of the condition including development from latent to declared disease should be adequately understood
Not understood well
bull There should be an agreed policy on whom to treat as patients No agreed policy
bull The cost of case-finding should be economically balanced in relation to possible expenditure as a whole
Not cost effectivebull Case-finding should be a continuing process and not a
once and for all project Case finding is once for all
Bad medicine osteoporosisbull Osteoporosis is not a disease but a risk factor
for fracture particularly of the hip bull Age over 80 is by far the single greatest risk bull It is an assumption that ldquotreatmentrdquo exists bull Limited evidence of the effectiveness of
bisphosphonates in the primary prevention of hip fracture in people with no history of fracture
bull Secondary prevention the small reduction in hip facture is again in highly selected elderly populations
Des Spence general practitioner Glasgow BMJ 2010340c643
Front line review ndash bad medicine
bull The term osteoporosis is an age dependent concept primary prevention is questionable in all but the most frail and ldquoosteopeniardquo should be struck from the medical lexicon
bull Research carries the scars of big pharma with relative risk reductions non-clinical outcomes and composite end points
Des Spence general practitioner Glasgow BMJ 2010340c643
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Osteoporosis - Definition
bull The World Health Organization defines osteoporosis as a progressive systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture WHO technical services 843 - 1994
Normal bone T-score better than -1 Osteopenia T-score between -1 and -25 Osteoporosis T-score less than -25 Established osteoporosis Presence of a non-traumatic fracture
A disease created
bull In a single conference one disease mdash osteoporosis mdash had been expanded from an elderly person with a fracture to anyone who had a -25 T-score And another condition Osteopenia was created
The Definition
bull In classic 1968 monograph Wilson and Jungner defined for the World Health Organization (WHO) principles intended to serve as the basis for recommending or planning screening for early detection of a disease
bull Can osteoporosis fall in the category of a disease
WHO principles for recommending or planning screening for early detection of a disease
bull The condition should be an important health problem Yes
bull There should be an accepted treatment for patients with recognized disease +-
bull Facilities for diagnosis and treatment should be available No
bull There should be a recognizable latent or early symptomatic stage Silent Thief
bull There should be a suitable test or examination
WHO principles hellip disease
bull The test should be acceptable to the population What choice
bull The natural history of the condition including development from latent to declared disease should be adequately understood
Not understood well
bull There should be an agreed policy on whom to treat as patients No agreed policy
bull The cost of case-finding should be economically balanced in relation to possible expenditure as a whole
Not cost effectivebull Case-finding should be a continuing process and not a
once and for all project Case finding is once for all
Bad medicine osteoporosisbull Osteoporosis is not a disease but a risk factor
for fracture particularly of the hip bull Age over 80 is by far the single greatest risk bull It is an assumption that ldquotreatmentrdquo exists bull Limited evidence of the effectiveness of
bisphosphonates in the primary prevention of hip fracture in people with no history of fracture
bull Secondary prevention the small reduction in hip facture is again in highly selected elderly populations
Des Spence general practitioner Glasgow BMJ 2010340c643
Front line review ndash bad medicine
bull The term osteoporosis is an age dependent concept primary prevention is questionable in all but the most frail and ldquoosteopeniardquo should be struck from the medical lexicon
bull Research carries the scars of big pharma with relative risk reductions non-clinical outcomes and composite end points
Des Spence general practitioner Glasgow BMJ 2010340c643
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
A disease created
bull In a single conference one disease mdash osteoporosis mdash had been expanded from an elderly person with a fracture to anyone who had a -25 T-score And another condition Osteopenia was created
The Definition
bull In classic 1968 monograph Wilson and Jungner defined for the World Health Organization (WHO) principles intended to serve as the basis for recommending or planning screening for early detection of a disease
bull Can osteoporosis fall in the category of a disease
WHO principles for recommending or planning screening for early detection of a disease
bull The condition should be an important health problem Yes
bull There should be an accepted treatment for patients with recognized disease +-
bull Facilities for diagnosis and treatment should be available No
bull There should be a recognizable latent or early symptomatic stage Silent Thief
bull There should be a suitable test or examination
WHO principles hellip disease
bull The test should be acceptable to the population What choice
bull The natural history of the condition including development from latent to declared disease should be adequately understood
Not understood well
bull There should be an agreed policy on whom to treat as patients No agreed policy
bull The cost of case-finding should be economically balanced in relation to possible expenditure as a whole
Not cost effectivebull Case-finding should be a continuing process and not a
once and for all project Case finding is once for all
Bad medicine osteoporosisbull Osteoporosis is not a disease but a risk factor
for fracture particularly of the hip bull Age over 80 is by far the single greatest risk bull It is an assumption that ldquotreatmentrdquo exists bull Limited evidence of the effectiveness of
bisphosphonates in the primary prevention of hip fracture in people with no history of fracture
bull Secondary prevention the small reduction in hip facture is again in highly selected elderly populations
Des Spence general practitioner Glasgow BMJ 2010340c643
Front line review ndash bad medicine
bull The term osteoporosis is an age dependent concept primary prevention is questionable in all but the most frail and ldquoosteopeniardquo should be struck from the medical lexicon
bull Research carries the scars of big pharma with relative risk reductions non-clinical outcomes and composite end points
Des Spence general practitioner Glasgow BMJ 2010340c643
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
The Definition
bull In classic 1968 monograph Wilson and Jungner defined for the World Health Organization (WHO) principles intended to serve as the basis for recommending or planning screening for early detection of a disease
bull Can osteoporosis fall in the category of a disease
WHO principles for recommending or planning screening for early detection of a disease
bull The condition should be an important health problem Yes
bull There should be an accepted treatment for patients with recognized disease +-
bull Facilities for diagnosis and treatment should be available No
bull There should be a recognizable latent or early symptomatic stage Silent Thief
bull There should be a suitable test or examination
WHO principles hellip disease
bull The test should be acceptable to the population What choice
bull The natural history of the condition including development from latent to declared disease should be adequately understood
Not understood well
bull There should be an agreed policy on whom to treat as patients No agreed policy
bull The cost of case-finding should be economically balanced in relation to possible expenditure as a whole
Not cost effectivebull Case-finding should be a continuing process and not a
once and for all project Case finding is once for all
Bad medicine osteoporosisbull Osteoporosis is not a disease but a risk factor
for fracture particularly of the hip bull Age over 80 is by far the single greatest risk bull It is an assumption that ldquotreatmentrdquo exists bull Limited evidence of the effectiveness of
bisphosphonates in the primary prevention of hip fracture in people with no history of fracture
bull Secondary prevention the small reduction in hip facture is again in highly selected elderly populations
Des Spence general practitioner Glasgow BMJ 2010340c643
Front line review ndash bad medicine
bull The term osteoporosis is an age dependent concept primary prevention is questionable in all but the most frail and ldquoosteopeniardquo should be struck from the medical lexicon
bull Research carries the scars of big pharma with relative risk reductions non-clinical outcomes and composite end points
Des Spence general practitioner Glasgow BMJ 2010340c643
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
WHO principles for recommending or planning screening for early detection of a disease
bull The condition should be an important health problem Yes
bull There should be an accepted treatment for patients with recognized disease +-
bull Facilities for diagnosis and treatment should be available No
bull There should be a recognizable latent or early symptomatic stage Silent Thief
bull There should be a suitable test or examination
WHO principles hellip disease
bull The test should be acceptable to the population What choice
bull The natural history of the condition including development from latent to declared disease should be adequately understood
Not understood well
bull There should be an agreed policy on whom to treat as patients No agreed policy
bull The cost of case-finding should be economically balanced in relation to possible expenditure as a whole
Not cost effectivebull Case-finding should be a continuing process and not a
once and for all project Case finding is once for all
Bad medicine osteoporosisbull Osteoporosis is not a disease but a risk factor
for fracture particularly of the hip bull Age over 80 is by far the single greatest risk bull It is an assumption that ldquotreatmentrdquo exists bull Limited evidence of the effectiveness of
bisphosphonates in the primary prevention of hip fracture in people with no history of fracture
bull Secondary prevention the small reduction in hip facture is again in highly selected elderly populations
Des Spence general practitioner Glasgow BMJ 2010340c643
Front line review ndash bad medicine
bull The term osteoporosis is an age dependent concept primary prevention is questionable in all but the most frail and ldquoosteopeniardquo should be struck from the medical lexicon
bull Research carries the scars of big pharma with relative risk reductions non-clinical outcomes and composite end points
Des Spence general practitioner Glasgow BMJ 2010340c643
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
WHO principles hellip disease
bull The test should be acceptable to the population What choice
bull The natural history of the condition including development from latent to declared disease should be adequately understood
Not understood well
bull There should be an agreed policy on whom to treat as patients No agreed policy
bull The cost of case-finding should be economically balanced in relation to possible expenditure as a whole
Not cost effectivebull Case-finding should be a continuing process and not a
once and for all project Case finding is once for all
Bad medicine osteoporosisbull Osteoporosis is not a disease but a risk factor
for fracture particularly of the hip bull Age over 80 is by far the single greatest risk bull It is an assumption that ldquotreatmentrdquo exists bull Limited evidence of the effectiveness of
bisphosphonates in the primary prevention of hip fracture in people with no history of fracture
bull Secondary prevention the small reduction in hip facture is again in highly selected elderly populations
Des Spence general practitioner Glasgow BMJ 2010340c643
Front line review ndash bad medicine
bull The term osteoporosis is an age dependent concept primary prevention is questionable in all but the most frail and ldquoosteopeniardquo should be struck from the medical lexicon
bull Research carries the scars of big pharma with relative risk reductions non-clinical outcomes and composite end points
Des Spence general practitioner Glasgow BMJ 2010340c643
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Bad medicine osteoporosisbull Osteoporosis is not a disease but a risk factor
for fracture particularly of the hip bull Age over 80 is by far the single greatest risk bull It is an assumption that ldquotreatmentrdquo exists bull Limited evidence of the effectiveness of
bisphosphonates in the primary prevention of hip fracture in people with no history of fracture
bull Secondary prevention the small reduction in hip facture is again in highly selected elderly populations
Des Spence general practitioner Glasgow BMJ 2010340c643
Front line review ndash bad medicine
bull The term osteoporosis is an age dependent concept primary prevention is questionable in all but the most frail and ldquoosteopeniardquo should be struck from the medical lexicon
bull Research carries the scars of big pharma with relative risk reductions non-clinical outcomes and composite end points
Des Spence general practitioner Glasgow BMJ 2010340c643
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Front line review ndash bad medicine
bull The term osteoporosis is an age dependent concept primary prevention is questionable in all but the most frail and ldquoosteopeniardquo should be struck from the medical lexicon
bull Research carries the scars of big pharma with relative risk reductions non-clinical outcomes and composite end points
Des Spence general practitioner Glasgow BMJ 2010340c643
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Fear psychosis
bull uarr Cholesterol rarr Coronaryrarr Myocardial infarct
bull uarr BPrarr Hypertension rarr Stroke
bull uarr Uric acid rarr Gout rarr Arthritis
bull darr BMD rarr Osteoporosis rarr Fragility Fracture
Risk Factor Disease Clinical expression
WHO TRS 843_ 1994
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
HOPE SELLING
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Ray Moynihan journalist Iona Heath general practitioner David Henry professor of clinical
pharmacology BMJ 2002324886-891
bull The social construction of illness is being replaced by the corporate construction of disease
bull A lot of money can be made from healthy people who believe they are sick
bull A lot of money can be made by telling healthy people that they are sick
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Diagnosis by DEXA
bull The burden of diagnosis was shifted from clinicians to machines
bull Machines will decide who are at risk of fracture and who needs treatment
bull Machines of all types and make were permitted for primary screening
bull Only DEXA was approved by WHO
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
DEXA ndash Flaws
bull The WHO has defined the categories based on bone density in white women
bull The WHO committee did not have enough data to create definitions for men or other ethnic groups
bull There is no uniformity between various machines
Talk to your Physician or refer to your ldquoOsteoporosis societyrdquo for further information
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
DEXAndash Flawsbull DEXA overestimate the bone mineral
density of taller subjects and underestimate the bone mineral density of smaller subjects
bull In DEXA bone mineral content is divided by the area of the site being scanned
bull DEXA calculates BMD using area (aBMD areal Bone Mineral Density) it is not an accurate measurement of true bone mineral density which is mass divided by a volume
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
DEXAndash Flaws
bull The confounding effect of differences in bone size is due to the missing depth value in the calculation of bone mineral density
bull The radiation dose is approximately 110th that of a standard chest X-ray
bull BMD testing with DXA is very susceptible to operator error
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
DEXAndash Flawsbull A repeat BMD measurements should be done on
the same machine each time or at least a machine from the same manufacturer
bull Error between machines or trying to convert measurements from one manufacturers standard to another can introduce errors large enough to wipe out the sensitivity of the measurements
bull DEXA results need to be adjusted if the patient is taking strontium and calcium supplements
bull Metallic artifacts in cloths or pockets cause errorsbull Osteomalacia Osteoarthritis of spine old
Fractures of spine and hip aortic calcification affect BMD readings
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
BMD monitoring
bull Osteoporosis is an arbitrary point on a scale bull Process of micro-architectural deteriorationbull Accelerated bone resorption exists throughout
postmenopausal life whereas osteoporosis does not
bull Bone densitometry measures bone density not bone turnover or bone stability
bull 85 of the rise in risk of fracture in ageing women is attributable to something other than the loss of BMD
bull Age is a better predictor of hip fracture than radial bone density
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Do you know
Do you know what is your T ndash Score
Take one minute test
Do you know what are your chances of getting fractures in next 10 years
Go online FRAX site
For Treatment consult your physician
or your ldquoOsteoporosis Societyrdquo
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Do you know yourBlood pressure
Cholesterol level Weight T-score
httpwwwusbjdorgprojectsFit2aT_opcfm
Program especially aimed at men and women in mid-40s to late 60s
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Patient is at risk
bull White Caucasian Female
bull Countries with aging population
bull Countries with high numbers of population above the age of 65 years
bull Countries with more female to male ratio
bull Country where female are living longer
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Risk Factors ndash are they applicable to us
bull Female Non-modifiablebull Age Non-modifiablebull Genetics Non-modifiablebull Incidence of RA Non-modifiablebull Corticosteroid Non-modifiablebull Smoking Modifiablebull Alcohol Modifiablebull BMI Modifiable (Wt)
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
25
15
35
40
30 40
35
35
25
30
25
30
20
20
40
The global median age 2010
Be scared of 2050
Hip fractures in USA Europe amp Oceania ndash 57 in the year 1990Hip fractures in Asia Africa and South America will be 71 in 2050
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Percentage of aging population of world 2010
lt5
9
14
gt15 gt15
Be scared of 2050
Osteoporosis affects 75 million people in Europe Japan and USA and causes 23 million fractures annually in Europe and the USA alone
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Aging population of the worldLook at Europe
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Sex ratio of population aged over 65 years per country (2006 CIA World Fact book)smooth scale from blue to redBlue below 039 malesfemale White 079 malesfemale (World)Red above 129 malesfemale(Grey no data)
Male Female ratio in world population
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
bull 17 million hip fractures occurred in 1990 world over Fractures rate vary by geographical regions bull Higher in Scandinavia than in USA or Oceania and lower in southern Europe bull Absolute number of fractures is determined by ethnic composition size amp age distribution of the population bull Half of the hip fractures occur in Europe USA and Oceania even though the population was smaller (380 million of 35 years of age compared with 920 million in Asia in 1990 because the population was older and largely of whitesbull About one third of hip fractures In 1990 occurred in Asia despite lower incidence rates among Asians
NORTH OLD amp WHITE
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
India and the World
bull Mean age 25 years
bull Population above 65 is 9
bull Male female ratio is above 129
bull Average age of life expectancy is 647
bull Average Female life expectancy is 664
bull Average Female height is 5rsquo
Dark skin in cold countries may be a cause of Vit D deficiency not in India
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
USA and Europe
bull Mean age around 35 - 40 years
bull Population above 65 is 14 ndash 15
bull Male female ratio is below -39
bull Average age of life expectancy is 782 ndash 81 Yrs
bull Average female life expectancy is 802 ndash 84
bull Average female height is 5rsquo5rdquo
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Japan
bull Japan has a highest number of elderly
bull The osteoporotic fractures are 50 less
bull Osteoporotic fractures are much less in the so called small thin low BMI Asians as compare to Americans (Caucasians)
bull Over all Life expectancy in Japan 826
bull MF Life expectancy- 790 for M amp 861 for F
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Country overall Male Female1 Japan 826 790 8612 Hong Kong 822 794 8513 Iceland 818 802 8334 Switzerland 817 790 8425 Australia 812 789 8366 Spain 809 777 8427 Sweden 809 787 8308 Israel 807 785 8289 Macau 807 785 82810 France 807 771 84111 United States 782 756 80812 India 647 632 66413 World 672 650 695
In spite of Osteoporosis women are living long by 4 to 7 yrs
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
The United Nations 2005-2010
bull Women tend to have a lower mortality rate at every age In the womb male fetuses have a higher mortality rate
bull Babies are conceived in a ratio of about 124 males to 100 females but the ratio of those surviving to birth is only 105 males to 100 females
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
The United Nations 2005-2010
bull Among the smallest premature babies (those under 2 pounds or 900 g) females again have a higher survival rate
bull At the other extreme about 90 of individuals aged 110 are female
bull 1 30 FM ratio of Cardiac event during child bearing age
bull 1 9 FM ratio of Cardiac event after 65 yrsbull Mortality with in one year following fractures is
375 higher in males
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Internet Datas on Osteoporosis
bull About 48900000 articles are published in Google as of today (5th Sept2010)
bull In Pubmed 50145
bull Review articles 11842
bull Full text free articles 7155
bull Books on Google 1170300
bull Amazon 2991
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull 8 million women and 2 million men in the USbull 34 million Americans have low bone mass bull 15 million fragility fracture each yearbull 18 billion dollars as an annual cost of treatment
Endocrinologist Internal Medicine Rheumatologist amp GP Know
Osteoporosis in East is treated by Orthopedic surgeons
Need for reminder
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
What Every Orthopaedic Surgeon Should Know Richard M Dell
Bone Joint Surg Am 200991 Suppl 679-86 d
bull Reaching epidemic proportions bull 75 million baby boomers entering the age of
risk for osteoporosis bull One-half of all women and one-third of all
men will sustain a fragility fracture during their lifetime
Gynecologist Oncologists geriatrists amp Celebrities know
Need for reminder
Orthopedic Surgeons
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Internet data starts with American
bull An introduction of numbers of Americans having Osteoporosis (12 millions)
bull A projected raise in numbers in the year 2020 and 2050 (44 millions)
bull All of them have calculated the Cost of fracture treatment today and tomorrow in Dollars
bull All have projected fracture of hips solely due to osteoporosis (15 - 2 millions Yr)
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Americahellip
bull The total population of America 30 croresbull The population 65 and above 37 m (13)bull Females population 65 and above 18 mbull Patient population 12 millionsbull 75 million Baby Boomers reaching above 60bull Osteoporosis related fractures 15 ndash 2mbull Basic white American (Caucasians) problembull Declared osteoporosis as National problem in
1984
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
All agree to Americanhelliphelliphellip
bull Caucasians are more pronebull General deficiency of vitamin D and calcium bull Acute need for change in the dietbull Change in life style sun exposure smoking
alcohol and exercisesbull Almost all have calculated the amount of
Calcium and VitD on the basis of how much is their daily intake how much they are absorbing and how much they are excreting retaining
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
All agree to Americanhelliphelliphellip
bull Climatic conditions Boston less sun exposure than Miami
bull Diet - Low calcium high animal protein and high sodium less of dairy products
bull Sun exposure Melanoma very high bull 2 million new cases and 84000 death bull Use of sun protection creambull Fortified Milk have high proteins and
hence cause more calcium loss in urine
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Asian Women
bull Asian women have lower bone mass than Caucasian women but the rate of hip fractures is not proportionally higher
bull Theories shorter hip-axis length bull Previous activity levels that were higher bull The cultural practice of taking care of the elderlybull Not allowing them to leave their beds - reducing
the opportunity for falling
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
How Big
Is ASIA
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Is Asia is comparable
bull 13rd world live in Asiabull From Bali island in south to Siberia and
Mongolia in north from Japan in the east to Iran in the west
bull The climatic condition and food habits differs markedly
bull The sun exposure protein diet skin color height and weight differ which changes their demand for calcium and Vit D
bull Differ genetically from Caucasians
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Are these criteria applicable to all races age group and gender
The WHO criteria are derived from Caucasian postmenopausal women population and are thus best applicable to that group However in the absence of normative data from other races WHO criteria have been widely accepted and used in clinical practice Normative data for Indians are not available It is possible that if we use the WHO criteria substantial number of patients may be over diagnosed and over treated ACTION PLAN OSTEOPOROSIS CONSENSUS STATEMENT ndash Osteoporosis Society of India New Delhi 2003
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Disease expands through marriage of marketing and machinesA sidewalk sign at Kelley-Ross Pharmacy in Seattle advertises bone-density screening Such screening has proliferated in recent years targeting younger healthier people
BETTY UDESEN THE SEATTLE TIMES
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Who should be screenedbull Over the last decade - many debates
bull Several organizations performed detailed cost-benefit studies and developed guidelines
bull US Preventive services Task Force American Association of Clinical Endocrinologists National Osteoporosis Foundation
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Who should be screenedbull Problem of over-interpretation of results amp
healthy average people think they are at a much higher risk
bull In 2000 an NIH consensus conference concluded Until there is good evidence to support the cost-effectiveness of routine screening or the efficacy of early initiation of preventive drugs an individualized approach is recommended
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Bone density at various sites for prediction of hip fractures Cummings SR Black DM Nevitt MC Browner W Cauley J Ensrud K et
al The Study of Osteoporotic Fractures Research Group Lancet 1993 34 72-75
bull BMD poor predictor of fractures
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull Over 80 of low trauma fractures occur in people who do not have osteoporosis (T score ndash25)
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Bone density at various sites for prediction of hip fractures
bull Even if a T score of ndash15 is used 75 of fractures would still occur in people without osteoporosis
bull BMD gives general practitioners little indication which patient will sustain a fracture
bull Changes in bone density in people taking antiresorptive drugs explain only 4-30 of the reduction in risk of vertebral and non-vertebral fractures
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Bone density at various sites for prediction of hip fractures
bull With each standard deviation decrease in femoral neck bone density there is a 26 times increase in the age adjusted risk of hip fracture
bull Women with bone density in the lowest quarter had an 85-fold greater risk of hip fracture than those in the highest quarter
bull The data are based on just 65 women who sustained a fracture out of 8134 observed
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Bone density at various sites for prediction of hip fractures
Treatment of the entire 8000 with an antiresorptive drug (assuming acceptance compliance and a budget) could be expected to save a maximum 33 fractures (a generous estimate as the 50 reduction in fractures claimed for bisphosphonates is based on populations already selected for low bone density or existing fracture)
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Bone density at various sites for prediction of hip fractures
bull Alternatively 8000 scans to classify the 2000 women in the lowest quarter of bone density would according to the trial data identify only 34 of the 65 who suffered fractures and only half (or 17) of these fractures could be prevented by drugs
bull Bone densitometry can tell us about populations but the chances of predicting a preventable fracture by bone densitometry in an osteoporosis clinic of largely self referred individuals must be close to random
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Bone densitometry is not a good predictor of hip fractureBMJ 2001323795-799
Education and debate For and againstTerence J Wilkin Devasenan Devendra
bull The ability of bone densitometry to predict future fracture is overstated and the data on which such claims are based are over interpreted
bull Bone densitometry is a major industry (an estimated 34 000 densitometry machines were in existence worldwide in the year 2000)
bull And much of the research into osteoporosis depends on it
bull Clinical trials test efficaciousness (can it work) in selected groups The clinician is concerned with effectiveness (does it work) in unselected individuals The challenge is to show the latter
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Screening for postmenopausal osteoporosis Nelson HD Helfand M Woolf SH Allan JD
Ann Intern Med 2002137529-41
bull When different scanners are used on the same patients the proportion of patients diagnosed with osteoporosis varies from 6 up to 15
bull This means that a patient with a bone mineral density T score of ndash15 may have a true value between ndash30 and 0ndashthat is a range from clear osteoporosis to normal
bull Bone mineral density is a poor predictor of fracture in individuals
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
BMD Screening - Cost Effectivebull The WHO task force on osteoporosis
management agrees that screening by densitometry before the age of 65 is not cost effective
bull But screening of high risk patients (case finding through education) is thought to be cost effective in particular at age 70 in people who already have a low bone mass together with other risk factors such as low body weight previous fracture or family history
Conclusion Although methods to identify risk for osteoporoticfractures are available and medications to reduce fractures are effectiveno trials directly evaluate screening effectiveness harms and intervalsUS Preventive Services Task Force Heidi D Nelson annimed 2010
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
NOF recommendationsbull National Osteoporosis Foundation US and the
American Association of Clinical Endocrinologists recommend routine monitoring of bone mineral density within two years of starting treatment
bull The UK National Osteoporosis Guidelines Group US National Institutes of Health and the Osteoporosis Society of Canada do not make a recommendation either way on monitoring
NHS no recommendation
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Recommendationshellip
bull Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent Bisphosphonate is unnecessary and may be misleading Routine monitoring should be avoided in this early period after Bisphosphonates treatment is commenced
Research Value of routine monitoring of bone mineral density after starting bisphosphonate treatment secondary analysis of trial data Katy J L Bell Andrew Hayen Petra Macaskill Les Irwig Jonathan C Craig Kristine Ensrud Douglas C Bauer Published 23 June 2009 doi101136bmjb2266 BMJ 2009338b2266
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Meta-analysis of how well measures of bone mineral density predict occurrence of
osteoporotic fracturesDeborah Marshall Olof Johnell Hans Wedel
BMJ 19963121254-1259 (18 May)
bull Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture
bull We do not recommend a program of screening menopausal women for osteoporosis by measuring bone density
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Fractures ndash Fall or BMDbull Prevention of fall prevent 15 to 50 fracturesbull Exercises Strength and balancing trainingbull Reduction of anti-psychotic drugsbull Dietary supplementation of Vit D +Calciumbull Modification at Homebull Visual impairment correctionbull Cognitive functionbull Cardiac pacing where indicatedbull Use of gait stabilizing bull Hip protectors (23-60)bull Antiskid devices when walking outdoors
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Streamlining assessment and intervention in a falls clinic using the timed up and go test and
physiological profile assessments Whitney JC Lord SR Close JC
Age Ageing 200534567-71
bull People who have difficulty in performing a simple sit to stand test or taking over 13 seconds to complete a simple timed up and go testldquo should be referred to a geriatrician or falls clinic for a more comprehensive evaluation
bull Fall prevention is a better method to prevent fractures than BMD
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
A fall to the side increases the risk of hip fractureby about 6 times compared to falls in other directions
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Fractures rarr Fall or BMDndash Falling not osteoporosis is the strongest single risk
factor for fractures in elderly people
ndash Bone mineral density is a poor predictor of an individualrsquos fracture risk
ndash Drug treatment is expensive and will not prevent most fractures in elderly people
ndash Randomized controlled trials show that falls in older people can be reduced by up to 50
BMJ 2008336124-126 (19 January) doi101136bmj39428470752AD
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Go for BMD
Go for FRAX
One minute test
Fracture Index
Absolute fracture risk
13 seconds to complete up and go testldquo
Watch Be careful Dont fallOsteoporosis ahead
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
FRAX- 10 year risk of fragility fracture
bull Age Sex Height Weight
bull Previous fracture
bull Family history of fracture
bull Smoking Alcohol
bull Rheumatoid Corticosteroid
bull Secondary Osteoporosis
bull BMD
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Dr Judith Brenner power of FRAX tool
bull Using FRAX the risk a hip fracture within 10 years for a 60-year-old white woman of 5 feet and 110 pounds with no family or personal history of fracture and no history of smoking or using steroids is 15 percent
bull If the same woman instead weighed 200 pounds her risk would drop to 05 percent
bull But if the 110-pound woman had a parent who suffered a hip fracture her risk would rise to 19 percent
bull Add smoking and the risk goes to about 29 percent
bull Add steroids and the risk rises to 59 percent
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Dr Judith Brenner New York University power of the FRAX tool
bull Add daily consumption of two or more alcoholic drinks and the risk becomes 9 percent
bull Instead of 60 say the woman is 80 years old slender and with no family or personal history of fractures smoking or steroid use Dr Brenner calculated her risk of fracturing a hip in 10 years as 10 percent and of having any major osteoporotic fracture at 35 percent
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Pre-Osteoporosis or Osteopenia
bull Osteopenia was defined in June 1992 by the World Health Organization
bull It was meant to indicate the emergence of a problem
bull It didnt have any particular diagnostic or therapeutic significance at that time
ldquoWe never imagined that people would come to think of Osteopenia as a disease in itself to be treatedrdquo
Dr John A Kanis emeritus professor of medicine University of Sheffield England Director of the WHO center that defined BMD amp developed FRAX
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Implications Of Expanding Disease Definitions The Case Of Osteoporosis
M Brooke Herndon Lisa M Schwartz Steven
Woloshin and H Gilbert Welch
bull The new threshold changes the number of women for whom treatment is recommended from 64 million to 108 million among women age sixty-five and older (at a net cost of at least $28 billion) and from 16 million to 40 million among women ages 50ndash64 (at a net cost of at least $18 billion)
bull Whether or not offering treatment to these additional women will reduce the number of hip fractures is unknown
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Selling sickness how drug companies are turning us all into patients Moynihan R
Cassels A BMJ 2002324886-91 Sydney Allen and Unwin 2005
Osteoporosis is a controversial condition An informal global alliance of drug companies doctors and sponsored advocacy groups portray and promote osteoporosis as a silent but deadly epidemic bringing misery to tens of millions of postmenopausal women For others less entwined with the drug industry that promotion represents a classic case of disease mongeringmdasha risk factor has been transformed into a medical disease in order to sell tests and drugs to relatively healthy women
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Drugs for pre-osteoporosis prevention or disease mongering
bull To treat 133 (95 confidence interval 104 to 270) women for three years to prevent a single vertebral fracture In other words up to 270 women with pre-osteoporosis might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Steven R Cummings University of California San
Francisco 2003 JAMA 20062962601-2610
bull There is no basis no biological social economic or treatment basis no basis whatsoever
bull As a consequence though more than half of the population is told arbitrarily that they have a condition they need to worry about
bull Osteopenia is not a disease and the label can cause unnecessary anxiety
bull Osteopenia by itself is not an indication for treatment
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Osteopenia To Treat or Not To TreatMichael R McClung MD Annals of Internal Medicine
May 3 2005vol 142 no 9 796-7
bull Fracture risk depends not on BMD valuebull Independent risk factors are
ndash age ndash previous fracture ndash the tendency to fall ndash BMD in older women are at substantially greater risk
for fracture than younger postmenopausal women ndash Moreover younger postmenopausal women are more
likely to have fractures of the forearm or lower leg than the more serious hip and spine fractures experienced by elderly patients
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Osteopenia To Treat or Not To Treat
bull The diagnostic category of osteopenia in individual patients does not serve the clinical community well
bull Bone density measurement remains an important tool in assessing skeletal health
bull The determinants of fracture are complex and interesting than simply the T-score
bull The objective of using osteoporosis drugs is to prevent fractures
bull This can be accomplished only by treating patients who are likely to have a fracture not by simply treating T-scores
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Drugs for pre-osteoporosis prevention or disease mongering
ndash Drug treatment reduce the risk of fracture in women with Osteoporosis
ndash Drug marketing is being directed at women with Osteopenia with a low risk of fracture
ndash The rationale for this strategy comes from questionable post-hoc re-analyses that understate side effects and overstate potential benefits
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Change a number create a patient
The number of people with at least one of four major medical conditions has increased dramatically in the past decade because of changes in the definitions of disease The new definitions ultimately label 75 percent of the adult US population as diseased according to calculations by two Dartmouth Medical School researchers
Suddenly sick A special report by Susan Kelleher and Duff Wilson middot June 26 - June 30 2005 httpseattletimesnwsourcecomnewshealthsuddenlysicksickdefinitions26html
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Diagnosis Old Definition
New definition
People under Old
People under New
increase
Year
Diabetes Fasting Sugargt 140mgdl
Fasting gt 126mgdl
117 M 17 M 14 1997
Hypertension BP gt 160100 BPgt 14090 387 M 135 M 35 1997
Cholesterol gt 250mgdl gt 200mgdl 495 M 426 M 86 1998
Obesity(BMI)
BMIgt 27kgmsup2 BMIgt 25kgmsup2 706 M 305 M 43 1998
Prehypertension
Nil 12080 to13989
Nil 45 M - 2003
The Number Game
Source ldquoChanging Disease Definitions Implications for Disease PrevalencerdquoDrLisa Schwartz and Steven Woloshin Effective Clinical Practice MarchApril 1999
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Osteoporosis - treatment (and prevention of fragility fractures) - Management
NICE review Suspended
National Institute for Health and Clinical Excellence (NICE) UK was assessing the cost effectiveness of different interventions in the primary and secondary prevention of osteoporotic fractures in 2006 has suspended the project for preparing guidelines for treatment of osteoporosis as experts could not come to any conclusion after going through various published reports on the management of osteoporosis
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Fast Track
bull The absolute fracture risk in 50 yr woman with T score ndash3 is same that of an 80 yr old woman with a T score of ndash1
bull MORE trial The prevalence of fractures (not rate) is far greater with Osteopenia
bull ROTTERDAM trial 12 of non-vertebral fractures were in women with normal BMDs
bull NORA trial Of postmenopausal women who suffered a new fracture within 1 year 82 had Osteopenia
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
The Industry
bull Since 2003 annual sales of osteoporosis drugs have about doubled to $83 billion according to Kalorama Information a provider of market research on medicine
bull After a few years peak sales of any effective osteoporosis agent could reach well over $1 billion said McDonald
bull Market sales are predicted to reach $104 billion by 2011
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
The Industryhellip
bull Should the drug makers and their shareholders be worried about overcrowding No according to Lehman Brothers analyst Anthony Butler because there is no lack of patients needing drugs for osteoporosis treatment
bull A bone drug battle aheadSeven bone ailment blockbusters could crowd the market in 2007 analysts sayBy Aaron Smith CNNMoney staff writer
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Time Line - Fosamax Fosamax Sales
1996 $ 282 millions
1997 $ 531 millions
1998 $ 775 millions
1999 $ 104 billions
2000 $ 12 billions
2001 $ 16 billions
2002 $ 22 billions
2003 $ 27 billions
2004 $ 30 billions
Sources Food and Drug Administration World Health Organization Securities and Exchange Commission Preventive Services Task Force Science magazine
1999 ndash WHO panel recommends ways to measure osteoporosis burden on health systems but fails to disclose that eight of the 11 panelists were employed by drug companies
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Create a non-profit organization ldquoBone Measurement Instituterdquo Set up own factory to manufacture small portable peripheral scanning machines amp make machines affordable for individual doctors and clinics Tie-ups with other manufacturerslobby directly or through other organizations to governments to pass legislation allowing medical insurance plansCreate Direct To Consumer TV commercials Own scientific journals write or help in writing articles and sponsor articles in reputed journals Formation of National and International ldquoSocietiesrdquo amp ldquoFoundationsrdquo of Bone Bone and Mineral Densitometry Osteoporosis and Calcified TissueEvent creation like Bone and joint decade and world osteoporosis day
Game Plan
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
bull ldquoMenopause is the single most important cause of osteoporosisrdquo Merckrsquos targeted aids and brochures at younger women
bull The US FDA warned Merck in 1997 to stop this campaign
bull Congress passed the ldquoBone Mass Measurement Act in 1997rdquo It authorized Medicare to reimburse doctors for performing bone-density tests opening the door to coverage by other insurers
Merck - Menopause amp Osteoporosis
httpwwwfdagovcderwarnjuly97fosamaxpdf
httpwwwfdagovCDERwarnwarn2001htm
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Disease expands through marriage of marketing and machines
bull Merck pushes bone-measurement technology into doctors offices
bull Merck promoted portable bone-measuring devices for office use
bull Merck helped peripherals by funding trials and assisting doctors with submissions
By - Susan Kelleher Acircmiddot Seattle Times staff reporter
httpseattletimesnwsourcecomhtmlhealthsick3htmlSusan
June 28 2005
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Marrying machine to medicine
bull Merck bought the exclusive rights to one companys bone-testing technology
bull Merck gave loan to another company to help develop a different machine
bull Merck financed two other firms to increase the number of machines in doctors offices
bull Merck also created a leasing program so that doctors could finance the purchase of a machine large or small
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Merck establishes new nonprofit Bone Measurement Institute WEST POINT Pa Aug 31 1995PRNewswire
The Bone Measurement Institute will conduct activities to help increase the availability of bone measurement technologies increase their accessibility to physicians and reduce the cost of bone mass measurement to health care payersldquo It also will provide educational support to physicians about the role of bone measurements and promote scientific research and development of bone testing methodologies
Super salersquos Man Jeremy Allen
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Bone Measurement Institute
On its board were six of the most respected osteoporosis researchers in the country The institute itself had a rather slim staff Jeremy Allen was the only employee There was no payroll there was no building there was no office with the name Bone Measurement Institutersquo Allen says Essentially Allens desk at Merck was the only physical space the Bone Measurement Institute actually inhabited I was it he says
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Merck + CompuMed + Norland Deal 111996 -Executive summary
bull CompuMed (devices and computer technology for measuring physiological parameters) has licensed exclusive worldwide rights to its OsteoGram bone mineral density testing technology to Merck amp Co s non-profit subsidiary Bone Measurement Institute
bull Norland Medical Systems Inc + Merck Business Wire Feb 25 1997 - The objective of the agreement is to accelerate placement of peripheral bone measurement devices in physicians offices and clinics
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
A diagnosis was born
bull Medicare claims for screening exams increased from 77000 in 1994 to more than 15 million annually by 1999
bull The sale of peripheral machines went up more than 500 percent over the same period of time And through this process of testing and advertising eventually a cultural consensus took hold
bull Osteopenia simply became a condition that was seriously considered for treatment
bull A diagnosis was born
Annual bone density screening rates in North America increased by 263 from 2002 to 2007 amp people on Fosamax had increased by 153
Game plan worked
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
JAMAs Fosamax study funded by Merck
By - Martha Rosenberg Writer Jan 9 2007
Effects of Continuing or Stopping Alendronate After 5 Years of Treatment in the December 27 2006 issue of JAMA was funded and supported by contracts with Merck and Co according to JAMA it was designed jointly by the non-Merck investigators and Merck employees and written with editorial input from Merck throughout the processldquo
bull The studys 11 non-Merck authors disclosed 40 research grants consultancies and other financial relationships with drug companies including Eli Lilly Pfizer Roche SmithGlaxoKline Wyeth Novartis Procter amp Gamble and of course Merck
bull Three Merck authors disclosed they potentially own stock andor stock options
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Fosamax ndash Insufficiency fracturesbull A Merck-funded review paper published in
the NEJM on March 24 2010 concludes
bull ldquoThe occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare even among women who had
been treated with bisphosphonates for as long as 10 yearsrdquo
bull ldquoThe study was underpowered for definitive conclusionsrdquo
Give drug a ldquoHOLYDAYrdquo after 3 ndash 5 Yrs
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
The Hip Fractures Very high morbidity mortality and financial impact
bull 325000 patients sustain a hip fracture each year
bull 25 will enter a nursing homebull 50 will never reach their previous
functional capacity bull 25 will die within the first year after the
fracture
Age 75 to 85 + Co morbidity
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
The variables - Hip fractures
bull Different in different ethnic groups
bull Geographical locations
bull Genetic determinants of height and weight
bull Life style and social structure
bull Aging population
bull Life expectancy
bull And Female Male ratio in the population
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Hype about hip fractures
Published in The New York Times May 10 2010Company With Osteoporosis Treatment Wins the lsquoSuper Bowlrsquo By LORA KOLODNY
Courtesy of McCombs School of Business Texas Venture Labs
Biologics MD team competing at Global Moot Corp
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Incidence of hip fractures darrbull Hip Fracture Rates Decline In Canadabull 1985 ndash 2006 over the 21 years rates of hip fracture
declined 318 percent in females and 25 percent in males
bull The largest percentage decrease was observed among individuals age 55 to 64 years hip fracture rates decreased by almost one-half in females and about one-third in males in this age range
bull Overweight and obesity may contribute to reduced
fracture ratesWilliam D Leslie MD MSc of the University of Manitoba Winnipeg Canada
JAMA 2009302[8]883-889
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Hip fractures on decline darrbull In Australia 1997-98 and 2006-07 years period
the incidence rate for osteoporotic hip fracture decreased by 14 for men and by 20 for women
bull In the United States hip fracture rates and subsequent mortality among persons 65 years and older are declining Carmen A Brauer-JAMA 2009302(14)1573-1579
bull Declining hip fracture rates in the United StatesAge and Ageing 2010 39(4)500-503 doi101093ageingafq044 -Judy A Stevens and Rose Anne Rudd
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Hip fractures on decline darr
bull Nationwide Decline in Incidence of Hip Fracture in Finland
Pekka Kannus et al J Bone Miner Res 2006211836ndash1838 Published online on August 28 2006 doi 101359JBMR060815
bull Declining incidence of hip fractures and the extent of use of anti-osteoporotic therapy in Denmark 1997-2006 Osteoporosis Int 2010 Mar21(3)373-80 Epub 2009 May 13 Abrahamsen B Vestergaard P
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Fewer Hip fracturesA study of Canadian Hospital data found that rates of hipfractures have declined significantly over past two decadesSource JAMA 2009302[8]883-889
Published in The New York Times
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Treatment and controversybull T-score between -10 and -25 at the femoral
neck or spine and a 10-year probability of hip fracture ge3 or a 10-year probability of major osteoporotic fracture ge10
bull Actual benefits of drugs may be marginal bull Approximately 270 women with osteopenia
might need to be treated with drugs for three years so that one of them could avoid a single vertebral fracture
BMJ 2008336126-129 (19 January) doi101136bmj39435656250AD
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Incidence of clinically diagnosed vertebral fractures Cooper C Atkinson EJ OFallon WM Melton LJ
J Bone Miner Res 19927221-7
bull Although most fractures due to osteoporosis present clinically vertebral fractures may be asymptomatic in as many as two thirds of patients
bull Although osteoporosis indicates a high likelihood of fracture many fragility fractures occur in people with bone density values above the defined level
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Osteoporosis ndash a deficiency state
bull Osteoporosis is now more of a deficiency disease rather than a metabolic adjustment
bull Vit D + Calcium supplementations in early life for higher peak bone mass
bull No convincing literature on protective effect of supplementations start early in pre or post menopause
bull Benefit in terms of reduced fracture risk has been quoted for home bound population above the age of 65 years
bull Vit D helps in fall prevention due to better muscle strength
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Bisphosphonates have reduced vertebral fractures in clinical trials of efficacy when about 90 of patients complied with three years of treatment However if a T score of ndash25 is used as the indication for treatment the cost of preventing one vertebral fracture is about pound23 500 and 70 of fractures would still occur in the population Adjusting the threshold to treat more people would sharply increase the costs per averted fracture
Drug treatment is not a panacea
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
What is not Talked - Fosamax
bull Less than 1 absorption by oral intake
bull Immediate attachment to Hydroxyapatite
bull Excretion by Kidney
bull Cardiac check up ndash Atrial Fibrillation
bull Renal check up ndash Retention in the body
bull Dental check up ndash Osteonecrosis of Jaw
bull GI check up ndash Oesophagitis Gastritis Ca
bull Metabolic check up ndash Hypocalcaemia
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
What is not Talked - Fosamax
bull No known Metabolism of the drug in Vivobull Remains in body for ever and goes for recyclingbull Insufficiency fracturesbull Immediate Osteoclasts apoptosisbull Osteoblastic activity continuesbull Mineralization and maturation take long timebull Increased BMD is due to non absorption of
hydroxyapatite and continued mineralizationbull Increased mineral content with diminished
elasticity increased brittleness
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Cost-Effectiveness of Alendronate Therapy for Osteopenic Postmenopausal WomenJohn T Schousboe MD MS Annals of Internal Medicine
May 3 2005vol 142 no 9 734-741
bull Alendronate therapy for postmenopausal women with femoral neck T-scores better than minus25 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective assuming US costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Under idealized circumstances 577 postmenopausal women must be treated for one year to avert one hip fracture at a cost of about pound120 000Among women older than 80 (a high risk population) for whom drug therapy would theoretically be most effective prevention of one hip fracture costs about pound28 500 This case-finding strategy however would prevent only about 20 of hip fractures occurring in the total population
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Effect of Risedronate on the risk of hip fracture in elderly women
McClung MR Geusens P Miller PD Zippel H Bensen WG Roux C et al
N Engl J Med 2001344333-40
bull The only adequately sized clinical trial assessing the efficacy of bisphosphonates on hip fracture among this older age group found no significant effect Additionally the efficacy expense and adverse effects of osteoporosis drugs have not been examined in nursing homes where many hip fractures occur
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
women with low BMD + fragility fracture of SpineFracture of the spine - 12 out of 100 women with placebo - 6 out of 100 women with alendronateFracture in the hip or wrist - 2 out of 100 women with placebo - 1 out of 100 women with alendronateFractures in bones other than the spine - 9 out of 100 women placebo - 7 out of 100 women alendronate
Cochrane Review Alendronate amp Risedronate
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
women with normal BMD and no fragility fractures of their spineFracture of the spine - 3 out of 100 women with placebo - 1 out of 100 women with alendronate Fractures in bones other than the spine - 1 out of 100 women with placebo - 1 out of 100 women with alendronate
- 3 out of 100 women with placebo - 4 out of 100 women with alendronate - 13 out of 100 women with placebo - 12 out of 100 women with alendronate
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Cochrane review Risedronate
Risedronate for preventing fractures by osteoporosis
In women with low BMD with or without fracture
probably prevents fractures in the bones of the spine and in bones other than in the spine- may prevent hip fractures- may not lead to any difference in wrist fractures
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Cochrane reviewhellip
bull In women with normal BMD and no fracture
may not lead to any difference in fractures in the bones of the spine hip fractures or wrist fractures
there is not enough information to tell if Risedronate prevents fractures in bones other than in the spine
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
What should you do
1 you should prescribe antiresorptive agents after the age of 65 just because the patient will develop osteoporosis
2 you should prescribe antiresorptive agents after the age of 65 just because the patient has osteoporosis and might develop a fragility fracture
3 you should prescribe antiresorptive agents after you have fixed a fragility fracture
4 you should prescribe exercises calcium of 1000 mgday and Vit D at 700 iuday for reducing the risk of fracture in elderly patients
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
The NEW Interactive IOF One-Minute Osteoporosis Risk Test
19 easy questions to help you understand the status of your bone health
Your language Your gender
Woman Man
httpwwwiofbonehealthorgpatients-publicrisk-testhtml
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Few Simple ways
bull If you are or consider your self Obesebull If you are exposed to Sun during your
shopping in open markets at least twice a week
bull If you take Milk and you are a vegetarianbull If you are taking regular Morning walkbull If you are regular about exercises (YOGA)
bull Your Death is not due to Fractures but due to age and co morbidity
You need not know about your T-score
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
Summary
ndash Globalization of Diagnosis of Osteoporosis amp Osteopenia
ndash BMD screeningndash Redefining Risk factors amp role of fall and BMD in
fracturesndash Cost effectiveness of drug treatmentndash Hype about Hip fractures ndash Role of Big Pharma in propaganda of diagnosis
management corruption in scientific literature misuse political system and creation a state of
ldquoFear psychosis amp Hope sellingrdquo
There is an acute need for reconsidering
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
A lie told often enough becomes the truth Vladimir Lenin
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
DISCLAIMERbull It is intended for use only by the students of orthopaedic surgery bull Views and opinion expressed in this presentation are personalbull For any confusion please contact the sole author for clarificationbull Every body is allowed to copy or download and use the material best suited to him I am not responsible for any controversies arise out of this presentation
IMPORTANT INFORMATIONAll animation slides are taken from ldquoOsteoporosis and Bone Physiologyrdquo web site 1999 - 2006 httpcourseswashingtonedubonephys of Dr Susan Marie Ott MD Some details are taken from an article by Alix Spiegel - Related NPR StoriesSome of the photographs are taken from IOF web siteSome of the photographs are taken from The New York Times and from article By Susan Kelleher Acircmiddot Seattle Times staff reporterSome slides are from ldquoWikipediardquoSome slides are from teaching slides of British Medical JournalIf there is any copy right violation please notify immediately Most of the quotes used have their authorrsquos name under it For any omission please inform naneriayahoocom
