Advances in Diagnosis and Treatment of Osteoporosis

7/30/2019 Advances in Diagnosis and Treatment of Osteoporosis

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ADVANCES IN DIAGNOSIS &

TREATMENT OF

OSTEOPOROSISJerry Tenenbaum MD FRCPC

Professor of Medicine:University of Toronto

Mount Sinai Hospital


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DISCLOSURES

SPEAKER ON OCCASION FOR

1. P&G

2. Pfizer3. Merck

4. Novartis


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GOAL

Review advances in the diagnosis and

treatment of osteoporosis


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OBJECTIVES

1. Show the impact of osteoporosis on the

health of the elderly

2. Advise on screening and diagnosis of

osteoporosis

3. Outline evidence-based treatment


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Osteoporosis

Osteoporosis is defined as a skeletaldisorder characterized by compromised

bone strength predisposing to an

increased risk of fracture.NIH Consensus Development Conference, March 2000

Normal Bone Osteoporotic Bone


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Vertebral Fracture Cascade


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THE HUMAN COSTDownward Spiral


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Definition of a Fragility Fracture

A fragility fracture is one that resultsfrom mechanical forces that would

not ordinarily cause fracture in ahealthy young adult.

This is quantified as forcesequivalent to a fall from a standingheight or less.


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Osteoporosis

8 million Osteoporotic Women and 2.5 million Osteoporotic Men in USAExpected to increase by about 40% by 2020 1

Estimated Direct costs in 2001 = $ 11.6 - 17.1 billion annually 1

Based on relative older Canadian population 2 &

Australian estimates of 7:1 ratio for Indirect to direct costs 3

$6 - $40 million every single day in Canada

Mortality increased 2-3 fold in women and women

after all types of Osteoporotic fractures 4

1 Surgeon-Generals Report2 Canadian and US census data

3

Access Economics,4

Center 1999


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Prevalence of VCFs

Lifetime prevalence in Caucasians:15% in women

5-9% in men

Higher than risk of breast cancer


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Osteoporotic fractures, Cardiovascular events &Breast cancer

in osteoporotic postmenopausal women

No prior spine fracture (938)

Prior spine fracture (1627)

0

20

40

60

80

100

120

from Silverman et al, 2004

J Am Geriatr Soc 52:1543-8

Eventsper 1000women-yr

MORE studyplacebo armover 3 years


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SITE INCREASE IN

MORTALITY RISK

Vertebrae 8.6

Hip 6.7

Any Clinical Fracture 2.2

Fracture and Mortality Risk


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Each year, one in three Ontarians over the ageof 65 will take a serious tumble that may landthem in hospital with a broken hip. One in threeof those who do break their hip will die within

a year. Two thirds will experience dementia-likesymptoms. Most will never see home again.


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Osteoporosis-associatedMortality

Age-standardised mortality riskincreased 2-3 fold

after all types of osteoporotic fracture

Women MenProximal femur 2.2 3.2

Vertebral 1.7 2.4

Other major 1.9 2.2

Center et al, Lancet 1999


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THE CARE GAPIN OSTEOPOROSIS

Despite the introduction of methods toidentify those with osteoporosis anddespite effective treatment, a largecare gap continues to exist for these

patients.


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THE TIP OF THE ICEBERG

ASSESSMENTMANAGEMENT


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Recommendat ions for Bone

Mineral Density Repo rt ing inCanada.

Siminoski K, Leslie WD, Brown JP, Frame H, Hodsman A,

Josse RG, Khan A, Lentle BC, Levesque J, Lyons DJ, Tarulli G

Can Assoc Radiol J 2005; 56: 178-188


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2002 Definitions: BMD Results

1. Kanis JA, et al. J Bone Miner Res 1994;9:1137-1141.

2. WHO, Geneva1994.

Status1, 2 T-score

Normal +2.5 to 1.0, inclusive

Osteopenia Between 1.0 and 2.5

Osteoporosis 2.5Severe osteoporosis 2.5 + fragility fracture


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ABOUT

T-SCORES?

Advantages

Unitless

Basis for the majority ofosteoporosis guidelines

Simplicity

Disadvantages

Depends on site measured

Depends on technology

Depends on referencedatabasepopulation mean

and standard deviationOnly includes BMD

information and not additionalrisk factors

Adapted from Faulkner K. Osteoporos Int 2005;16(4):347-52.


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Fracture Risk

vs. BMD

At Different Ages

BMD PREDICTS FRACTURES

Hui et al. J Clin Invest 1988; 81:1804-9


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AGE T-Score

= -1.0

T-Score

= -2.5

50 6 % 11 %

60 8 % 16 %

70 12 % 23 %

80 13 % 26 %

Risk of Fractures Over 10 Years in Women


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Proposed Change

Previous OSC guidelines advised interventionbased on WHO category as a marker of relative

fracture risk.

Now propose that an individuals 10-yearabsolute fracture risk, rather than BMD alone,be used for fracture risk categorization


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5-STEPS IN

TREATING OSTEOPOROSIS

STEPS 1 and 2

Begin with the table appropriate forthe patients sex

Identify the row that is closest tothe patient's age


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CATEGORIZATION BASED ON 10-YEARFRACTURE RISK

Absolute fracture risk in 10 years:

low: 20%


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USING LOWEST T-SCORE TO FIND 10-YEAR

FRACTURE RISK - WOMEN

WOMEN

-4.5

-4.0

-3.5

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

50 55 60 65 70 75 80 85

AGE (years)

LOWESTT-Score

Moderate Risk

High Risk

LowRisk


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5-STEPS IN


STEP 3

Determine the preliminary fracture riskcategory by using the lowest T-score

from the recommended skeletal sites


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5-STEPS IN


STEP 4

Evaluate clinical factors that may movethe patient into an even higher fracture

risk category


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USING LOWEST T-SCORE TO FIND 10-YEARFRACTURE RISK - MEN

MEN

-4.5

-4.0

-3.5

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

50 55 60 65 70 75 80 85

AGE (years)

LOWESTT-Score

Low Risk

High Risk

Moderate Risk


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Additional Clinical Factors

Certain clinical factors increase fracture

risk independent of BMD.The most important are:

Fragility fractures after age 40 (especially

vertebral compression fractures) Systemic glucocorticoid therapy >3 months

duration.


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Additional Risk Factors

Each factor effectively increases risk

categorization to the next level: from low risk to moderate risk, or

from moderate risk to high risk

When both factors are present thepatient should be considered at high

risk regardless of the BMD result.


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5-STEPS IN


STEP 5

Determine the individuals final

absolute fracture risk category.


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Woman age 52

- t is -2.6

Fracture Risk Category?

CASE EXAMPLE


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High Risk

Moderate RiskLow Risk

WOMEN

-4.5

-4.0

-3.5

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

50 55 60 65 70 75 80 85

AGE (years)

LOWESTT-Sc

ore

CASE EXAMPLE

Low Risk

Moderate Risk

High Risk


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AGE LOW MODERATE HIGH

20%

50 >-2.3 -2.2 to -3.9 -1.9 1.9 to -3.4 -1.4 -1.4 to -3.0 -1.0 -1.0 to -2.6 -0.8 -0.8 to -2.2 -0.7 -0.7 to -2.1 -0.6 -0.6 to -2.0 -0.7 -0.7 to -2.2


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Fracture Risk CategoryModerate Risk

CASE EXAMPLE


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Fracture Risk Category

High Risk

Moderate Risk

If Fragility Fracture History

CASE EXAMPLE


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70 year-old man

CASE EXAMPLE

Lowest T-score2.7 in total hip

BMD done because of strong family

history of osteoporosis (mother fractured hip, sisterhas OP)


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USING LOWEST T-SCORE TO FIND 10-YEARFRACTURE RISK - MEN

MEN

-4.5

-4.0

-3.5

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

50 55 60 65 70 75 80 85

AGE (years)

LOWESTT-Scor

e

Low Risk

High Risk

Moderate RiskX


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Moderate Risk

CASE EXAMPLE


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OTHER ISSUES FOR THIS 70

YEAR OLD MALE

Chest x-ray mild loss of vertebral height

at T4, T5

What if he had had polymyalgia

rheumatica at age 69 and was on

prednisone 10 mg./day?


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Moderate Risk

If Fragility Fracture History,

Corticosteroid use

High Risk

CASE EXAMPLE


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Endorsements

Canadian Association of Nuclear Medicine

Canadian Association of Radiologists

Canadian Rheumatology Association

International Society of Clinical Densitometry

Society of Obstetricians and Gynecologists of Canada

Canadian Society of Endocrinology and MetabolismCanadian Orthopedic Association

College of Family Physicians of Canada


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Osteoporosis Prevention andTreatment

Age

Hormonal Replacement

Bisphosphonates

Strontium

SERM

20 40 60 80

Vitamin D

PTH

Life Style

Treatmentchoice

Antifracture efficacy of antiosteoporotic agents


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* with prev vert fracture(s) ** without prev vert fractures *** with or without prev verfractures

Antifracture efficacy of antiosteoporotic agents

0.6 1.00.2

Incident nonvertebralfractures

Relative risk

RLX 60, 120(MORE)***

CT 200 (PROOF)*

Teriparatide 20g*

ALN 5/10 (FIT1)*

ALN 5/10 (FIT2)**

RIS 5 (VERT-NA)*RIS 5 (VERT-MN)*RIS 2.5/5 (Hip Study)***

Incident vertebralfractures

Relative risk

0.6 1.00.2

RLX 60 (MORE)*

RLX 60 (MORE)**

CT 200 (PROOF)*

Teriparatide 20g*

ALN 5/10 (FIT1)*

ALN 5/10 (FIT2)**

RIS 5 (VERT-NA)*

RIS 5 (VERT-MN)*

Strontium ranelate(SOTI)*

Strontium ranelate(SOTI +TROPOS)**

Strontium ranelate(TROPOS)***

Strontium ranelate(SOTI)*

Updated from Delmas, Lancet 2002

RR 95% CI


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Medications Available for

Post-Menopausal Osteoporosis

Actonel(risedronate sodium tablets) (1/day;1/wk; 1/mo)

Didrocal (etidronate sodium tablets)

Fosamax(alendronate sodium tablets) 1day/1/wk; Fosovance)

Aclasta (zolendronate IV)

Estrogen (some use)

Evista(raloxifene HCl)

Miacalcin (calcitonin salmon) Nasal Spray

Forteo (Teriparatide) (sc)

Consult with your physician to determine what medication may

be best for you


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Bisphosphonates Cyclical

Etidronate

p=NS

0

10

20

30

40

50

18

Etidronate (n = 20)

43

Placebo (n = 20)

Lumbarspinefr

acturerate

(fractures/100pa

tient-years)

Storm T. N Engl J Med1990;322:1265.

3-year RCT, 66 subjects

High risk subgroup: reduction in fracture rate with etidronate,p = 0.023

No statistically significant effect at nonvertebral sites

Cumulative Hip Fracture


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Cumulative Hip Fracture

Incidence

Baseline Month 6 Month 12

%o

fc

ohortwithahipfracture

0.00

0.10

0.20

0.30

0.40

0.50

0.58

alendronate

risedronate

Silverman SL. Osteoporos Int 2007 Jan;18(1):25-34. Epub 2006 Nov 15.

43%*

Adjusted Relative RateReduction at Month 12

p = 0.01

95% CI: 13% - 63%

46%*

Adjusted Relative RateReduction at Month 6

p = 0.02

95% CI: 9% - 68%

80 fracturesn= 21,615

29 fracturesn = 12,215


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Osteoporosis in Men

Has Its Time Come?

HEADLINES


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HEADLINES

7.8.07

HIP FRACTURES


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HIP FRACTURES

MORBIDITY AND MORTALITY

One-third of all hip fractures occur in men and areassociated with as much illness and increased risk

of death as those that occur in women .

The average 50-year-old Caucasian man has a 13

per cent chance of having a fracture related toosteoporosis sometime in his remaining lifetime. A60-year-old Caucasian man has a 29 per centchance.

Dr. John Schousboe, Minneapolis 2007

M l O t i M bidit d


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Male Osteoporosis: Morbidity and

Mortality

As compared to women, while lifetime

fracture risk may be less,

Men have higher rates of morbidity and

mortality due to fractures

Men are twice as likely to die in hospital after

a hip fracture

Men have a higher mortality rate than womenone year after a hip fracture

Cooper C, et al. Osteoporos Int 1992;2:285-9; Singer BR, et al. J Bone Joint Surg

Br 1998;80:243-8; Center JR, et al. The Lancet 1999;353:878-82; Forsen L, et al.

Osteoporos Int 1999;10:73-8; Johnell O., et al. Calcif Tissue Int 2001;69:182-4;Amin S. Curr Osteoporos Rep 2003;1:71-7; Campion JM, et al. Am Fam Phys


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GLUCOCORTICOIDS and BONE

Have a reflex! SGC > 3 mo > 7.5 mg./day

-Ca, vitamin D, bisphosphonate

Bone density evaluation?


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Back injuries. If you think that golf is for wimps, considerthis: A golf swing puts a higher compressive load on thelow back (8 times body weight) than running (3 times) oreven rowing (7 times). Thats why a single swing canproduce a herniated disc or even a compression fracture

of one of the vertebral bodies. Although these injuriesare extremely painful and can be quite serious, they arerare. Muscle strains, however, are quite commonbecause of the twisting that is required for a good swing.The modern swing, with its inverted-C follow-through,may make for longer drives than the classic swing but italso produces more torque and more injuries (seeGolf injuries above).

Harvard Mens Health Watch Aug 2004

SUMMARY


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SUMMARY

REDUCING THE CARE GAP

Assess bone health in woman >50 and in

men > 60.

Evaluate risk factors; evaluate BMD

Consider preventative approach to

reduction of fracture risk (the way you

think of hypertension and MI and stroke)

Treat and monitor

Documents

Advances in Diagnosis and Treatment of Osteoporosis