3 Osteoporosis

8/9/2019 3 Osteoporosis

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Osteoporosis

Osteoporosis (porous bones, from Greek:/ostoun meaning bone and /porosmeaning pore) is a progressive bone disease that ischaracterized by a decrease in bone mass and densitywhich can lead to an increased risk offracture.[1] In os-teoporosis, thebone mineral density(BMD) is reduced,bone microarchitecture deteriorates, and the amountand variety of proteins in bone are altered. Osteoporosisis defined by the World Health Organization (WHO)as a bone mineral density of 2.5 standard deviations

or more below the mean peak bone mass (average ofyoung, healthy adults) as measured bydual-energy X-rayabsorptiometry; the term established osteoporosisincludes the presence of a fragility fracture.[2] Thedisease may be classified as primary type 1, primary type2, or secondary. The form of osteoporosis most commonin women aftermenopauseis referred to as primary type1 or postmenopausal osteoporosis, which is attributableto the decrease in estrogen production after menopause.Primary type 2 osteoporosis or senile osteoporosisoccurs after age 75 and is seen in both females and malesat a ratio of 2:1. Secondary osteoporosis may arise atany age and affect men and women equally; this form

results from chronic predisposing medical problemsor disease, or prolonged use of medications such asglucocorticoids, when the disease is called steroid- orglucocorticoid-induced osteoporosis.

The risk of osteoporosis fractures can be reduced withlifestyle changes and in those with previous osteoporosisrelated fractures, medications. Lifestyle change includesdiet, exercise, andpreventing falls. A review by the U.S.Preventive Services Task Force (USPSTF) found insuf-ficient evidence to recommend calciumandvitamin Dsupplements to prevent fractures.[3] Bisphosphonatesareuseful in those with previous fractures from osteoporosis

but are of minimal benefit in those who have osteoporosisbut no previous fractures. Osteoporosis is a componentof thefrailty syndrome.

1 Signs and symptoms

Osteoporosis itself has no symptoms; its main conse-quence is the increased risk of bone fractures. Osteo-poroticfracturesoccur in situations where healthy people

would not normally break a bone; they are therefore re-garded as fragility fractures. Typical fragility fracturesoccur in thevertebral column,rib, hip andwrist.

Osteoporosis is an age-related disorder that causes the gradual

loss of bone density and strength. When the thoracic vertebrae

are affected, there can be a gradual collapse of the vertebrae.

This results in kyphosis, an excessive curvature of the thoracic

region.

Illustration depicting normal standing posture and osteoporosis

1
https://en.wikipedia.org/wiki/Wristhttps://en.wikipedia.org/wiki/Ribhttps://en.wikipedia.org/wiki/Vertebral_columnhttps://en.wikipedia.org/wiki/Fractureshttps://en.wikipedia.org/wiki/Asymptomatichttps://en.wikipedia.org/wiki/Frailty_syndromehttps://en.wikipedia.org/wiki/Bisphosphonatehttps://en.wikipedia.org/wiki/Vitamin_Dhttps://en.wikipedia.org/wiki/Calciumhttps://en.wikipedia.org/wiki/Fall_preventionhttps://en.wikipedia.org/wiki/Glucocorticoid-induced_osteoporosishttps://en.wikipedia.org/wiki/Glucocorticoidhttps://en.wikipedia.org/wiki/Senile_osteoporosishttps://en.wikipedia.org/wiki/Menopausehttps://en.wikipedia.org/wiki/Fragility_fracturehttps://en.wikipedia.org/wiki/Dual-energy_X-ray_absorptiometryhttps://en.wikipedia.org/wiki/Dual-energy_X-ray_absorptiometryhttps://en.wikipedia.org/wiki/Standard_deviationhttps://en.wikipedia.org/wiki/World_Health_Organizationhttps://en.wikipedia.org/wiki/Bone_mineral_densityhttps://en.wikipedia.org/wiki/Bone_fracturehttps://en.wikipedia.org/wiki/Diseasehttps://en.wikipedia.org/wiki/Bone


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2 2 RISK FACTORS

1.1 Fractures

Fractures are the most dangerous aspect of osteoporosis.Debilitating acute and chronic pain in the elderly is oftenattributed to fractures from osteoporosis and can lead tofurther disability and early mortality.[4] These fractures

may also be asymptomatic. The most common osteo-porotic fractures are of the wrist, spine, shoulder and hip.Thesymptoms of a vertebral collapse ("compression frac-ture") are suddenback pain, often with radicular pain(shooting pain due to nerve root compression) and rarelywithspinal cord compressionorcauda equina syndrome.Multiple vertebral fractures lead to a stooped posture, lossof height, and chronic pain with resultant reduction inmobility.[5]

Fractures of the long bones acutely impair mobility andmay requiresurgery. Hip fracture, in particular, usuallyrequires prompt surgery, as serious risks are associated

with it, such asdeep vein thrombosisandpulmonary em-bolism, and increased mortality.

Fracture risk calculators assess the risk of fracture basedupon several criteria, includingBMD, age, smoking, al-cohol usage, weight, and gender. Recognized calculatorsincludeFRAX[6] and Dubbo.

1.2 Falls risk

Theincreased risk of falling associated with aging leads tofractures of the wrist, spine, and hip. The risk of falling,

in turn, is increased by impaired eyesight due to anycause (e.g. glaucoma, macular degeneration), balancedisorder,movement disorders(e.g.Parkinsons disease),dementia, and sarcopenia (age-related loss of skeletalmuscle).Collapse(transient loss of postural tone with orwithout loss of consciousness) leads to a significant riskof falls; causes of syncope are manifold, but may includecardiac arrhythmias(irregular heart beat),vasovagal syn-cope, orthostatic hypotension(abnormal drop in bloodpressure on standing up), andseizures. Removal of ob-stacles and loose carpets in the living environment maysubstantially reduce falls. Those with previous falls, aswell as those with gait or balance disorders, are most atrisk.[7]

2 Risk factors

Risk factors for osteoporotic fracture can be split betweennonmodifiable and (potentially) modifiable. In addition,osteoporosis is a recognized complication in specific dis-eases and disorders. Medication use is theoretically mod-ifiable, although in many cases, the use of medication thatincreases osteoporosis risk may be unavoidable. Caffeine

is not a risk factor for osteoporosis.

[8]

It is more likely for a female to get osteoporosis than amale.[9]

2.1 Nonmodifiable

Bone density peaks at about 30 years of age. Women lose bone

mass more rapidly than men.

The most important risk factors for osteoporosis areadvanced age (in both men and women) andfemalesex; estrogen deficiency following menopause oroophorectomy is correlated with a rapid reductionin bone mineral density, while in men, a decrease intestosterone levels has a comparable (but less pro-nounced) effect.[10][11]

Race: While osteoporosis occurs in people from allethnic groups,EuropeanorAsianancestry predis-poses for osteoporosis.[12]

Heredity: Those with afamily historyof fracture orosteoporosis are at an increased risk; theheritabilityof the fracture, as well as low bone mineral den-sity, are relatively high, ranging from 25 to 80%. Atleast 30 genes are associated with the developmentof osteoporosis.[13]

Those who have already had a fracture are at leasttwice as likely to have another fracture comparedto someone of the same age and sex.[14] Earlymenopause/hysterectomy is another predisposingfactor.

Build: A small stature is also a nonmodifiablerisk factor associated with the development ofosteoporosis.[1]

2.2 Potentially modifiable

Excess consumption of alcohol: Although smallamounts of alcohol are probably beneficial (bonedensity increases with increasing alcohol intake),chronic heavy drinking (alcohol intake greater thanthree units/day) probably increases fracture risk de-spite any beneficial effects on bone density.[15][16]

Vitamin D deficiency:[17][18] Low circulating Vita-min D is common among the elderly worldwide.[19]
https://en.wikipedia.org/wiki/Vitamin_D_deficiencyhttps://en.wikipedia.org/wiki/Heritabilityhttps://en.wikipedia.org/wiki/Family_history_(medicine)https://en.wikipedia.org/wiki/Asian_peoplehttps://en.wikipedia.org/wiki/European_ethnic_groupshttps://en.wikipedia.org/wiki/Testosteronehttps://en.wikipedia.org/wiki/Estrogenhttps://en.wikipedia.org/wiki/Femalehttps://en.wikipedia.org/wiki/Caffeinehttps://en.wikipedia.org/wiki/Seizurehttps://en.wikipedia.org/wiki/Orthostatic_hypotensionhttps://en.wikipedia.org/wiki/Vasovagal_syncopehttps://en.wikipedia.org/wiki/Vasovagal_syncopehttps://en.wikipedia.org/wiki/Cardiac_arrhythmiahttps://en.wikipedia.org/wiki/Collapse_(medical)https://en.wikipedia.org/wiki/Skeletal_musclehttps://en.wikipedia.org/wiki/Skeletal_musclehttps://en.wikipedia.org/wiki/Sarcopeniahttps://en.wikipedia.org/wiki/Dementiahttps://en.wikipedia.org/wiki/Parkinson%2527s_diseasehttps://en.wikipedia.org/wiki/Movement_disorderhttps://en.wikipedia.org/wiki/Balance_disorderhttps://en.wikipedia.org/wiki/Balance_disorderhttps://en.wikipedia.org/wiki/Macular_degenerationhttps://en.wikipedia.org/wiki/Glaucomahttps://en.wikipedia.org/wiki/FRAXhttps://en.wikipedia.org/wiki/BMDhttps://en.wikipedia.org/wiki/Pulmonary_embolismhttps://en.wikipedia.org/wiki/Pulmonary_embolismhttps://en.wikipedia.org/wiki/Deep_vein_thrombosishttps://en.wikipedia.org/wiki/Hip_fracturehttps://en.wikipedia.org/wiki/Surgeryhttps://en.wikipedia.org/wiki/Cauda_equina_syndromehttps://en.wikipedia.org/wiki/Spinal_cord_compressionhttps://en.wikipedia.org/wiki/Radicular_painhttps://en.wikipedia.org/wiki/Back_painhttps://en.wikipedia.org/wiki/Compression_fracturehttps://en.wikipedia.org/wiki/Compression_fracturehttps://en.wikipedia.org/wiki/Vertebra


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2.3 Medical disorders 3

Mild vitamin D insufficiency is associated with in-creasedparathyroid hormone(PTH) production.[19]

PTH increases bone resorption, leading to boneloss. A positive association exists between serum1,25-dihydroxycholecalciferollevels and bone min-eral density, while PTH is negatively associated with

bone mineral density.[19]

Tobacco smoking: Many studies have associatedsmoking with decreased bone health, but the mech-anisms are unclear. Tobacco smoking has been pro-posed to inhibit the activity of osteoblasts, and isan independent risk factor for osteoporosis.[15][20]

Smoking also results in increased breakdown of ex-ogenous estrogen, lower body weight and earliermenopause, all of which contribute to lower bonemineral density.[19]

Malnutrition: Nutrition has an important and com-

plex role in maintenance of good bone. Identifiedrisk factors include low dietary calcium and/or phos-phorus, magnesium, zinc, boron, iron, fluoride, cop-per, vitamins A, K, E and C (and D where skin ex-posure to sunlight provides an inadequate supply).Excess sodium is a risk factor. High blood acid-ity may be diet-related, and is a known antagonistof bone.[21] Some have identified low protein in-take as associated with lower peak bone mass dur-ing adolescence and lower bone mineral density inelderly populations.[19] Conversely, some have iden-tified low protein intake as a positive factor, protein

is among the causes of dietary acidity. Imbalanceof omega-6 to omega-3 polyunsaturated fats is yetanother identified risk factor.[22]

High dietary protein: Research has found an as-sociation between diets high in animal protein andincreased urinary calcium,[23][24][25] and have beenlinked to an increase in fractures.[26] However, therelevance of this observation to bone density is un-clear, since higher protein diets tend to increase ab-sorption of calcium from the diet and are associ-ated with higher bone density.[27] Indeed, it has re-cently been argued that low protein diets cause poor

bone health.[28] No interventional trials have beenperformed on dietary protein in the prevention andtreatment of osteoporosis.[29]

Underweight/inactive: Bone remodeling occurs inresponse to physical stress, so physical inactivitycan lead to significant bone loss.[19] Weight bear-ingexercise can increase peak bone mass achievedin adolescence,[19] and a highly significant correla-tion between bone strength and muscle strength hasbeen determined.[30] The incidence of osteoporosisis lower in overweight people.[31]

Endurance training: In female endurance athletes,large volumes of training can lead to decreased bonedensity and an increased risk of osteoporosis.[32]

This effect might be caused by intense training sup-pressing menstruation, producingamenorrhea, andit is part of thefemale athlete triad.[33] However, formale athletes, the situation is less clear, and althoughsome studies have reported low bone density in elitemale endurance athletes,[34] others have instead seen

increased leg bone density.[35][36]

Heavy metals: A strong association betweencadmiumandleadwith bone disease has been es-tablished. Low-level exposure to cadmium is asso-ciated with an increased loss of bone mineral den-sity readily in both genders, leading to pain and in-creased risk of fractures, especially in the elderlyand in females. Higher cadmium exposure resultsinosteomalacia(softening of the bone).[37]

Soft drinks: Some studies indicate soft drinks (manyof which containphosphoric acid) may increase risk

of osteoporosis, at least inwomen.[38] Others sug-gest soft drinks may displace calcium-containingdrinks from the diet rather than directly causingosteoporosis.[39]

2.3 Medical disorders

Many diseases and disorders have been associated withosteoporosis.[40] For some, the underlying mechanisminfluencing the bone metabolism is straightforward,whereas for others the causes are multiple or unknown.

In general, immobilizationcauses bone loss (follow-ing the 'use it or lose it' rule). For example, local-ized osteoporosis can occur after prolonged immo-bilization of a fractured limb in a cast. This is alsomore common in active people with a high boneturn-over (for example, athletes). Other examplesinclude bone loss during space flight or in peoplewho are bedridden or use wheelchairs for variousreasons.

Hypogonadalstates can cause secondary osteoporo-sis. These include Turner syndrome, Klinefeltersyndrome, Kallmann syndrome, anorexia ner-vosa, andropause,[41] hypothalamicamenorrhea orhyperprolactinemia.[41] In females, the effect of hy-pogonadism is mediated by estrogen deficiency. Itcan appear as early menopause (1 year).Bilateral oophorectomy (surgical removal of theovaries) andpremature ovarian failure cause defi-cient estrogen production. In males, testosterone de-ficiency is the cause (for example, andropause or af-ter surgical removal of thetestes).

Endocrine disorders that can inducebone loss include Cushings syndrome,[19]
https://en.wikipedia.org/wiki/Cushing%2527s_syndromehttps://en.wikipedia.org/wiki/Testeshttps://en.wikipedia.org/wiki/Premature_ovarian_failurehttps://en.wikipedia.org/wiki/Oophorectomyhttps://en.wikipedia.org/wiki/Hyperprolactinemiahttps://en.wikipedia.org/wiki/Hypothalamushttps://en.wikipedia.org/wiki/Andropausehttps://en.wikipedia.org/wiki/Anorexia_nervosahttps://en.wikipedia.org/wiki/Anorexia_nervosahttps://en.wikipedia.org/wiki/Kallmann_syndromehttps://en.wikipedia.org/wiki/Klinefelter_syndromehttps://en.wikipedia.org/wiki/Klinefelter_syndromehttps://en.wikipedia.org/wiki/Turner_syndromehttps://en.wikipedia.org/wiki/Hypogonadismhttps://en.wikipedia.org/wiki/Space_flighthttps://en.wikipedia.org/wiki/Muscle_immobilizationhttps://en.wikipedia.org/wiki/Womenhttps://en.wikipedia.org/wiki/Phosphoric_acidhttps://en.wikipedia.org/wiki/Soft_drinkhttps://en.wikipedia.org/wiki/Osteomalaciahttps://en.wikipedia.org/wiki/Leadhttps://en.wikipedia.org/wiki/Cadmiumhttps://en.wikipedia.org/wiki/Heavy_metalshttps://en.wikipedia.org/wiki/Female_athlete_triadhttps://en.wikipedia.org/wiki/Amenorrheahttps://en.wikipedia.org/wiki/Weight_bearinghttps://en.wikipedia.org/wiki/Weight_bearinghttps://en.wikipedia.org/wiki/Bone_remodelinghttps://en.wikipedia.org/wiki/Physical_exercisehttps://en.wikipedia.org/wiki/Body_mass_indexhttps://en.wikipedia.org/wiki/Protein_in_nutritionhttps://en.wikipedia.org/wiki/Calciumhttps://en.wikipedia.org/wiki/Malnutritionhttps://en.wikipedia.org/wiki/Tobacco_smokinghttps://en.wikipedia.org/wiki/1,25-dihydroxycholecalciferolhttps://en.wikipedia.org/wiki/Parathyroid_hormone


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4 2 RISK FACTORS

The body regulates calcium homeostasis with two pathways; one

is signaled to turn on when blood calcium levels drop below nor-

mal and one is the pathway that is signaled to turn on when bloodcalcium levels are elevated.

hyperparathyroidism,[19] hyperthyroidism,[19]

hypothyroidism,diabetes mellitustype 1 and 2,[42]

acromegaly, andadrenal insufficiency. Inpregnancyandlactationcan cause reversible bone loss.[40]

Malnutrition, parenteral nutrition[19] andmalabsorptioncan lead to osteoporosis. Nutritionaland gastrointestinal disorders that can predisposeto osteoporosis includecoeliac disease,[19] Crohnsdisease,[43] Ulcerative colitis,[43] cystic fibrosis,[43]

lactose intolerance, surgery[41] (after gastrectomy,intestinal bypass surgery or bowel resection) andsevere liver disease (especially primary biliarycirrhosis).[41] People withbulimiacan also developosteoporosis. Those with an otherwise adequatecalcium intake can develop osteoporosis due to theinability to absorb calcium and/or vitamin D. Othermicronutrients such as vitamin K or vitamin B12deficiencymay also contribute.

People with rheumatologic disorders such asrheumatoid arthritis,[41] ankylosing spondylitis,[41]

systemic lupus erythematosus and polyarticularjuvenile idiopathic arthritis are at increased riskof osteoporosis, either as part of their disease orbecause of other risk factors (notably corticosteroidtherapy). Systemic diseases such as amyloidosisandsarcoidosiscan also lead to osteoporosis.

Renal insufficiencycan lead torenal osteodystrophy.

Hematologic disorders linked to osteoporosisare multiple myeloma[41] and other monoclonalgammopathies,[42] lymphoma and leukemia,mastocytosis,[41] hemophilia,sickle-cell diseaseandthalassemia.

Several inherited disorders have beenlinked to osteoporosis. These include

osteogenesis imperfecta,[41] Marfan syndrome,[41]

hemochromatosis,[19] hypophosphatasia[44] (forwhich it is often misdiagnosed),[45] glycogenstorage diseases,homocystinuria,[41] EhlersDanlossyndrome,[41] porphyria, Menkes syndrome,epidermolysis bullosaandGauchers disease.

People withscoliosis of unknown cause also havea higher risk of osteoporosis. Bone loss can be afeature of complex regional pain syndrome. It isalso more frequent in people with Parkinsons dis-ease andchronic obstructive pulmonary disease.

People withParkinsons diseasehave a higher riskof broken bones. This is related to poor balance andpoor bone density.[46] In Parkinsons disease theremay be a link between the loss of dopaminergic neu-rons and alteredcalcium metabolism[47] (and ironmetabolism) causing a stiffening of the skeleton and

kyphosis.

2.4 Medication

Certain medications have been associated with an in-crease in osteoporosis risk; only steroids and anticonvul-sants are classically associated, but evidence is emergingwith regard to other drugs.

Steroid-induced osteoporosis (SIOP) arises due touse of glucocorticoids analogous to Cushingssyndrome and involving mainly the axial skele-ton. The synthetic glucocorticoid prescription drugprednisone is a main candidate after prolonged in-take. Some professional guidelines recommendprophylaxis in patients who take the equivalent ofmore than 30 mg hydrocortisone (7.5 mg of pred-nisolone), especially when this is in excess of threemonths.[48] Alternate day use may not prevent thiscomplication.[49]

Barbiturates, phenytoin and some other enzyme-inducing antiepileptics these probably acceleratethe metabolism of vitamin D.[50]

L-Thyroxine over-replacement may contribute toosteoporosis, in a similar fashion as thyrotoxicosisdoes.[40] This can be relevant in subclinical hypothy-roidism.

Several drugs induce hypogonadism, for exam-ple aromatase inhibitors used in breast cancer,methotrexate and other antimetabolite drugs,depotprogesterone and gonadotropin-releasing hormoneagonists.

Anticoagulants long-term use of heparin is associ-ated with a decrease in bone density,[51] and warfarin

(and related coumarins) have been linked with anincreased risk in osteoporotic fracture in long-termuse.[52]
https://en.wikipedia.org/wiki/Warfarinhttps://en.wikipedia.org/wiki/Anticoagulanthttps://en.wikipedia.org/wiki/Gonadotropin-releasing_hormone_agonisthttps://en.wikipedia.org/wiki/Gonadotropin-releasing_hormone_agonisthttps://en.wikipedia.org/wiki/Depo-Proverahttps://en.wikipedia.org/wiki/Depo-Proverahttps://en.wikipedia.org/wiki/Methotrexatehttps://en.wikipedia.org/wiki/Aromatase_inhibitorshttps://en.wikipedia.org/wiki/L-Thyroxinehttps://en.wikipedia.org/wiki/Antiepileptichttps://en.wikipedia.org/wiki/Phenytoinhttps://en.wikipedia.org/wiki/Barbituratehttps://en.wikipedia.org/wiki/Prednisonehttps://en.wikipedia.org/wiki/Steroid-induced_osteoporosishttps://en.wikipedia.org/wiki/Kyphosishttps://en.wikipedia.org/wiki/Iron_metabolismhttps://en.wikipedia.org/wiki/Iron_metabolismhttps://en.wikipedia.org/wiki/Calcium_metabolismhttps://en.wikipedia.org/wiki/Dopaminergic_neuronhttps://en.wikipedia.org/wiki/Dopaminergic_neuronhttps://en.wikipedia.org/wiki/Parkinson%2527s_diseasehttps://en.wikipedia.org/wiki/Chronic_obstructive_pulmonary_diseasehttps://en.wikipedia.org/wiki/Complex_regional_pain_syndromehttps://en.wikipedia.org/wiki/Idiopathichttps://en.wikipedia.org/wiki/Scoliosishttps://en.wikipedia.org/wiki/Gaucher%2527s_diseasehttps://en.wikipedia.org/wiki/Epidermolysis_bullosahttps://en.wikipedia.org/wiki/Menkes_diseasehttps://en.wikipedia.org/wiki/Porphyriahttps://en.wikipedia.org/wiki/Ehlers%E2%80%93Danlos_syndromehttps://en.wikipedia.org/wiki/Ehlers%E2%80%93Danlos_syndromehttps://en.wikipedia.org/wiki/Homocystinuriahttps://en.wikipedia.org/wiki/Glycogen_storage_diseasehttps://en.wikipedia.org/wiki/Glycogen_storage_diseasehttps://en.wikipedia.org/wiki/Hypophosphatasiahttps://en.wikipedia.org/wiki/Hemochromatosishttps://en.wikipedia.org/wiki/Marfan_syndromehttps://en.wikipedia.org/wiki/Osteogenesis_imperfectahttps://en.wikipedia.org/wiki/Thalassemiahttps://en.wikipedia.org/wiki/Sickle-cell_diseasehttps://en.wikipedia.org/wiki/Hemophiliahttps://en.wikipedia.org/wiki/Mastocytosishttps://en.wikipedia.org/wiki/Leukemiahttps://en.wikipedia.org/wiki/Lymphomahttps://en.wikipedia.org/wiki/Monoclonal_gammopathyhttps://en.wikipedia.org/wiki/Monoclonal_gammopathyhttps://en.wikipedia.org/wiki/Multiple_myelomahttps://en.wikipedia.org/wiki/Renal_osteodystrophyhttps://en.wikipedia.org/wiki/Renal_insufficiencyhttps://en.wikipedia.org/wiki/Sarcoidosishttps://en.wikipedia.org/wiki/Amyloidosishttps://en.wikipedia.org/wiki/Juvenile_idiopathic_arthritishttps://en.wikipedia.org/wiki/Systemic_lupus_erythematosushttps://en.wikipedia.org/wiki/Ankylosing_spondylitishttps://en.wikipedia.org/wiki/Rheumatoid_arthritishttps://en.wikipedia.org/wiki/Vitamin_B12_deficiencyhttps://en.wikipedia.org/wiki/Vitamin_B12_deficiencyhttps://en.wikipedia.org/wiki/Vitamin_Khttps://en.wikipedia.org/wiki/Bulimiahttps://en.wikipedia.org/wiki/Primary_biliary_cirrhosishttps://en.wikipedia.org/wiki/Primary_biliary_cirrhosishttps://en.wikipedia.org/wiki/Liver_diseasehttps://en.wikipedia.org/wiki/Bowel_resectionhttps://en.wikipedia.org/wiki/Partial_ileal_bypass_surgeryhttps://en.wikipedia.org/wiki/Gastrectomyhttps://en.wikipedia.org/wiki/Cystic_fibrosishttps://en.wikipedia.org/wiki/Ulcerative_colitishttps://en.wikipedia.org/wiki/Crohn%2527s_diseasehttps://en.wikipedia.org/wiki/Crohn%2527s_diseasehttps://en.wikipedia.org/wiki/Coeliac_diseasehttps://en.wikipedia.org/wiki/Malabsorptionhttps://en.wikipedia.org/wiki/Parenteral_nutritionhttps://en.wikipedia.org/wiki/Lactationhttps://en.wikipedia.org/wiki/Pregnancyhttps://en.wikipedia.org/wiki/Adrenal_insufficiencyhttps://en.wikipedia.org/wiki/Acromegalyhttps://en.wikipedia.org/wiki/Diabetes_mellitushttps://en.wikipedia.org/wiki/Hypothyroidismhttps://en.wikipedia.org/wiki/Hyperthyroidismhttps://en.wikipedia.org/wiki/Hyperparathyroidism


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5

Proton pump inhibitors these drugs inhibit the pro-duction of stomach acid; this is thought to inter-fere with calcium absorption.[53] Chronicphosphatebinding may also occur withaluminium-containingantacids.[40]

Thiazolidinediones (used for diabetes) rosiglitazone and possibly pioglitazone, inhibitorsofPPAR, have been linked with an increased riskof osteoporosis and fracture.[54]

Chronic lithium therapy has been associated withosteoporosis.[40]

2.5 Evolutionary

Age related bone loss is common among humans due toexhibiting less dense bones than other primate species.[55]

Because of the more porous bones of humans, frequencyof severe osteoporosis and osteoporosis related fracturesis higher.[56] The human vulnerability to osteoporosis isan obvious cost but it can be justified by the advantage ofbipedalism inferring that this vulnerability is the byprod-uct of such.[56] It has been suggested that porous boneshelp to absorb the increased stress that we have on twosurfaces compared to our primate counterparts who havefour surfaces to disperse the force.[55] In addition, theporosity allows for more flexibility and a lighter skeletonthat is easier to support.[56] One other consideration maybe that diets today have much lower amounts of calciumthan the diets of other primates or the tetrapedal ances-tors to humans which may lead to higher likelihood toshow signs of osteoporosis.[57]

3 Pathogenesis

Osteoclast, with bone below it, showing typical distinguishing

characteristics: a large cell with multiple nuclei and a foamy

cytosol.

The underlying mechanism in all cases of osteoporosisis an imbalance betweenbone resorptionand bone for-mation. In normal bone, matrixremodeling of bone is

constant; up to 10% of all bone mass may be undergoingremodeling at any point in time. The process takes placein bone multicellular units (BMUs) as first described by

Frost in 1963.[58] Bone is resorbed by osteoclast cells(which derive from the bone marrow), after which newbone is deposited byosteoblastcells.[13]

The three main mechanisms by which osteoporosis de-velops are an inadequate peak bone mass (the skeleton

develops insufficient mass and strength during growth),excessive bone resorption, and inadequate formation ofnew bone during remodeling. An interplay of these threemechanisms underlies the development of fragile bonetissue.[13] Hormonal factors strongly determine the rateof bone resorption; lack of estrogen (e.g. as a resultof menopause) increases bone resorption, as well as de-creasing the deposition of new bone that normally takesplace in weight-bearing bones. The amount of estrogenneeded to suppress this process is lower than that nor-mally needed to stimulate the uterus and breast gland.The -form of theestrogen receptor appears to be themost important in regulating bone turnover.[13] In addi-

tion to estrogen,calcium metabolismplays a significantrole in bone turnover, and deficiency of calcium and vita-min D leads to impaired bone deposition; in addition, theparathyroid glandsreact to low calcium levels by secret-ing parathyroid hormone (parathormone, PTH), whichincreases bone resorption to ensure sufficient calcium inthe blood. The role ofcalcitonin, a hormone generatedby thethyroidthat increases bone deposition, is less clearand probably not as significant as that of PTH.[13]

Osteoblasts, several displaying a prominent Golgi apparatus, ac-

tively synthesizing osteoid containing two osteocytes.

The activation of osteoclasts is regulated by variousmolecular signals, of which the receptor activator fornuclear factor Bligand (RANKL) is one of best studied.This molecule is produced by osteoblasts and other cells(e.g. lymphocytes), and stimulatesRANK(receptor acti-vator of nuclear factor B). Osteoprotegerin (OPG) bindsRANKL before it has an opportunity to bind to RANK,and hence suppresses its ability to increase bone resorp-tion. RANKL, RANK and OPG are closely related totumor necrosis factorand its receptors. The role of theWnt signaling pathwayis recognized, but less well under-stood. Local production of eicosanoids and interleukins is

thought to participate in the regulation of bone turnover,and excess or reduced production of these mediators mayunderlie the development of osteoporosis.[13]
https://en.wikipedia.org/wiki/Interleukinhttps://en.wikipedia.org/wiki/Eicosanoidhttps://en.wikipedia.org/wiki/Wnt_signaling_pathwayhttps://en.wikipedia.org/wiki/Tumor_necrosis_factorhttps://en.wikipedia.org/wiki/Osteoprotegerinhttps://en.wikipedia.org/wiki/RANKhttps://en.wikipedia.org/wiki/Lymphocytehttps://en.wikipedia.org/wiki/RANKLhttps://en.wikipedia.org/wiki/NF-%CE%BABhttps://en.wikipedia.org/wiki/Thyroidhttps://en.wikipedia.org/wiki/Calcitoninhttps://en.wikipedia.org/wiki/Parathyroid_glandhttps://en.wikipedia.org/wiki/Calcium_metabolismhttps://en.wikipedia.org/wiki/Estrogen_receptorhttps://en.wikipedia.org/wiki/Mammary_glandhttps://en.wikipedia.org/wiki/Uterushttps://en.wikipedia.org/wiki/Osteoblasthttps://en.wikipedia.org/wiki/Bone_marrowhttps://en.wikipedia.org/wiki/Osteoclasthttps://en.wikipedia.org/wiki/Matrix_(biology)https://en.wikipedia.org/wiki/Bone_developmenthttps://en.wikipedia.org/wiki/Bone_developmenthttps://en.wikipedia.org/wiki/Bone_resorptionhttps://en.wikipedia.org/wiki/Lithiumhttps://en.wikipedia.org/wiki/Peroxisome_proliferator-activated_receptor_gammahttps://en.wikipedia.org/wiki/Pioglitazonehttps://en.wikipedia.org/wiki/Rosiglitazonehttps://en.wikipedia.org/wiki/Thiazolidinedionehttps://en.wikipedia.org/wiki/Antacidshttps://en.wikipedia.org/wiki/Aluminiumhttps://en.wikipedia.org/wiki/Phosphatehttps://en.wikipedia.org/wiki/Gastric_acidhttps://en.wikipedia.org/wiki/Proton_pump_inhibitors


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6 4 DIAGNOSIS

Trabecular bone(or cancellous bone) is the sponge-likebone in the ends of long bones and vertebrae. Corticalboneis the hard outer shell of bones and the middle oflong bones. Because osteoblasts and osteoclasts inhabitthe surface of bones, trabecular bone is more active, andis more subject to bone turnover and remodeling. Not

only is bone density decreased, but the microarchitectureof bone is also disrupted. The weaker spicules of tra-becular bone break (microcracks), and are replaced byweaker bone. Common osteoporotic fracture sites, thewrist, the hip and the spine, have a relatively high tra-becular bone to cortical bone ratio. These areas rely ontrabecular bone for strength, so the intense remodelingcauses these areas to degenerate most when the remodel-ing is imbalanced. Around the ages of 3035, cancellousor trabecular bone loss begins. Women may lose as muchas 50%, while men lose about 30%.[1]

4 Diagnosis

Multiple osteoporotic wedge fractures demonstrated on a lateral

thoraco-lumbar spine X-ray

The diagnosis of osteoporosis can be made using con-ventional radiography and by measuring the bone mineraldensity (BMD).[59] The most popular method of measur-ing BMD is dual-energy x-ray absorptiometry. In addi-

tion to the detection of abnormal BMD, the diagnosis ofosteoporosis requires investigations into potentially mod-ifiable underlying causes; this may be done with blood

tests. Depending on the likelihood of an underlying prob-lem, investigations forcancerwithmetastasisto the bone,multiple myeloma, Cushings disease and other above-mentioned causes may be performed.

4.1 Conventional radiography

Conventional radiography is useful, both by itself and inconjunction with CT or MRI, for detecting complicationsof osteopenia (reduced bone mass; preosteoporosis), suchas fractures; for differential diagnosis of osteopenia; orfor follow-up examinations in specific clinical settings,such as soft tissue calcifications, secondary hyperparathy-roidism, or osteomalacia in renal osteodystrophy. How-ever, radiography is relatively insensitive to detection of

early disease and requires a substantial amount of boneloss (about 30%) to be apparent on X-ray images.

The main radiographic features of generalized osteoporo-sis are cortical thinning and increased radiolucency. Fre-quent complications of osteoporosis are vertebral frac-tures for which spinal radiography can help considerablyin diagnosis and follow-up. Vertebral height measure-ments can objectively be made using plain-film X-raysby using several methods such as height loss together witharea reduction, particularly when looking at vertical de-formity in T4-L4, or by determining a spinal fracture in-dex that takes into account the number of vertebrae in-

volved. Involvement of multiple vertebral bodies leads tokyphosis of the thoracic spine, leading to what is knownasdowagers hump.

4.2 Dual-energy X-ray

Dual-energy X-ray absorptiometry(DXA) is consideredthegold standardfor the diagnosis of osteoporosis. Os-teoporosis is diagnosed when thebone mineral densityisless than or equal to 2.5 standard deviations below that

of a young (3040-year-old[19]:58), healthy adult womenreference population. This is translated as aT-score. Butbecause bone densitydecreases with age, more people be-come osteoporotic with increasing age.[19] :58 The WorldHealth Organization has established the following diag-nostic guidelines:[2][19]

The International Society for Clinical Densitometry takesthe position that a diagnosis of osteoporosis in men under50 years of age should not be made on the basis of densit-ometric criteria alone. It also states, for premenopausalwomen, Z-scores (comparison with age group rather thanpeak bone mass) rather than T-scores should be used,

and the diagnosis of osteoporosis in such women alsoshould not be made on the basis of densitometric crite-ria alone.[60]
https://en.wikipedia.org/wiki/Bone_density#T-scorehttps://en.wikipedia.org/wiki/Bone_densityhttps://en.wikipedia.org/wiki/Gold_standard_(test)https://en.wikipedia.org/wiki/Dual-energy_X-ray_absorptiometryhttps://en.wikipedia.org/wiki/Hyperkyphosishttps://en.wikipedia.org/wiki/Osteopeniahttps://en.wikipedia.org/wiki/Cushing%2527s_diseasehttps://en.wikipedia.org/wiki/Metastasishttps://en.wikipedia.org/wiki/Cancerhttps://en.wikipedia.org/wiki/Blood_testshttps://en.wikipedia.org/wiki/Blood_testshttps://en.wikipedia.org/wiki/Cortical_bonehttps://en.wikipedia.org/wiki/Cortical_bonehttps://en.wikipedia.org/wiki/Trabecular_bone


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4.3 Biomarkers

Chemicalbiomarkersare a useful tool in detecting bonedegradation. The enzyme cathepsin K breaks down type-I collagen protein, an important constituent in bones. Pre-pared antibodies can recognize the resulting fragment,

called a neoepitope, as a way to diagnose osteoporosis.[61]Increased urinary excretion of C-telopeptides, a type-Icollagen breakdown product, also serves as a biomarkerfor osteoporosis.[62]

4.4 Other measuring tools

Quantitative computed tomographydiffers from DXA inthat it gives separate estimates of BMD for trabecularand cortical bone and reports precise volumetric mineraldensity in mg/cm3 rather than BMDs relative Z score.

Among QCTs advantages: it can be performed at ax-ial and peripheral sites, can be calculated from existingCT scans without a separate radiation dose, is sensitiveto change over time, can analyze a region of any size orshape, excludes irrelevant tissue such as fat, muscle, andair, and does not require knowledge of the patients sub-population in order to create a clinical score (e.g. theZ-score of all females of a certain age). Among QCTsdisadvantages: it requires a high radiation dose comparedto DXA, CT scanners are large and expensive, and be-cause its practice has been less standardized than BMD,its results are more operator-dependent. Peripheral QCThas been introduced to improve upon the limitations ofDXA and QCT.[59]

Quantitativeultrasoundhas many advantages in assessingosteoporosis. The modality is small, no ionizing radia-tion is involved, measurements can be made quickly andeasily, and the cost of the device is low compared withDXA and QCT devices. The calcaneus is the most com-mon skeletal site for quantitative ultrasound assessmentbecause it has a high percentage of trabecular bone thatis replaced more often than cortical bone, providing earlyevidence of metabolic change. Also, the calcaneus isfairly flat and parallel, reducing repositioning errors. Themethod can be applied to children, neonates, and preterminfants, just as well as to adults. Once microimaging toolsto examine specific aspects of bone quality are developed,it is expected that quantitative ultrasound will be increas-ingly used in clinical practice.[59]

4.5 Screening

TheU.S. Preventive Services Task Force(USPSTF) rec-ommend that all women 65 years of age or older bescreened bybone densitometry.[63] Additionally they rec-ommend screening women with increased risk factors

that puts them at risk equivalent to a 65 year old.[63] Thereis insufficient evidence to make recommendations aboutthe intervals for repeated screening and the appropriate

age to stop screening.[63] In men the harm versus bene-fit of screening for osteoporosis is unknown.[63] A num-ber of tool exist to help determine who is reasonable totest.[64]

5 Management

5.1 Lifestyle

Lifestyle prevention of osteoporosis is in many aspectsthe inverse of the potentially modifiable risk factors. Astobacco smoking and high alcohol intake have beenlinkedwith osteoporosis, smoking cessation and moderation ofalcohol intake are commonly recommended as ways tohelp prevent it.[65]

Weight-bearing endurance exercise and/or exercises to

strengthen muscles improve bone strength in those withosteoporosis.[66] Aerobics, weight bearing, and resis-tance exercises all maintain or increase BMD in post-menopausal women.[67] Fall prevention can help preventosteoporosis complications. There is some evidence forhip protectorsspecifically among those who are in carehomes.[68]

5.2 Nutrition

Studies of the benefits of supplementation with calciumand vitamin D are conflicting, possibly because most

studies did not have patients with low dietary intakes. [69]A 2013 review by the USPSTF found insufficient evi-dence to determine if supplementation with calcium andvitamin D results in greater harm or benefit in men andpremenopausal women.[3] The USPSTF did not recom-mend low dose supplementation (less than 1 g of calciumand 400 IU of vitamin D) in postmenopausal women asthere does not appear to be a difference in fracture risk. [3]

It is unknown what effect higher doses have.[3]

While some meta-analyses have found a benefit of vi-tamin D supplements combined with calcium for frac-tures, they did not find a benefit of vitamin D supplements

alone.[70][71]

While supplementation does not appear to affectthe risk of death,[71] there is an increased risk ofmyocardial infarctions,[72][73] kidney stones,[3] and stom-ach problems.[71] Vitamin K supplementation may reducethe risk of fractures in post menopausal women;[74] how-ever there is no evidence for men.[75]

5.3 Medications

Bisphosphonatesare useful in decreasing the risk of fu-

ture fractures in those who have already sustained a frac-ture due to osteoporosis.[65][76][77] This benefit is presentwhen taken for three to four years.[78] They have not
https://en.wikipedia.org/wiki/Bisphosphonatehttps://en.wikipedia.org/wiki/Kidney_stoneshttps://en.wikipedia.org/wiki/Myocardial_infarctionhttps://en.wikipedia.org/wiki/Hip_protectorhttps://en.wikipedia.org/wiki/Bone_densitometryhttps://en.wikipedia.org/wiki/U.S._Preventive_Services_Task_Forcehttps://en.wikipedia.org/wiki/Ultrasoundhttps://en.wikipedia.org/wiki/Quantitative_computed_tomographyhttps://en.wikipedia.org/wiki/Biomarkers


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been compared directly to each other, though, so it is notknown if one is better.[65] Fracture risk reduction is be-tween 25 and 70% depending on the bone involved.[65]

There are concerns of atypical femoral fractures andosteonecrosis of the jaw with long term use, but theserisks are low.[65][79] With evidence of little benefit when

used for more than three to five years and in light of thepotential adverse events, it may be appropriate to stoptreatment after this time in some.[78]

For those with osteoporosis but who have not hadany fractures evidence does not support a reductionof in fracture risk with risedronate[77] or etidronate.[80]

Alendronatemay decreasefractures of the spinebut doesnot have any effect on other types of fractures.[76] Halfstop their medications within a year.[81]

Teriparatide( arecombinantparathyroid hormone ) hasbeen shown to be effective in treatment of women with

postmenopausal osteoporosis.

[82]

Some evidence also in-dicates strontium ranelateis effective in decreasing therisk of vertebral and nonvertebral fractures in post-menopausal women with osteoporosis.[83] Hormone re-placement therapy, while effective for osteoporosis, isonly recommended in women who also have menopausalsymptoms.[65] Raloxifene, while effective in decreasingvertebral fractures, does not affect the risk of nonverte-bral fracture.[65] And while it reduces the risk ofbreastcancer, it increases the risk ofblood clotsandstrokes.[65]

Denosumabis also effective for preventing osteoporoticfractures.[65] In hypogonadal men, testosterone has beenshown to improve bone quantity and quality, but, as of

2008, no studies evaluated its effect on fracture risk orin men with a normal testosterone levels.[42] Calcitoninwhile once recommended is no longer due to the associ-ated risk ofcancerwith its use and questionable effect onfracture risk.[84]

Certain drugs like alendronate, etidronate, risedronate,raloxifene and strontium ranelate can be helpful for thepreventing of osteoporotic fragility fractures in post-menopausal women with osteoporosis.[85]

6 Prognosis

Although osteoporosis patients have an increased mortal-ity rate due to the complications of fracture, it is rarelylethal.

Hip fractures can lead to decreased mobility and ad-ditional risks of numerous complications (such as deepvenous thrombosis and/or pulmonary embolism, andpneumonia). The six-month mortality rate following hipfracture is around 13.5%, and a substantial proportion (al-most 13%) of people who have suffered a hip fractureneed total assistance to mobilize after a hip fracture. [87]

Vertebral fractures, while having a smaller impact onmortality, can lead to severe chronic pain of neurogenicorigin, which can be hard to control, as well as deformity.

Though rare, multiple vertebral fractures can lead to suchsevere hunch back (kyphosis), the resulting pressure oninternal organs can impair ones ability to breathe.

Apart from risk of death and other complications, osteo-porotic fractures are associated with a reduced health-

relatedquality of life.

[88]

7 Epidemiology

Osteoporosis affects 55% of Americans aged 50 andabove. Of these, approximately 80% are women.[89] Thecondition is responsible for millions of fractures annually,mostly involving the lumbar vertebrae, hip, and wrist.Fragility fractures of ribs are also common in men.

7.1 Hip fractures

Hip fractures are responsible for the most serious con-sequences of osteoporosis. In the United States, morethan 250,000 hip fractures annually are attributable toosteoporosis.[90] A 50-year-old white woman is estimatedto have a 17.5% lifetime risk of fracture of the proxi-malfemur. The incidence of hip fractures increases eachdecade from the sixth through the ninth for both womenand men for all populations. The highest incidence isfound among men and women ages 80 or older. [91]

7.2 Vertebral fractures

Between 35 and 50% of all women over 50 had at leastonevertebral fracture. In the United States, 700,000 ver-tebral fractures occur annually, but only about a third arerecognized. In a series of 9704 women aged 68.8 on av-erage studied for 15 years, 324 had already suffered avertebral fracture at entry into the study and 18.2% de-veloped a vertebral fracture, but that risk rose to 41.4%in women who had a previous vertebral fracture.[92]

7.3 Wrist fractures

In the United States, 250,000 wrist fractures annuallyare attributable to osteoporosis.[90] Wrist fractures are thethird most common type of osteoporotic fractures. Thelifetime risk of sustaining aColles fractureis about 16%for white women. By the time women reach age 70, about20% have had at least one wrist fracture. [91]

7.4 Rib fractures

Fragility fractures of the ribs are common in men as

young as age 35. These are often overlooked as signsof osteoporosis, as these men are often physically activeand suffer the fracture in the course of physical activity.
https://en.wikipedia.org/wiki/Colles%2527_fracturehttps://en.wikipedia.org/wiki/Distal_radius_fracturehttps://en.wikipedia.org/wiki/Vertebral_fracturehttps://en.wikipedia.org/wiki/Femurhttps://en.wikipedia.org/wiki/Quality_of_lifehttps://en.wikipedia.org/wiki/Kyphosishttps://en.wikipedia.org/wiki/Pneumoniahttps://en.wikipedia.org/wiki/Deep_venous_thrombosishttps://en.wikipedia.org/wiki/Deep_venous_thrombosishttps://en.wikipedia.org/wiki/Cancerhttps://en.wikipedia.org/wiki/Calcitoninhttps://en.wikipedia.org/wiki/Denosumabhttps://en.wikipedia.org/wiki/Strokehttps://en.wikipedia.org/wiki/Venous_thromboembolismhttps://en.wikipedia.org/wiki/Breast_cancerhttps://en.wikipedia.org/wiki/Breast_cancerhttps://en.wikipedia.org/wiki/Raloxifenehttps://en.wikipedia.org/wiki/Strontium_ranelatehttps://en.wikipedia.org/wiki/Recombinant_DNAhttps://en.wikipedia.org/wiki/Teriparatidehttps://en.wikipedia.org/wiki/Vertebral_fractureshttps://en.wikipedia.org/wiki/Alendronatehttps://en.wikipedia.org/wiki/Etidronatehttps://en.wikipedia.org/wiki/Risedronatehttps://en.wikipedia.org/wiki/Osteonecrosis_of_the_jaw


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An example would be as a result of falling while waterskiing or jet skiing. However, a quick test of the indi-viduals testosterone level following the diagnosis of thefracture will readily reveal whether that individual mightbe at risk.

8 History

The link between age-related reductions in bone densityand fracture risk goes back at least to Astley Cooper,and the term osteoporosis and recognition of its patho-logical appearance is generally attributed to the FrenchpathologistJean Lobstein.[93] The American endocrinol-ogistFuller Albright linked osteoporosis with the post-menopausal state.[94] Bisphosphonates, which revolution-ized the treatment of osteoporosis, were discovered in the1960s.[95]

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10 External links

OsteoporosisatDMOZ

Handout on Health: Osteoporosis- US National In-stitute of Arthritis and Musculoskeletal and SkinDiseases

Osteoporosis- NIH Osteoporosis and Related BoneDiseases ~ National Resource Center
http://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/http://niams.nih.gov/Health_Info/Osteoporosis/default.asphttps://en.wikipedia.org/wiki/DMOZhttps://www.dmoz.org/Health/Conditions_and_Diseases/Musculoskeletal_Disorders/Osteoporosis/https://www.ncbi.nlm.nih.gov/pubmed/11481214https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1096%252Ffj.15.10.1677ehttps://en.wikipedia.org/wiki/Digital_object_identifierhttp://books.google.com/books?id=6m3eAgAAQBAJ&pg=PA5http://books.google.com/books?id=6m3eAgAAQBAJ&pg=PA5https://www.ncbi.nlm.nih.gov/pubmed/18165669https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1001%252Fjama.298.23.2761https://en.wikipedia.org/wiki/Digital_object_identifier


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14 11 TEXT AND IMAGE SOURCES, CONTRIBUTORS, AND LICENSES

11 Text and image sources, contributors, and lic

Documents

3 Osteoporosis