Osteoporosis: Difference between revisions
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{{Infobox disease |
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| Name = Osteoporosis |
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| Image = Osteoporosis.JPG |
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| Caption = A stooped back is often the result of osteoporosis. |
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| DiseasesDB = 9385 |
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| ICD10 = {{ICD10|M|80||m|80}}-{{ICD10|M|82||m|80}} |
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| ICD9 = {{ICD9|733.0}} |
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| OMIM = 166710 |
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| MedlinePlus = 000360 |
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| eMedicineSubj = med |
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| eMedicineTopic = 1693 |
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| eMedicine_mult = {{eMedicine2|ped|1683}} {{eMedicine2|pmr|94}} {{eMedicine2|pmr|95}} |
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| MeshID = D010024 |
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}} |
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'''Osteoporosis''' ("porous bones", from Greek: ὀστέον/''osteon'' meaning "bone" and πόρος/''poros'' meaning "pore") is a [[disease]] of [[bones]] that leads to an increased risk of [[bone fracture|fracture]].<ref name=AppTher>{{cite book |author=Brian K Alldredge; Koda-Kimble, Mary Anne; Young, Lloyd Y.; Wayne A Kradjan; B. Joseph Guglielmo |title=Applied therapeutics: the clinical use of drugs |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |year=2009 |pages=101–3 |isbn=0-7817-6555-2}}</ref> In osteoporosis the [[bone mineral density]] (BMD) is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered. Osteoporosis is defined by the [[World Health Organization]] (WHO) as a bone mineral density that is 2.5 [[standard deviation]]s or more below the mean peak bone mass (average of young, healthy adults) as measured by [[Dual energy X-ray absorptiometry|DXA]]; the term "established osteoporosis" includes the presence of a [[fragility fracture]].<ref name=WHO1994>{{cite journal |author=WHO |title=Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group |journal=World Health Organization technical report series |volume=843 |issue= |pages=1–129 |year=1994 |pmid=7941614 |doi=}}</ref> The disease may be classified as primary type 1, primary type 2, or secondary.<ref name=AppTher/> |
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The form of osteoporosis most common in women after [[menopause]] is referred to as primary type 1 or '''postmenopausal osteoporosis'''. Primary type 2 osteoporosis or '''senile osteoporosis''' occurs after age 75 and is seen in both females and males at a ratio of 2:1. Finally, secondary osteoporosis may arise at any age and affects men and women equally. This form of osteoporosis results from chronic predisposing medical problems or disease, or prolonged use of medications such as [[glucocorticoid]]s, when the disease is called steroid- or [[glucocorticoid-induced osteoporosis]] (SIOP or GIOP). |
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Osteoporosis risks can be reduced with lifestyle changes and sometimes medication; in people with osteoporosis, treatment may involve both. Lifestyle change includes diet and exercise, and [[Fall prevention|preventing falls]]. Medication includes [[calcium in biology|calcium]], [[vitamin D]], [[bisphosphonate]]s and several others. Fall-prevention advice includes exercise to tone deambulatory muscles, proprioception-improvement exercises; equilibrium therapies may be included. Exercise with its anabolic effect, may at the same time stop or reverse osteoporosis. Osteoporosis is a component of the [[frailty syndrome]]. |
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==Signs and symptoms== |
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Osteoporosis itself has [[asymptomatic|no specific symptoms]]; its main consequence is the increased risk of bone fractures. Osteoporotic [[fractures]] are those that occur in situations where healthy people would not normally break a bone; they are therefore regarded as ''[[fragility fracture]]s''. Typical fragility fractures occur in the [[vertebral column]], [[rib]], [[hip fracture|hip]] and [[wrist]]. |
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===Fractures=== |
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Fractures are the most dangerous aspect of osteoporosis. Debilitating acute and chronic pain in the elderly is often attributed to fractures from osteoporosis and can lead to further disability and early mortality.<ref>{{cite journal|last=Old|first=JL|coauthors=Calvert, M|title=Vertebral compression fractures in the elderly|journal=American Family Physician|year=2004|volume=69|issue=1|pages=111–116|pmid=14727827|url=http://www.aafp.org/afp/2004/0101/p111.html|accessdate=31 March 2011}}</ref> The fractures from osteoporosis may also be asymptomatic. The symptoms of a [[vertebra]]l collapse ("[[compression fracture]]") are sudden [[back pain]], often with [[Radiculopathy|radiculopathic pain]] (shooting pain due to nerve root compression) and rarely with [[spinal cord compression]] or [[cauda equina syndrome]]. Multiple vertebral fractures lead to a stooped posture, loss of height, and chronic pain with resultant reduction in mobility.<ref>{{cite journal |author=Kim DH, Vaccaro AR |title=Osteoporotic compression fractures of the spine; current options and considerations for treatment |journal=The spine journal : official journal of the North American Spine Society |volume=6 |issue=5 |pages=479–87 |year=2006 |pmid=16934715 |doi=10.1016/j.spinee.2006.04.013}}</ref> |
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Fractures of the long bones acutely impair mobility and may require [[surgery]]. [[Hip fracture]], in particular, usually requires prompt surgery, as there are serious risks associated with a hip fracture, such as [[deep vein thrombosis]] and a [[pulmonary embolism]], and increased mortality. |
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Fracture Risk Calculators assess the risk of fracture based upon several criteria, including BMD, age, smoking, alcohol usage, weight, and gender. Recognised calculators include [[FRAX]]<ref>{{cite web|url= http://courses.washington.edu/bonephys/FxRiskCalculator.html|title= Fracture Risk Calculator|author=Susan Ott |accessdate=2009-11-03 }}</ref> and Dubbo. |
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===Falls risk=== |
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The increased risk of falling associated with aging leads to fractures of the wrist, spine and hip. The risk of falling, in turn, is increased by impaired eyesight due to any cause (e.g. [[glaucoma]], [[macular degeneration]]), [[balance disorder]], [[movement disorder]]s (e.g. [[Parkinson's disease]]), [[dementia]], and [[sarcopenia]] (age-related loss of [[skeletal muscle]]). [[Collapse (medical)|Collapse]] (transient loss of postural tone with or without loss of consciousness) leads to a significant risk of falls; causes of syncope are manifold but may include [[cardiac arrhythmia]]s (irregular heart beat), [[vasovagal syncope]], [[orthostatic hypotension]] (abnormal drop in blood pressure on standing up) and [[seizure]]s. Removal of obstacles and loose carpets in the living environment may substantially reduce falls. Those with previous falls, as well as those with a gait or balance disorder, are most at risk.<ref>{{cite journal |author=Ganz DA, Bao Y, Shekelle PG, Rubenstein LZ |title=Will my patient fall? |journal=JAMA |volume=297 |issue=1 |pages=77–86 |year=2007 |pmid=17200478 |doi=10.1001/jama.297.1.77}}</ref> |
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==Risk factors== |
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Risk factors for osteoporotic fracture can be split between non-modifiable and (potentially) modifiable. In addition, there are specific diseases and disorders in which osteoporosis is a recognized complication. Medication use is theoretically modifiable, although in many cases the use of medication that increases osteoporosis risk is unavoidable. |
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[[Caffeine]] is not a risk factor osteoporosis.<ref>{{cite journal|last=Waugh|first=EJ|coauthors=Lam, MA, Hawker, GA, McGowan, J, Papaioannou, A, Cheung, AM, Hodsman, AB, Leslie, WD, Siminoski, K, Jamal, SA, Perimenopause BMD Guidelines Subcommittee of Osteoporosis, Canada|title=Risk factors for low bone mass in healthy 40-60 year old women: a systematic review of the literature.|journal=Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA|date=2009 Jan|volume=20|issue=1|pages=1–21|pmid=18523710|doi=10.1007/s00198-008-0643-x}}</ref> |
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===Nonmodifiable=== |
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The most important risk factors for osteoporosis are advanced age (in both men and women) and [[female]] gender; [[estrogen]] deficiency following [[menopause]] or oophorectomy is correlated with a rapid reduction in [[bone mineral density]], while in men a decrease in [[testosterone]] levels has a comparable (but less pronounced) effect. While osteoporosis occurs in people from all ethnic groups, [[European ethnic groups|European]] or [[Asian people|Asian]] ancestry predisposes for osteoporosis.<ref>{{cite journal |author=Melton LJ |title=Epidemiology worldwide |journal=Endocrinol. Metab. Clin. North Am. |volume=32 |issue=1 |pages=1–13, v |year=2003 |pmid=12699289 |doi=10.1016/S0889-8529(02)00061-0}}</ref> Those with a [[family history (medicine)|family history]] of fracture or osteoporosis are at an increased risk; the [[heritability]] of the fracture as well as low bone mineral density are relatively high, ranging from 25 to 80 percent. There are at least 30 genes associated with the development of osteoporosis.<ref name=Raisz/> Those who have already had a fracture are at least twice as likely to have another fracture compared to someone of the same age and sex.<ref>{{cite journal |author=Ojo F, Al Snih S, Ray LA, Raji MA, Markides KS |title=History of fractures as predictor of subsequent hip and nonhip fractures among older Mexican Americans |journal=Journal of the National Medical Association |volume=99 |issue=4 |pages=412–8 |year=2007 |pmid=17444431 |doi= |pmc=2569658}}</ref> A small stature is also a non-modifiable risk factor associated with the development of osteoporosis.<ref name=AppTher/> |
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===Potentially modifiable=== |
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* Excess [[Alcoholic beverage|alcohol]]—small amounts of alcohol do not increase osteoporosis risk and may even be beneficial, but chronic heavy drinking (alcohol intake greater than 3 units/day),<ref name="BMJosteoporosis">{{cite journal |author=Poole KE, Compston JE |title=Osteoporosis and its management |journal=BMJ |volume=333 |issue=7581 |pages=1251–6 |year=2006 |month=December |pmid=17170416 |doi=10.1136/bmj.39050.597350.47 |url= |pmc=1702459}}</ref> especially at a younger age, increases risk significantly.<ref>{{cite journal | author=Berg KM, Kunins HV, Jackson JL ''et al.'' | title= Association between alcohol consumption and both osteoporotic fracture and bone density | journal=Am J Med | year=2008 | volume=121 | issue=5 | pages=406–18 | doi= 10.1016/j.amjmed.2007.12.012 | pmid=18456037 | pmc=2692368}}</ref> |
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* [[Vitamin D deficiency]]<ref name=micronutrients>{{cite journal |author=Nieves JW |title=Osteoporosis: the role of micronutrients. |journal=Am J Clin Nutr |volume=81 |issue=5 |pages=1232S–1239S |date=1 May 2005|pmid=15883457 |url=http://www.ajcn.org/cgi/content/full/81/5/1232S }}</ref>—low circulating Vitamin D is common among the elderly worldwide.<ref name="WHOcriteria"/> Mild vitamin D insufficiency is associated with increased [[Parathyroid hormone|Parathyroid Hormone (PTH)]] production.<ref name="WHOcriteria"/> PTH increases bone resorption, leading to bone loss. A positive association exists between serum [[1,25-dihydroxycholecalciferol]] levels and bone mineral density, while PTH is negatively associated with bone mineral density.<ref name="WHOcriteria"/> |
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* [[Tobacco smoking]]—tobacco smoking inhibits the activity of osteoblasts, and is an independent risk factor for osteoporosis.<ref name="BMJosteoporosis"/><ref>{{cite journal |author=Wong PK, Christie JJ, Wark JD |title=The effects of smoking on bone health |journal=Clin. Sci. |volume=113 |issue=5 |pages=233–41 |year=2007 |pmid=17663660 |doi=10.1042/CS20060173| url=http://www.clinsci.org/cs/113/0233/cs1130233.htm}}</ref> Smoking also results in increased breakdown of exogenous estrogen, lower body weight and earlier menopause, all of which contribute to lower bone mineral density.<ref name="WHOcriteria"/> |
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* [[Malnutrition]]—nutrition has an important and complex role in maintenance of good bone. Identified risk factors include low dietary [[calcium]] and/or phosphorus, magnesium, zinc, boron, iron, fluoride, copper, vitamins A, K, E and C (and D where skin exposure to sunlight provides an inadequate supply). Excess sodium is a risk factor. High blood acidity may be diet-related, and is a known antagonist of bone.<ref>{{cite journal |author=Jasminka Z. Ilich, PhD, RD and Jane E Kerstetter, PhD, RD |title=Nutrition in Bone Health Revisited: A Story Beyond Calcium |journal=Journal of the American College of Nutrition |volume=19 |issue=6 |pages=715–737 |year=2000 |pmid=11194525 |url=http://www.jacn.org/cgi/content/full/19/6/715}}</ref> Some have identified low protein intake as associated with lower peak bone mass during adolescence and lower bone mineral density in elderly populations.<ref name="WHOcriteria"/> Conversely, some have identified low protein intake as a positive factor, protein is among the causes of dietary acidity. Imbalance of omega 6 to omega 3 polyunsaturated fats is yet another identified risk factor.[http://www.ajcn.org/cgi/content/full/81/4/934] |
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* High protein diet—Research has found an association between diets high in animal protein and increased urinary calcium loss from the bones.<ref>{{cite journal |doi=10.1007/BF00297291 |author=Abelow BJ, Holford TL and Insogna KL |title=Cross-cultural association between dietary animal protein and hip fracture: a hypothesis |journal=Calcified tissue international |volume=50 |issue=1 |pages=14–18 |year=1992 |pmid=1739864 |url=http://www.ncbi.nlm.nih.gov/pubmed/1739864}}</ref><ref>{{cite journal |author=Hegsted M, Schuette SA, Zemel MB and Linkswiler HM |title=Urinary calcium and calcium balance in young men as affected by level of protein and phosphorus intake |journal=The Journal of nutrition |volume=111 |issue=3 |pages=553–562 |year=1981 |pmid=7205408 |url=http://www.ncbi.nlm.nih.gov/pubmed/7205408}}</ref><ref>{{cite journal|url=http://jn.nutrition.org/cgi/reprint/120/1/134.pdf|author=Kerstetter JE and Allen LH|title=Dietary protein increases urinary calcium|journal=Journal of Nutrition|volume= 120|year=1990|pages=134–6|pmid=2406396|issue=1}}</ref> |
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* [[body mass index|Underweight]]/[[Physical exercise|inactive]]—[[bone remodeling]] occurs in response to physical stress, and [[weight bearing]] exercise can increase peak bone mass achieved in adolescence.<ref name="WHOcriteria"/> In adults, physical activity helps maintain bone mass, and can increase it by 1 or 2%. {{Citation needed|date=May 2008}} Conversely, physical inactivity can lead to significant bone loss.<ref name="WHOcriteria"/> (Incidence of osteoporosis is lower in overweight people.)<ref>{{cite journal |author=Shapses SA, Riedt CS |title=Bone, body weight, and weight reduction: what are the concerns? |journal=J. Nutr. |volume=136 |issue=6 |pages=1453–6 |date=1 June 2006|pmid=16702302 |url=http://jn.nutrition.org/cgi/content/full/136/6/1453 }}</ref> |
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* Excess physical activity—excessive exercise can lead to constant damage to the bones which can cause exhaustion of the structures as described above. There are numerous examples of marathon runners who developed severe osteoporosis later in life.{{who|date=December 2010}} In women, heavy exercise can lead to decreased estrogen levels, which predisposes to osteoporosis. In addition, intensive training without proper compensatory increased nutrition increases the risk.{{citation needed|date=December 2010}} |
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* [[Heavy metals]]—a strong association between [[cadmium]], lead and bone disease has been established. Low level exposure to cadmium is associated with an increased loss of bone mineral density readily in both genders, leading to pain and increased risk of fractures, especially in the elderly and in females. Higher cadmium exposure results in [[osteomalacia]] (softening of the bone).<ref>{{cite journal | author = Staessen J, Roels H, Emelianov D, Kuznetsova T, Thijs L, Vangronsveld J, Fagard R | title = Environmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group. | journal = Lancet | volume = 353 | issue = 9159 | pages = 1140–4 | year = 1999 | month = Apr 3 | pmid = 10209978 | doi = 10.1016/S0140-6736(98)09356-8}}</ref> |
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* Soft drinks—some studies indicate that [[soft drink]]s (many of which contain [[phosphoric acid]]) may increase risk of osteoporosis;<ref>{{cite journal |author=Tucker KL, Morita K, Qiao N, Hannan MT, Cupples LA, Kiel DP |title=Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study |journal=Am. J. Clin. Nutr. |volume=84 |issue=4 |pages=936–42 |year=2006 |pmid=17023723 |doi=}}</ref> Others suggest soft drinks may displace calcium-containing drinks from the diet rather than directly causing osteoporosis.<ref>{{cite journal |author= |title=Soft drinks in schools |journal=Pediatrics |volume=113 |issue=1 Pt 1 |pages=152–4 |year=2004 |pmid=14702469 |doi=10.1542/peds.113.1.152 |author1= American Academy of Pediatrics Committee on School Health}}</ref> |
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===Diseases and disorders=== |
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Many diseases and disorders have been associated with osteoporosis.<ref name=ICSI>{{cite web |url=http://www.icsi.org/osteoporosis/diagnosis_and_treatment_of_osteoporosis__3.html |title=ICSI Health Care Guideline: Diagnosis and Treatment of Osteoporosis, 5th edition |accessdate=2008-04-08 |author=Simonelli, C ''et al.'' |month=July|year=2006 |format=PDF |publisher=Institute for Clinical Systems Improvement}}</ref> For some, the underlying mechanism influencing the bone metabolism is straight-forward, whereas for others the causes are multiple or unknown. |
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* In general, [[immobilization]] causes bone loss (following the 'use it or lose it' rule). For example, localized osteoporosis can occur after prolonged immobilization of a fractured limb in a cast. This is also more common in active patients with a high bone turn-over (for example, athletes). Other examples include bone loss during [[space flight]] or in people who are bedridden or who use wheelchairs for various reasons. |
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* [[Hypogonadism|Hypogonadal]] states can cause secondary osteoporosis. These include [[Turner syndrome]], [[Klinefelter syndrome]], [[Kallmann syndrome]], [[anorexia nervosa]], [[andropause]],<ref name='medscapeosteoporosis'/> [[hypothalamus|hypothalamic]] [[amenorrhea]] or [[hyperprolactinemia]].<ref name='medscapeosteoporosis'/> In females, the effect of hypogonadism is mediated by [[estrogen]] deficiency. It can appear as early [[menopause]] (<45 years) or from prolonged premenopausal amenorrhea (>1 year). A bilateral [[oophorectomy]] (surgical removal of the ovaries) or a [[premature ovarian failure]] cause deficient estrogen production. In males, [[testosterone]] deficiency is the cause (for example, andropause or after surgical removal of the [[testes]]). |
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* Endocrine disorders that can induce bone loss include [[Cushing's syndrome]],<ref name="WHOcriteria"/> [[hyperparathyroidism]],<ref name="WHOcriteria"/> [[thyrotoxicosis]],<ref name="WHOcriteria"/> [[hypothyroidism]], [[diabetes mellitus]] type 1 and 2,<ref name=OsteoporosisMen>{{cite journal|author=Ebeling PR|title=Clinical practice. Osteoporosis in men| journal=N Engl J Med| year=2008| volume=358| issue=14| pages=1474–82| pmid=18385499 |doi=10.1056/NEJMcp0707217}}</ref> [[acromegaly]] and [[adrenal insufficiency]]. In [[pregnancy]] and [[lactation]], there can be a reversible bone loss.<ref name=ICSI/> |
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* [[Malnutrition]], [[parenteral nutrition]]<ref name="WHOcriteria"/> and [[malabsorption]] can lead to osteoporosis. Nutritional and gastrointestinal disorders that can predispose to osteoporosis include [[coeliac disease]],<ref name="WHOcriteria"/> [[Crohn's disease]], lactose intolerance, surgery<ref name='medscapeosteoporosis'/> (after [[gastrectomy]], [[Partial ileal bypass surgery|intestinal bypass surgery]] or [[bowel resection]]) and severe [[liver disease]] (especially [[primary biliary cirrhosis]]).<ref name='medscapeosteoporosis'/> Patients with [[bulimia]] can also develop osteoporosis. Those with an otherwise adequate calcium intake can develop osteoporosis due to the inability to absorb calcium and/or vitamin D. Other micro-nutrients such as [[vitamin K]] or [[vitamin B12 deficiency]] may also contribute. |
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* Patients with rheumatologic disorders like [[rheumatoid arthritis]],<ref name='medscapeosteoporosis'/> [[ankylosing spondylitis]],<ref name='medscapeosteoporosis'>{{cite web|url=http://www.medscape.com/viewarticle/427342 |title=Osteoporosis - Risk Factors, Screening, and Treatment |accessdate=2008-05-11 |last=Kohlmeier |first=Lynn Kohlmeier |year=1998 |publisher=Medscape Portals }} {{Dead link|date=September 2010|bot=H3llBot}}</ref> [[systemic lupus erythematosus]] and polyarticular [[juvenile idiopathic arthritis]] are at increased risk of osteoporosis, either as part of their disease or because of other risk factors (notably corticosteroid therapy). Systemic diseases such as [[amyloidosis]] and [[sarcoidosis]] can also lead to osteoporosis. |
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* [[Renal insufficiency]] can lead to [[osteodystrophy]]. |
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* Hematologic disorders linked to osteoporosis are [[multiple myeloma]]<ref name='medscapeosteoporosis'/> and other [[monoclonal gammopathy|monoclonal gammopathies]],<ref name=OsteoporosisMen/> [[lymphoma]] and [[leukemia]], [[mastocytosis]],<ref name='medscapeosteoporosis'/> [[hemophilia]], [[sickle-cell disease]] and [[thalassemia]]. |
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* Several inherited disorders have been linked to osteoporosis. These include [[osteogenesis imperfecta]],<ref name='medscapeosteoporosis'/> [[Marfan syndrome]],<ref name='medscapeosteoporosis'/> [[hemochromatosis]],<ref name="WHOcriteria"/> [[hypophosphatasia]], [[glycogen storage disease]]s, [[homocystinuria]],<ref name='medscapeosteoporosis'/> [[Ehlers–Danlos syndrome]],<ref name='medscapeosteoporosis'/> [[porphyria]], [[Menkes disease|Menkes' syndrome]], [[epidermolysis bullosa]] and [[Gaucher's disease]]. |
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* People with [[scoliosis]] [[idiopathic|of unknown cause]] also have a higher risk of osteoporosis. Bone loss can be a feature of [[complex regional pain syndrome]]. It is also more frequent in people with [[Parkinson's disease]] and [[chronic obstructive pulmonary disease]]. |
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===Medication=== |
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Certain medications have been associated with an increase in osteoporosis risk; only steroids and anticonvulsants are classically associated, but evidence is emerging with regard to other drugs. |
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* [[Steroid-induced osteoporosis]] (SIOP) arises due to use of [[glucocorticoid]]s - analogous to Cushing's syndrome and involving mainly the axial skeleton. The synthetic glucocorticoid prescription drug [[prednisone]] is a main candidate after prolonged intake. Some professional guidelines recommend prophylaxis in patients who take the equivalent of more than 30 mg hydrocortisone (7.5 mg of prednisolone), especially when this is in excess of three months.<ref>{{cite book |author=Bone and Tooth Society of Great Britain, [[National Osteoporosis Society]], Royal College of Physicians |title=Glucocorticoid-induced Osteoporosis |year=2003 |publisher=Royal College of Physicians of London |location=London, UK |isbn=1-860-16173-1 | url=http://www.rcplondon.ac.uk/pubs/contents/966c62dd-8011-4f65-a61d-dd0c7fe4fa4b.pdf}}</ref> Alternate day use may not prevent this complication.<ref name=GIOP>{{cite journal|author=Gourlay M, Franceschini N, Sheyn Y| title=Prevention and treatment strategies for glucocorticoid-induced osteoporotic fractures |journal=Clin Rheumatol| year=2007|volume=26|issue=2|pages=144–53|pmid=16670825 |doi=10.1007/s10067-006-0315-1}}</ref> |
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* [[Barbiturate]]s, [[phenytoin]] and some other enzyme-inducing [[antiepileptic]]s - these probably accelerate the metabolism of vitamin D.<ref>{{cite journal |author=Petty SJ, O'Brien TJ, Wark JD |title=Anti-epileptic medication and bone health |journal=Osteoporosis international |volume=18 |issue=2 |pages=129–42 |year=2007 |pmid=17091219 |doi=10.1007/s00198-006-0185-z}}</ref> |
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* [[L-Thyroxine]] over-replacement may contribute to osteoporosis, in a similar fashion as [[thyrotoxicosis]] does.<ref name="ICSI"/> This can be relevant in subclinical hypothyroidism. |
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* Several drugs induce [[hypogonadism]], for example [[aromatase inhibitors]] used in breast cancer, [[methotrexate]] and other anti-metabolite drugs, [[Depo-Provera|depot progesterone]] and [[gonadotropin-releasing hormone agonist]]s. |
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* [[Anticoagulant]]s - long-term use of heparin is associated with a decrease in bone density,<ref>{{cite journal |author=Ruiz-Irastorza G, Khamashta MA, Hughes GR |title=Heparin and osteoporosis during pregnancy: 2002 update |journal=Lupus |volume=11 |issue=10 |pages=680–82 |year=2002 |pmid=12413068| doi = 10.1191/0961203302lu262oa}}</ref> and [[warfarin]] (and related coumarins) have been linked with an increased risk in osteoporotic fracture in long-term use.<ref>{{cite journal |author=Gage BF, Birman-Deych E, Radford MJ, Nilasena DS, Binder EF |title=Risk of osteoporotic fracture in elderly patients taking warfarin: results from the National Registry of Atrial Fibrillation 2 |journal=Arch. Intern. Med. |volume=166 |issue=2 |pages=241–46 |year=2006 |pmid=16432096 |doi=10.1001/archinte.166.2.241|url=http://archinte.ama-assn.org/cgi/content/full/166/2/241}}</ref> |
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* [[Proton pump inhibitors]] - these drugs inhibit the production of [[gastric acid|stomach acid]]; it is thought that this interferes with calcium absorption.<ref>{{cite journal | author = Yang YX, Lewis JD, Epstein S, Metz DC | title=Long-term proton pump inhibitor therapy and risk of hip fracture | journal=JAMA | year=2006 | volume=296 | pages=2947–53 | pmid=17190895 | doi = 10.1001/jama.296.24.2947 | issue = 24}}</ref> Chronic [[phosphate]] binding may also occur with [[aluminium]]-containing [[antacids]].<ref name="ICSI"/> |
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* [[Thiazolidinedione]]s (used for diabetes) - [[rosiglitazone]] and possibly [[pioglitazone]], inhibitors of [[Peroxisome proliferator-activated receptor gamma|PPARγ]], have been linked with an increased risk of osteoporosis and fracture.<ref>{{cite journal |author=Murphy CE, Rodgers PT |title=Effects of thiazolidinediones on bone loss and fracture |journal=Ann Pharmacother |volume=41 |issue=12 |pages=2014–18 |year=2007 |pmid=17940125 |doi=10.1345/aph.1K286}}</ref> |
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* Chronic [[lithium]] therapy has been associated with osteoporosis.<ref name="ICSI"/> |
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==Pathogenesis== |
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[[Image:Osteoclast.jpg|thumb|Osteoclast, with bone below it, showing typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol.]] |
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The underlying mechanism in all cases of osteoporosis is an imbalance between [[bone resorption]] and [[Bone#Formation|bone formation]]. In normal bone, there is constant [[matrix (biology)|matrix]] remodeling of bone; up to 10% of all bone mass may be undergoing remodeling at any point in time. The process takes place in bone multicellular units (BMUs) as first described by Frost in 1963.<ref>Frost HM, Thomas CC. Bone Remodeling Dynamics. Springfield, IL: 1963.</ref> Bone is resorbed by [[osteoclast]] cells (which derive from the [[bone marrow]]), after which new bone is deposited by [[osteoblast]] cells.<ref name=Raisz>{{cite journal | author = Raisz L | title = Pathogenesis of osteoporosis: concepts, conflicts, and prospects. | journal = J Clin Invest | volume = 115 | issue = 12 | pages = 3318–25 | year = 2005 | pmid = 16322775 | url=http://www.jci.org/cgi/content/full/115/12/3318 | doi=10.1172/JCI27071 | pmc = 1297264}}</ref> |
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The three main mechanisms by which osteoporosis develops are an inadequate ''peak bone mass'' (the skeleton develops insufficient mass and strength during growth), excessive bone resorption and inadequate formation of new bone during remodeling. An interplay of these three mechanisms underlies the development of fragile bone tissue.<ref name=Raisz/> Hormonal factors strongly determine the rate of bone resorption; lack of [[estrogen]] (e.g. as a result of menopause) increases bone resorption as well as decreasing the deposition of new bone that normally takes place in weight-bearing bones. The amount of estrogen needed to suppress this process is lower than that normally needed to stimulate the [[uterus]] and [[Mammary gland|breast gland]]. The α-form of the [[estrogen receptor]] appears to be the most important in regulating bone turnover.<ref name=Raisz/> In addition to estrogen, [[calcium metabolism]] plays a significant role in bone turnover, and deficiency of [[calcium in biology|calcium]] and [[vitamin D]] leads to impaired bone deposition; in addition, the [[parathyroid gland]]s react to low calcium levels by secreting [[parathyroid hormone]] (parathormone, PTH), which increases bone resorption to ensure sufficient calcium in the blood. The role of [[calcitonin]], a hormone generated by the [[thyroid]] that increases bone deposition, is less clear and probably not as significant as that of PTH.<ref name=Raisz/> |
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[[Image:Active osteoblasts.jpg|thumb|Osteoblasts, several displaying a prominent Golgi apparatus, actively synthesizing osteoid containing two osteocytes.]] |
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The activation of osteoclasts is regulated by various molecular signals, of which [[RANKL]] (receptor activator for [[NF-κB|nuclear factor κB]] ligand) is one of best studied. This molecule is produced by osteoblasts and other cells (e.g. [[lymphocyte]]s), and stimulates [[RANK]] (receptor activator of nuclear factor κB). [[Osteoprotegerin]] (OPG) binds RANKL before it has an opportunity to bind to RANK, and hence suppresses its ability to increase bone resorption. RANKL, RANK and OPG are closely related to [[tumor necrosis factor]] and its receptors. The role of the [[Wnt signaling pathway|''wnt'' signalling pathway]] is recognized but less well understood. Local production of [[eicosanoid]]s and [[interleukin]]s is thought to participate in the regulation of bone turnover, and excess or reduced production of these mediators may underlie the development of osteoporosis.<ref name=Raisz/> |
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[[Trabecular bone]] (or cancellous bone) is the sponge-like bone in the ends of long bones and vertebrae. [[Cortical bone]] is the hard outer shell of bones and the middle of long bones. Because osteoblasts and osteoclasts inhabit the surface of bones, trabecular bone is more active, more subject to bone turnover, to remodeling. Not only is bone density decreased, but the microarchitecture of bone is disrupted. The weaker spicules of trabecular bone break ("microcracks"), and are replaced by weaker bone. Common osteoporotic fracture sites, the wrist, the hip and the spine, have a relatively high trabecular bone to cortical bone ratio. These areas rely on trabecular bone for strength, and therefore the intense remodeling causes these areas to degenerate most when the remodeling is imbalanced.{{Citation needed|date=September 2007}} Around the ages of 30-35, cancellous or trabecular bone loss begins. Women may lose as much as 50%, while men lose about 30%.<ref name=AppTher /> |
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==Diagnosis== |
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[[Image:L1 2 vertebral fracture.jpg|thumb|Multiple osteoporotic wedge fractures demonstrated on a lateral thoraco-lumbar spine X-ray]] |
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[[Image:Bone density scanner.jpg|thumb|A scanner used to measure bone density with [[Dual energy X-ray absorptiometry]].]] |
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The diagnosis of osteoporosis can be made using conventional radiography and by measuring the [[bone mineral density]] (BMD).<ref name="diagnosticimaging.com">Guglielmi G, Scalzo G. [http://www.diagnosticimaging.com/display/article/113619/1565165 Imaging tools transform diagnosis of osteoporosis]. ''Diagnostic Imaging Europe.'' 2010;26(May):7-11.</ref> The most popular method of measuring BMD is dual energy x-ray absorptiometry (DXA or DEXA). In addition to the detection of abnormal BMD, the diagnosis of osteoporosis requires investigations into potentially modifiable underlying causes; this may be done with [[blood tests]]. Depending on the likelihood of an underlying problem, investigations for [[cancer]] with [[metastasis]] to the bone, [[multiple myeloma]], [[Cushing's disease]] and other above-mentioned causes may be performed. |
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===Conventional radiography=== |
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Conventional radiography is useful, both by itself and in conjunction with CT or MRI, for detecting complications of [[osteopenia]] (reduced bone mass; pre-osteoporosis), such as fractures; for differential diagnosis of osteopenia; or for follow-up examinations in specific clinical settings, such as soft tissue calcifications, secondary hyperparathyroidism, or osteomalacia in renal osteodystrophy. However, radiography is relatively insensitive to detection of early disease and requires a substantial amount of bone loss (about 30%) to be apparent on x-ray images. |
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The main radiographic features of generalized osteoporosis are cortical thinning and increased radiolucency. Frequent complications of osteoporosis are vertebral fractures for which spinal radiography can help considerably in diagnosis and follow-up. Vertebral height measurements can objectively be made using plain-film x-rays by using several methods such as height loss together with area reduction, particularly when looking at vertical deformity in T4-L4, or by determining a spinal fracture index that takes into account the number of vertebrae involved. Involvement of multiple vertebral bodies leads to kyphosis of the thoracic spine, obvious to the clinician as "dowager's hump." |
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===Clinical decision rule=== |
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A number of clinical decision rules have been created to predict the risk of osteoporotic fractures. The QFracture score was developed in 2009 and is based on age, BMI, smoking status, alcohol use, rheumatoid arthritis, cardiovascular disease, type 2 diabetes, asthma, use of tricyclic antidepressants or corticosteroids, liver disease, and a history of falls in men. In women hormone replacement therapy, parental history of osteoporosis, gastrointestinal malabsorption, and menopausal symptoms are also taken into account.<ref>{{cite web |url=http://www.bmj.com/cgi/content/full/339/nov19_1/b4229 |title=Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores -- Hippisley-Cox and Coupland 339: b4229 -- BMJ |format= |work= |accessdate=}}</ref> A website is available to help apply this score.<ref>{{cite web |url=http://www.qfracture.org/ |title=www.qfracture.org |format= |work= |accessdate=}}</ref> |
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===Dual energy X-ray absorptiometry=== |
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[[Dual energy X-ray absorptiometry]] (DXA, formerly DEXA) is considered the [[gold standard (test)|gold standard]] for the diagnosis of osteoporosis. Osteoporosis is diagnosed when the [[bone density|bone mineral density]] is less than or equal to 2.5 standard deviations below that of a young adult reference population. This is translated as a [[Bone density#T-score|T-score]]. The [[World Health Organization]] has established the following diagnostic guidelines:<ref name=WHO1994/><ref name="WHOcriteria">{{cite web | author=WHO Scientific Group on the Prevention and Management of Osteoporosis (2000 : Geneva, Switzerland) |url=http://whqlibdoc.who.int/trs/WHO_TRS_921.pdf |title=Prevention and management of osteoporosis : report of a WHO scientific group| year=2003 |accessdate=2007-05-31 |format=pdf |work=}}</ref> |
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* [[Bone density#T-score|T-score]] -1.0 or greater is "normal" |
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* T-score between -1.0 and -2.5 is "low bone mass" (or "[[osteopenia]]") |
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* T-score -2.5 or below is osteoporosis |
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When there has also been an osteoporotic fracture (also termed "low trauma-fracture" or "fragility fracture"), defined as one that occurs as a result of a fall from a standing height, the term "severe or established" osteoporosis is used.<ref name=WHO1994/> |
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The International Society for Clinical Densitometry takes the position that a diagnosis of osteoporosis in men under 50 years of age should not be made on the basis of densitometric criteria alone. It also states that for pre-menopausal women, Z-scores (comparison with age group rather than peak bone mass) rather than T-scores should be used, and that the diagnosis of osteoporosis in such women also should not be made on the basis of densitometric criteria alone.<ref name="pmid14742881">{{cite journal |author=Leib ES, Lewiecki EM, Binkley N, Hamdy RC |title=Official positions of the International Society for Clinical Densitometry |journal=J Clin Densitom |volume=7 |issue=1 | page=1799 |year=2004 |pmid=14742881 | doi=10.1385/JCD:7:1:1}} quoted in: [http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=6567&nbr=4129 "Diagnosis of osteoporosis in men, premenopausal women, and children"]</ref> |
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===Biomarkers=== |
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Chemical [[biomarkers]] are a useful tool in detecting bone degradation. The enzyme cathepsin K breaks down type-I collagen protein, an important constituent in bones. Prepared antibodies can recognize the resulting fragment, called a neoepitope, as a way to diagnose osteoporosis.<ref>{{cite journal|last=Yasuda|first=Y|coauthors=Kaleta K, Brömme D|title=The role of cathepsins in osteoporosis and arthritis: Rationale for the design of new therapeutics|journal=Advanced Drug Delivery Reviews|year=2005|volume=57|issue=7|pages=973–993|pmid=15876399|accessdate=1 May 2011}}</ref> Increased urinary excretion of C-telopeptides, a type-I collagen breakdown product, also serves as a biomarker for osteoporosis.<ref>{{cite book|last=Meunier|first=Pierre|title=Osteoporosis: Diagnosis and Management|year=1998|publisher=Taylor and Francis|location=London|isbn=1-85317-412-2}}</ref> |
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===Other measuring tools=== |
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Quantitative [[computer tomography]] differs from DXA in that it gives separate estimates of BMD for trabecular and cortical bone and reports precise volumetric mineral density in mg/cm<sup>3</sup> rather than BMD's relative Z score. Among QCT's advantages: it can be performed at axial and peripheral sites, is sensitive to change over time, can analyze a region of any size or shape, excludes irrelevant tissue such as fat, muscle, and air, and does not require knowledge of the patient's subpopulation in order to create a clinical score (e.g. the Z-score of all females of a certain age). Among QCT's disadvantages: it requires a high radiation dose, CT scanners are large and expensive, and because its practice has been less standardized than BMD, its results are more operator-dependent. Peripheral QCT has been introduced to improve upon the limitations of DXA and QCT.<ref name="diagnosticimaging.com"/> |
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Quantitative [[ultrasound]] has many advantages in assessing osteoporosis. The modality is small, no ionizing radiation is involved, measurements can be made quickly and easily, and the cost of the device is low compared with DXA and QCT devices. The calcaneus is the most common skeletal site for quantitative ultrasound assessment because it has a high percentage of trabecular bone that is replaced more often than cortical bone, providing early evidence of metabolic change. Also, the calcaneus is fairly flat and parallel, reducing repositioning errors. The method can be applied to children, neonates, and preterm infants, just as well as to adults. Once microimaging tools to examine specific aspects of bone quality are developed, it is expected that quantitative ultrasound will be increasingly used in clinical practice.<ref name="diagnosticimaging.com"/> |
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===Screening=== |
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The [[U.S. Preventive Services Task Force]] (USPSTF) recommended in 2011 that all women 65 years of age or older should be [[screening (medicine)|screened]] with [[bone densitometry]].<ref name=USP2011>{{cite journal|last=U.S. Preventive Services Task|first=Force|title=Screening for osteoporosis: U.S. preventive services task force recommendation statement.|journal=Annals of internal medicine|date=2011-03-01|volume=154|issue=5|pages=356–64|pmid=21242341}}</ref> They recommend screening women of any age with increased risk factors that puts them at risk equivalent to a 65 year old without additional risk factors.<ref name=USP2011/> The most significant risk factors is lower body weight (weight < 70 kg), with less evidence for history of smoking or family history. There was insufficient evidence to make recommendations about the optimal intervals for repeated screening and the appropriate age to stop screening. [[Clinical prediction rules]] are available to guide selection of women ages 60–64 for screening. The Osteoporosis Risk Assessment Instrument (ORAI) may be the most [[sensitivity (tests)|sensitive]].<ref name="pmid17552058">{{cite journal |author=Martínez-Aguilà D, Gómez-Vaquero C, Rozadilla A, Romera M, Narváez J, Nolla JM |title=Decision rules for selecting women for bone mineral density testing: application in postmenopausal women referred to a bone densitometry unit |journal=J. Rheumatol. |volume=34 |issue=6 |pages=1307–12 |year=2007 |pmid=17552058 |doi=}}</ref> |
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The USPSTF concludes that the harm versus benefit of screening for osteoporosis in men of any age is unknown.<ref name=USP2011/> Others have however claimed that screening may be cost effective in those 80 to 85 years of age.<ref name="pmid17684185">{{cite journal |author=Schousboe JT, Taylor BC, Fink HA, ''et al.'' |title=Cost-effectiveness of bone densitometry followed by treatment of osteoporosis in older men |journal=JAMA |volume=298 |issue=6 |pages=629–37 |year=2007 |pmid=17684185 |doi=10.1001/jama.298.6.629}}</ref> |
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==Prevention== |
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Methods to prevent osteoporosis include changes of lifestyle. However, there are medications that can be used for prevention as well. As a different concept there are osteoporosis ortheses which help to prevent spine fractures and support the building up of muscles.{{Citation needed|date=May 2011}} [[Fall prevention]] can help prevent osteoporosis complications. |
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===Lifestyle=== |
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Lifestyle prevention of osteoporosis is in many aspects inversions from potentially modifiable risk factors. As [[tobacco smoking]] and unsafe [[alcoholic beverage|alcohol]] intake have been linked with osteoporosis, smoking cessation and moderation of alcohol intake are commonly recommended in the prevention of osteoporosis. Many other risk factors, some modifiable and others non modifiable such as genetic may be involved in osteoporosis.<ref>{{cite journal | author = Davis S, Oliver A, Goeckeritz B, Sachdeva A | year = 2010 | title = All about osteoporosis: a comprehensive analysis | url = http://www.musculoskeletalnetwork.com/rheumatoid-arthritis/content/article/1145622/1551345 | journal = Journal of Musculoskeletal Medicine | volume = 27 | issue = 4| pages = 149–153 }}</ref> |
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Achieving a higher peak bone mass through exercise and proper nutrition during adolescence is important for the prevention of osteoporosis. Exercise and nutrition throughout the rest of the life delays bone degeneration. Jogging, walking, or stair climbing at 70-90% of maximum effort three times per week, along with 1,500 mg of calcium per day, increased bone density of the lumbar (lower) spine by 5% over nine months. Individuals already diagnosed with osteopenia or osteoporosis should discuss their exercise program with their physician to avoid fractures.<ref name="pmid3259410">{{cite journal |author=Dalsky GP, Stocke KS, Ehsani AA, Slatopolsky E, Lee WC, Birge SJ |title=Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women |journal=Ann. Intern. Med. |volume=108 |issue=6 |pages=824–28 |year=1988 |pmid=3259410 |doi=}}</ref> |
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===Nutrition=== |
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Proper nutrition includes a diet sufficient in [[calcium]] and [[vitamin D]]. People at risk for osteoporosis (e.g. [[steroid]] use) are generally treated with [[vitamin D]] and calcium supplements and often with bisphosphonates. Vitamin D supplementation alone does not prevent fractures, and needs to be combined with calcium.<ref>{{cite journal|author=Sahota O|title=Reducing the risk of fractures with calcium and vitamin D: The combination is more effective than vitamin D alone|journal=BMJ|year=2009|volume=339|pages=b5492|doi=10.1136/bmj.b5492|last1=Sahota|first1=O.}}</ref><ref>{{cite journal|author=DIPART (vitamin D Individual Patient Analysis of Randomized Trials|title=Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe|journal=BMJ|year=2010|volume=340|pages=b5463|doi=10.1136/bmj.b5463 |pmid=20068257|pmc=2806633}}</ref> Calcium supplements come in two forms: calcium carbonate and calcium citrate. Due to its lower cost, calcium carbonate is often the first choice, however it needs to be taken with food to maximize absorption. Calcium citrate is more expensive, but it is better absorbed than calcium carbonate and can be taken without food. In addition, patients who are taking proton pump inhibitors or H2 blockers do not absorb calcium carbonate well; calcium citrate is the supplement of choice in this population.<ref name="Rosen, Hillel N 2010">Rosen, Hillel N. Calcium and vitamin D supplementation in osteoporosis. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2010.</ref> In [[kidney|renal]] disease, more active forms of Vitamin D such as cholecalciferol or (1,25-dihydroxycholecalciferol or [[calcitriol]] which is the main biologically active form of vitamin D) is used, as the kidney cannot adequately generate calcitriol from calcidiol (25-hydroxycholecalciferol) which is the storage form of vitamin D.In vitamin D assays, vitamin D<sub>2</sub> (ergocalitrol) is not accurately measured, therefore vitamin D<sub>3</sub> (cholecalciferol) is recommended for supplementation.<ref name="Rosen, Hillel N 2010"/> |
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High [[Protein in nutrition|dietary protein]] intake increases calcium excretion in [[urine]] and has been linked to increased risk of fractures in research studies.<ref>{{cite journal |author=Feskanich D, Willett WC, Stampfer MJ, Colditz GA |title=Protein consumption and bone fractures in women |journal=Am. J. Epidemiol. |volume=143 |issue=5 |pages=472–79 |year=1996 |pmid=8610662 |doi=}}</ref> Other investigations have shown that protein is required for calcium absorption, but that excessive protein consumption inhibits this process. No interventional trials have been performed on dietary protein in the prevention and treatment of osteoporosis.<ref name="pmid12936953">{{cite journal |author=Kerstetter JE, O'Brien KO, Insogna KL |title=Dietary protein, calcium metabolism, and skeletal homeostasis revisited |journal=Am. J. Clin. Nutr. |volume=78 |issue=3 Suppl |pages=584S–592S |year=2003 |pmid=12936953 |doi=}}</ref> |
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===Medication=== |
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Just as for treatment, [[bisphosphonate]] can be used in cases of very high risk. Other medicines prescribed for prevention of osteoporosis include [[raloxifene]], a [[selective estrogen receptor modulator]] (SERM). |
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[[Hormone replacement therapy (menopause)|Estrogen replacement therapy]] remains a good treatment for prevention of osteoporosis but, at this time, is not recommended unless there are other indications for its use as well. There is uncertainty and controversy about whether estrogen should be recommended in women in the first decade after the menopause. |
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In hypogonadal men [[testosterone]] has been shown to give improvement in bone quantity and quality, but, as of 2008, there are no studies of the effects on fractures or in men with a normal testosterone level.<ref name="OsteoporosisMen"/> |
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==Treatment== |
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There are several medications used to treat osteoporosis, depending on gender. Medications themselves can be classified as antiresorptive or bone anabolic agents. Antiresorptive agents work primarily by reducing [[bone resorption]], while bone anabolic agents build bone rather than inhibit resorption. Lifestyle changes are an important aspect of treatment. A major problem is gaining long-term adherence to therapy from patients with osteoporosis. Fifty percent of patients do not take their medications and most discontinue within 1 year.<ref name="dbt.consultantlive.com">{{cite journal | author = Davis S, Sachdeva A, Goeckeritz B, Oliver A | year = 2010 | title = Approved treatments for osteoporosis and what's in the pipeline | url = http://dbt.consultantlive.com/display/article/1145628/1583209 | journal = Drug Benefit Trends | volume = 22 | issue = 4| pages = 121–124 }}</ref> |
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=== Antiresorptive agents === |
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* '''Bisphosphonates''' |
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: Bisphosphonates are the main pharmacological measures for treatment. However, newer drugs have appeared in the 1990s, such as teriparatide and strontium ranelate. |
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: In confirmed osteoporosis, [[bisphosphonate]] drugs are the first-line treatment in women. The most often prescribed bisphosphonates are {{As of|2005|alt=presently}} [[sodium alendronate]] (Fosamax) 10 mg a day or 70 mg once a week, [[risedronate]] (Actonel) 5 mg a day or 35 mg once a week and/or [[ibandronate]] (Boniva) once a month. |
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: A 2007 manufacturer-supported study suggested that in patients who had suffered a low-impact hip fracture, annual infusion of 5 mg [[Zoledronate|zoledronic acid]] reduced risk of any fracture by 35% (from 13.9 to 8.6%), vertebral fracture risk from 3.8% to 1.7% and non-vertebral fracture risk from 10.7% to 7.6%. This study also found a mortality benefit: after 1.9 years, 9.6% of the study group (as opposed to 13.3% of the control group) had died of any cause, indicating a mortality benefit of 28%.<ref>{{cite journal |author=Lyles KW, Colón-Emeric CS, Magaziner JS, ''et al.'' |title=Zoledronic acid and clinical fractures and mortality after hip fracture |journal=N Engl J Med |volume=357 |year=2007 |pmid=17878149 |doi=10.1056/NEJMoa074941 |issue=18 |pages=1799–809}}</ref> There are currently no studies which examine the efficacy or side-effects of zoledronic acid past the three-year period.<ref>National Prescribing Service (2009). "Zoledronic Acid for osteoporosis". ''Medicines Update'', Available at http://www.nps.org.au/consumers/publications/medicine_update/issues/Zoledronic_acid</ref> |
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: Oral bisphosphonates are relatively poorly absorbed, and must therefore be taken on an empty stomach, with no food or drink to follow for the next 30 minutes. They are associated with [[esophagitis|inflammation of the esophagus]] (esophagitis) and are therefore sometimes poorly tolerated; weekly or monthly administration (depending on the preparation) decreases likelihood of esophagitis, and is now standard. Although intermittent dosing with the intravenous formulations such as zolendronate (zoledronic acid) avoids oral tolerance problems, these agents are implicated at higher rates in a rare but severe bone disease called [[osteonecrosis of the jaw]].<ref>{{cite journal |author=Purcell, P. Boyd, I|title=Bisphosphonates and osteonecrosis of the jaw|journal=Medical Journal of Australia|volume=182 |issue=8 |pages=417–18 |year=2005 |pmid= 15850440|doi=}}</ref> For this reason, oral bisphosphonate therapy is probably to be preferred, and doctors now recommend that any needed remedial dental work be done before treatment begins.<ref>{{cite book |title=[[British National Formulary]] |chapter=6.6.2 Bisphosphonates |edition=54 |page=403 |month=September | year=2007 |publisher=[[British Medical Association]] and [[Royal Pharmaceutical Society of Great Britain]]}}</ref> |
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* '''Estrogen analogs''' |
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: [[Hormone replacement therapy (menopause)|Estrogen replacement therapy]] remains a good treatment for prevention of osteoporosis but, at this time, is not recommended unless there are other indications for its use as well. There is uncertainty and controversy about whether estrogen should be recommended in women in the first decade after the menopause. |
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: In hypogonadal men [[testosterone]] has been shown to give improvement in bone quantity and quality, but, as of 2008, there are no studies of the effects on fractures or in men with a normal testosterone level.<ref name="OsteoporosisMen"/> |
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* '''Raloxifene |
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: [[Selective Estrogen Receptor Modulators (SERMs)]] are a class of medications that act on the estrogen receptors throughout the body in a selective manner. Normally, [[bone mineral density]] (BMD) is tightly regulated by a balance between [[osteoblast]] and [[osteoclast]] activity in the trabecular bone. Estrogen has a major role in regulation of the bone formation-resorption equilibrium, as it stimulates osteoblast activity. Some SERMs such as [[raloxifene]], act on the bone by slowing bone resorption by the osteoclasts.<ref>{{cite journal |author=Taranta A, Brama M, Teti A, ''et al.'' |title=The selective estrogen receptor modulator raloxifene regulates osteoclast and osteoblast activity in vitro |journal=Bone |volume=30 |issue=2 |pages=368–76 |year=2002 |month=February |pmid=11856644 |doi= 10.1016/S8756-3282(01)00685-8|url=http://linkinghub.elsevier.com/retrieve/pii/S8756328201006858}}</ref> Raloxifene has the added advantage of reducing the risk of invasive breast cancer.<ref name="dbt.consultantlive.com"/> SERMs have been proven effective in clinical trials.<ref>{{cite journal |author=Meunier PJ, Vignot E, Garnero P, ''et al.'' |title=Treatment of postmenopausal women with osteoporosis or low bone density with raloxifene. Raloxifene Study Group |journal=Osteoporos Int |volume=10 |issue=4 |pages=330–36 |year=1999 |pmid=10692984 |doi= 10.1007/s001980050236|url=http://link.springer.de/link/service/journals/00198/bibs/9010004/90100330.htm}}</ref> |
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* '''Calcitonin |
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: Calcitonin works by directly inhibiting osteoclast activity via the [[calcitonin receptor]]. Calcitonin receptors have been identified on the surface of osteoclasts.<ref>Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization. |
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Nicholson GC, Moseley JM, Sexton PM, Mendelsohn FA, Martin TJ. Abundant calcitonin receptirs in solated rat osteoclasts. J Clin Invest; 1986; 78:355-360.</ref> Calcitonin directly induces inhibition of osteoclastic bone resorption by affecting actin cytoskeleton which is needed for the osteoclastic activity.<ref>Okumura S, Mizoguchi T, Sato N, Yamaki M, Kobayashi Y, Yamauchi H, Ozawa H, Udagawa N, Takahashi N (2006). “Coordination of microtubules and the actin cytoskeleton is important in osteoclast function, but calcitonin disrupts sealing zones without affecting microtubule networks“. Bone. 39 (4): 684-693. doi:10.1016/j.bone.2006.04.010. PMID 16774853</ref> |
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=== Bone anabolic agents === |
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* '''Teriparatide''' |
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: Recently, [[teriparatide]] (Forteo, [[Recombinant DNA|recombinant]] [[parathyroid hormone]] residues 1–34) has been shown to be effective in osteoporosis. It acts like parathyroid hormone and stimulates osteoblasts, thus increasing their activity. It is used mostly for patients with established osteoporosis (who have already fractured), have particularly low BMD or several risk factors for fracture or cannot tolerate the oral bisphosphonates. It is given as a daily injection with the use of a pen-type injection device. In some countries, Teriparatide is licensed to be used for treatment only if bisphosphonates have failed or are contraindicated. (In the US, this restriction has not been imposed by the FDA.) Patients with previous radiation therapy, or [[Paget's disease]], or young patients, should avoid this medication. |
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* '''Calcium salts''' |
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: Calcium salts come as water insoluble and soluble formulations. Calcium carbonate is the primary water insoluble drug, while calcium citrate, lactate, and gluconate are water soluble. Calcium carbonate's absorption is improved in acidic conditions, while the water soluble salts are relatively unaffected by acidic conditions. |
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* '''Sodium fluoride''' |
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: Sodium fluoride treatment in patients with osteoporosis has been shown to cause skeletal changes such as pronounced bone density with increased number and thickness of trabeculae, cortical thickening, and partial obliteration of the medullary space.<ref>El-Khoury GY, Moore TE, Albright JP, Huang HK, Martin RK. Sodium Fluoride Treatment of Osteoporosis: Radiologic Findings. AJR. 1982;139:39-43</ref> |
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=== Other agents === |
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* '''[[RANKL]] inhibitors''' |
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: [[Denosumab]] is a fully human [[monoclonal antibody]] that mimics the activity of [[osteoprotegerin]]. It binds to RANKL, thereby preventing RANKL from interacting with [[RANK]] and reducing its bone resorption. It was approved for use in the treatment of osteoporosis by the European Commission on May 28, 2010 and by the United States Food and Drug Administration on June 2, 2010. |
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* '''Strontium ranelate''' |
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: Oral [[strontium ranelate]] is an alternative oral treatment, belonging to a class of drugs called "dual action bone agents" (DABAs) by its manufacturer. It has proven efficacy, especially in the prevention of vertebral fracture.<ref>{{cite journal |author=Meunier PJ, Roux C, Seeman E, ''et al.'' |title=The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis |journal=N. Engl. J. Med. |volume=350 |issue=5 |pages=459–68 |year=2004 |pmid=14749454 |doi=10.1056/NEJMoa022436}}</ref> In laboratory experiments, strontium ranelate was noted to stimulate the proliferation of osteoblasts, as well as inhibiting the proliferation of osteoclasts. |
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: Strontium ranelate is taken as a 2 g oral suspension daily, and is licenced for the treatment of osteoporosis to prevent vertebral and hip fracture. Strontium ranelate has side effect benefits over the bisphosphonates, as it does not cause any form of upper GI side effect, which is the most common cause for medication withdrawal in osteoporosis.{{Citation needed|date=November 2010}} In studies a small increase in the risk of [[venous thromboembolism]] was noted,<ref>{{cite journal |author=O'Donnell S, Cranney A, Wells GA, Adachi JD, Reginster JY |editor1-last=Cranney |editor1-first=Ann |title=Strontium ranelate for preventing and treating postmenopausal osteoporosis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=4 |pages=CD005326 |year=2006 |pmid=17054253 |doi=10.1002/14651858.CD005326.pub3}}</ref> the cause for which has not been determined. This suggests it may be less suitable in patients at risk for thrombosis for different reasons. The uptake of (heavier) strontium in place of calcium into bone matrix results in a substantial and disproportionate increase in bone mineral density as measured on DXA scanning,<ref>{{cite journal |author=Reginster JY, Seeman E, De Vernejoul MC, ''et al.'' |title=Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study. |journal=J Clin Endorinol Metab |volume=90 |issue= 5|pages=2816–22|year=2005 |pmid=15728210 |doi=10.1210/jc.2004-1774}}</ref> making further followup of bone density by this method harder to interpret for strontium treated patients. A correction algorithm has been devised.<ref>{{cite journal |author=Blake GM, Fogelman I |title=The correction of BMD measurements for bone strontium content |journal=J Clin Densitom |volume=10 |issue=3 |pages=259–65 |year=2007 |pmid=17543560 |doi=10.1016/j.jocd.2007.03.102}}</ref> |
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: Although strontium ranelate is effective, it is not approved for use in the United States yet. However, strontium citrate is available in the US from several well-known vitamin manufacturers. Most researchers believe that strontium is safe and effective no matter what form it is used. The ranelate form is simply a device invented by the Servier company of France so that they could patent their version of strontium.{{Citation needed|date=April 2008}} |
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: Strontium, no matter what the form, must be water-soluble and ionized in the stomach acid. Strontium is then protein-bound for transport from the intestinal tract into the blood stream. Unlike drugs like [[sodium alendronate]] (Fosamax), strontium doesn't inhibit bone recycling and, in fact, may produce stronger bones. Studies have shown that after five years alendronate may even cause bone loss, while strontium continues to build bone during lifetime use.{{Citation needed|date=April 2008}} |
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: Strontium must not be taken with food or calcium-containing preparations as calcium competes with strontium during uptake. However, it is essential that calcium, magnesium, and vitamin D in therapeutic amounts must be taken daily, but not at the same time as strontium. Strontium should be taken on an empty stomach at night.{{Citation needed|date=April 2008}} |
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===Nutrition=== |
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* '''Calcium''' |
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: [[Calcium]] is required to support [[Ossification|bone growth]], [[bone healing]] and maintain bone strength and is one aspect of treatment for osteoporosis. Recommendations for calcium intake vary depending country and age; for individuals at higher risk of osteoporosis (after fifty years of age) the amount recommended by [[United States|US]] health agencies is 1,200 mg per day. Calcium supplements can be used to increase dietary intake, and absorption is optimized through taking in several small (500 mg or less) [[Dose (pharmacology)|doses]] throughout the day.<ref>{{cite web | url = http://www.niams.nih.gov/Health_Info/Bone/Bone_Health/Nutrition/default.asp | accessdate = 2008-01-28 | title = Nutrition and Bone Health | publisher = [[National Institute of Arthritis and Musculoskeletal and Skin Diseases|NIAMS]] | date = 2005-11-01 }}</ref> The role of calcium in preventing and treating osteoporosis is unclear — some populations with extremely low calcium intake also have extremely low rates of bone fracture, and others with high rates of calcium intake through [[milk]] and milk products have higher rates of bone fracture. Other factors, such as protein, salt and vitamin D intake, exercise and exposure to sunlight, can all influence bone mineralization, making calcium intake one factor among many in the development of osteoporosis.<ref name = Harvard>{{cite web | url = http://www.hsph.harvard.edu/nutritionsource/calcium.html | title = Calcium & Milk | publisher = Harvard School of Public Health | accessdate = 2008-01-28 | year = 2007 }}</ref> In the report of [[WHO]] (World Health Organization) in 2007, because calcium is consumed by an acid load with food, it influences osteoporosis.<ref>Report of a Joint WHO/FAO/UNU Expert Consultation(2007) ''[http://whqlibdoc.who.int/trs/WHO_TRS_935_eng.pdf Protein and amino acid requirements in human nutrition]'', pp224-26. ISBN 978-92-4-120935-9</ref><ref>Report of a Joint WHO/FAO/UNU Expert Consultation(2002), ''[http://www.fao.org/DOCREP/004/Y2809E/y2809e0h.htm#bm17 Human Vitamin and Mineral Requirements]'', pp166-167.</ref> |
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: A [[meta-analysis]] of [[randomized controlled trial]]s involving calcium and calcium plus vitamin D supported the use of high levels of calcium (1,200 mg or more) and vitamin D (800 IU or more), though outcomes varied depending on which measure was used to assess bone health (rates of fracture versus rates of bone loss).<ref name="pmid17720017">{{cite journal |author=Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A |title=Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis |journal=Lancet |volume=370 |issue=9588 |pages=657–66 |year=2007 |pmid=17720017 |doi=10.1016/S0140-6736(07)61342-7}}</ref> The meta-analysis, along with another study, also supported much better outcomes for patients with high [[Compliance (medicine)|compliance]] to the treatment protocol.<ref>{{cite journal |author=Prince RL, Devine A, Dhaliwal SS, Dick IM |title=Effects of calcium supplementation on clinical fracture and bone structure: results of a 5-year, double-blind, placebo-controlled trial in elderly women |journal=Arch. Intern. Med. |volume=166 |issue=8 |pages=869–75 |year=2006 |pmid=16636212 |doi=10.1001/archinte.166.8.869}}</ref> In contrast, despite earlier reports in improved [[high density lipoprotein]] (HDL, "good cholesterol") in calcium supplementation, a possible increase in the rate of [[myocardial infarction]] (heart attack) was found in a study in [[New Zealand]] in which 1471 women participated. If confirmed, this would indicate that calcium supplementation in women otherwise at low risk of fracture may cause more harm than good.<ref name="pmid18198394">{{cite journal |author=Bolland MJ, Barber PA, Doughty RN, ''et al.'' |title=Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial |journal=BMJ |volume= 336|issue= 7638| page = 262|year=2008 |pmid=18198394 |doi=10.1136/bmj.39440.525752.BE |pmc=2222999}}</ref> |
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* '''Vitamin D''' |
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: Several studies have shown that a high intake of [[vitamin D]] reduces fractures in the elderly,<ref name="pmid17720017"/><ref>{{cite journal |author=Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B |title=Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials |journal=JAMA |volume=293 |issue=18 |pages=2257–64 |year=2005 |pmid=15886381 |doi=10.1001/jama.293.18.2257}}</ref> The [[Women's Health Initiative]] found that though calcium plus vitamin D did increase bone density by 1% but it did not affect hip fracture. It did increase formation of [[kidney stone]]s by 17%.<ref>{{cite journal |author=Jackson RD, LaCroix AZ, Gass M, ''et al.'' |title=Calcium plus vitamin D supplementation and the risk of fractures |journal=N. Engl. J. Med. |volume=354 |issue=7 |pages=669–83 |year=2006 |pmid=16481635 |doi=10.1056/NEJMoa055218}}</ref> This study has been criticised for using an inadequate dose of vitamin D (400 U) and for allowing the control arm to take supplemental vitamin D. |
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: Calcium and vitamin D are currently recommended for the primary prevention of osteoporosis and the primary and secondary prevention of osteoporotic fractures. However, calcium and vitamin D may reduce fracture risk by only 16%.<ref>{{cite journal|last=Larsen|first=ER|coauthors=Mosekilde L, Foldspang A|title=Vitamin D and Calcium Supplementation Prevents Osteoporotic Fractures in Elderly Community Dwelling Residents: A Pragmatic Population-Based 3-Year Intervention Study|journal=Journal of Bone and Mineral Research|year=2004|volume=19|issue=3|pages=370–378|pmid=15040824}}</ref> This study followed 2532 community-dwelling residents (median age, 73 years; 59.8% female) over 3 years who supplemented with 400 IU vitamin D3 and 1000 mg calcium as calcium carbonate daily. |
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* '''Vitamin K''' |
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: In osteoporosis research, [[vitamin K]] has been extensively studied for its ability to stimulate collagen production, promote bone health and decrease fracture risk. Vitamin K is a category that includes vitamin K1 and vitamin K2. Vitamin K1 (phylloquinone) is found in green leafy vegetables. Vitamin K2 itself is a category that contains various forms of vitamin K2, including menaquinone-4 (menatetrenone, MK4) and menaquinone-7 (MK7). Among the vitamin K analogues, the form most researched for osteoporosis treatment and fracture reduction is MK4. MK4 is produced via conversion of K1 in the body, in the testes, pancreas and arterial walls.<ref>{{cite journal|last=Shearer|first=MJ|coauthors=Newman P|title=Metabolism and cell biology of vitamin K|journal=Thrombosis and haemostasis|year=2008|volume=100|pages=530–547|pmid=18841274}}</ref> MK7 is instead not produced in humans, but converted from vitamin K1 in the intestines by bacteria.<ref>{{cite journal|last=Vermeer|first=C|coauthors=Braam L|title=Role of K vitamins in the regulation of tissue calcification|journal=Journal of bone and mineral metabolism|year=2001|volume=19|issue=4|pages=201–206|pmid=11448011}}</ref> |
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: MK4 and MK7 are both found in the United States in dietary supplements for bone health. The US FDA has not approved any form of vitamin K for the prevention or treatment of osteoporosis. With respect to osteoporosis, MK7 has never been shown to reduce fractures. However, MK4 has been shown to reduce fractures in clinical trials and has been approved for the prevention and treatment of osteoporosis by the Ministry of Health in Japan since 1995.<ref>{{cite journal|last=Iwamoto|first=I|coauthors=Kosha S, Noguchi S-i|title=A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy|journal=Maturitas|year=1999|volume=31|issue=2|pages=161–164|pmid=10227010}}</ref> In Japan MK4 is used in the amount of 45 mg daily for the prevention and treatment of osteoporosis. As an approved medication in Japan it has been extensively studied and shown to decrease fractures in clinical trials up to 87% independent of the number of falls sustained.<ref>{{cite journal|last=Sato|first=Y|coauthors=Kanoko T, Satoh K, Iwamoto J|title=Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease|journal=Bone|year=2005|volume=36|issue=1|pmid=15664003}}</ref> In clinical trials MK4 (45 mg daily) prevented bone loss and/or fractures caused by corticosteroids (e.g., [[prednisone]], [[dexamethasone]], [[prednisolone]]),<ref>{{cite journal|last=Inoue|first=T|coauthors=Sugiyama T, Matsubara T, Kawai S, Furukawa S|title=Inverse correlation between the changes of lumbar bone mineral density and serum undercarboxylated osteocalcin after vitamin K2 (menatetrenone) treatment in children treated with glucocorticoid and alfacalcidol.|journal=Endocrine Journal|year=2001|volume=48|issue=1|pages=11–18|pmid=11403096}}</ref><ref>{{cite journal|last=Sasaki|first=N, Kusano E, Takahashi H, Ando Y, Yano K, Tsuda E, Asano Y|coauthors=Kusano E, Takahashi H, Ando Y, Yano K, Tsuda E, Asano Y|title=Vitamin K2 inhibits glucocorticoid-induced bone loss partly by preventing the reduction of osteoprotegerin (OPG)|journal=Journal of bone and mineral metabolism|year=2005|volume=23|issue=1|pages=41–47|pmid=15616893}}</ref><ref>{{cite journal|last=Yonemura|first=K|coauthors=Fukasawa H, Fujigaki Y, Hishida A.|title=Protective effect of vitamins K2 and D3 on prednisolone-induced loss of bone mineral density in the lumbar spine|journal=American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation|year=2004|volume=43|issue=1|pages=53–60|pmid=14712427}}</ref><ref>{{cite journal|last=Yonemura|first=K|coauthors=Kimura M, Miyaji T, Hishida A|title=Short-term effect of vitamin K administration on prednisolone-induced loss of bone mineral density in patients with chronic glomerulonephritis|journal=Calcified Tissue International|year=2000|volume=66|issue=2|pages=123–128|pmid=10652960}}</ref> anorexia nervosa,<ref>{{cite journal|last=Iketani|first=T|coauthors=Kiriike N, B. Stein M|title=Effect of menatetrenone (vitamin K2) treatment on bone loss in patients with anorexia nervosa|journal=Psychiatry Research|year=2003|volume=117|issue=3|pages=259–269|pmid=12686368}}</ref> cirrhosis of the liver,<ref>{{cite journal|last=Shiomi|first=S|coauthors=Nishiguchi S, Kubo S|title=Vitamin K2 (menatetrenone) for bone loss in patients with cirrhosis of the liver|journal=The American Journal of Gastroenterology|year=2002|volume=97|issue=4|pages=978–981|pmid=12003435}}</ref> postmenopausal osteoporosis,<ref>{{cite journal|last=Cockayne|first=S|coauthors=Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ|title=Vitamin K and the Prevention of Fractures: Systematic Review and Meta-analysis of Randomized Controlled Trials|journal=Archives of Internal Medicine|year=2006|volume=166|issue=12|pages=1256–1261|pmid=16801507}}</ref><ref>{{cite journal|last=Iwamoto|first=I|coauthors=Kosha S, Noguchi S-i|title=A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy.|journal=Maturitas|year=1999|volume=31|issue=2|pages=161–164|pmid=10227010}}</ref><ref>{{cite journal|last=Iwamoto|first=J|coauthors=Takeda T, Ichimura S|title=Effect of combined administration of vitamin D3 and vitamin K2 on bone mineral density of the lumbar spine in postmenopausal women with osteoporosis|journal=Journal of Orthopaedic Science|year=2000|volume=5|issue=6|pages=546–551|pmid=11180916}}</ref><ref>{{cite journal|last=Purwosunu|first=Y|coauthors=Muharram, Rachman IA, Reksoprodjo S, Sekizawa A|title=Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia|journal=The journal of obstetrics and gynaecology research|year=2006|volume=32|issue=2|pages=230–234|pmid=16594930}}</ref><ref>{{cite journal|last=Shiraki|first=M|coauthors=Shiraki Y, Aoki C, Miura M|title=Vitamin K2 (Menatetrenone) Effectively Prevents Fractures and Sustains Lumbar Bone Mineral Density in Osteoporosis|journal=Journal of Bone and Mineral Research|year=2000|volume=15|issue=3|pages=515–522|pmid=10750566}}</ref><ref name="Ushiroyama 2002 211–221">{{cite journal|last=Ushiroyama|first=T|coauthors=Ikeda A, Ueki M|title=Effect of continuous combined therapy with vitamin K2 and vitamin D3 on bone mineral density and coagulofibrinolysis function in postmenopausal women|journal=Maturitas|year=2002|volume=41|issue=3|pages=211–221|pmid=11886767}}</ref> disuse from stroke,<ref>{{cite journal|last=Sato|first=Y|coauthors=Honda Y, Kuno H, Oizumi K|title=Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients|journal=Bone|year=1998|volume=23|issue=3|pages=291–296|pmid=9737352}}</ref> [[Alzheimer’s disease]],<ref>{{cite journal|last=Sato|first=Y|coauthors=Kanoko T, Satoh K, Iwamoto J|title=Menatetrenone and vitamin D2 with calcium supplements prevent nonvertebral fracture in elderly women with Alzheimer's disease|journal=Bone|year=2005|volume=36|issue=1|pages=61–68|pmid=15664003}}</ref> [[Parkinson disease]],<ref>{{cite journal|last=Sato|first=Y|coauthors=Honda Y, Kaji M|title=Amelioration of osteoporosis by menatetrenone in elderly female Parkinson's disease patients with vitamin D deficiency|journal=Bone|year=2002|volume=31|issue=1|pages=114–118|pmid=12110423}}</ref> [[primary biliary cirrhosis]]<ref>{{cite journal|last=Nishiguchi|first=S|coauthors=Shimoi S, Kurooka H|title=Randomized pilot trial of vitamin K2 for bone loss in patients with primary biliary cirrhosis|journal=Journal of Hepatology|year=2001|volume=35|issue=4|pages=543–545|pmid=11682046}}</ref> and leuprolide treatment (for prostate cancer).<ref>{{cite journal|last=Somekawa|first=Y|coauthors=Chigughi M, Harada M, Ishibashi T|title=Use of vitamin K2 (menatetrenone) and 1,25-dihydroxyvitamin D3 in the prevention of bone loss induced by leuprolide|journal=The Journal of clinical endocrinology and metabolism|year=1999|volume=84|issue=8|pages=2700–2704|pmid=10443663}}</ref> |
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: Pathological fractures is a serious problem resulting from skeletal unloading in handicapped children. Sugiyama et al.<ref>{{cite journal|last=Sugiyama|first=T|coauthors=Tanaka H, Kawai S|title=Clinical vignette. Vitamin K plus vitamin D treatment of bone problems in a child with skeletal unloading|journal=Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research|year=1999|volume=14|issue=8|pages=1466–1467|pmid=10457281}}</ref> published a case report of an institutionalized, bedridden 8-year-old girl with [[Arnold-Chiari malformation]] with low BMD whose BMD increased with MK4 treatment. MK4 also inhibited phenytoin-induced bone loss in rats;<ref name="Onodera 2002 1533–1542">{{cite journal|last=Onodera|first=K|coauthors=Takahashi A, Sakurada S, Okano Y|title=Effects of phenytoin and/or vitamin K2 (menatetrenone) on bone mineral density in the tibiae of growing rats|journal=Life Sciences|year=2002|volume=70|issue=13|pages=1533–1542|pmid=11895104}}</ref> prevented and increased bone formation in neurectomized rats,<ref name="Iwamoto 2003 776–783">{{cite journal|last=Iwamoto|first=J|coauthors=Yeh JK, Takeda T|title=Effect of Vitamin K2 on Cortical and Cancellous Bones in Orchidectomized and/or Sciatic Neurectomized Rats|journal=Journal of Bone and Mineral Research|year=2003|volume=18|issue=4|pages=776–783|pmid=12674339}}</ref><ref>{{cite journal|last=Iwasaki|first=Y|coauthors=Yamato H, Murayama H, Takahashi T, Ezawa I, Kurokawa K, Fukagawa M|title=Menatetrenone prevents osteoblast dysfunction in unilateral sciatic neurectomized rats|journal=Japanese journal of pharmacology|year=2002|volume=90|issue=1|pages=88–93|pmid=12396032}}</ref> an animal model for immobilization osteoporosis; prevented and increased bone formation in orchidectomized (castrated) rats,<ref name="Iwamoto 2003 776–783"/> an animal model for secondary osteoporosis caused by testosterone deficiency; and improved healing time and bone quality in experimentally induced [[osteotomy]] in rats alone and in the presence of glucocorticoids.<ref>{{cite journal|last=Iwamoto|first=J|coauthors=Seki A, Sato Y, Matsumoto H, Tadeda T, Yeh JK|title=Vitamin K2 promotes bone healing in a rat femoral osteotomy model with or without glucocorticoid treatment|journal=Calcified Tissue International|year=2010|volume=86|issue=3|pages=234–241|pmid=20111958}}</ref> And MK4 therapy has been cited as a potential strategy for drug-induced bone loss.<ref name="Onodera 2002 1533–1542"/> |
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: The safety of MK4 in the doses used to treat and prevent osteoporosis (45 mg daily) and in even higher amounts have been shown in multiple studies. In two human studies, people using 45 mg per day of vitamin K2 (as MK4)<ref name="Ushiroyama 2002 211–221"/> and even up to 135 mg/day (45 mg three times daily) of MK4,<ref>{{cite journal|last=Asakura|first=H|coauthors=Myou S, Ontachi Y|title=Vitamin K administration to elderly patients with osteoporosis induces no hemostatic activation, even in those with suspected vitamin K deficiency|journal=Osteoporosis International|year=2001|volume=12|issue=12|pages=996–1000|pmid=11846334}}</ref> showed no increase blood clot risk. Even doses in rats as high as 250 mg/kg body weight did not alter the tendency for blood-clot formation to occur.<ref>{{cite journal|last=Ronden|first=JE|coauthors=Groenen-van Dooren MMCL, Hornstra G, Vermeer C|title=Modulation of arterial thrombosis tendency in rats by vitamin K and its side chains|journal=Atherosclerosis|year=1997|volume=132|issue=1|pages=61–67|pmid=9247360}}</ref> MK4 appears safe except in people taking the blood clotting medication Coumadin ([[warfarin]]). Since warfarin, which was originally used as a rat poison, decreases blood clot risk by interrupting the vitamin K-dependent clotting factors, taking vitamin K in any amount interferes with the actions of warfarin and can increase blood clot risk. |
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=== Exercise === |
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: Multiple studies have shown that aerobics, weight bearing, and resistance exercises can all maintain or increase BMD in postmenopausal women.<ref>{{cite journal |author=Bonaiuti D, Shea B, Iovine R, ''et al.'' |editor1-last=Bonaiuti |editor1-first=Donatella |title=Exercise for preventing and treating osteoporosis in postmenopausal women |journal=Cochrane database of systematic reviews (Online) |volume= |issue=3 |pages=CD000333 |year=2002 |pmid=12137611| doi = 10.1002/14651858.CD000333}}</ref> Many researchers have attempted to pinpoint which types of exercise are most effective at improving BMD and other metrics of bone quality, however results have varied. The BEST (Bone-Estrogen Strength Training) Project at the University of Arizona identified six specific weight training exercises that yielded the largest improvements in BMD; this project suggests squat, military press, lat pulldown, leg press, back extension, and seated row, with three weight training sessions a week of two sets of each exercise, alternating between moderate (6-8 reps at 70% of 1-rep max) and heavy (4-6 reps at 80% of 1-rep max).<ref>{{cite journal|author=Houtkooper, LB, Stanford, VA, Metcalfe, LL, Lohman, TG, and Going, |
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SB |title=Preventing osteoporosis the Bone Estrogen Strength Training way. |journal=ACSM's Health & Fitness Journal|volume=11|issue=1|pages=21–27|year=2007}}</ref> One year of regular jumping exercises appears to increase the BMD and [[moment of inertia]] of the proximal [[tibia]]<ref>{{cite journal |author=Cheng S, Sipilä S, Taaffe DR, Puolakka J, Suominen H |title=Change in bone mass distribution induced by hormone replacement therapy and high-impact physical exercise in post-menopausal women |journal=Bone |volume=31 |issue=1 |pages=126–35 |year=2002 |pmid=12110425| doi = 10.1016/S8756-3282(02)00794-9}}</ref> in normal postmenopausal women. Treadmill walking, gymnastic training, stepping, jumping, endurance, and strength exercises all resulted in significant increases of L2-L4 BMD in osteopenic postmenopausal women.<ref>{{cite journal |author=Chien MY, Wu YT, Hsu AT, Yang RS, Lai JS |title=Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal women |journal=Calcif. Tissue Int. |volume=67 |issue=6 |pages=443–48 |year=2000 |pmid=11289692| doi = 10.1007/s002230001180}}</ref><ref>{{cite journal |author=Iwamoto J, Takeda T, Ichimura S |title=Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis |journal=Journal of Orthopaedic Science |volume=6 |issue=2 |pages=128–32 |year=2001 |pmid=11484097 |doi=10.1007/s007760100059 }}</ref><ref>{{cite journal |author=Kemmler W, Engelke K, Weineck J, Hensen J, Kalender WA |title=The Erlangen Fitness Osteoporosis Prevention Study: a controlled exercise trial in early postmenopausal women with low bone density-first-year results |journal=Archives of physical medicine and rehabilitation |volume=84 |issue=5 |pages=673–82 |year=2003 |pmid=12736880 |doi=}}</ref> Strength training elicited improvements specifically in [[distal]] [[Radius (bone)|radius]] and hip BMD.<ref>{{cite journal |author=Kerr D, Morton A, Dick I, Prince R |title=Exercise effects on bone mass in postmenopausal women are site-specific and load-dependent |journal=J. Bone Miner. Res. |volume=11 |issue=2 |pages=218–25 |year=1996 |pmid=8822346 |doi=10.1002/jbmr.5650110211}}</ref> Exercise combined with other pharmacological treatments such as [[Hormone replacement therapy (menopause)|hormone replacement therapy]] (HRT) has been shown to increases BMD more than HRT alone.<ref name="Villareal2003">{{cite journal|author=Villareal DT, Binder EF, Yarasheski KE, et al.|title=Effects of exercise training added to ongoing hormone replacement therapy on bone mineral density in frail elderly women|journal=J Am Geriatr Soc|year=2003|volume=51|issue=7|pages=985–90|pmid=12834519 | doi = 10.1046/j.1365-2389.2003.51312.x}}</ref> |
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: Additional benefits for osteoporotic patients other than BMD increase include improvements in balance, gait, and a reduction in risk of falls.<ref name="Mayo2005">{{cite journal|author=Sinaki M, Brey RH, Hughes CA, Larson DR, Kaufman KR|title=Significant reduction in risk of falls and back pain in osteoporotic-kyphotic women through a Spinal Proprioceptive Extension Exercise Dynamic (SPEED) program|journal=Mayo Clin Proc|year=2005|volume=80|issue=7|pages=849–55|pmid=16007888|doi=10.4065/80.7.849}}</ref> |
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==Prognosis== |
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{| class="wikitable" align="right" |
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|+ Hip fractures per 1000 patient-years<ref name="pmid17846439">{{cite journal |author=Cranney A, Jamal SA, Tsang JF, Josse RG, Leslie WD |title=Low bone mineral density and fracture burden in postmenopausal women |journal=CMAJ |volume=177 |issue=6 |pages=575–80 |year=2007 |pmid=17846439 |doi=10.1503/cmaj.070234 |pmc=1963365}}</ref> |
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! WHO category !! Age 50-64 !! Age > 64 || Overall |
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|- |
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| Normal || 5.3 || 9.4 || 6.6 |
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|- |
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| [[Osteopenia]] || 11.4 || 19.6 || 15.7 |
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|- |
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| Osteoporosis || 22.4 || 46.6 || 40.6 |
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|} |
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Although osteoporosis patients have an increased mortality rate due to the complications of fracture, it is rarely lethal. |
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Hip fractures can lead to decreased mobility and an additional risk of numerous complications (such as [[deep venous thrombosis]] and/or [[pulmonary embolism]], [[pneumonia]]). The 6-month mortality rate following hip fracture is approximately 13.5%, and a substantial proportion (almost 13%) of people who have suffered a hip fracture need total assistance to mobilize after a hip fracture.<ref>{{cite journal |author=Hannan EL, Magaziner J, Wang JJ, ''et al.'' |title=Mortality and locomotion 6 months after hospitalization for hip fracture: risk factors and risk-adjusted hospital outcomes |journal=JAMA |volume=285 |issue=21 |pages=2736–42 |year=2001 |pmid=11386929| doi = 10.1001/jama.285.21.2736}}</ref> |
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Vertebral fractures, while having a smaller impact on mortality, can lead to severe chronic pain of neurogenic origin, which can be hard to control, as well as deformity. Though rare, multiple vertebral fractures can lead to such severe hunch back ([[kyphosis]]) that the resulting pressure on internal organs can impair one's ability to breathe. |
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Apart from risk of death and other complications, osteoporotic fractures are associated with a reduced health-related [[quality of life]].<ref>{{cite journal |author=Brenneman SK, Barrett-Connor E, Sajjan S, Markson LE, Siris ES |title=Impact of recent fracture on health-related quality of life in postmenopausal women |journal=J. Bone Miner. Res. |volume=21 |issue=6 |pages=809–16 |year=2006 |pmid=16753011 |doi=10.1359/jbmr.060301}}</ref> |
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==Epidemiology== |
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Osteoporosis is a major public health threat which afflicts 55% of Americans aged 50 and above. Of these, approximately 80% are women.<ref>National Osteoporosis Foundation. America’s Bone Health: The State of Osteoporosis and Low Bone Mass in Our Nation. |
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Washington, DC: National Osteoporosis Foundation; 2002.</ref> It is estimated{{Citation needed|date=September 2007}} that 1 in 3 women and 1 in 12 men over the age of 50 worldwide have osteoporosis. It is responsible for millions of fractures annually, mostly involving the lumbar [[vertebrae]], [[hip]], and wrist. Fragility fractures of ribs are also common in men. |
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===Hip fractures=== |
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{{Main|hip fractures}} |
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Hip fractures are responsible for the most serious consequences of osteoporosis. In the United States, more than 250,000 hip fractures annually are attributable to osteoporosis.<ref name=RiggsEtAl2005>{{cite journal |
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| pmid = 8573428 |
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| title = The worldwide problem of osteoporosis: insights afforded by epidemiology. |
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| author = Riggs, B.L.; Melton, Lj 3.r.d. |
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| year = 2005 |
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| journal = Bone |
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| volume = 17 |
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| issue = 5 Suppl |
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| pages = 505S–511S |
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| doi = 10.1016/8756-3282(95)00258-4 |
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}}</ref> It is estimated that a 50-year-old white woman has a 17.5% lifetime risk of fracture of the proximal [[femur]]. The incidence of hip fractures increases each decade from the sixth through the ninth for both women and men for all populations. The highest incidence is found among men and women ages 80 or older.<ref name='Merkepid'/> |
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===Vertebral fractures=== |
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Between 35-50% of all women over 50 had at least one [[vertebral fracture]]. In the United States, 700,000 vertebral fractures occur annually, but only about a third are recognized. In a series of 9704 of women aged 68.8 on average studied for 15 years, 324 had already suffered a vertebral fracture at entry into the study; 18.2% developed a vertebral fracture, but that risk rose to 41.4% in women who had a previous vertebral fracture.<ref>{{cite journal | author = Cauley JA, Hochberg MC, Lui LY ''et al.'' | year=2007 | title=Long-term Risk of Incident Vertebral Fractures |journal = JAMA |volume =298|pages=2761–67|doi= 10.1001/jama.298.23.2761 | pmid=18165669 | issue = 23}}</ref> |
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===Wrist=== |
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In the United States, 250,000 [[Distal radius fracture|wrist fractures]] annually are attributable to osteoporosis.<ref name=RiggsEtAl2005/> Wrist fractures are the third most common type of osteoporotic fractures. The lifetime risk of sustaining a Colles' fracture is about 16% for white women. By the time women reach age 70, about 20% have had at least one wrist fracture.<ref name='Merkepid'>{{cite web|url=http://www.merckmedicus.com/pp/us/hcp/diseasemodules/osteoporosis/epidemiology.jsp |title=MerckMedicus Modules: Osteoporosis - Epidemiology |accessdate=2008-06-13 |publisher=Merck & Co., Inc |archiveurl = http://web.archive.org/web/20071228030929/http://www.merckmedicus.com/pp/us/hcp/diseasemodules/osteoporosis/epidemiology.jsp |archivedate = 2007-12-28}}</ref> |
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===Rib Fractures=== |
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Fragility fractures of the ribs are common in men as young as age thirty-five on. These are often overlooked as signs of osteoporosis as these men are often physically active and suffer the fracture in the course of physical activity. An example would be as a result of falling while water skiing or jet skiing. However, a quick test of the individual's testosterone level following the diagnosis of the fracture will readily reveal whether that individual might be at risk. |
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==History== |
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The link between age-related reductions in bone density and fracture risk goes back at least to [[Astley Cooper]], and the term "osteoporosis" and recognition of its pathological appearance is generally attributed to the French pathologist [[Jean Lobstein]].<ref>Lobstein JGCFM. ''Lehrbuch der pathologischen Anatomie.'' Stuttgart: Bd II, 1835.</ref> The American endocrinologist [[Fuller Albright]] linked osteoporosis with the postmenopausal state.<ref>{{cite journal | author=Albright F, Bloomberg E, Smith PH |year=1940 |title= Postmenopausal osteoporosis |journal=Trans. Assoc. Am. Physicians. |volume=55 |pages=298–305}}</ref> Bisphosponates, which revolutionized the treatment of osteoporosis, were discovered in the 1960s.<ref>{{cite journal |author=Patlak M |title=Bone builders: the discoveries behind preventing and treating osteoporosis |journal=FASEB J. |volume=15 |issue=10 |pages=1677E–E |year=2001 |pmid=11481214 |doi= 10.1096/fj.15.10.1677e}}</ref> |
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==Awareness== |
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Various organizations have been established to raise awareness on osteoporosis. |
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The [[National Osteoporosis Society]], established in 1986, is a [[United Kingdom]] [[Charitable organization|charity]] dedicated to improving the diagnosis, prevention and treatment of osteoporosis.<ref>[http://www.nos.org.uk/NetCommunity/Page.aspx?pid=223&srcid=183 "About Us"], National Osteoporosis Society.</ref> |
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The '''National Osteoporosis Foundation''' (headquartered in Washington, D.C., US) seeks to prevent osteoporosis and related fractures, to promote lifelong bone health, to help improve the lives of those affected by osteoporosis and to find a cure through programs of awareness, advocacy, public and health professional education and research.[http://www.nof.org] |
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The [[International Osteoporosis Foundation]] (IOF) (headquartered in Nyon, Switzerland) functions as a global alliance of patient, medical and research societies, scientists, health care professionals, and international companies concerned about bone health.[http://www.iofbonehealth.org] |
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The '''Orthopaedic Research Society''' (headquartered in Rosemont, IL, US) is a research and professional development society that has emphasized osteoporosis research, treatment and prevention for many years.[http://www.ors.org] |
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==See also== |
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* [[Back pain]] |
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* [[Bone seeker]] |
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* [[Hip protector]] |
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* [[International Bone and Mineral Society]] |
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* [[Dental X-ray]] |
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* [[Osteopetrosis]] |
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* [[Osteoimmunology]] |
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* [[Ovariectomized rat]] model for osteoporosis research |
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* [[Spaceflight osteopenia]] |
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==References== |
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{{Reflist|2}} |
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==External links== |
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* {{dmoz|Health/Conditions_and_Diseases/Musculoskeletal_Disorders/Osteoporosis/}} |
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* [http://osteoed.org/tools.php Osteoporosis risk assessment tools] |
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* [http://www.who.int/nutrition/topics/5_population_nutrient/en/index25.html Diet, Nutrition and the prevention of osteoporosis] the [[World Health Organization]] and [[Food and Agriculture Organization]] (2003) |
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* [http://www.surgeongeneral.gov/library/bonehealth/ Bone Health and Osteoporosis: A Report of the Surgeon General] distributed by the US [[Department of Health and Human Services]] |
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* [http://www.iofbonehealth.org International Osteoporosis Foundation] |
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* [http://www.nof.org NOF.org] [[The National Osteoporosis Foundation]] |
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* [http://www.niams.nih.gov/Health_Info/Bone/ The NIH Osteoporosis and Related Bone Diseases ~ National Resource Center] |
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* [http://www.nos.org.uk National Osteoporosis Society] [[National Osteoporosis Society]] (UK) |
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</br> |
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{{Osteochondropathy}} |
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[[Category:Aging-associated diseases]] |
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[[Category:Endocrine diseases]] |
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[[Category:Osteopathies]] |
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[[ar:تخلخل العظم]] |
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[[bn:অস্টিওপোরোসিস]] |
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[[bs:Osteoporoza]] |
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[[bg:Остеопороза]] |
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[[ca:Osteoporosi]] |
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[[cs:Osteoporóza]] |
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[[da:Osteoporose]] |
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[[de:Osteoporose]] |
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[[dv:ކަށި ފީވުން]] |
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[[el:Οστεοπόρωση]] |
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[[es:Osteoporosis]] |
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[[fa:پوکی استخوان]] |
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[[fr:Ostéoporose]] |
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[[ko:골다공증]] |
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[[hi:ऑस्टियोपोरोसिस]] |
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[[hr:Osteoporoza]] |
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[[id:Osteoporosis]] |
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[[is:Beinþynning]] |
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[[it:Osteoporosi]] |
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[[he:דלדול עצם]] |
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[[kn:ಆಸ್ಟಿಯೊಪೊರೋಸಿಸ್]] |
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[[ka:ოსტეოპოროზი]] |
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[[kk:Остеопороз]] |
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[[la:Osteoporosis]] |
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[[lv:Osteoporoze]] |
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[[lt:Osteoporozė]] |
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[[ms:Osteoporosis]] |
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[[nl:Osteoporose]] |
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[[ja:骨粗鬆症]] |
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[[no:Osteoporose]] |
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[[pl:Osteoporoza]] |
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[[pt:Osteoporose]] |
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[[ro:Osteoporoză]] |
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[[ru:Остеопороз]] |
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[[sq:Osteoporoza]] |
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[[simple:Osteoporosis]] |
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[[sl:Osteoporoza]] |
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[[sr:Osteoporoza]] |
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[[sh:Osteoporoza]] |
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[[su:Ostéoporosis]] |
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[[fi:Osteoporoosi]] |
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[[sv:Benskörhet]] |
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[[ta:எலும்புப்புரை]] |
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[[te:బోలు ఎముకల వ్యాధి]] |
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[[tr:Osteoporoz]] |
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[[uk:Остеопороз]] |
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[[zh:骨質疏鬆症]] |
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Revision as of 03:47, 1 August 2011
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