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{{Short description|Skeletal disorder}} {{Distinguish| Osteosclerosis}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Use dmy dates|date=March 2018}} {{Infobox medical condition (new) | name = Osteoporosis | image = OsteoCutout.png | alt = andro | caption = Elderly woman with osteoporosis showing a [[Hyperkyphosis|curved back]] from [[vertebral compression fracture|compression fractures of her back bones]]. | field = [[Rheumatology]], [[Endocrinology]], [[orthopedics]] | pronounce = {{IPAc-en|ˌ|ɒ|s|t|i|oʊ|p|ə|ˈ|r|oʊ|s|ᵻ|s|}}{{refn|{{cite book | vauthors = Jones D |author-link=Daniel Jones (phonetician) |title=English Pronouncing Dictionary | veditors = Roach P, Hartmann J, Setter J |place=Cambridge |publisher=Cambridge University Press |orig-year=1917 |year=2003 |isbn=978-3-12-539683-8 }}}}{{refn|{{MerriamWebsterDictionary|Osteoporosis}}}} | symptoms = Increased risk of a [[bone fracture|broken bone]]<ref name=NIH2014/> | complications = [[Chronic pain]]<ref name=NIH2014/> | onset = Older age<ref name=NIH2014/> | duration = | causes = | risks = [[Alcoholism]], [[anorexia nervosa|anorexia]], European or Asian ethnicity, [[hyperthyroidism]], [[gastrointestinal disease]]s, [[oophorectomy|surgical removal of the ovaries]], [[kidney disease]], [[Tobacco smoking|smoking]], certain medications<ref name=NIH2014/> | diagnosis = Dexa Scan ([[Dual-energy X-ray absorptiometry|Bone density scan]])<ref name="WHOcriteria"/> | differential = | prevention = | treatment = Good diet, [[Physical exercise|exercise]], [[fall prevention]], stopping smoking<ref name=NIH2014/> | medication = [[Bisphosphonate]]s<ref name=Wells2008/><ref name=Wells2008a/> | prognosis = | frequency = 15% (50 year olds), 70% (over 80 year olds)<ref name=WHOEpi/> }} <!-- Definition and symptoms --> '''Osteoporosis''' is a systemic skeletal disorder characterized by low [[bone mass]], micro-architectural deterioration of [[bone tissue]] leading to more porous bone, and consequent increase in [[Bone fracture|fracture]] risk. It is the most common reason for a broken bone among the [[Old age|elderly]].<ref name="NIH2014">{{cite web |title= Handout on Health: Osteoporosis |url=http://www.niams.nih.gov/health_info/Osteoporosis/default.asp |website=[[NIAMS]] |access-date=16 May 2015|date=August 2014|url-status=live|archive-url=https://web.archive.org/web/20150518091922/http://www.niams.nih.gov/health_info/Osteoporosis/default.asp|archive-date=18 May 2015}}</ref> Bones that commonly break include the [[vertebrae]] in the [[Vertebral column|spine]], the bones of the [[forearm]], the [[wrist]], and the [[hip]].<ref name="Gol2015">{{cite journal | vauthors = Golob AL, Laya MB | title = Osteoporosis: screening, prevention, and management | journal = The Medical Clinics of North America | volume = 99 | issue = 3 | pages = 587–606 | date = May 2015 | pmid = 25841602 | doi = 10.1016/j.mcna.2015.01.010 | url = https://zenodo.org/record/1259215 }}</ref><ref>{{Cite web | author = NIAMS Science Communications and Outreach Branch |date=2017-04-07 |title=Osteoporosis |url=https://www.niams.nih.gov/health-topics/osteoporosis |access-date=2023-09-16 |website=National Institute of Arthritis and Musculoskeletal and Skin Diseases |language=en}}</ref> Until a broken bone occurs there are typically no symptoms. Bones may weaken to such a degree that a break may occur with minor stress or spontaneously. After the broken bone heals, some people may have [[chronic pain]] and a decreased ability to carry out normal activities.<ref name="NIH2014" /> <!-- Cause and diagnosis --> Osteoporosis may be due to lower-than-normal [[peak bone mass|maximum bone mass]] and greater-than-normal bone loss. Bone loss increases after [[menopause]] in women due to lower levels of [[estrogen]], and after [[andropause]] in older men due to lower levels of [[testosterone]].<ref>{{Cite web |date=2018-06-04 |title=Clinical Challenges: Managing Osteoporosis in Male Hypogonadism |url=https://www.medpagetoday.com/clinical-challenges/aace-osteoporosis/73256 |access-date=2022-03-22 |website=MedPage Today|publisher=Ziff Davis|language=en|author-last1=Monaco|author-first1=Kristen}}</ref> Osteoporosis may also occur due to a number of diseases or treatments, including [[alcoholism]], [[anorexia nervosa|anorexia]], [[hyperthyroidism]], [[kidney disease]], and after [[oophorectomy]] (surgical removal of the ovaries). Certain medications increase the rate of bone loss, including some [[Anticonvulsant|antiseizure medications]], [[chemotherapy]], [[proton pump inhibitor]]s, [[selective serotonin reuptake inhibitors]], and [[glucocorticoid|glucocorticosteroids]]. [[Tobacco smoking|Smoking]] and getting an inadequate amount of [[exercise]] are also risk factors.<ref name="NIH2014" /> Osteoporosis is defined as a [[bone density]] of 2.5 [[standard deviation]]s below that of a young adult. This is typically measured by [[dual-energy X-ray absorptiometry]] (DXA or DEXA).<ref name="WHOcriteria">{{cite book |title=Prevention and management of osteoporosis |series=World Health Organization Technical Report Series |date=2003 |volume=921 |pages=1–164, back cover |publisher=World Health Organization |isbn=978-92-4-120921-2 |hdl=10665/42841 |pmid=15293701 }}{{page needed|date=July 2024}}</ref> <!-- Prevention and treatment --> Prevention of osteoporosis includes a proper diet during childhood, [[hormone replacement therapy]] for menopausal women, and efforts to avoid medications that increase the rate of bone loss. Efforts to prevent broken bones in those with osteoporosis include a good diet, exercise, and [[fall prevention]]. Lifestyle changes such as stopping smoking and not drinking alcohol may help.<ref name=NIH2014/> [[Bisphosphonate|Bisphosphonate medications]] are useful to decrease future broken bones in those with previous broken bones due to osteoporosis. In those with osteoporosis but no previous broken bones, they are less effective.<ref name=Wells2008>{{cite journal | vauthors = Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P | title = Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD001155 | date = January 2008 | pmid = 18253985 | doi = 10.1002/14651858.CD001155.pub2 }}</ref>{{Update inline|reason=Updated version https://www.ncbi.nlm.nih.gov/pubmed/39868546|date = March 2025}}<ref name="Wells2008a">{{cite journal |vauthors=Wells GA, Hsieh SC, Zheng C, Peterson J, Tugwell P, Liu W |date=May 2022 |title=Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue= 7|pages= CD004523|doi=10.1002/14651858.CD004523.pub4 |pmid=35502787|pmc=9062986 }}</ref><ref name="Wells-2024">{{Cite journal |last1=Wells |first1=George A. |last2=Hsieh |first2=Shu-Ching |last3=Peterson |first3=Joan |last4=Zheng |first4=Carine |last5=Kelly |first5=Shannon E. |last6=Shea |first6=Beverley |last7=Tugwell |first7=Peter |date=2024-04-09 |title=Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women |journal=The Cochrane Database of Systematic Reviews |volume=2024 |issue=4 |pages=CD003376 |doi=10.1002/14651858.CD003376.pub4 |issn=1469-493X |pmc=11003221 |pmid=38591743}}</ref> They do not appear to affect the risk of death.<ref name="ABDTJAMA2019">{{cite journal | vauthors = Cummings SR, Lui LY, Eastell R, Allen IE | title = Association Between Drug Treatments for Patients With Osteoporosis and Overall Mortality Rates: A Meta-analysis | journal = JAMA Internal Medicine | date = August 2019 | volume = 179 | issue = 11 | pages = 1491–1500 | pmid = 31424486 | pmc = 6704731 | doi = 10.1001/jamainternmed.2019.2779 }}</ref> <!-- Epidemiology --> Osteoporosis becomes more common with age. About 15% of [[Caucasian race|Caucasians]] in their 50s and 70% of those over 80 are affected.<ref name=WHOEpi>{{cite web|title=Chronic rheumatic conditions|url=https://www.who.int/chp/topics/rheumatic/en/|website=World Health Organization|access-date=18 May 2015|archive-url=https://web.archive.org/web/20150427154245/http://www.who.int/chp/topics/rheumatic/en|archive-date=27 April 2015}}</ref> It is more common in women than men.<ref name=NIH2014/> In the [[developed world]], depending on the method of diagnosis, 2% to 8% of males and 9% to 38% of females are affected.<ref name=Wade2014/> Rates of disease in the [[developing world]] are unclear.<ref name=Han2008>{{cite journal | vauthors = Handa R, Ali Kalla A, Maalouf G | title = Osteoporosis in developing countries | journal = Best Practice & Research. Clinical Rheumatology | volume = 22 | issue = 4 | pages = 693–708 | date = August 2008 | pmid = 18783745 | doi = 10.1016/j.berh.2008.04.002 }}</ref> About 22 million women and 5.5 million men in the [[European Union]] had osteoporosis in 2010.<ref name=Sve2013>{{cite journal | vauthors = Svedbom A, Hernlund E, Ivergård M, Compston J, Cooper C, Stenmark J, McCloskey EV, Jönsson B, Kanis JA | title = Osteoporosis in the European Union: a compendium of country-specific reports | journal = Archives of Osteoporosis | volume = 8 | issue = 1–2 | pages = 137 | date = 2013 | pmid = 24113838 | pmc = 3880492 | doi = 10.1007/s11657-013-0137-0 }}</ref> In the United States in 2010, about 8 million women and between 1 and 2 million men had osteoporosis.<ref name=Wade2014>{{cite journal | vauthors = Wade SW, Strader C, Fitzpatrick LA, Anthony MS, O'Malley CD | s2cid = 19534928 | title = Estimating prevalence of osteoporosis: examples from industrialized countries | journal = Archives of Osteoporosis | volume = 9 | issue = 1 | pages = 182 | date = 2014 | pmid = 24847682 | doi = 10.1007/s11657-014-0182-3 }}</ref><ref name=Will2015>{{cite journal | vauthors = Willson T, Nelson SD, Newbold J, Nelson RE, LaFleur J | title = The clinical epidemiology of male osteoporosis: a review of the recent literature | journal = Clinical Epidemiology | volume = 7 | pages = 65–76 | date = 2015 | pmid = 25657593 | pmc = 4295898 | doi = 10.2147/CLEP.S40966 | doi-access = free }}</ref> White and [[Asian people]] are at greater risk.<ref name=NIH2014/> The word "osteoporosis" is from the Greek terms for "porous bones".<ref name=Grob2014 /> ==Signs and symptoms== [[File:Blausen 0686 Osteoporosis 01.png|thumb|left|Illustration depicting normal standing posture and osteoporosis]] Osteoporosis has [[asymptomatic|no symptoms]] and the person usually does not know that they have osteoporosis until a bone is broken. Osteoporotic [[fractures]] occur in situations where healthy people would not normally break a bone; they are therefore regarded as [[fragility fractures]]. Typical fragility fractures occur in the [[vertebral column]], [[rib]], hip and [[wrist]].<ref name=niams/> Examples of situations where people would not normally break a bone include a fall from standing height, normal day-to-day activities such as lifting, bending, or coughing.<ref name="niams">{{Cite web |date=1 December 2022 |title=Osteoporosis |url=https://www.niams.nih.gov/health-topics/osteoporosis |access-date=16 September 2023 |publisher=National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health |language=en}}</ref> ===Fractures=== Fractures are a common complication of osteoporosis and can result in disability.<ref>{{Cite book|title=Harrison's principles of internal medicine.| vauthors = Jameson JL, Kasper DL, Longo DL, Fauci AS, Hauser SL, Loscalzo J |isbn=9781259644047|edition= Twentieth|publisher=McGraw-Hill Education|location=New York|oclc=990065894 |date=2018-02-06}}</ref> 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 | vauthors = Old JL, Calvert M | title = Vertebral compression fractures in the elderly | journal = American Family Physician | volume = 69 | issue = 1 | pages = 111–116 | date = January 2004 | pmid = 14727827 | url = http://www.aafp.org/afp/2004/0101/p111.html | access-date = 31 March 2011 | url-status = live | archive-url = https://web.archive.org/web/20110805184810/http://www.aafp.org/afp/2004/0101/p111.html | archive-date = 5 August 2011 }}</ref> These fractures may also be asymptomatic.<ref>{{cite journal | vauthors = Yang J, Mao Y, Nieves JW | title = Identification of prevalent vertebral fractures using Vertebral Fracture Assessment (VFA) in asymptomatic postmenopausal women: A systematic review and meta-analysis | journal = Bone | volume = 136 | pages = 115358 | date = July 2020 | pmid = 32268210 | doi = 10.1016/j.bone.2020.115358 | s2cid = 215620114 }}</ref> The most common osteoporotic fractures are of the wrist, spine, shoulder and hip. The symptoms of a [[vertebra]]l collapse ("[[compression fracture]]") are sudden [[back pain]], often with [[radicular 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 | vauthors = Kim DH, Vaccaro AR | title = Osteoporotic compression fractures of the spine; current options and considerations for treatment | journal = The Spine Journal | volume = 6 | issue = 5 | pages = 479–487 | year = 2006 | pmid = 16934715 | doi = 10.1016/j.spinee.2006.04.013 | s2cid = 28448924 }}</ref> Fractures of the long bones acutely impair mobility and may require [[surgery]]. [[Hip fracture]], in particular, usually requires prompt surgery, as serious risks are associated with it, such as [[deep vein thrombosis]] and [[pulmonary embolism]]. There is also an increased risk of mortality associated with osteoporosis-related hip fracture, with the mean average mortality rate within one year for Europe being 23.3%, for Asia 17.9%, United States 21% and Australia 24.9%.<ref>{{cite journal | vauthors = Downey C, Kelly M, Quinlan JF | title = Changing trends in the mortality rate at 1-year post hip fracture - a systematic review | journal = World Journal of Orthopedics | volume = 10 | issue = 3 | pages = 166–175 | date = March 2019 | pmid = 30918799 | pmc = 6428998 | doi = 10.5312/wjo.v10.i3.166 | doi-access = free }}</ref> Fracture risk calculators assess the risk of fracture based upon several criteria, including [[bone mineral density]], age, smoking, alcohol usage, weight, and gender. Recognized calculators include [[FRAX]],<ref>{{cite web|url= http://courses.washington.edu/bonephys/FxRiskCalculator.html|title= Fracture Risk Calculator|author= Susan Ott|archive-url= https://web.archive.org/web/20091014090245/http://courses.washington.edu/bonephys/FxRiskCalculator.html|archive-date=2009-10-14|date=October 2009}}</ref> the Garvan FRC calculator and QFracture as well as the open access FREM tool.<ref>{{cite journal | vauthors = Rubin KH, Möller S, Holmberg T, Bliddal M, Søndergaard J, Abrahamsen B | title = A New Fracture Risk Assessment Tool (FREM) Based on Public Health Registries | journal = Journal of Bone and Mineral Research | volume = 33 | issue = 11 | pages = 1967–1979 | date = November 2018 | pmid = 29924428 | doi = 10.1002/jbmr.3528 | s2cid = 49312906 | doi-access = free }}</ref> The FRAX tool can also be applied in a modification adapted to routinely collected health data.<ref>{{cite journal | vauthors = Yang S, Leslie WD, Morin SN, Lix LM | title = Administrative healthcare data applied to fracture risk assessment | journal = Osteoporosis International | volume = 30 | issue = 3 | pages = 565–571 | date = March 2019 | pmid = 30554259 | doi = 10.1007/s00198-018-4780-6 | s2cid = 54632462 }}</ref> The term "established osteoporosis" is used when a [[fragility fracture|broken bone due to osteoporosis]] has occurred.<ref name=WHO1994>{{cite book |title=Assessment of fracture risk and its application to screening for postmenopausal osteoporosis |series=World Health Organization Technical Report Series |date=1994 |volume=843 |pages=1–129 |publisher=World Health Organization |isbn=978-92-4-120843-7 |hdl=10665/39142 |pmid=7941614 }}{{page needed|date=July 2024}}</ref> Osteoporosis is a part of [[frailty syndrome]]. ===Risk of falls=== [[File:Menopause - Osteoporosis -- Smart-Servier (cropped).jpg|thumb|left|Progression of the shape of vertebral column with age in osteoporosis]] There is an increased risk of falls associated with aging. These falls can lead to skeletal damage at the wrist, spine, hip, knee, foot, and ankle. Part of the fall risk is because of impaired eyesight (e.g. [[glaucoma]], [[macular degeneration]]), [[balance disorder]], [[movement disorder]]s (e.g. [[Parkinson's disease]]), [[dementia]], [[sarcopenia]] (age-related loss of [[skeletal muscle]]), and collapse (transient loss of postural tone with or without loss of consciousness). Causes of [[syncope (medicine)|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 gait or balance disorders, are most at risk.<ref>{{cite journal |vauthors=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> === Complications === As well as susceptibility to breaks and fractures, osteoporosis can lead to other complications. Bone fractures from osteoporosis can lead to disability and an increased risk of death after the injury in elderly people.<ref name="mayo">{{Cite web |title=Osteoporosis - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/osteoporosis/symptoms-causes/syc-20351968 |access-date=2022-03-25 |website=Mayo Clinic |language=en}}</ref> Osteoporosis can decrease the quality of life, increase disabilities, and increase the financial costs to health care systems.<ref name="sozen">{{cite journal |vauthors=Sözen T, Özışık L, Başaran NÇ |title=An overview and management of osteoporosis |journal=European Journal of Rheumatology |volume=4 |issue=1 |pages=46–56 |date=March 2017 |pmid=28293453 |pmc=5335887 |doi=10.5152/eurjrheum.2016.048}}</ref> ==Risk factors== The risk of having osteoporosis includes age and sex. Risk factors include both nonmodifiable (for example, age and some medications that may be necessary to treat a different condition) and modifiable (for example, alcohol use, smoking, vitamin deficiency). In addition, osteoporosis is a recognized complication of specific diseases and disorders. Medication use is theoretically modifiable, although in many cases, the use of medication that increases osteoporosis risk may be unavoidable. [[Caffeine]] is not a risk factor for osteoporosis.<ref>{{cite journal |vauthors=Waugh EJ, Lam MA, Hawker GA, McGowan J, Papaioannou A, Cheung AM, Hodsman AB, Leslie WD, Siminoski K, Jamal SA | title = Risk factors for low bone mass in healthy 40–60 year old women: a systematic review of the literature | journal = Osteoporosis International | volume = 20 | issue = 1 | pages = 1–21 | date = January 2009 | pmid = 18523710 | doi = 10.1007/s00198-008-0643-x | pmc = 5110317 }}</ref> [[White people]] have a higher risk for the disease.<ref>{{cite web|url=https://pmc.ncbi.nlm.nih.gov/articles/PMC8607440/|title=Racial and Ethnic Disparities in Bone Health and Outcomes in the United States}}</ref> ===Nonmodifiable=== [[File:615 Age and Bone Mass.jpg|thumb|upright=1.3|Bone density peaks at about 30 years of age. Women lose bone mass more rapidly than men.<ref>{{cite book|title=Anatomy & Physiology|publisher=Openstax CNX|isbn=978-1-938168-13-0|chapter-url=http://cnx.org/contents/FPtK1zmh@6.27:g-vsB2Y2@4/Exercise-Nutrition-Hormones-an|chapter=6.6 Exercise, Nutrition, Hormones, and Bone Tissue|url-status=live|archive-url=https://web.archive.org/web/20170110085931/http://cnx.org/contents/FPtK1zmh%406.27%3Ag-vsB2Y2%404/Exercise-Nutrition-Hormones-an|archive-date=10 January 2017|year=2013}}</ref>]] * The most important risk factors for osteoporosis are advanced age (in both men and women) and [[female]] sex; [[estrogen]] deficiency following menopause or [[oophorectomy|surgical removal of the ovaries]] 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.<ref>{{cite journal |vauthors=Sinnesael M, Claessens F, Boonen S, Vanderschueren D | s2cid = 1637184 | title = Novel insights in the regulation and mechanism of androgen action on bone | journal = Current Opinion in Endocrinology, Diabetes and Obesity | volume = 20 | issue = 3 | pages = 240–44 | year = 2013 | pmid = 23449008 | doi = 10.1097/MED.0b013e32835f7d04 }}</ref><ref>{{cite journal |vauthors=Sinnesael M, Boonen S, Claessens F, Gielen E, Vanderschueren D | title = Testosterone and the male skeleton: a dual mode of action | journal = Journal of Osteoporosis | volume = 2011 | pages = 1–7 | year = 2011 | pmid = 21941679 | doi = 10.4061/2011/240328 | pmc=3173882 | doi-access = free }}</ref> * Ethnicity: 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 =v, 1–13 | year = 2003 | pmid = 12699289 | doi = 10.1016/S0889-8529(02)00061-0 }}</ref> * Heredity: Those with a [[family history (medicine)|family history]] of fracture or osteoporosis are at an increased risk; the [[heritability]] of fracture risk, as well as low bone mineral density, is relatively high, ranging from 25 to 80%. At least 30 genes are associated with the development of osteoporosis.<ref name="Raisz">{{cite journal |last1=Raisz |first1=L. G. |title=Pathogenesis of osteoporosis: concepts, conflicts, and prospects |journal=Journal of Clinical Investigation |date=December 2005 |volume=115 |issue=12 |pages=3318–3325 |doi=10.1172/JCI27071 |pmid=16322775 |pmc=1297264 }}</ref> * 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 |vauthors=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 = 412–418 | year = 2007 | pmid = 17444431 | pmc = 2569658 }}</ref> * Build: A small stature is also a nonmodifiable risk factor associated with the development of osteoporosis.<ref name=AppTher>{{cite book |author1=Brian K Alldredge |author2=Koda-Kimble, Mary Anne |author3=Young, Lloyd Y. |author4=Wayne A Kradjan |author5=B. Joseph Guglielmo |title=Applied therapeutics: the clinical use of drugs |publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins |location=Philadelphia |year=2009 |pages=101–103 |isbn=978-0-7817-6555-8}}</ref> ===Potentially modifiable=== * Alcohol: Alcohol intake greater than three units/day may increase the risk of osteoporosis, and people who consumed 0.5-1 drinks a day may have 1.38 times the risk compared to people who do not consume alcohol.<ref name="BMJosteoporosis">{{cite journal |vauthors=Poole KE, Compston JE | title = Osteoporosis and its management | journal = BMJ | volume = 333 | issue = 7581 | pages = 1251–1256 | date = December 2006 | pmid = 17170416 | pmc = 1702459 | doi = 10.1136/bmj.39050.597350.47 }}</ref><ref>{{cite journal |vauthors=Berg KM, Kunins HV, Jackson JL, Nahvi S, Chaudhry A, Harris KA, Malik R, Arnsten JH | title = Association between alcohol consumption and both osteoporotic fracture and bone density | journal = Am J Med | volume = 121 | issue = 5 | pages = 406–418 | year = 2008 | pmid = 18456037 | pmc = 2692368 | doi = 10.1016/j.amjmed.2007.12.012 }}</ref> * [[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 | year = 2005 | pmid = 15883457 | doi=10.1093/ajcn/81.5.1232| doi-access = free }}</ref><ref>{{cite journal |vauthors=Gielen E, Boonen S, Vanderschueren D, Sinnesael M, Verstuyf A, Claessens F, Milisen K, Verschueren S | title = Calcium and vitamin d supplementation in men | journal = Journal of Osteoporosis | volume = 2011 | pages = 1–6 | year = 2011 | pmid = 21876835 | doi = 10.4061/2011/875249 | pmc=3163142 | doi-access = free }}</ref> Low circulating Vitamin D is common among the elderly worldwide.<ref name="WHOcriteria"/> Mild vitamin D insufficiency is associated with increased [[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"/> * [[Tobacco smoking]]: Many studies have associated smoking with decreased bone health, but the mechanisms are unclear.<ref>{{cite journal | vauthors = Agoons DD, Agoons BB, Emmanuel KE, Matawalle FA, Cunningham JM |date= January 2021 |title=Association between electronic cigarette use and fragility fractures among US adults |journal=American Journal of Medicine Open |language=en |volume=1-6 |pages=100002 |doi=10.1016/j.ajmo.2021.100002 |s2cid= 244502249 |issn=2667-0364|doi-access=free |pmid= 39036626 |pmc=11256257 }}</ref><ref>{{cite journal | vauthors = Hollenbach KA, Barrett-Connor E, Edelstein SL, Holbrook T | title = Cigarette smoking and bone mineral density in older men and women | journal = American Journal of Public Health | volume = 83 | issue = 9 | pages = 1265–1270 | date = September 1993 | pmid = 8363002 | pmc = 1694953 | doi = 10.2105/AJPH.83.9.1265 }}</ref><ref>{{cite journal | vauthors = Kanis JA, Johnell O, Oden A, Johansson H, De Laet C, Eisman JA, Fujiwara S, Kroger H, McCloskey EV, Mellstrom D, Melton LJ, Pols H, Reeve J, Silman A, Tenenhouse A | title = Smoking and fracture risk: a meta-analysis | journal = Osteoporosis International | volume = 16 | issue = 2 | pages = 155–162 | date = February 2005 | pmid = 15175845 | doi = 10.1007/s00198-004-1640-3 | s2cid = 19890259 }}</ref> Tobacco smoking has been proposed to inhibit the activity of osteoblasts, and is an independent risk factor for osteoporosis.<ref name="BMJosteoporosis"/><ref>{{cite journal |last1=Wong |first1=Peter K. K. |last2=Christie |first2=Jemma J. |last3=Wark |first3=John D. |title=The effects of smoking on bone health |journal=Clinical Science |date=September 2007 |volume=113 |issue=5 |pages=233–241 |doi=10.1042/CS20060173 |pmid=17663660 }}</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"/> * [[Malnutrition]]: Nutrition has an important and complex role in maintenance of good bone. Identified risk factors include low dietary [[calcium]] or phosphorus, magnesium, zinc, boron, iron, fluoride, copper, vitamins A, K, E, and C (and vitamin 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 name="pmid11194525">{{cite journal |last1=Ilich |first1=Jasminka Z. |last2=Kerstetter |first2=Jane E. |title=Nutrition in Bone Health Revisited: A Story Beyond Calcium |journal=Journal of the American College of Nutrition |date=December 2000 |volume=19 |issue=6 |pages=715–737 |doi=10.1080/07315724.2000.10718070 |pmid=11194525 }}</ref> Imbalance of [[omega-6]] to [[omega-3]] polyunsaturated fats is yet another identified risk factor.<ref>{{cite journal | vauthors = Weiss LA, Barrett-Connor E, von Mühlen D | title = Ratio of n−6 to n−3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study | journal = Am J Clin Nutr | volume = 81 | issue = 4 | pages = 934–38 | year = 2005 | pmid = 15817874 | doi=10.1093/ajcn/81.4.934| doi-access = free }}</ref> * A 2017 meta-analysis of published medical studies shows that higher protein diet helps slightly with lower spine density but does not show significant improvement with other bones.<ref name="pmid28404575"/> A 2023 meta-analysis sees no evidence for the relation between protein intake and bone health.<ref>{{cite journal | vauthors = Zittermann A, Schmidt A, Haardt J, Kalotai N, Lehmann A, Egert S, Ellinger S, Kroke A, Lorkowski S, Louis S, Schulze MB, Schwingshackl L, Siener R, Stangl GI, Volkert D, Watzl B, Bischoff-Ferrari HA | title = Protein intake and bone health: an umbrella review of systematic reviews for the evidence-based guideline of the German Nutrition Society | journal = Osteoporosis International | volume = 34 | issue = 8 | pages = 1335–1353 | date = August 2023 | pmid = 37126148 | pmc = 10382330 | doi = 10.1007/s00198-023-06709-7 }}</ref> * [[body mass index|Underweight]]/[[Physical exercise|inactive]]: [[Bone remodeling]] occurs in response to physical stress, so physical inactivity can lead to significant bone loss.<ref name="WHOcriteria"/> [[Weight bearing]] exercise can increase peak bone mass achieved in adolescence,<ref name="WHOcriteria"/> and a highly significant correlation between bone strength and muscle strength has been determined.<ref>{{cite journal |vauthors=Schönau E, Werhahn E, Schiedermaier U, Mokow E, Schiessl H, Scheidhauer K, Michalk D | title = Influence of muscle strength on bone strength during childhood and adolescence | journal = Hormone Research | volume = 45 | issue = Suppl. 1 | pages = 63–66 | year = 1996 | pmid = 8805035 | doi = 10.1159/000184834 }}</ref> The incidence of osteoporosis is lower in overweight people.<ref>{{cite journal | vauthors = Shapses SA, Riedt CS | title = Bone, body weight, and weight reduction: what are the concerns? | journal = J. Nutr. | volume = 136 | issue = 6 | pages = 1453–1456 | date = 1 June 2006 | pmid = 16702302 | pmc = 4016235 | doi=10.1093/jn/136.6.1453}}</ref> * [[Endurance training]]: In female endurance athletes, large volumes of training can lead to decreased bone density and an increased risk of osteoporosis.<ref>{{cite journal |last1=Pollock |first1=Noel |last2=Grogan |first2=Claire |last3=Perry |first3=Mark |last4=Pedlar |first4=Charles |last5=Cooke |first5=Karl |last6=Morrissey |first6=Dylan |last7=Dimitriou |first7=Lygeri |title=Bone-Mineral Density and Other Features of the Female Athlete Triad in Elite Endurance Runners: A Longitudinal and Cross-Sectional Observational Study |journal=International Journal of Sport Nutrition and Exercise Metabolism |date=October 2010 |volume=20 |issue=5 |pages=418–426 |doi=10.1123/ijsnem.20.5.418 |pmid=20975110 |url=http://journals.humankinetics.com/ijsnem }}</ref> This effect might be caused by intense training suppressing menstruation, producing [[amenorrhea]], and it is part of the [[female athlete triad]].<ref>{{cite journal |vauthors=Gibson JH, Mitchell A, Harries MG, Reeve J | s2cid = 42115482 | title = Nutritional and exercise-related determinants of bone density in elite female runners | journal = Osteoporosis International | volume = 15 | issue = 8 | pages = 611–618 | year = 2004 | pmid = 15048548 | doi = 10.1007/s00198-004-1589-2 }}</ref> However, for male athletes, the situation is less clear, and although some studies have reported low bone density in elite male endurance athletes,<ref>{{cite journal |vauthors=Hetland ML, Haarbo J, Christiansen C | title = Low bone mass and high bone turnover in male long distance runners | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 77 | issue = 3 | pages = 770–775 | year = 1993 | pmid = 8370698 | doi=10.1210/jcem.77.3.8370698}}</ref> others have instead seen increased leg bone density.<ref>{{cite journal |vauthors=Brahm H, Ström H, Piehl-Aulin K, Mallmin H, Ljunghall S | s2cid = 32005973 | title = Bone metabolism in endurance trained athletes: A comparison to population-based controls based on DXA, SXA, quantitative ultrasound, and biochemical markers | journal = Calcified Tissue International | volume = 61 | issue = 6 | pages = 448–454 | year = 1997 | pmid = 9383270 | doi = 10.1007/s002239900366 }}</ref><ref>{{cite journal |vauthors=MacKelvie KJ, Taunton JE, McKay HA, Khan KM | title = Bone mineral density and serum testosterone in chronically trained, high mileage 40–55 year old male runners | journal = British Journal of Sports Medicine | volume = 34 | issue = 4 | pages = 273–278 | year = 2000 | pmid = 10953900 | pmc = 1724199 | doi=10.1136/bjsm.34.4.273}}</ref> * [[Heavy metals]]: A strong association between [[cadmium]] and [[lead]] with 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 |vauthors=Staessen JA, Roels HA, Emelianov D, Kuznetsova T, Thijs L, Vangronsveld J, Fagard R | s2cid = 33697569 | 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 = 1140–1144 | year = 1999 | pmid = 10209978 | doi = 10.1016/S0140-6736(98)09356-8 }}</ref> * Soft drinks: Some studies indicate [[soft drink]]s (many of which contain [[phosphoric acid]]) may increase risk of osteoporosis, at least in [[women]].<ref>{{cite journal |vauthors=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 = 936–942 | year = 2006 | pmid = 17023723 | doi = 10.1093/ajcn/84.4.936 | doi-access = free }}</ref> Others suggest soft drinks may displace calcium-containing drinks from the diet rather than directly causing osteoporosis.<ref>{{cite journal | title = Soft drinks in schools | journal = Pediatrics | volume = 113 | issue = 1 Pt 1 | pages = 152–54 | year = 2004 | pmid = 14702469 | doi = 10.1542/peds.113.1.152 | author1 = American Academy of Pediatrics Committee on School Health | doi-access = free }}</ref> * [[Proton pump inhibitors]] (such as [[lansoprazole]], [[esomeprazole]], and [[omeprazole]]), which decrease the production of [[stomach acid]], are a risk factor for bone fractures if taken for two or more years, due to decreased absorption of [[calcium]] in the [[stomach]].<ref>{{cite journal | vauthors = Zhou B, Huang Y, Li H, Sun W, Liu J | s2cid = 13532091 | title = Proton-pump inhibitors and risk of fractures: an update meta-analysis | journal = Osteoporosis International | volume = 27 | issue = 1 | pages = 339–347 | date = January 2016 | pmid = 26462494 | doi = 10.1007/s00198-015-3365-x }}</ref> ===Medical disorders=== [[File:625 Calcium Homeostasis.jpg|thumb|upright=1.4|The body regulates calcium homeostasis with two pathways; one is signaled to turn on when blood calcium levels drop below normal and one is the pathway that is signaled to turn on when blood calcium levels are elevated.]] 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 |access-date=2008-04-08 |author=Simonelli, C |date=July 2006 |format=PDF |publisher=Institute for Clinical Systems Improvement |display-authors=etal |url-status=dead |archive-url=https://web.archive.org/web/20070718014056/http://www.icsi.org/osteoporosis/diagnosis_and_treatment_of_osteoporosis__3.html |archive-date=18 July 2007 }}</ref> For some, the underlying mechanism influencing the bone metabolism is straightforward, whereas for others the causes are multiple or unknown. * In general, [[Muscle immobilization|immobilization]] causes bone loss. For example, localized osteoporosis can occur after prolonged immobilization of a fractured limb in a cast. This is also more common in active people with a high bone turn-over (for example, athletes). Other examples include bone loss during [[space flight]] or in people who are bedridden or use wheelchairs for various reasons.{{citation needed|date=October 2020}} * [[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). Bilateral [[oophorectomy]] (surgical removal of the ovaries) and [[premature ovarian failure]] cause deficient estrogen production. In males, testosterone deficiency is the cause (for example, andropause or after surgical removal of the [[testes]]). * Endocrine disorders that can induce bone loss include [[Cushing's syndrome]],<ref name="WHOcriteria"/> [[hyperparathyroidism]],<ref name="WHOcriteria"/> [[hyperthyroidism]],<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 | volume = 358 | issue = 14 | pages = 1474–1482 | year = 2008 | pmid = 18385499 | doi = 10.1056/NEJMcp0707217 }}</ref> [[acromegaly]], and [[adrenal insufficiency]].<ref name="ICSI" /> * Malnutrition, [[parenteral nutrition]]<ref name="WHOcriteria"/> and [[malabsorption]] can lead to osteoporosis. Nutritional and gastrointestinal disorders that can predispose to osteoporosis include undiagnosed and untreated [[coeliac disease]] (both symptomatic and asymptomatic people),<ref name="WHOcriteria"/><ref name=MirzaCanalis2015>{{cite journal|vauthors=Mirza F, Canalis E|title=Management of endocrine disease: Secondary osteoporosis: pathophysiology and management|journal=Eur J Endocrinol|volume=173|issue=3|pages=R131–151|date=Sep 2015|pmid=25971649|pmc=4534332|doi=10.1530/EJE-15-0118|type=Review}}</ref> [[Crohn's disease]],<ref name="Pediatric">{{cite journal |last1=Henwood |first1=Maria J. |last2=Binkovitz |first2=Larry |title=Update on pediatric bone health |journal=The Journal of the American Osteopathic Association |date=January 2009 |volume=109 |issue=1 |pages=5–12 |pmid=19193819 }}</ref> [[ulcerative colitis]],<ref name="Pediatric"/> [[cystic fibrosis]],<ref name="Pediatric"/> 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'/> People with [[lactose intolerance]] or [[milk allergy]] may develop osteoporosis due to restrictions of calcium-containing foods.<ref name=Beto2015>{{cite journal|vauthors=Beto JA|title=The role of calcium in human aging|journal=Clin Nutr Res|volume=4|issue=1|pages=1–8|date=Jan 2015|pmid=25713787|pmc=4337919|doi=10.7762/cnr.2015.4.1.1|type=Review}}</ref> Individuals 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 micronutrients such as [[vitamin K]] or [[vitamin B12 deficiency|vitamin B<sub>12</sub> deficiency]] may also contribute. * People with rheumatologic disorders such as [[rheumatoid arthritis]],<ref name='medscapeosteoporosis'/> [[ankylosing spondylitis]],<ref name='medscapeosteoporosis'>{{EMedicine|article|330598|Osteoporosis}}</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. * [[Chronic kidney disease]] can lead to [[renal osteodystrophy]].<ref>{{cite web |url= https://www.lecturio.com/concepts/chronic-kidney-disease/| title= Chronic Kidney Disease |website=The Lecturio Medical Concept Library |access-date= 24 August 2021}}</ref> * Hematologic disorders linked to osteoporosis are [[multiple myeloma]]<ref name='medscapeosteoporosis'/> and other [[monoclonal gammopathy|monoclonal gammopathies]],<ref name=OsteoporosisMen/> [[lymphoma]], [[leukemia]], [[mastocytosis]],<ref name="medscapeosteoporosis" /> [[hemophilia]], [[sickle-cell disease]] and [[thalassemia]]. * Immune disorders: Osteoporosis can be a symptom of [[mast cell activation syndrome]].<ref name="PMID27012973">{{cite journal |vauthors=Afrin LB, Butterfield JH, Raithel M, Molderings GJ |title=Often seen, rarely recognized: mast cell activation disease--a guide to diagnosis and therapeutic options |journal=The American Journal of the Medical Science |volume=48 |issue=3 |date=2016 |pages=190–201 |doi=10.3109/07853890.2016.1161231 |pmid=27012973 |url=|doi-access=free}}</ref><ref name="PMID38948000">{{cite journal |vauthors=Özdemir Ö, Kasımoğlu G, Bak A et al. |title=Mast cell activation syndrome: An up-to-date review of literature |journal=World J Clin Pediatr |date=2024-06-09 |volume=13 |issue=2 |doi=10.5409/wjcp.v13.i2.92813 |pmc=11212760 |pmid=38948000 |url=|doi-access=free}}</ref><ref name="PMID24801454">{{cite journal |vauthors=Molderings GJ, Homann J, Brettner S, Raithel M, Frieling T |title=Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options |journal= Dtsch Med Wochenschr |volume=129 |issue=30 |date=Jul 2014 |doi= 10.1055/s-0034-1370055 |pmid=24801454 |pages=1523–34 }}</ref> * Several inherited or genetic disorders have been linked to osteoporosis. These include [[osteogenesis imperfecta]],<ref name='medscapeosteoporosis'/> [[Multicentric carpotarsal osteolysis syndrome]],<ref>{{cite journal | vauthors = Park PG, Kim KH, Hyun HS, Lee CH, Park JS, Kie JH, Choi YH, Moon KC, Cheong HI | title = Three cases of multicentric carpotarsal osteolysis syndrome: a case series | journal = BMC Medical Genetics | volume = 19 | issue = 1 | pages = 164 | date = September 2018 | pmid = 30208859 | pmc = 6134760 | doi = 10.1186/s12881-018-0682-x | doi-access = free }}</ref> [[Winchester syndrome|Multicentric Osteolysis, Nodulosis, and Arthropathy]],<ref>{{cite journal | vauthors = Elsebaie H, Mansour MA, Elsayed SM, Mahmoud S, El-Sobky TA | title = Multicentric Osteolysis, Nodulosis, and Arthropathy in two unrelated children with matrix metalloproteinase 2 variants: Genetic-skeletal correlations | journal = Bone Reports | volume = 15 | pages = 101106 | date = December 2021 | pmid = 34307793 | pmc = 8283316 | doi = 10.1016/j.bonr.2021.101106 }}</ref> [[Marfan syndrome]],<ref name='medscapeosteoporosis'/> [[hemochromatosis]],<ref name="WHOcriteria"/> [[hypophosphatasia]]<ref>{{cite book |last1=Nunes |first1=Mark E. |title=GeneReviews® |date=1993 |publisher=University of Washington, Seattle |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK1150/ |chapter=Hypophosphatasia |pmid=20301329 }}</ref> (for which it is often misdiagnosed),<ref>{{cite web|title=Hypophosphatasia Case Studies: Dangers of Misdiagnosis|url=http://www.hypophosphatasia.com/hcp/dangers-of-misdiagnosis|website=Hypophosphatasia.com|access-date=5 August 2014|url-status=live|archive-url=https://web.archive.org/web/20140808054019/http://www.hypophosphatasia.com/hcp/dangers-of-misdiagnosis|archive-date=8 August 2014}}</ref> [[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]]. * 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]]. * People with [[Parkinson's disease]] have a higher risk of broken bones. This is related to poor balance and poor bone density.<ref>{{cite journal |vauthors=Invernizzi M, Carda S, Viscontini GS, Cisari C | title = Osteoporosis in Parkinson's disease | journal = Parkinsonism & Related Disorders | volume = 15 | issue = 5 | pages = 339–346 | year = 2009 | pmid = 19346153 | doi = 10.1016/j.parkreldis.2009.02.009 }}</ref> In Parkinson's disease there may be a link between the loss of [[dopaminergic neuron]]s and altered [[calcium metabolism]]<ref>{{cite journal |vauthors=Celsi F, Pizzo P, Brini M, Leo S, Fotino C, Pinton P, Rizzuto R | title = Mitochondria, calcium and cell death: A deadly triad in neurodegeneration | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1787 | issue = 5 | pages = 335–344 | year = 2009 | pmid = 19268425 | pmc = 2696196 | doi = 10.1016/j.bbabio.2009.02.021 }}</ref> (and [[iron metabolism]]) causing a stiffening of the skeleton and [[kyphosis]]. ===Medication=== Certain medications have been associated with an increase in osteoporosis risk; only glucocorticosteroids and anticonvulsants are classically associated, but evidence is emerging with regard to other drugs. * [[Steroid-induced osteoporosis]] (SIOP) arises due to use of glucocorticoids – 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 |author2=National Osteoporosis Society |author3=Royal College of Physicians |title=Glucocorticoid-induced Osteoporosis |year=2003 |publisher=Royal College of Physicians of London |location=London |isbn=978-1-86016-173-5 |url=http://bookshop.rcplondon.ac.uk/contents/pub89-a953a6c0-06c0-46d8-b79a-e951536d9070.pdf |url-status=dead |archive-url=https://web.archive.org/web/20120114134537/http://bookshop.rcplondon.ac.uk/contents/pub89-a953a6c0-06c0-46d8-b79a-e951536d9070.pdf |archive-date=14 January 2012 |df=dmy-all |access-date=3 October 2011 |author2-link=National Osteoporosis Society }}</ref> It is recommended to use calcium or Vitamin D as prevention.<ref>{{cite journal | vauthors = Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P | title = Calcium and vitamin D for corticosteroid-induced osteoporosis | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD000952 | date = 1998-04-27 | volume = 1998 | pmid = 10796394 | doi = 10.1002/14651858.cd000952 | pmc = 7046131 }}</ref> Alternate day use may not prevent this complication.<ref name=GIOP>{{cite journal | vauthors = Gourlay M, Franceschini N, Sheyn Y | s2cid = 26017061 | title = Prevention and treatment strategies for glucocorticoid-induced osteoporotic fractures | journal = Clinical Rheumatology | volume = 26 | issue = 2 | pages = 144–153 | date = February 2007 | pmid = 16670825 | doi = 10.1007/s10067-006-0315-1 }}</ref> * [[Barbiturate]]s, [[phenytoin]] and some other enzyme-inducing [[antiepileptic]]s – these probably accelerate the metabolism of vitamin D.<ref>{{cite journal |vauthors=Petty SJ, O'Brien TJ, Wark JD | s2cid = 2953573 | title = Anti-epileptic medication and bone health | journal = Osteoporosis International | volume = 18 | issue = 2 | pages = 129–142 | year = 2007 | pmid = 17091219 | doi = 10.1007/s00198-006-0185-z }}</ref> * [[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. * Several drugs induce hypogonadism, for example [[aromatase inhibitors]] used in breast cancer, [[methotrexate]] and other antimetabolite drugs, [[Depo-Provera|depot progesterone]] and [[gonadotropin-releasing hormone agonist]]s. * [[Anticoagulant]]s – long-term use of heparin is associated with a decrease in bone density,<ref>{{cite journal |vauthors=Ruiz-Irastorza G, Khamashta MA, Hughes GR | s2cid = 2922860 | title = Heparin and osteoporosis during pregnancy: 2002 update | journal = Lupus | volume = 11 | issue = 10 | pages = 680–682 | 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 | vauthors = 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 = 241–246 | year = 2006 | pmid = 16432096 | doi = 10.1001/archinte.166.2.241 | doi-access = free }}</ref> * [[Proton pump inhibitors]] – these drugs inhibit the production of [[gastric acid|stomach acid]]; this is thought to interfere with calcium absorption.<ref>{{cite journal |vauthors=Yang YX, Lewis JD, Epstein S, Metz DC | title = Long-term proton pump inhibitor therapy and risk of hip fracture | journal = JAMA | volume = 296 | issue = 24 | pages = 2947–2953 | year = 2006 | pmid = 17190895 | doi = 10.1001/jama.296.24.2947 | doi-access = free }}</ref> Chronic [[phosphate]] binding may also occur with [[aluminium]]-containing [[antacids]].<ref name="ICSI"/> * [[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 |vauthors=Murphy CE, Rodgers PT | s2cid = 21577063 | title = Effects of thiazolidinediones on bone loss and fracture | journal = Annals of Pharmacotherapy | volume = 41 | issue = 12 | pages = 2014–2018 | year = 2007 | pmid = 17940125 | doi = 10.1345/aph.1K286 }}</ref> * Chronic [[Lithium (medication)|lithium therapy]] has been associated with osteoporosis.<ref name="ICSI"/> ===Pregnancy-associated osteoporosis=== {{Expand section|date=July 2024}} Osteoporosis due to pregnancy and lactation is a rare condition of unknown cause.<ref>{{cite journal |last1=Hardcastle |first1=Sarah A. |title=Pregnancy and Lactation Associated Osteoporosis |journal=Calcified Tissue International |date=May 2022 |volume=110 |issue=5 |pages=531–545 |doi=10.1007/s00223-021-00815-6 |pmid=33620518 }}</ref><ref>{{cite journal |last1=Lujano-Negrete |first1=Abraham Yair |last2=Rodríguez-Ruiz |first2=Martha Cecilia |last3=Skinner-Taylor |first3=Cassandra Michele |last4=Perez-Barbosa |first4=Lorena |last5=Cardenas de la Garza |first5=Jesus Alberto |last6=García-Hernández |first6=Pedro Alberto |last7=Espinosa-Banuelos |first7=Luis Gerardo |last8=Gutierrez-Leal |first8=Luz Fernanda |last9=Jezzini-Martínez |first9=Sofia |last10=Galarza-Delgado |first10=Dionicio Ángel |title=Bone metabolism and osteoporosis during pregnancy and lactation |journal=Archives of Osteoporosis |date=December 2022 |volume=17 |issue=1 |page=36 |doi=10.1007/s11657-022-01077-x |pmid=35182221 }}</ref><ref>{{cite journal |last1=Phillips |first1=A. J. |last2=Ostlere |first2=S. J. |last3=Smith |first3=R. |title=Pregnancy-Associated Osteoporosis: Does the Skeleton Recover? |journal=Osteoporosis International |date=May 2000 |volume=11 |issue=5 |pages=449–454 |doi=10.1007/s001980070113 |pmid=10912848 }}</ref><ref>{{cite journal |title=Gestational osteoporosis: Myth or true? |journal=International Journal of Biology and Pharmacy Research Updates |date=30 January 2024 |volume=3 |issue=1 |pages=001–011 |doi=10.53430/ijbpru.2024.3.1.0040 |first1=George A. |last1=Komnos |first2=Dionyssios |last2=Paridis |first3=Christos |last3=Donoudis |first4=Sotirios |last4=Sotiriou |doi-access=free }}</ref><ref>{{cite journal |last1=Rizzoli |first1=R |last2=Bonjour |first2=JP |title=Pregnancy-associated osteoporosis |journal=The Lancet |date=August 1996 |volume=348 |issue=9024 |pages=403 |doi=10.1016/S0140-6736(05)65018-0 }}</ref> ===Evolutionary=== Age-related bone loss is common among humans due to exhibiting less dense bones than other primate species.<ref name="Latimer_2005">{{cite journal | author = Latimer B | s2cid = 43294733 | title = The perils of being bipedal | journal = Ann Biomed Eng | volume = 33 | issue = 1 | pages = 3–6 | year = 2005 | pmid = 15709701 | doi = 10.1007/s10439-005-8957-8 }}</ref> Because of the more porous bones of humans, frequency of severe osteoporosis and osteoporosis related fractures is higher.<ref name=Cot2011>{{cite journal | author=Cotter M |display-authors=et al |year=2011 |title= Human evolution and osteoporosis-related spinal fractures |journal= PLOS ONE |volume=6 | issue=10|doi=10.1371/journal.pone.0026658 |pages=e26658 |pmid=22028933 |pmc=3197574|bibcode=2011PLoSO...626658C |doi-access=free }}</ref> The human vulnerability to osteoporosis is an obvious cost but it can be justified by the advantage of bipedalism inferring that this vulnerability is the byproduct of such.<ref name=Cot2011/> It has been suggested that porous bones help to absorb the increased stress that we have on two surfaces compared to our primate counterparts who have four surfaces to disperse the force.<ref name="Latimer_2005"/> In addition, the porosity allows for more flexibility and a lighter skeleton that is easier to support.<ref name=Cot2011/> One other consideration may be that diets today have much lower amounts of calcium than the diets of other primates or the tetrapedal ancestors to humans which may lead to higher likelihood to show signs of osteoporosis.<ref name="pmid2053574">{{cite journal |vauthors=Eaton SB, Nelson DA | title = Calcium in evolutionary perspective | journal = Am. J. Clin. Nutr. | volume = 54 | issue = 1 Suppl | pages = 281S–287S | year = 1991 | pmid = 2053574 | doi = 10.1093/ajcn/54.1.281S| doi-access = free }}</ref> === Fracture risk assessment === In the absence of risk factors other than sex and age a BMD measurement using dual-energy X-ray absorptiometry (DXA) is recommended for women at age 65. For women with risk factors a clinical FRAX is advised at age 50. === Mechanics === Osteoporosis occurs when reduction in bone mass surpasses a critical threshold with greater susceptibility to fracturing.<ref>{{cite book |doi=10.1007/3-540-27376-X_3 |chapter=Overview of osteoporosis: Pathophysiology and determinants of bone strength |title=The Aging Spine |date=2005 |last1=Bono |first1=Christopher M. |last2=Einhorn |first2=Thomas A. |series=European Spine Journal |volume=12 |issue=Suppl 2 |pages=8–14 |isbn=978-3-540-24408-0 |pmid=13680312 |pmc=3591823 }}</ref> Fractures occur when the force acting on a bone is greater than the strength of the bone.<ref name="Chen-2014">{{cite journal | vauthors = Chen H, Kubo KY | title = Bone three-dimensional microstructural features of the common osteoporotic fracture sites | journal = World Journal of Orthopedics | volume = 5 | issue = 4 | pages = 486–495 | date = September 2014 | pmid = 25232524 | doi = 10.5312/wjo.v5.i4.486 | doi-broken-date = 14 November 2024 | doi-access = free | pmc = 4133454 }}</ref> To understand the pathology of osteoporosis and skeletal degradation, studying the mechanical properties and behavior of bone is crucial, due to the under-diagnosing of osteoporosis.<ref>{{cite journal | vauthors = Osterhoff G, Morgan EF, Shefelbine SJ, Karim L, McNamara LM, Augat P | title = Bone mechanical properties and changes with osteoporosis | journal = Injury | volume = 47 | issue = Suppl 2 | pages = S11–S20 | date = June 2016 | pmid = 27338221 | pmc = 4955555 | doi = 10.1016/s0020-1383(16)47003-8 }}</ref> Mechanical properties of a material depend on the geometry and inherent structure of the materials.<ref name = "Sharir_2008">{{cite journal | vauthors = Sharir A, Barak MM, Shahar R | title = Whole bone mechanics and mechanical testing | journal = Veterinary Journal | volume = 177 | issue = 1 | pages = 8–17 | date = July 2008 | pmid = 17986396 | doi = 10.1016/j.tvjl.2007.09.012 }}</ref> Bone as a material is very complex because of its hierarchal structure in which characteristics vary across length scales.<ref name = "Sharir_2008" /><ref name="Zimmermann-2015">{{cite journal | vauthors = Zimmermann EA, Busse B, Ritchie RO | title = The fracture mechanics of human bone: influence of disease and treatment | journal = BoneKEy Reports | volume = 4 | pages = 743 | date = 2015-09-02 | pmid = 26380080 | pmc = 4562496 | doi = 10.1038/bonekey.2015.112 }}</ref> At the basic scale, bone is composed of an organic matrix of collagen type-I.<ref name="Sharir_2008" /> Collagen type-I molecules form a composite material with hydroxyapatite to make up collagen fibrils.<ref name="Zimmermann-2015" /> The hierarchal structure continuous with the fibrils being arranged into different patterns such as lamellae.<ref name="Zimmermann-2015" /> The microstructure of bone then forms vascular channels, called osteons, which are surrounded by lamellae.<ref name="Zimmermann-2015" /> At the subsequent scale of bones, there are different types of bone based on morphology: cortical (solid), cancellous (sponge), or trabecular (thin plates).<ref name="Zimmermann-2015" /> A basic picture of the hierarchical structure of bones is essential because the structure will translate to the mechanical behavior of bones. Previous work indicates that osteoporotic bones undergo specific structural changes that contribute to altered mechanical behavior. For instance, a study demonstrated that osteoporotic bone exhibits reduced bone volume fraction, trabecular thickness, and connectivity.<ref>{{cite journal | vauthors = Boskey AL, Imbert L | title = Bone quality changes associated with aging and disease: a review | journal = Annals of the New York Academy of Sciences | volume = 1410 | issue = 1 | pages = 93–106 | date = December 2017 | pmid = 29265417 | doi = 10.1111/nyas.13572 | pmc = 5774017 | bibcode = 2017NYASA1410...93B }}</ref> In another study, osteoporosis in human cancellous bone led to 3-27% variability in the stiffness and strength compared to health bone.<ref>{{cite journal | vauthors = Kim G, Cole JH, Boskey AL, Baker SP, van der Meulen MC | title = Reduced tissue-level stiffness and mineralization in osteoporotic cancellous bone | journal = Calcified Tissue International | volume = 95 | issue = 2 | pages = 125–131 | date = August 2014 | pmid = 24888692 | pmc = 4104238 | doi = 10.1007/s00223-014-9873-4 }}</ref> Additionally, bone mineral density (BMD) is a parameter used to evaluate fracture risk in bones and is used as a predictor of osteoporosis.<ref name="Chen-2014" /> A lower BMD value correlates to decreased bone and a higher bone fragility.<ref name="Chen-2014" /> Furthermore, bone diseases, such as osteoporosis, are known to alter the composition of collagen and other proteins that make up the bone matrix.<ref name = "Sroga_2012">{{cite journal | vauthors = Sroga GE, Vashishth D | title = Effects of bone matrix proteins on fracture and fragility in osteoporosis | journal = Current Osteoporosis Reports | volume = 10 | issue = 2 | pages = 141–150 | date = June 2012 | pmid = 22535528 | doi = 10.1007/s11914-012-0103-6 | pmc = 3375270 }}</ref> These alterations in composition contribute to how bone can handle mechanical loading.<ref name = "Sroga_2012" /> Thus, osteoporosis-induced changes at the macroscopic and microscopic levels significantly impact the mechanical properties of bone, predisposing individuals to fractures even under relatively low mechanical loads. Understanding these structural alterations is vital for developing effective diagnostic and therapeutic strategies for osteoporosis. ==Pathogenesis== [[File:Osteoporosis Locations.png|thumb|Osteoporosis locations]] The underlying mechanism in all cases of osteoporosis is an imbalance between [[bone resorption]] and [[Bone development|bone formation]].<ref name="Dance">{{cite journal |last1=Dance |first1=Amber |title=Fun facts about bones: More than just scaffolding |journal=Knowable Magazine |date=23 February 2022 |doi=10.1146/knowable-022222-1 |doi-access=free }}</ref><ref name="Robling">{{cite journal | vauthors = Robling AG, Bonewald LF | title = The Osteocyte: New Insights | journal = Annual Review of Physiology | volume = 82 | issue = 1 | pages = 485–506 | date = February 2020 | pmid = 32040934 | pmc = 8274561 | doi = 10.1146/annurev-physiol-021119-034332 }}</ref> In normal bone, [[matrix (biology)|matrix]] remodeling of bone is constant; 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 & Thomas in 1963.<ref>Frost HM, Thomas CC. Bone Remodeling Dynamics. Springfield, IL: 1963.</ref> [[Osteoclasts]] are assisted by transcription factor PU.1 to degrade the bone matrix, while [[osteoblasts]] rebuild the bone matrix. Low bone mass density can then occur when osteoclasts are degrading the bone matrix faster than the osteoblasts are rebuilding the bone.<ref name="Dance"/><ref>{{cite journal | vauthors = Wu S, Liu Y, Zhang L, Han Y, Lin Y, Deng HW | title = Genome-wide approaches for identifying genetic risk factors for osteoporosis | journal = Genome Medicine | volume = 5 | issue = 5 | pages = 44 | date = 2013 | pmid = 23731620 | pmc = 3706967 | doi = 10.1186/gm448 | doi-access = free }}</ref> 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, likely due to mesenchymal stem cells biasing away from the [[osteoblast]] and toward the [[Marrow Adipose Tissue|marrow adipocyte]] lineage.<ref>{{cite journal | vauthors = Paccou J, Hardouin P, Cotten A, Penel G, Cortet B | title = The Role of Bone Marrow Fat in Skeletal Health: Usefulness and Perspectives for Clinicians | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 100 | issue = 10 | pages = 3613–21 | date = October 2015 | pmid = 26244490 | doi = 10.1210/jc.2015-2338 | doi-access = free }}</ref> 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 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/> The activation of osteoclasts is regulated by various molecular signals, of which [[RANKL]] (receptor activator of [[NF-κB|nuclear factor kappa-B]] ligand) is one of the best-studied.<ref name="Robling"/> 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]] 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/> Osteoclast maturation and activity is also regulated by activation of [[colony stimulating factor 1 receptor]] (CSF1R).<ref>{{cite journal | vauthors = El-Gamal MI, Al-Ameen SK, Al-Koumi DM, Hamad MG, Jalal NA, Oh CH | title = Recent Advances of Colony-Stimulating Factor-1 Receptor (CSF-1R) Kinase and Its Inhibitors | journal = Journal of Medicinal Chemistry | volume = 61 | issue = 13 | pages = 5450–5466 | date = July 2018 | pmid = 29293000 | doi = 10.1021/acs.jmedchem.7b00873 }}</ref> [[Menopause]]-associated increase production of [[Tumor necrosis factor|TNF-α]] stimulates stromal cells to produce [[colony stimulating factor 1]] (CSF-1) which activates CSF1R and stimulates osteoclasts to reabsorb bone.<ref>{{cite journal | vauthors = Zhao R | title = Immune regulation of osteoclast function in postmenopausal osteoporosis: a critical interdisciplinary perspective | journal = International Journal of Medical Sciences | volume = 9 | issue = 9 | pages = 825–832 | date = 2012 | pmid = 23136547 | pmc = 3491443 | doi = 10.7150/ijms.5180 }}</ref> [[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 and is more subject to bone turnover and remodeling. Not only is bone density decreased, but the microarchitecture of bone is also 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 the trabecular bone for strength, so 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 /> <gallery> File:Osteoclast.jpg|[[Micrograph|Light micrograph]] of an [[osteoclast]] displaying typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol. File:Active osteoblasts.jpg|[[Micrograph|Light micrograph]] of [[osteoblast]]s, several displaying a prominent [[Golgi apparatus]], actively synthesizing [[osteoid]] containing two [[osteocyte]]s. File:722 Feature Osteoprosis of Spine.jpg|Collapse of vertebra on the right, normal on the left </gallery> ==Diagnosis== [[Image:L1 2 vertebral fracture.jpg|thumb|Multiple osteoporotic wedge fractures demonstrated on a lateral thoraco-lumbar spine X-ray]] Osteoporosis often has no clear symptoms<ref>{{Cite journal |last1=Liu |first1=Xudong |last2=Wang |first2=Qi |date=August 2015 |title=Screening of feature genes in distinguishing different types of breast cancer using support vector machine |journal=OncoTargets and Therapy |language=en |volume=8 |pages=2311–2317 |doi=10.2147/OTT.S85271 |doi-access=free |pmid=26347014 |pmc=4556031 |issn=1178-6930 }}</ref> in the early stages, making it difficult to detect without screening. However, you may experience signs such as unexplained back pain, loss of height, or a stooped posture as the condition progresses.[https://wellnessextract.com/blogs/wellness/osteoporosis-uncovered] <ref>{{Cite journal |last1=Rowland |first1=Nathan C. |last2=Breshears |first2=Jonathan |last3=Chang |first3=Edward F. |date=2013 |title=Neurosurgery and the dawning age of Brain-Machine Interfaces |journal=Surgical Neurology International |volume=4 |issue=Suppl 1 |pages=S11–14 |doi=10.4103/2152-7806.109182 |doi-access=free |issn=2229-5097 |pmc=3642748 |pmid=23653884}}</ref> Osteoporosis can be diagnosed using conventional radiography and by measuring the [[bone mineral density]] (BMD).<ref name="Guglielmi Scalzo 2010 Imaging tools">{{cite journal |last1=Guglielmi |first1=Giuseppe |last2=Scalzo |first2=Giacomo |title=Imaging tools transform diagnosis of osteoporosis |journal=Diagnostic Imaging Europe |date=6 May 2010 |volume=26 |issue=3 |url=https://www.diagnosticimaging.com/view/imaging-tools-transform-diagnosis-osteoporosis }}</ref> The most popular method of measuring BMD is [[dual-energy X-ray absorptiometry]].<ref>{{Cite journal |last1=Kim |first1=Ho Sung |last2=Jeong |first2=Eun Sun |last3=Yang |first3=Myung Hwa |last4=Yang |first4=Seoung-Oh |date=2018-09-27 |title=Bone mineral density assessment for research purpose using dual energy X-ray absorptiometry |journal=Osteoporosis and Sarcopenia |language=en |volume=4 |issue=3 |pages=79–85 |doi=10.1016/j.afos.2018.09.003 |pmid=30775548 |pmc=6362959 }}</ref> 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.<ref>{{cite journal | vauthors = Sheu A, Diamond T | title = Secondary osteoporosis | journal = Australian Prescriber | volume = 39 | issue = 3 | pages = 85–87 | date = June 2016 | pmid = 27346916 | pmc = 4919174 | doi = 10.18773/austprescr.2016.038 }}</ref> ===Conventional radiography=== 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.<ref>{{cite journal | vauthors = Brunader R, Shelton DK | title = Radiologic bone assessment in the evaluation of osteoporosis | journal = American Family Physician | volume = 65 | issue = 7 | pages = 1357–1364 | date = April 2002 | pmid = 11996418 | url = https://www.aafp.org/afp/2002/0401/p1357.html }}</ref><ref>{{cite journal | vauthors = Grampp S, Steiner E, Imhof H | title = Radiological diagnosis of osteoporosis | journal = European Radiology | volume = 7 | issue = Suppl 2 | pages = S11–S19 | date = 1997 | doi = 10.1007/PL00006859 | pmid = 9126455 | s2cid = 10799509 }}</ref> 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, leading to what is known as [[hyperkyphosis|dowager's hump]].<ref>{{cite journal | vauthors = Fon GT, Pitt MJ, Thies AC | title = Thoracic kyphosis: range in normal subjects | journal = AJR. American Journal of Roentgenology | volume = 134 | issue = 5 | pages = 979–983 | date = May 1980 | pmid = 6768276 | doi = 10.2214/ajr.134.5.979 }}</ref><ref>{{cite journal | vauthors = Voutsinas SA, MacEwen GD | title = Sagittal profiles of the spine | journal = Clinical Orthopaedics and Related Research | issue = 210 | pages = 235–242 | date = September 1986 | pmid = 3757369 }}</ref> ===Dual-energy X-ray=== [[Dual-energy X-ray absorptiometry]] (DEXA scan) 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 (30–40-year-old<ref name="WHOcriteria"/><sup>:58</sup>), healthy adult women reference population. This is translated as a [[Bone density#T-score|T-score]]. But because bone density decreases with age, more people become osteoporotic with increasing age.<ref name="WHOcriteria"/><sup>:58</sup> The World Health Organization has established the following diagnostic guidelines:<ref name="WHOcriteria"/><ref name=WHO1994/> {| class="wikitable" ! Category !! [[Bone density#T-score|T-score]] range !! % young women |- | Normal || [[Bone density#T-score|T-score]] ≥ −1.0 || 85% |- | [[Osteopenia]] || −2.5 < T-score < −1.0 || 14% |- | Osteoporosis || T-score ≤ −2.5 || 0.6% |- | Severe osteoporosis || T-score ≤ −2.5 with fragility fracture<ref name=WHO1994/> || |} 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, for premenopausal women, Z-scores (comparison with age group rather than peak bone mass) rather than T-scores should be used, and the diagnosis of osteoporosis in such women also should not be made on the basis of densitometric criteria alone.<ref name="pmid14742881">{{cite journal |vauthors=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 | year=2004 |pmid=14742881 | doi=10.1385/JCD:7:1:1 |pages=1–5|s2cid=32856123 }} 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"] {{webarchive|url=https://web.archive.org/web/20080224001118/http://www.guideline.gov/summary/summary.aspx?ss=15&doc_id=6567&nbr=4129 |date=24 February 2008 }}</ref> ===Biomarkers=== Chemical [[biomarkers]] are a useful tool in detecting bone degradation. The enzyme [[cathepsin K]] breaks down [[Type I collagen|type-I collagen]], an important constituent in bones. Prepared antibodies can recognize the resulting fragment, called a [[neoepitope]], as a way to diagnose osteoporosis.<ref name="pmid15876399">{{cite journal |vauthors=Yasuda Y, Kaleta J, [[Dieter Brömme|Brömme D]] | title = The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics | journal = Adv. Drug Deliv. Rev. | volume = 57 | issue = 7 | pages = 973–993 | year = 2005 | pmid = 15876399 | doi = 10.1016/j.addr.2004.12.013 }}</ref> Increased urinary excretion of [[C-Telopeptide|C-telopeptides]], a type-I collagen breakdown product, also serves as a biomarker for osteoporosis.<ref>{{cite book| vauthors = Meunier P |title=Osteoporosis: Diagnosis and Management|year=1998|publisher=Taylor and Francis|location=London|isbn=978-1-85317-412-4}}</ref> {{Bone pathology}} ===Other measuring tools=== [[Quantitative computed tomography]] (QCT) 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, can be calculated from existing CT scans without a separate radiation dose, 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 compared to DXA, 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="Guglielmi Scalzo 2010 Imaging tools"/> 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.<ref name="Guglielmi Scalzo 2010 Imaging tools"/> Some ultrasound devices can be used on the [[tibia]].<ref>{{Cite web|url=https://www.medgadget.com/2016/05/bindex-a-radiation-free-device-for-osteoporosis-screening-fda-cleared.html|archiveurl=https://web.archive.org/web/20160615042358/http://www.medgadget.com/2016/05/bindex-a-radiation-free-device-for-osteoporosis-screening-fda-cleared.html|url-status=live|date=27 May 2016|title=Bindex, a Radiation-Free Device for Osteoporosis Screening, FDA Cleared|publisher=Medgadget|archive-date=15 June 2016}}</ref> ==Screening== The [[U.S. Preventive Services Task Force]] (USPSTF) recommend that all women 65 years of age or older be screened by [[bone densitometry]].<ref name=USPSTF2018b/> Additionally they recommend screening younger women with risk factors.<ref name="USPSTF2018b">{{cite journal | vauthors = Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW, Kemper AR, Kubik M, Landefeld CS, Mangione CM, Phipps MG, Pignone M, Silverstein M, Simon MA, Tseng CW, Wong JB | title = Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement | journal = JAMA | volume = 319 | issue = 24 | pages = 2521–2531 | date = June 2018 | pmid = 29946735 | doi = 10.1001/jama.2018.7498 | doi-access = free }}</ref> There is insufficient evidence to make recommendations about the intervals for repeated screening and the appropriate age to stop screening.<ref name=USP2011>{{cite journal | title = Screening for osteoporosis: U.S. preventive services task force recommendation statement | journal = Annals of Internal Medicine | volume = 154 | issue = 5 | pages = 356–364 | date = March 2011 | pmid = 21242341 | doi = 10.7326/0003-4819-154-5-201103010-00307 | author1 = U.S. Preventive Services Task Force | doi-access = free }}</ref> In men the harm versus benefit of screening for osteoporosis is unknown.<ref name=USPSTF2018b/> [[Prescrire]] states that the need to test for osteoporosis in those who have not had a previous bone fracture is unclear.<ref>{{cite journal|title=100 most recent Archives 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 Bone fragility: preventing fractures|journal=Prescrire International|date=April 2017|volume=26|issue=181|pages=103–106|url=http://english.prescrire.org/en/81/168/52990/0/2017/ArchiveNewsDetails.aspx?page=1|url-status=live|archive-url=https://web.archive.org/web/20170908174355/http://english.prescrire.org/en/81/168/52990/0/2017/ArchiveNewsDetails.aspx?page=1|archive-date=8 September 2017}}</ref> The International Society for Clinical Densitometry suggest BMD testing for men 70 or older, or those who are indicated for risk equal to that of a 70‑year‑old.<ref>International Society for Clinical Densitometry (ISCD). 2013 ISCD Official Positions – Adult. (2013). at {{cite web |url=http://www.iscd.org/official-positions/2013-iscd-official-positions-adult |title=2013 ISCD Official Positions – Adult – International Society for Clinical Densitometry (ISCD) |access-date=2015-05-04 |url-status=live |archive-url=https://web.archive.org/web/20150505080031/http://www.iscd.org/official-positions/2013-iscd-official-positions-adult/ |archive-date=5 May 2015 }}</ref> A number of tools exist to help determine who is reasonable to test.<ref name="pmid18716823">{{cite journal | vauthors = Rud B, Hilden J, Hyldstrup L, Hróbjartsson A | s2cid = 13641749 | title = The Osteoporosis Self-Assessment Tool versus alternative tests for selecting postmenopausal women for bone mineral density assessment: a comparative systematic review of accuracy | journal = Osteoporosis International | volume = 20 | issue = 4 | pages = 599–607 | date = April 2009 | pmid = 18716823 | doi = 10.1007/s00198-008-0713-0 }}</ref> ==Prevention== Lifestyle prevention of osteoporosis is in many aspects the inverse of the potentially modifiable risk factors.<ref name="pmid25370432">{{cite journal | vauthors = Ebeling PR, Daly RM, Kerr DA, Kimlin MG | title = Building healthy bones throughout life: an evidence-informed strategy to prevent osteoporosis in Australia | journal = The Medical Journal of Australia | volume = 199 | issue = 7 Suppl | pages = 90–91 | date = October 2013 | pmid = 25370432 | doi = 10.5694/mja12.11363| hdl = 10536/DRO/DU:30060407 | s2cid = 29255357 | url = https://eprints.qut.edu.au/77058/1/Ebe11363_web.pdf }}</ref> As tobacco smoking and high alcohol intake have been linked with osteoporosis, smoking cessation and moderation of alcohol intake are commonly recommended as ways to help prevent it.<ref name=Review2011/> In people with [[coeliac disease]] adherence to a [[gluten-free diet]] decreases the risk of developing osteoporosis<ref name=LudvigssonBai2014>{{cite journal|vauthors=Ludvigsson JF, Bai JC, Biagi F, Card TR, Ciacci C, Ciclitira PJ, Green PH, Hadjivassiliou M, Holdoway A, van Heel DA, Kaukinen K, Leffler DA, Leonard JN, Lundin KE, McGough N, Davidson M, Murray JA, Swift GL, Walker MM, Zingone F, Sanders DS, ((BSG Coeliac Disease Guidelines Development Group)), ((British Society of Gastroenterology))|title=Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology|journal=Gut|volume=63|issue=8|pages=1210–1228|date=Aug 2014|pmid=24917550|pmc=4112432|doi=10.1136/gutjnl-2013-306578|type=Review}}</ref> and increases bone density.<ref name=MirzaCanalis2015 /> The diet must ensure optimal [[calcium]] intake (of at least one gram daily) and measuring [[vitamin D]] levels is recommended, and to take specific supplements if necessary.<ref name=LudvigssonBai2014 /> Osteoporosis can affect nearly 1 in 3 women and the bone loss is the most rapid within the first 2–3 years after menopause. This can be prevented by menopause hormone therapy or MHT, which is meant to prevent bone loss and the degradation of the bone microarchitecture and is noted to reduce the risk of fractures in bones by 20-30%. However, MHT has been linked to safety concerns, so it is not generally recommended.<ref>{{Cite journal |last1=Gosset |first1=Anna |last2=Pouillès |first2=Jean-Michel |last3=Trémollieres |first3=Florence |date=December 2021 |title=Menopausal hormone therapy for the management of osteoporosis |url=https://pubmed.ncbi.nlm.nih.gov/34119418/ |journal=Best Practice & Research. Clinical Endocrinology & Metabolism |volume=35 |issue=6 |pages=101551 |doi=10.1016/j.beem.2021.101551 |issn=1878-1594 |pmid=34119418}}</ref> As far as management goes with this potentially limiting disease, there are practices that can and should be implemented within the daily lifestyle. For example, it would be beneficial if the individual with osteoporosis refrained from consuming excess alcohol and to avoid smoking.<ref>{{Cite journal |date=2021-09-01 |title=Management of osteoporosis in postmenopausal women: the 2021 position statement of The North American Menopause Society |url=https://pubmed.ncbi.nlm.nih.gov/34448749/ |journal=Menopause (New York, N.Y.) |volume=28 |issue=9 |pages=973–997 |doi=10.1097/GME.0000000000001831 |issn=1530-0374 |pmid=34448749}}</ref> These individuals should also be intentional about intaking an adequate amount of protein, calcium, and vitamin D. If the woman has an even higher risk of fracture, managing this may require therapy. Generally, the recommended treatment of prevention for a decrease in bone mineral density is physical activity. Exercise is sometimes the best medicine. Resistance training is the most recommended method of physical activity but that can come in multiple forms. High intensity and high impact training is shown to be extremely beneficial in improving bone health and the most effective in improving, maintaining, bone density in the lower spine and femur. Although these types of exercises are safe for postmenopausal women, there still may be a need for supervision and precautionary measures.<ref>{{Cite journal |last=Compston |first=Juliet |date=2005-12-01 |title=How to manage osteoporosis after the menopause |url=https://www.sciencedirect.com/science/article/abs/pii/S152169420500080X |journal=Best Practice & Research Clinical Rheumatology |volume=19 |issue=6 |pages=1007–1019 |doi=10.1016/j.berh.2005.06.010 |pmid=16301194 |issn=1521-6942}}</ref> ===Nutrition=== Studies of the benefits of supplementation with calcium and vitamin D are conflicting, possibly because most studies did not have people with low dietary intakes.<ref name="MedicalLetter">{{cite journal| title =Drugs for Postmenopausal Osteoporosis| journal =The Medical Letter on Drugs and Therapeutics | date =29 September 2014 | volume =56| issue =1452| pages =91–96| url =https://secure.medicalletter.org/TML-article-1452a| pmid =25247344}}</ref> A 2018 review by the USPSTF found low-quality evidence that the routine use of calcium and vitamin D supplements (or both supplements together) did not reduce the risk of having an osteoporotic fracture in male and female adults living in the community who had no known history of vitamin D deficiency, osteoporosis, or a fracture.<ref name=USPSTF2018>{{cite journal | vauthors = Kahwati LC, Weber RP, Pan H, Gourlay M, LeBlanc E, Coker-Schwimmer M, Viswanathan M | s2cid = 205090176 | title = Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force | journal = JAMA | volume = 319 | issue = 15 | pages = 1600–1612 | date = April 2018 | pmid = 29677308 | doi = 10.1001/jama.2017.21640 | type = Systematic Review & Meta-Analysis | doi-access = free }}</ref> The USPSTF does not recommend low dose supplementation (less than 1 g of calcium and 400 IU of vitamin D) in [[postmenopause|postmenopausal women]] as there does not appear to be a difference in fracture risk.<ref name="USPSTF2018Recs">{{cite web|title=Final Recommendation Statement Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: Preventive Medication|url=https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/vitamin-d-calcium-or-combined-supplementation-for-the-primary-prevention-of-fractures-in-adults-preventive-medication|website=www.uspreventiveservicestaskforce.org|publisher=USPSTF Program Office}}</ref> A 2015 review found little data that supplementation of calcium decreases the risk of fractures.<ref>{{cite journal | vauthors = Bolland MJ, Leung W, Tai V, Bastin S, Gamble GD, Grey A, Reid IR | title = Calcium intake and risk of fracture: systematic review | journal = BMJ | volume = 351 | pages = h4580 | date = September 2015 | pmid = 26420387 | pmc = 4784799 | doi = 10.1136/bmj.h4580 }}</ref> While some meta-analyses have found a benefit of vitamin D supplements combined with calcium for prevention of fractures, they did not find a benefit of vitamin D supplements (800 IU/day or less) alone.<ref>{{cite journal | vauthors = ((DIPART Group)) | title = Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe | journal = BMJ | volume = 340 | pages = b5463 | date = January 2010 | pmid = 20068257 | pmc = 2806633 | doi = 10.1136/bmj.b5463 }}</ref><ref name="Ave2014">{{cite journal | vauthors = Avenell A, Mak JC, O'Connell D | title = Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men | journal = The Cochrane Database of Systematic Reviews | volume = 4 | issue = 4 | pages = CD000227 | date = April 2014 | pmid = 24729336 | doi = 10.1002/14651858.CD000227.pub4 | pmc = 7032685 }}</ref> Regarding adverse effects, supplementation does not appear to affect overall risk of death,<ref name="USPSTF2018" /><ref name="Ave2014" /> although calcium supplementation could potentially be associated with some increased risk of [[myocardial infarction]]s, [[stroke]], [[kidney stones]],<ref name="USPSTF2018" /> and [[gastrointestinal]] symptoms.<ref name="Ave2014"/> There is no evidence that supplementation before menopause can enhance bone mineral density.<ref>{{cite journal |vauthors=Méndez-Sánchez L, Clark P, Winzenberg TM, Tugwell P, Correa-Burrows P, Costello R |title=Calcium and vitamin D for increasing bone mineral density in premenopausal women |journal=Cochrane Database Syst Rev |volume=1 |issue=1 |pages=CD012664 |date=January 2023 |pmid=36705288 |pmc=9881395 |doi=10.1002/14651858.CD012664.pub2 |url=}}</ref> [[Vitamin K deficiency]] is also a risk factor for osteoporotic fractures.<ref>{{cite journal | vauthors = Rodríguez-Olleros Rodríguez C, Díaz Curiel M | title = Vitamin K and Bone Health: A Review on the Effects of Vitamin K Deficiency and Supplementation and the Effect of Non-Vitamin K Antagonist Oral Anticoagulants on Different Bone Parameters | journal = Journal of Osteoporosis | volume = 2019 | pages = 2069176 | date = 2019-12-31 | pmid = 31976057 | pmc = 6955144 | doi = 10.1155/2019/2069176 | doi-access = free }}</ref> The gene [[Gamma-glutamyl carboxylase|gamma-glutamyl carboxylase (GGCX)]] is dependent on vitamin K. Functional polymorphisms in the gene could attribute to variation in bone metabolism and BMD.<ref>{{cite journal | vauthors = De Vilder EY, Debacker J, Vanakker OM | title = GGCX-Associated Phenotypes: An Overview in Search of Genotype-Phenotype Correlations | journal = International Journal of Molecular Sciences | volume = 18 | issue = 2 | pages = 240 | date = January 2017 | pmid = 28125048 | pmc = 5343777 | doi = 10.3390/ijms18020240 | doi-access = free }}</ref> [[Vitamin K2]] is also used as a means of treatment for osteoporosis and the polymorphisms of GGCX could explain the individual variation in the response to treatment of vitamin K.<ref>{{cite journal | vauthors = Hosoi T | title = Genetic aspects of osteoporosis | journal = Journal of Bone and Mineral Metabolism | volume = 28 | issue = 6 | pages = 601–607 | date = November 2010 | pmid = 20697753 | doi = 10.1007/s00774-010-0217-9 | s2cid = 35412918 }}</ref> Dietary sources of calcium include dairy products, leafy greens, legumes, and beans.<ref>{{Cite web|url=https://www.pcrm.org/good-nutrition/nutrition-information/health-concerns-about-dairy/preventing-and-reversing-osteoporosis|title=Preventing and Reversing Osteoporosis|website=Physicians Committee for Responsible Medicine|language=en|access-date=2019-08-05}}</ref> There has been conflicting evidence about whether or not dairy is an adequate source of calcium to prevent fractures. The National Academy of Sciences recommends 1,000 mg of calcium for those aged 19–50, and 1,200 mg for those aged 50 and above.<ref>{{cite web | url = https://www.ncbi.nlm.nih.gov/books/NBK56056/#:~:text=The%20EAR%20is%20therefore%20set,1%2C300%20mg%2Fday%20is%20established. | title = Dietary Reference Intakes for Adequacy: Calcium and Vitamin D – Dietary Reference Intakes for Calcium and Vitamin D – NCBI Bookshelf | access-date = 18 December 2020}}</ref> A review of the evidence shows no adverse effect of higher protein intake on bone health.<ref name="pmid28404575">{{cite journal | vauthors = Shams-White MM, Chung M, Du M, Fu Z, Insogna KL, Karlsen MC, LeBoff MS, Shapses SA, Sackey J, Wallace TC, Weaver CM | title = Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation | journal = The American Journal of Clinical Nutrition | volume = 105 | issue = 6 | pages = 1528–1543 | date = June 2017 | pmid = 28404575 | doi = 10.3945/ajcn.116.145110 | doi-access = free }}</ref> === Physical exercise === Evidence suggests that exercise can help promote bone health in older people.<ref name=Pinheiro2020>{{cite journal |vauthors=Pinheiro MB, Oliveira J, Bauman A, Fairhall N, Kwok W, Sherrington C |title=Evidence on physical activity and osteoporosis prevention for people aged 65+ years: a systematic review to inform the WHO guidelines on physical activity and sedentary behaviour |journal=The International Journal of Behavioral Nutrition and Physical Activity |volume=17 |issue=1 |pages=150 |date=November 2020 |pmid=33239014 |pmc=7690138 |doi=10.1186/s12966-020-01040-4|doi-access=free }}</ref> In particular, physical exercise can be beneficial for bone density in postmenopausal women,<ref name=Mohebbi2023/> and lead to a slightly reduced risk of a bone fracture (absolute difference 4%).<ref name=":Howe2011">{{cite journal | vauthors = Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G | title = Exercise for preventing and treating osteoporosis in postmenopausal women | journal = The Cochrane Database of Systematic Reviews | volume = Art. No.: CD000333 | issue = 7 | pages = CD000333 | date = July 2011 | pmid = 21735380 | doi = 10.1002/14651858.CD000333.pub2 }}</ref> Weight bearing exercise has been found to cause an adaptive response in the skeleton,<ref>{{cite journal | vauthors = Giangregorio L, Blimkie CJ | title = Skeletal adaptations to alterations in weight-bearing activity: a comparison of models of disuse osteoporosis | journal = Sports Medicine | volume = 32 | issue = 7 | pages = 459–476 | date = 2002 | pmid = 12015807 | doi = 10.2165/00007256-200232070-00005 | s2cid = 25835205 }}</ref> promoting osteoblast activity and protecting bone density.<ref>{{cite journal | vauthors = Uda Y, Azab E, Sun N, Shi C, Pajevic PD | title = Osteocyte Mechanobiology | journal = Current Osteoporosis Reports | volume = 15 | issue = 4 | pages = 318–325 | date = August 2017 | pmid = 28612339 | pmc = 5656287 | doi = 10.1007/s11914-017-0373-0 }}</ref> A position statement concluded that increased bone activity and weight-bearing exercises at a young age prevent bone fragility in adults.<ref>{{cite journal | vauthors = Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, O'Karma M, Wallace TC, Zemel BS | title = The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations | journal = Osteoporosis International | volume = 27 | issue = 4 | pages = 1281–1386 | date = April 2016 | pmid = 26856587 | pmc = 4791473 | doi = 10.1007/s00198-015-3440-3}}</ref> Limitations in the available evidence hinder the production of detailed evidence-based exercise recommendations.<ref name=Mohebbi2023>{{cite journal |vauthors=Mohebbi R, Shojaa M, Kohl M, von Stengel S, Jakob F, Kerschan-Schindl K, Lange U, Peters S, Thomasius F, Uder M, Kemmler W |title=Exercise training and bone mineral density in postmenopausal women: an updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators |journal=Osteoporosis International |volume=34 |issue=7 |pages=1145–1178 |date=July 2023 |pmid=36749350 |pmc=10282053 |doi=10.1007/s00198-023-06682-1 |url=}}</ref> Some expert consensus guidance does exist.<ref>{{cite journal |vauthors=Brooke-Wavell K, Skelton DA, Barker KL, et al |title=Strong, steady and straight: UK consensus statement on physical activity and exercise for osteoporosis |journal=British Journal of Sports Medicine |volume=56 |issue=15 |pages=837–46 |date=May 2022 |pmid=35577538 |pmc=9304091 |doi=10.1136/bjsports-2021-104634}}</ref><ref>{{cite journal |vauthors=Bae S, Lee S, Park H, et al |title=Position statement: Exercise guidelines for osteoporosis management and fall prevention in osteoporosis patients |journal=Journal of Bone Metabolism |volume=30 |issue=2 |pages=149–165 |date=May 2023 |pmid=37449348 |pmc=10345999 |doi=10.11005/jbm.2023.30.2.149 |url=}}</ref> International guidelines recommend multicomponent exercise tailored to individual needs that includes "balance and mobility training, paired with weight bearing exercise, progressive resistance training, and posture exercises" (generally accompanied by optimal nutrition).<ref>{{cite journal |vauthors=Karlsson MK, Rosengren BE |title=Exercise and peak bone mass |journal=Current Osteoporosis Reports |volume=18 |issue=3 |pages=285–290 |date=June 2020 |pmid=32249382 |pmc=7250943 |doi=10.1007/s11914-020-00588-1}}</ref> Cycling and swimming are not considered weight-bearing exercise, and neither helps slow age-related bone loss (professional bicycle racing has a negative effect on bone density).<ref>{{cite journal | vauthors = Abrahin O, Rodrigues RP, Marçal AC, Alves EA, Figueiredo RC, de Sousa EC | title = Swimming and cycling do not cause positive effects on bone mineral density: a systematic review | journal = Revista Brasileira de Reumatologia | volume = 56 | issue = 4 | pages = 345–351 | date = 2016 | pmid = 27476628 | doi = 10.1016/j.rbre.2016.02.013 | doi-access = free }}</ref> Risk of adverse events from the types of exercise usually considered appropriate for people with osteoporosis is generally low (though repeated forceful forward spinal bends are discouraged).<ref name="NOGG2019-5">{{cite web |title=Non-pharmacological management of osteoporosis |url=https://www.nogg.org.uk/full-guideline/section-5-non-pharmacological-management-osteoporosis |website=www.nogg.org.uk |publisher=National Osteoporosis Guideline Group UK |archive-url=https://web.archive.org/web/20240612230817/https://www.nogg.org.uk/full-guideline/section-5-non-pharmacological-management-osteoporosis |archive-date=12 June 2024 |language=en |date=September 2021 |url-status=live}}</ref> For people who have had vertebral fractures, there is moderate-quality evidence that exercise is likely to improve physical performance, as well as some low-quality evidence suggesting that exercise may reduce pain and improve quality of life.<ref name = "Gibbs_2019">{{cite journal | vauthors = Gibbs JC, MacIntyre NJ, Ponzano M, Templeton JA, Thabane L, Papaioannou A, Giangregorio LM | title = Exercise for improving outcomes after osteoporotic vertebral fracture | journal = The Cochrane Database of Systematic Reviews | volume = 7 | pages = CD008618 | date = July 2019 | issue = 7 | pmid = 31273764 | pmc = 6609547 | doi = 10.1002/14651858.CD008618.pub3 | collaboration = Cochrane Musculoskeletal Group }}</ref> === Physical exercise prescription === Osteoporosis is a very prevalent disease in the elderly population but not much is known about the optimal prescription and dosage of physical exercise to help prevent bone mineral loss. A lot of the focus around osteoporosis is prevention oriented, rather than maintenance focused, which should be the front runner when considering what approach to take. When prescribing exercise, an aspect to take into consideration is the individual’s need this can be attained by conducting a pre-exercise evaluation or screening, exercise should also be tailored to the individual and what works for them. Important things often overlooked when treating osteoporosis are muscle strength and maintenance of BMD, which should be incorporated into the program to optimize the benefits of exercise. This entails including exercises that focus on and improve muscle strength and exercises that focus on and improve skeletal strength or BMD as these go hand in hand for reducing fall and fracture risk.<ref name="Daly-2019">{{Cite journal |last1=Daly |first1=Robin M. |last2=Dalla Via |first2=Jack |last3=Duckham |first3=Rachel L. |last4=Fraser |first4=Steve F. |last5=Helge |first5=Eva Wulff |date=March 2019 |title=Exercise for the prevention of osteoporosis in postmenopausal women: an evidence-based guide to the optimal prescription |journal=Brazilian Journal of Physical Therapy |language=en |volume=23 |issue=2 |pages=170–180 |doi=10.1016/j.bjpt.2018.11.011 |pmc=6429007 |pmid=30503353}}</ref> It’s also important to reference the ACSM general training principle to better design a program for the individual. Which mode of exercise and dosage has been a recurring question for treating osteoporosis, many articles have found that multimodal exercise programs have had findings of significant improvement in factors related to osteoporosis. Factors include lower limb strength, balance, flexibility, and risk of falls.<ref>{{Cite journal |last1=Linhares |first1=Diego Gama |last2=Borba-Pinheiro |first2=Claudio Joaquim |last3=Castro |first3=Juliana Brandão Pinto de |last4=Santos |first4=Andressa Oliveira Barros dos |last5=Santos |first5=Luciano Lima dos |last6=Cordeiro |first6=Lilliany de Souza |last7=Drigo |first7=Alexandre Janotta |last8=Nunes |first8=Rodolfo de Alkmim Moreira |last9=Vale |first9=Rodrigo Gomes de Souza |date=2022-10-30 |title=Effects of Multicomponent Exercise Training on the Health of Older Women with Osteoporosis: A Systematic Review and Meta-Analysis |journal=International Journal of Environmental Research and Public Health |language=en |volume=19 |issue=21 |pages=14195 |doi=10.3390/ijerph192114195 |doi-access=free |issn=1660-4601 |pmc=9655411 |pmid=36361073}}</ref> Other modes of exercise have also proven to improve individuals with osteoporosis, some of these modes include weight-bearing, resistance specifically progressive resistance, and aerobic exercise. The recommendations for these types of exercises are as follows, weight-bearing exercise should be done 4–7 days a week, moderate to high intensity, activities should be multidirectional, and load should be more than typical everyday load on bones.<ref name="Daly-2019" /> Some examples of exercises are jumping, skipping, hopping, depth jumps, etc. Recommended dosage for progressive resistance training is 2 or more days a week, intensity (load) should start low and increase gradually.<ref name="Daly-2019" /> Resistance training should focus on major muscle groups used for functional movements as well as muscles that have direct stress on bones susceptible to fracture. Considerations for resistance training are to teach proper lifting techniques and be careful with lifting weights above the head.<ref name="Daly-2019" /> Lastly, aerobic exercise has minimal effect on preventing BMD loss unless done at a higher intensity or with a load like a weighted vest. Considerations with this mode are that this may cause a higher risk of fall or fracture.<ref name="Daly-2019" /> Improvements can also be observed in other ways, such as decreased Timed-Up-and-Go, increased Sit-To-Stand, and increased One-Leg-Stance-Test. A study with a 12-week exercise intervention on postmenopausal osteoporotic women observed a 2.27 decrease in TUG times in their experimental group.<ref>{{Cite journal |last1=Filipović |first1=Tamara N. |last2=Lazović |first2=Milica P. |last3=Backović |first3=Ana N. |last4=Filipović |first4=Aleksandar N. |last5=Ignjatović |first5=Aleksandra M. |last6=Dimitrijević |first6=Sanja S. |last7=GopčEvić |first7=Kristina R. |date=February 2021 |title=A 12-week exercise program improves functional status in postmenopausal osteoporotic women: randomized controlled study |url=https://www.minervamedica.it/index2.php?show=R33Y2021N01A0120 |journal=European Journal of Physical and Rehabilitation Medicine |volume=57 |issue=1 |pages=120–130 |doi=10.23736/S1973-9087.20.06149-3|pmid=32902207 }}</ref> The overall thing to note when prescribing exercise for individuals with osteoporosis is to evaluate the individual's needs and then individualize their program with multiple exercise modalities that work for them, emphasizing increasing muscle strength as well as maintaining bone mass. === Physical therapy === People with osteoporosis are at higher risk of falls due to poor postural control, muscle weakness, and overall deconditioning.<ref name="Effect of balance training on falls">{{cite journal | vauthors = Zhou X, Deng H, Shen X, Lei Q | title = Effect of balance training on falls in patients with osteoporosis: A systematic review and meta-analysis | journal = Journal of Rehabilitation Medicine | volume = 50 | issue = 7 | pages = 577–581 | date = July 2018 | pmid = 29767225 | doi = 10.2340/16501977-2334 | doi-access = free }}</ref> Postural control is important to maintaining functional movements such as walking and standing. Physical therapy may be an effective way to address postural weakness that may result from vertebral fractures, which are common in people with osteoporosis. Physical therapy treatment plans for people with vertebral fractures include balance training, postural correction, trunk and lower extremity muscle strengthening exercises, and moderate-intensity aerobic physical activity.<ref name = "Gibbs_2019" /> The goal of these interventions are to regain normal spine curvatures, increase spine stability, and improve functional performance.<ref name = "Gibbs_2019" /> Physical therapy interventions were also designed to slow the rate of bone loss through home exercise programs.<ref name="Effect of balance training on falls"/> [[Whole body vibration]] therapy has also been suggested as a physical therapy intervention. Moderate to low-quality evidence indicates that whole body vibration therapy may reduce the risk of falls.<ref name=Jepsen2017>{{cite journal | vauthors = Jepsen DB, Thomsen K, Hansen S, Jørgensen NR, Masud T, Ryg J | title = Effect of whole-body vibration exercise in preventing falls and fractures: a systematic review and meta-analysis | journal = BMJ Open | volume = 7 | issue = 12 | pages = e018342 | date = December 2017 | pmid = 29289937 | pmc = 6027066 | doi = 10.1136/bmjopen-2017-018342 }}</ref> There are conflicting reviews as to whether vibration therapy improves bone mineral density.<ref name=Jepsen2017 /><ref name=MarinCascales2018>{{cite journal | vauthors = Marín-Cascales E, Alcaraz PE, Ramos-Campo DJ, Martinez-Rodriguez A, Chung LH, Rubio-Arias JÁ | title = Whole-body vibration training and bone health in postmenopausal women: A systematic review and meta-analysis | journal = Medicine | volume = 97 | issue = 34 | pages = e11918 | date = August 2018 | pmid = 30142802 | pmc = 6112924 | doi = 10.1097/MD.0000000000011918 }}</ref> Physical therapy can aid in overall prevention in the development of osteoporosis through therapeutic exercise. Prescribed amounts of mechanical loading or increased forces on the bones promote bone formation and vascularization in various ways, therefore offering a preventative measure that is not reliant on drugs. Specific exercise interacts with the body's hormones and signaling pathways which encourages the maintenance of a healthy skeleton.<ref>{{cite journal | vauthors = Tong X, Chen X, Zhang S, Huang M, Shen X, Xu J, Zou J | title = The Effect of Exercise on the Prevention of Osteoporosis and Bone Angiogenesis | journal = BioMed Research International | volume = 2019 | pages = 8171897 | date = 2019-04-18 | pmid = 31139653 | pmc = 6500645 | doi = 10.1155/2019/8171897 | doi-access = free }}</ref> === Hormone therapy === Reduced [[oestrogen|estrogen]] levels increase the risk of osteoporosis, so [[hormone replacement therapy]] when women reach the [[menopause]] may reduce the incidence of osteoporosis. A more natural way of restoring hormone levels in postmenopausal women include participating in specific forms of exercise. Weight-bearing exercises and resistance training exercises such as squats with weights, step-ups, lunges, stair climbing, and even jogging can elicit hormone responses that are advantageous for post-menopausal women living with osteoporosis. These exercises result in the release of growth hormone and Insulin-like growth factor-1 or IGF-1 that participate in bone remodeling.<ref>{{Cite journal |last1=Moreira |first1=Linda Denise Fernandes |last2=Oliveira |first2=Mônica Longo de |last3=Lirani-Galvão |first3=Ana Paula |last4=Marin-Mio |first4=Rosângela Villa |last5=Santos |first5=Rodrigo Nolasco dos |last6=Lazaretti-Castro |first6=Marise |date=July 2014 |title=Physical exercise and osteoporosis: effects of different types of exercises on bone and physical function of postmenopausal women |url=https://www.scielo.br/j/abem/a/fHhb6PgkgYsN5cZ8fwYQdjC/?lang=en |journal=Arquivos Brasileiros de Endocrinologia & Metabologia |language=en |volume=58 |issue=5 |pages=514–522 |doi=10.1590/0004-2730000003374 |pmid=25166042 |issn=1677-9487}}</ref> Stress is applied to the bones, thus activating osteoblast, which are cells that form new bones and grow and heal existing bones<ref>{{Citation |last1=Henry |first1=James P. |title=Histology, Osteoblasts |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK557792/ |access-date=2024-11-15 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32491724 |last2=Bordoni |first2=Bruno}}</ref> while restoring hormones that increase bone density. Resistance training exercises, like weight lifting, can lead to brief increased in anabolic hormones, like testosterone, which aid in muscle and bone strength.<ref>{{Cite journal |last1=Christenson |first1=E. S. |last2=Jiang |first2=X. |last3=Kagan |first3=R. |last4=Schnatz |first4=P. |date=June 2012 |title=Osteoporosis management in post-menopausal women |url=https://pubmed.ncbi.nlm.nih.gov/22635014/ |journal=Minerva Ginecologica |volume=64 |issue=3 |pages=181–194 |issn=0026-4784 |pmid=22635014}}</ref> The increase in mechanical tension during resistance exercise will likely help stimulate the production of Insulin-like growth factors in the bone, but at a greater extent. Post-menopausal women experience a reduction of estrogen, which is essential for density, so these exercise-induced hormonal enhancements can counteract the loss of bone mineral density in the most critical area, like the lumbar spine and the femoral neck.<ref>{{Cite journal |title=Exercise for preventing and treating osteoporosis in postmenopausal women |url=https://www.cochrane.org/CD000333/MUSKEL_exercise-for-preventing-and-treating-osteoporosis-in-postmenopausal-women |access-date=2024-11-15 |journal=Cochrane Database of Systematic Reviews |date=2011 |doi=10.1002/14651858.CD000333.pub2 |language=en |pmid=21735380 | vauthors = Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G |issue=7 |pages=CD000333 }}</ref> Research suggest that regular resistance training accompanied with weight-bearing activities help reduce the progression of osteoporosis and risk of fracture. ==Management== ===Lifestyle Changes=== Weight-bearing endurance exercise and/or exercises to strengthen muscles improve bone strength in those with osteoporosis.<ref name=":Howe2011" /><ref name="pmid21360219">{{cite journal | vauthors = Body JJ, Bergmann P, Boonen S, Boutsen Y, Bruyere O, Devogelaer JP, Goemaere S, Hollevoet N, Kaufman JM, Milisen K, Rozenberg S, Reginster JY | title = Non-pharmacological management of osteoporosis: a consensus of the Belgian Bone Club | journal = Osteoporosis International | volume = 22 | issue = 11 | pages = 2769–2788 | date = November 2011 | pmid = 21360219 | pmc = 3186889 | doi = 10.1007/s00198-011-1545-x }}</ref> Aerobics, weight bearing, and resistance exercises all maintain or increase [[Bone mineral density|BMD]] in [[Menopause|postmenopausal]] women.<ref name=":Howe2011" /><ref name="Kanis-2019">{{cite journal | vauthors = Kanis JA, Cooper C, Rizzoli R, Reginster JY | title = European guidance for the diagnosis and management of osteoporosis in postmenopausal women | journal = Osteoporosis International | volume = 30 | issue = 1 | pages = 3–44 | date = January 2019 | pmid = 30324412 | pmc = 7026233 | doi = 10.1007/s00198-018-4704-5 }}</ref> Daily intake of calcium and vitamin D is recommended for postmenopausal women.<ref name="Kanis-2019" /> [[Fall prevention]] can help prevent osteoporosis complications. There is some evidence for [[hip protector]]s specifically among those who are in care homes.<ref name="pmid21478069">{{cite journal | vauthors = Kasturi GC, Adler RA | title = Osteoporosis: nonpharmacologic management | journal = PM&R | volume = 3 | issue = 6 | pages = 562–572 | date = June 2011 | pmid = 21478069 | doi = 10.1016/j.pmrj.2010.12.014 | s2cid = 45409462 | doi-access = free }}</ref> === Pharmacologic therapy === The US National Osteoporosis Foundation recommends pharmacologic treatment for patients with hip or spine fracture thought to be related to osteoporosis, those with BMD 2.5 SD or more below the young normal mean (T-score -2.5 or below), and those with BMD between 1 and 2.5 SD below normal mean whose 10-year risk, using FRAX, for hip fracture is equal or more than 3%.<ref>{{cite journal | vauthors = Watts NB | title = Postmenopausal Osteoporosis: A Clinical Review | journal = Journal of Women's Health | volume = 27 | issue = 9 | pages = 1093–1096 | date = September 2018 | pmid = 29583083 | doi = 10.1089/jwh.2017.6706 | s2cid = 4795899 }}</ref> <!--Secondary fracture prevention with bisphosphonates --> [[Bisphosphonate]]s are useful in decreasing the risk of future fractures in those who have already sustained a fracture due to osteoporosis.<ref name="Wells2008" /><ref name="Wells2008a" /><ref name="Review2011" /><ref name="Cheng">{{cite journal | vauthors = Cheng C, Wentworth K, Shoback DM | title = New Frontiers in Osteoporosis Therapy | journal = Annual Review of Medicine | volume = 71 | issue = 1 | pages = 277–288 | date = January 2020 | pmid = 31509477 | doi = 10.1146/annurev-med-052218-020620 | s2cid = 202564164 }}</ref> This benefit is present when taken for three to four years.<ref name="FDA2012">{{cite journal | vauthors = Whitaker M, Guo J, Kehoe T, Benson G | title = Bisphosphonates for osteoporosis--where do we go from here? | journal = The New England Journal of Medicine | volume = 366 | issue = 22 | pages = 2048–2051 | date = May 2012 | pmid = 22571168 | doi = 10.1056/NEJMp1202619 | s2cid = 27821662 | doi-access = free }}</ref><ref name="Ward-2007">{{cite journal | vauthors = Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, Rauch F, Tugwell P, Moher D | title = Bisphosphonate therapy for children and adolescents with secondary osteoporosis | journal = The Cochrane Database of Systematic Reviews | volume = 2010 | issue = 4 | pages = CD005324 | date = October 2007 | pmid = 17943849 | pmc = 8884163 | doi = 10.1002/14651858.cd005324.pub2 }}</ref> They do not appear to change the overall risk of death.<ref name="ABDTJAMA2019" /> Tentative evidence does not support the use of bisphosphonates as a standard treatment for secondary osteoporosis in children.<ref name="Ward-2007" /> Different bisphosphonates have not been directly compared, therefore it is unknown if one is better than another.<ref name="Review2011" /> Fracture risk reduction is between 25 and 70% depending on the bone involved.<ref name="Review2011" /> There are concerns of atypical femoral fractures and [[osteonecrosis of the jaw]] with long-term use, but these risks are low.<ref name="Review2011" /><ref>{{cite journal | vauthors = Suresh E, Pazianas M, Abrahamsen B | title = Safety issues with bisphosphonate therapy for osteoporosis | journal = Rheumatology | volume = 53 | issue = 1 | pages = 19–31 | date = January 2014 | pmid = 23838024 | doi = 10.1093/rheumatology/ket236 | doi-access = free }}</ref> With evidence of little benefit when used for more than three to five years and in light of the potential adverse events, it may be appropriate to stop treatment after this time.<ref name="FDA2012" /> One medical organization recommends that after five years of medications by mouth or three years of intravenous medication among those at low risk, bisphosphonate treatment can be stopped.<ref name="Ad2016" /><ref name="Qa2017" /> In those at higher risk they recommend up to ten years of medication by mouth or six years of intravenous treatment.<ref name="Ad2016">{{cite journal | vauthors = Adler RA, El-Hajj Fuleihan G, Bauer DC, Camacho PM, Clarke BL, Clines GA, Compston JE, Drake MT, Edwards BJ, Favus MJ, Greenspan SL, McKinney R, Pignolo RJ, Sellmeyer DE | title = Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research | journal = Journal of Bone and Mineral Research | volume = 31 | issue = 1 | pages = 16–35 | date = January 2016 | pmid = 26350171 | pmc = 4906542 | doi = 10.1002/jbmr.2708 }}</ref> The goal of osteoporosis management is to prevent osteoporotic fractures, but for those who have sustained one already it is more urgent to prevent a secondary fracture.<ref name="Shi 2594149">{{cite journal | vauthors = Shi L, Min N, Wang F, Xue QY | title = Bisphosphonates for Secondary Prevention of Osteoporotic Fractures: A Bayesian Network Meta-Analysis of Randomized Controlled Trials | journal = BioMed Research International | volume = 2019 | pages = 2594149 | date = 2019-11-19 | pmid = 31828096 | pmc = 6885847 | doi = 10.1155/2019/2594149 | doi-access = free }} [[File:CC-BY icon.svg|50px]] Text was copied from this source, which is available under a [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License].</ref> That is because patients with a fracture are more likely to experience a recurrent fracture, with marked increase in morbidity and mortality compared.<ref name="Shi 2594149"/> Among the five bisphosphonates, no significant differences were found for a secondary fracture for all fracture endpoints combined.<ref name="Shi 2594149"/> That being said, alendronate was identified as the most efficacious for secondary prevention of vertebral and hip fractures while zoledronate showed better performance for nonvertebral non-hip fracture prevention.<ref name="Shi 2594149"/> There is concern that many people do not receive appropriate [[pharmacological therapy]] after a low-impact fracture.<ref>{{cite journal |last1=Hopkins |first1=Ria E. |last2=Warner |first2=Victoria |last3=Sztal-Mazer |first3=Shoshana |last4=Poole |first4=Susan |last5=Page |first5=Amy |title=The assessment and pharmacological management of osteoporosis after admission for minimal-trauma fracture at a major metropolitan centre |journal=Journal of Pharmacy Practice and Research |date=December 2020 |volume=50 |issue=6 |pages=481–489 |doi=10.1002/jppr.1674 }}</ref> <!--Primary fracture prevention with bisphosphonates --> For those with osteoporosis but who have not had a fracture, evidence does not support a reduction in fracture risk with [[risedronate]]<ref name=Wells2008a/> or [[etidronate]].<ref name="Wells-2024" /> [[Alendronate]] decreases [[vertebral fractures|fractures of the spine]] but does not have any effect on other types of fractures.<ref name=Wells2008/> Half stop their medications within a year.<ref>{{cite journal |last1=Davis |first1=Stacy |last2=Sachdeva |first2=Alok |last3=Goeckeritz |first3=Bruce |last4=Oliver |first4=Alyce |title=Approved treatments for osteoporosis and what's in the pipeline |journal=Drug Benefit Trends |date=May 2010 |volume=22 |issue=4 |pages=121–124 }}</ref> When on treatment with bisphosphonates rechecking bone mineral density is not needed.<ref name=Qa2017/> There is tentative evidence of benefit in males with osteoporosis.<ref name=Males2017>{{cite journal | vauthors = Nayak S, Greenspan SL | title = Osteoporosis Treatment Efficacy for Men: A Systematic Review and Meta-Analysis | journal = Journal of the American Geriatrics Society | volume = 65 | issue = 3 | pages = 490–495 | date = March 2017 | pmid = 28304090 | pmc = 5358515 | doi = 10.1111/jgs.14668 }}</ref> <!--Fluoride --> Fluoride supplementation does not appear to be effective in postmenopausal osteoporosis, as even though it increases bone density, it does not decrease the risk of fractures.<ref>{{cite journal | vauthors = Haguenauer D, Welch V, Shea B, Tugwell P, Wells G | title = Fluoride for treating postmenopausal osteoporosis | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD002825 | date = 2000 | volume = 2010 | pmid = 11034769 | doi = 10.1002/14651858.CD002825 | pmc = 8453489 }}</ref><ref>{{cite journal | vauthors = Vestergaard P, Jorgensen NR, Schwarz P, Mosekilde L | s2cid = 25890845 | title = Effects of treatment with fluoride on bone mineral density and fracture risk--a meta-analysis | journal = Osteoporosis International | volume = 19 | issue = 3 | pages = 257–268 | date = March 2008 | pmid = 17701094 | doi = 10.1007/s00198-007-0437-6 }}</ref> <!--Other medications --> [[Teriparatide]] (a [[Recombinant DNA|recombinant]] parathyroid hormone) has been shown to be effective in treatment of women with postmenopausal osteoporosis.<ref>{{cite journal | vauthors = Han SL, Wan SL | title = Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta-analysis of randomised controlled trials | journal = International Journal of Clinical Practice | volume = 66 | issue = 2 | pages = 199–209 | date = February 2012 | pmid = 22257045 | doi = 10.1111/j.1742-1241.2011.02837.x | s2cid = 44529401 | doi-access = free }}</ref><ref name="Cheng"/> Some evidence also indicates [[strontium ranelate]] is effective in decreasing the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis.<ref>{{cite journal | vauthors = O'Donnell S, Cranney A, Wells GA, Adachi JD, Reginster JY | title = Strontium ranelate for preventing and treating postmenopausal osteoporosis | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD005326 | date = October 2006 | volume = 2006 | pmid = 17054253 | doi = 10.1002/14651858.CD005326.pub3 | pmc = 8092570 | veditors = Cranney A }}</ref> Hormone replacement therapy, while effective for osteoporosis, is only recommended in women who also have menopausal symptoms.<ref name=Review2011>{{cite journal | vauthors = Body JJ | title = How to manage postmenopausal osteoporosis? | journal = Acta Clinica Belgica | volume = 66 | issue = 6 | pages = 443–447 | year = 2011 | pmid = 22338309 | doi = 10.1179/ACB.66.6.2062612 }}</ref> It is not recommended for osteoporosis by itself.<ref name=Qa2017>{{cite journal | vauthors = Qaseem A, Forciea MA, McLean RM, Denberg TD | title = Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians | journal = Annals of Internal Medicine | volume = 166 | issue = 11 | pages = 818–839 | date = June 2017 | pmid = 28492856 | doi = 10.7326/M15-1361 | doi-access = free }}</ref> [[Raloxifene]], while effective in decreasing vertebral fractures, does not affect the risk of nonvertebral fracture.<ref name=Review2011/> And while it reduces the risk of [[breast cancer]], it increases the risk of [[venous thromboembolism|blood clots]] and [[stroke]]s.<ref name=Review2011/> While [[denosumab]] is effective at preventing fractures in women,<ref name=Review2011/> there is not clear evidence of benefit in males.<ref name=Males2017/> In hypogonadal men, testosterone has been shown to improve bone quantity and quality, but, as of 2008, no studies evaluated its effect on fracture risk or in men with normal testosterone levels.<ref name="OsteoporosisMen"/> [[Calcitonin]] while once recommended is no longer recommended due to the associated risk of [[cancer]] and questionable effect on fracture risk.<ref>{{cite web | title = Background Document for Meeting of Advisory Committee for Reproductive Health Drugs and Drug Safety and Risk Management Advisory Committee | url = https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM341779.pdf | publisher = FDA | date = Mar 2013 | url-status = live | archive-url = https://web.archive.org/web/20130609063058/https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM341779.pdf | archive-date = 9 June 2013 }}</ref> [[Alendronic acid/colecalciferol]] can be taken to treat this condition in post-menopausal women.<ref>{{cite web |title=Alendronic acid: medicine to treat and prevent osteoporosis |url=https://www.nhs.uk/medicines/alendronic-acid/ |website=National Health Service (UK) |access-date=8 March 2022 |language=en |date=24 August 2018}}</ref> [[Romosozumab]] (sold under the brand name Evenity) is a monoclonal antibody against [[sclerostin]]. Romosozumab is usually reserved for patients with very high fracture risk and is the only available drug therapy for osteoporosis that leads to simultaneous inhibition of [[bone resorption]] together with an anabolic effect.<ref>{{cite journal | vauthors = McClung MR, Rothman MS, Lewiecki EM, Hanley DA, Harris ST, Miller PD, Kendler DL | title = The role of osteoanabolic agents in the management of patients with osteoporosis | journal = Postgraduate Medicine | volume = 134 | issue = 6 | pages = 541–551 | date = August 2022 | pmid = 35635798 | doi = 10.1080/00325481.2022.2069582 | s2cid = 249200643 | doi-access = free }}</ref><ref>{{Cite web | author = Office of the Commissioner|date=2020-03-24 |title=FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture |url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-osteoporosis-postmenopausal-women-high-risk-fracture |access-date=2022-09-12 |website=FDA |language=en}}</ref> Certain medications like alendronate, etidronate, risedronate, raloxifene, and strontium ranelate can help to prevent osteoporotic fragility fractures in postmenopausal women with osteoporosis.<ref>{{cite web|title=Osteoporosis – primary prevention (TA160) : Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women|url=http://guidance.nice.org.uk/TA160|publisher=National Institute for Health and Care Excellence (NICE)|location=UK|date=January 2011|url-status=live|archive-url=https://web.archive.org/web/20131022170354/http://guidance.nice.org.uk/TA160|archive-date=22 October 2013}}</ref> Tentative evidence suggests that Chinese herbal medicines may have potential benefits on bone mineral density.<ref name = "Liu_2014">{{cite journal | vauthors = Liu Y, Liu JP, Xia Y | title = Chinese herbal medicines for treating osteoporosis | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD005467 | date = March 2014 | volume = 2014 | pmid = 24599707 | doi = 10.1002/14651858.cd005467.pub2 | pmc = 10638660 }}</ref> ==Prognosis== {| class="wikitable" style="float:right; margin-left:15px" |+ Hip fractures per 1000 person-years<ref name="pmid17846439">{{cite journal |vauthors=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=575–580 |year=2007 |pmid=17846439 |doi=10.1503/cmaj.070234 |pmc=1963365}}</ref> ! WHO category !! Age 50–64 !! Age > 64 || Overall |- | Normal || 5.3 || 9.4 || 6.6 |- | [[Osteopenia]] || 11.4 || 19.6 || 15.7 |- | Osteoporosis || 22.4 || 46.6 || 40.6 |} Although people with osteoporosis have increased mortality due to the complications of fracture, the fracture itself is rarely lethal. Hip fractures can lead to decreased mobility and additional risks of numerous complications (such as [[deep venous thrombosis]] and/or pulmonary embolism, and [[pneumonia]]). The six-month mortality rate for those aged 50 and above following hip fracture was found to be around 13.5%, with a substantial proportion (almost 13%) needing total assistance to mobilize after a hip fracture.<ref name="pmid11386929">{{cite journal |vauthors=Hannan EL, Magaziner J, Wang JJ, Eastwood EA, Silberzweig SB, Gilbert M, Morrison RS, McLaughlin MA, Orosz GM, Siu 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 = 2736–2742 | year = 2001 | pmid = 11386929 | doi = 10.1001/jama.285.21.2736 | doi-access = free }}</ref> 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 hunchback ([[kyphosis]]), the resulting pressure on internal organs can impair one's ability to breathe. Apart from risk of death and other complications, osteoporotic fractures are associated with a reduced health-related [[quality of life]].<ref>{{cite journal |vauthors=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=809–816 |year=2006 |pmid=16753011 |doi=10.1359/jbmr.060301|s2cid=24283913 |doi-access=free }}</ref> The condition is responsible for millions of fractures annually, mostly involving the lumbar vertebrae, hip, and wrist. Fragility fractures of ribs are also common in men. ===Fractures=== 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 |vauthors=Riggs BL, Melton LJ | title = The worldwide problem of osteoporosis: insights afforded by epidemiology | journal = Bone | volume = 17 | issue = 5 Suppl | pages = 505S–511S | year = 1995 | pmid = 8573428 | doi = 10.1016/8756-3282(95)00258-4 }}</ref> A 50-year-old white woman is estimated to have 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'/> Between 35 and 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 women aged 68.8 on average studied for 15 years, 324 had already sustained a vertebral fracture at entry into the study and 18.2% developed a vertebral fracture, but that risk rose to 41.4% in women who had a previous vertebral fracture.<ref name="pmid18165669">{{cite journal |vauthors=Cauley JA, Hochberg MC, Lui LY, Palermo L, Ensrud KE, Hillier TA, Nevitt MC, Cummings SR | title = Long-term risk of incident vertebral fractures | journal = JAMA | volume = 298 | issue = 23 | pages = 2761–2767 | year = 2007 | pmid = 18165669 | doi = 10.1001/jama.298.23.2761 | doi-access = free }}</ref> 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 |access-date=2008-06-13 |publisher=Merck & Co., Inc |archive-url = https://web.archive.org/web/20071228030929/http://www.merckmedicus.com/pp/us/hcp/diseasemodules/osteoporosis/epidemiology.jsp |archive-date = 28 December 2007}}</ref> [[Fragility fractures]] of the ribs are common in men as young as age 35.{{citation needed|date=October 2020}} These are often overlooked as signs of osteoporosis, as these men are often physically active and develop the fracture in the course of physical activity, such as falling while [[water skiing]] or jet skiing. ==Epidemiology== {{update|date=December 2020}} [[File:Hip fracture incidence world map.svg|thumb|upright=1.4|Age-standardised hip fracture rates in 2012.<ref name="Kanis 2239–2256"/>{{legend|green|Low (< 150 / 100 000)}}{{legend|orange|Medium (150–250 / 100 000)}}{{legend|red|High (> 250 / 100 000)}}]] Osteoporosis becomes more common with age, especially after 50 years (its [[prevalence]] rises from about 2% at 50 years to almost 50% by the age of 80).<ref name=cks-prevalence2023>{{cite web |title=Osteoporosis − prevention of fragility fractures: How common is it? |url=https://cks.nice.org.uk/topics/osteoporosis-prevention-of-fragility-fractures/background-information/prevalence/ |website=NICE |access-date=29 October 2024 |date=April 2023}}</ref> It affects women more than men due to the sharp fall in estrogen production that follows menopause.<ref name=cks-prevalence2023/> Globally, it is estimated that 21.2% of women and 6.3% of men over the age of 50 have osteoporosis, corresponding to a total of around 500 million people worldwide.<ref name=Found-epi2024>{{cite web |title=Epidemiology of osteoporosis and fragility fractures |url=https://www.osteoporosis.foundation/facts-statistics/epidemiology-of-osteoporosis-and-fragility-fractures |website=www.osteoporosis.foundation |publisher=[[International Osteoporosis Foundation]] |language=en |date=8 February 2024 |archive-url=https://web.archive.org/web/20240826190548/https://www.osteoporosis.foundation/facts-statistics/epidemiology-of-osteoporosis-and-fragility-fractures |archive-date=26 August 2024 |url-status=live}}</ref> About 15% of [[Caucasian race|Caucasians]] in their 50s and 70% of those over 80 are affected.<ref name=WHOEpi/> In the [[developed world]], depending on the method of diagnosis, 2% to 8% of males and 9% to 38% of females are affected.<ref name=Wade2014/> Rates of disease in the [[developing world]] are unclear.<ref name=Han2008/> From the age of 50 onwards, fractures (including hip fractures) are roughly twice as common in women than in men.<ref name=Clynes2020>{{cite journal |vauthors=Clynes MA, Harvey NC, Curtis EM, Fuggle NR, Dennison EM, Cooper C |title=The epidemiology of osteoporosis |journal=British Medical Bulletin |volume=133 |issue=1 |pages=105–117 |date=May 2020 |pmid=32282039 |pmc=7115830 |doi=10.1093/bmb/ldaa005 |url=}}</ref> A 60-year-old woman has a 44% chance of experiencing a fracture in her lifetime, whereas the lifetime risk for a 60-year-old man is only 25%.<ref name="Ji-2015" /> Such differences can be attributed to the increased risk of osteoporosis due to decreased estrogen levels following menopause.<ref name="Ji-2015">{{cite journal | vauthors = Ji MX, Yu Q | title = Primary osteoporosis in postmenopausal women | journal = Chronic Diseases and Translational Medicine | volume = 1 | issue = 1 | pages = 9–13 | date = March 2015 | pmid = 29062981 | pmc = 5643776 | doi = 10.1016/j.cdtm.2015.02.006 }}</ref> In 2019,<ref name=GBD2019>{{cite journal |vauthors=Wu AM |collaboration=GBD 2019 Fracture Collaborators |title=Global, regional, and national burden of bone fractures in 204 countries and territories, 1990-2019: a systematic analysis from the Global Burden of Disease Study 2019 |journal=The Lancet. Healthy Longevity |volume=2 |issue=9 |pages=e580–e592 |date=September 2021 |pmid=34723233 |pmc=8547262 |doi=10.1016/S2666-7568(21)00172-0 |url=}}</ref> up to 37 million fragility fractures linked to osteoporosis were thought to occur in people over the age of 55 worldwide.<ref name=Found-epi2024/> Globally, 1 in 3 women and 1 in 5 men over the age of 50 will have an osteoporotic fracture.<ref name=Found-epi2024/> Data from the United States shows a decrease in osteoporosis within the general population and in white women, from 18% in 1994 to 10% in 2006.<ref name="Cauley 1891–1899">{{cite journal | vauthors = Cauley JA | title = Defining ethnic and racial differences in osteoporosis and fragility fractures | journal = Clinical Orthopaedics and Related Research | volume = 469 | issue = 7 | pages = 1891–1899 | date = July 2011 | pmid = 21431462 | pmc = 3111798 | doi = 10.1007/s11999-011-1863-5 }}</ref> White and [[Asian people]] are at greater risk.<ref name="NIH2014" /> People of African descent are at a decreased risk of fractures due to osteoporosis, although they have the highest risk of death following an osteoporotic fracture.<ref name="Cauley 1891–1899"/> It has been shown that latitude affects risk of osteoporotic fracture.<ref name="Kanis 2239–2256">{{cite journal | vauthors = Kanis JA, Odén A, McCloskey EV, Johansson H, Wahl DA, Cooper C | title = A systematic review of hip fracture incidence and probability of fracture worldwide | journal = Osteoporosis International | volume = 23 | issue = 9 | pages = 2239–2256 | date = September 2012 | pmid = 22419370 | pmc = 3421108 | doi = 10.1007/s00198-012-1964-3 }}</ref> Areas of higher latitude such as Northern Europe receive less Vitamin D through sunlight compared to regions closer to the equator, and consequently have higher fracture rates in comparison to lower latitudes.<ref name="Kanis 2239–2256"/> For example, Swedish men and women have a 13% and 28.5% risk of hip fracture by age 50, respectively, whereas this risk is only 1.9% and 2.4% in Chinese men and women.<ref name="Cauley 1891–1899"/> Diet may also be a factor that is responsible for this difference, as vitamin D, calcium, magnesium, and folate are all linked to bone mineral density.<ref>{{cite journal | vauthors = Herrmann M, Peter Schmidt J, Umanskaya N, Wagner A, Taban-Shomal O, Widmann T, Colaianni G, Wildemann B, Herrmann W | title = The role of hyperhomocysteinemia as well as folate, vitamin B(6) and B(12) deficiencies in osteoporosis: a systematic review | journal = Clinical Chemistry and Laboratory Medicine | volume = 45 | issue = 12 | pages = 1621–1632 | year = 2007 | pmid = 18067447 | doi = 10.1515/cclm.2007.362 | s2cid = 7641257 }}</ref> There is also an association between Celiac Disease and increased risk of osteoporosis.<ref name="Prevalence of osteoporosis and oste">{{cite journal | vauthors = Ganji R, Moghbeli M, Sadeghi R, Bayat G, Ganji A | title = Prevalence of osteoporosis and osteopenia in men and premenopausal women with celiac disease: a systematic review | journal = Nutrition Journal | volume = 18 | issue = 1 | page = 9 | date = February 2019 | pmid = 30732599 | pmc = 6504166 | doi = 10.1186/s12937-019-0434-6 | doi-access = free }}</ref> In studies with premenopausal females and males, there was a correlation between Celiac Disease and osteoporosis and osteopenia.<ref name="Prevalence of osteoporosis and oste"/> Celiac Disease can decrease absorption of nutrients in the small intestine such as calcium, and a gluten-free diet can help people with Celiac Disease to revert to normal absorption in the gut.<ref>{{Cite web|url=https://www.bones.nih.gov/health-info/bone/osteoporosis/conditions-behaviors/celiac|title=What People With Celiac Disease Need To Know About Osteoporosis {{!}} NIH Osteoporosis and Related Bone Diseases National Resource Center|website=www.bones.nih.gov|access-date=2019-08-01}}</ref> About 22 million women and 5.5 million men in the [[European Union]] had osteoporosis in 2010.<ref name=Sve2013/> In the United States in 2010 about 8 million women and one to 2 million men had osteoporosis.<ref name=Wade2014/><ref name=Will2015/> This places a large economic burden on the healthcare system due to costs of treatment, long-term disability, and loss of productivity in the working population. The EU spends 37 billion euros per year in healthcare costs related to osteoporosis, and the US spends an estimated US$19 billion annually for related healthcare costs.<ref name="iofbonehealth.org">{{Cite web|title = The Global Burden of Osteoporosis {{!}} International Osteoporosis Foundation|url = http://www.iofbonehealth.org/data-publications/fact-sheets/global-burden-osteoporosis|website = www.iofbonehealth.org|access-date = 2016-02-09|url-status = live|archive-url = https://web.archive.org/web/20160305005414/http://www.iofbonehealth.org/data-publications/fact-sheets/global-burden-osteoporosis|archive-date = 5 March 2016}}</ref> ==History== Research on age-related reductions in bone density goes back to the early 1800s. French pathologist [[Jean Lobstein]] coined the term ''osteoporosis''.<ref name=Grob2014>{{cite book |last1=Grob |first1=Gerald N. |title=Aging Bones: A Short History of Osteoporosis |date=2014 |publisher=JHU Press |isbn=978-1-4214-1318-1 |page=5 }}</ref> The American endocrinologist [[Fuller Albright]] linked osteoporosis with the postmenopausal state.<ref>{{cite journal |vauthors=Albright F, Bloomberg E, Smith PH |year=1940 |title= Postmenopausal osteoporosis |journal=Trans. Assoc. Am. Physicians |volume=55 |pages=298–305}}</ref> [[Anthropologist]]s have studied skeletal remains that showed loss of bone density and associated structural changes that were linked to a chronic malnutrition in the agricultural area in which these individuals lived. "It follows that the skeletal deformation may be attributed to their heavy labor in agriculture as well as to their chronic malnutrition", causing the osteoporosis seen when radiographs of the remains were made.<ref>{{cite journal | vauthors = Hirata K, Morimoto I |title=Vertebral Osteoporosis in Late Edo Japanese |volume=102 |issue=4 |pages=345–361 |date=1994 |journal=Anthropological Science |doi=10.1537/ase.102.345 |doi-access=free }}</ref> == See also == {{Portal|Medicine|Biology}} * [[FRAX|Fracture Risk Assessment Tool (FRAX)]] * [[Spaceflight osteopenia]] * [[World Osteoporosis Day]] ==References== {{reflist}} == External links == * {{Commons-inline}} * [http://niams.nih.gov/Health_Info/Osteoporosis/default.asp Handout on Health: Osteoporosis] – US National Institute of Arthritis and Musculoskeletal and Skin Diseases * [http://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/ Osteoporosis] – l NIH Osteoporosis and Related Bone Diseases – National Resource Center * {{cite book | author = Office of the Surgeon General |title=Bone Health and Osteoporosis: A Report of the Surgeon General |date=2004 |publisher=[[U.S. Department of Health and Human Services]] |location=Rockville, MD |url=https://www.ncbi.nlm.nih.gov/books/NBK45513/ |access-date=18 July 2016 |pmid=20945569 |author1-link=Office of the Surgeon General}} * {{cite web | url = https://medlineplus.gov/osteoporosis.html | publisher = U.S. National Library of Medicine | work = MedlinePlus | title = Osteoporosis }} {{Medical resources | eMedicine_mult = {{eMedicine2|ped|1683}} {{eMedicine2|pmr|94}} {{eMedicine2|pmr|95}} | DiseasesDB = 9385 | ICD11 = {{ICD11|FB83.1}} | ICD10 = {{ICD10|M80}}–{{ICD10|M82}} | ICD9 = {{ICD9|733.0}} | OMIM = 166710 | MedlinePlus = 000360 | eMedicineSubj = med | eMedicineTopic = 1693 | MeshID = D010024 }} {{Osteochondropathy}} {{Authority control}} [[Category:Aging-associated diseases]] [[Category:Endocrine diseases]] [[Category:Osteopathies]] [[Category:Rheumatology]] [[Category:Wikipedia medicine articles ready to translate]] [[Category:Wikipedia emergency medicine articles ready to translate]]
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