Sections

Osteoporosis

Presentation

History

Keep in mind that osteoporosis occurs in many people who have few or no risk factors for this condition. Often, patients who have not sustained a fracture do not report symptoms that would alert the clinician to suspect a diagnosis of osteoporosis; thus, this disease is a "silent thief" that generally does not become clinically apparent until a fracture occurs.

Screening at-risk populations is, therefore, essential; unfortunately, many women do not receive proper screening or treatment for osteoporosis, which, in turn, may result in improper management of this disease and its related complications.^[104]For example, the presence of a disorder known to cause secondary osteoporosis—such as rheumatoid arthritis, celiac disease, or Crohn disease—should increase a clinician’s suspicion that the patient may have osteoporosis and that screening may be indicated.

Multiple risk factors exist for osteoporosis. The National Osteoporosis Foundation (NOF) has categorized these risk factors into two categories: nonmodifiable and modifiable. Nonmodifiable risk factors include the following:

Personal history of fracture as an adult
History of fracture in a first-degree relative
White race
Advanced age
Female sex
Dementia
Poor health or fragility

Potentially modifiable risk factors include the following:

Current cigarette smoking
Low body weight (< 127 lb)
Estrogen deficiency such as that caused by early menopause (age < 45 years) or bilateral ovariectomy and prolonged premenopausal amenorrhea (>1 year)
Low lifelong calcium intake
Alcoholism ^[74]
Impaired eyesight despite adequate correction
Recurrent falls
Inadequate physical activity
Poor health or frailty

Assessment of fracture risk

A thorough history should be obtained to screen for and identify the presence of known risk factors for osteoporosis and osteoporotic fracture. Specifically, the history should focus on the following^{[105, 106]}:

Age (> 50 years), sex (female), and race (white or Asian)^[105]; the US Preventive Services Task Force (USPSTF) recommendations include screening for osteoporosis in women aged 65 years or older and in younger women with a fracture risk that is the same or greater than that of a 65-year-old white woman who has no additional risk factors^[106]
Family history of osteoporosis, particularly maternal history of fractures
Reproductive factors, especially regarding early menopause and estrogen replacement therapy: postmenopausal women are at high risk, as are women who have undergone hysterectomy and oophorectomy
Hypogonadal states: men with hypogonadism secondary to any genetic or other conditions are at higher risk^[105]; the USPSTF notes that there is insufficient current evidence to assess the risk versus benefit of screening for osteoporosis in men^[106]
Smoking: smokers are at higher risk
Alcohol consumption
Low levels of physical activity: immobility increases the risk^[65]; spinal cord injury and stroke cause physical impairment and are common causes of immobility
Strenuous exercise that results in amenorrhea (such as that which occurs in marathon runners)
Calcium and vitamin D intake
History of low-trauma "fragility" fracture in patients aged 40 years or older: a fragility fracture is defined as a fracture due to trauma that would not normally cause fracture (a force equal to or less than that resulting from a fall from standing height)
Signs of vertebral fracture (see below)
Coexisting medical conditions associated with bone loss: examples are hyperparathyroidism, hypogonadism, leukemia, rheumatoid arthritis, celiac disease, and Cushing syndrome^[107]
Medications associated with bone loss: examples are glucocorticoids, cyclosporine, anticonvulsants, heparin, lithium, and tacrolimus^[107]
Risk factors for falls in older patients: these include poor balance, orthostatic hypotension, weakness of the lower extremity muscles and deconditioning, use of medications with sedative effects, poor vision or hearing, and cognitive impairment

FRAX tool

The USPSTF did not find any studies that assessed whether patient outcomes are affected by the use of risk prediction instruments, either alone or in combination with bone measurement tests. Nevertheless, there are many validated instruments for predicting the risk for low bone mineral density (BMD) in postmenopausal women; few of these, however, have been validated for use in men.^[106]

The Fracture Risk Assessment (FRAX) tool, accessible to healthcare providers and patients, is a validated instrument used to estimate 10-year risks for fractures, including those for black, Asian, and Hispanic women.^[94]A 65-year-old white woman with no other risk factors has a 9.3% 10-year risk for any osteoporotic fracture. Generally, estimated fracture risks in nonwhite women are lower than those for white women of the same age.

Examples of white women aged 50 to 64 years with ≥10-year fracture risks, based on specific risk factors, include the following^[106]:

A 50-year-old current smoker with a body mass index (BMI) less than 21 kg/m ², daily alcohol use, and parental fracture history
A 55-year-old woman with a parental fracture history
A 60-year-old woman with a BMI less than 21 kg/m ² and daily alcohol use
A 60-year-old current smoker with daily alcohol use

Differentiating fracture types by history

Patients with acute insufficiency fractures may report a history of minimal or no trauma resulting in pain. They may report a fall from a standing or sitting position. Patients with compression fractures resulting in thoracic kyphosis may report iliocostal friction with associated abdominal protrusion, decreased tolerance for oral intake, and breathing difficulties. Patients with hip, pelvic, or sacral fractures may report pain that is worsened with weight-bearing.

Patients who have sustained a vertebral compression fracture may note progressive kyphosis with loss of height. They may also present with an episode of acute back pain after bending, lifting, or coughing. It should be noted, however, that two thirds of vertebral fractures are asymptomatic.

With respect to those vertebral fractures that are painful, typical subjective information may include the following:

The episode of acute pain may follow a fall or minor trauma.
Pain is localized to a specific, identifiable, vertebral level in the midthoracic to lower thoracic or upper lumbar spine.
The pain is described variably as sharp, nagging, or dull; movement may exacerbate pain; in some cases, pain radiates to the abdomen.
Pain is often accompanied by paravertebral muscle spasms exacerbated by activity and decreased by lying supine.
Patients often remain motionless in bed because they are afraid of exacerbating the pain.
Acute pain usually resolves after 4-6 weeks; in the setting of multiple fractures with severe kyphosis, the pain may become chronic.

Patients who have sustained a hip fracture may experience the following:

Pain in the groin, posterior buttock, anterior thigh, medial thigh, and/or medial knee during weight-bearing or attempted weight-bearing of the involved extremity
Diminished hip range of motion (ROM), particularly internal rotation and flexion
External rotation of the involved hip while in the resting position

Patients with osteoporosis may report lactose intolerance or celiac sprue. Celiac sprue has been shown to be associated with osteoporosis in approximately 5% of cases.

Physical Examination

Patients with suspected osteoporosis should undergo a comprehensive physical examination. The physical examination should begin with an inspection of the patient. Height measurement with a stadiometer at each visit may be useful. Examination of active and passive range of motion (ROM) assists in determining whether spine, hip, wrist, or other osseous pathology may be present. A thorough neurologic examination is essential to rule out spinal cord and/or peripheral nerve compromise.

The examination may elicit pain, or the patient may be pain free. Thoracic kyphosis may be present secondary to vertebral compression fractures, a dowager hump, and a history of loss of height. Patients may have an associated scoliosis.

Areas of concern include the following:

A history of loss of height
Low body weight (body mass index < 19 kg/m ²)
Signs that might indicate existing osteoporosis (eg, kyphosis or dowager hump; point tenderness over a vertebra or other suspected fracture site)
Signs suggestive of secondary osteoporosis
Signs in older patients that may indicate increased fall risk (eg, difficulty with balance or gait, orthostatic hypotension, lower-extremity weakness, poor vision or hearing, cognitive impairment)

A 10-year longitudinal study assessed the Timed Up and Go (TUG) test performance (a validated predictor of falling) and hip area BMD (bone mineral density calculated using bone area as opposed to bone volume). Using data from 1126 women (mean age, 75 years), the study noted that risks of nonvertebral fracture and hip fracture were significantly higher in those who had slow TUG test performance and normal hip BMD or both slow TUG test performance and low hip BMD. These results suggest that the TUG test is an independent risk factor for incident nonvertebral fracture; this inexpensive physical assessment may be beneficial in screening patients at increased risk of fracture.^[108]

Signs of fracture

Patients with vertebral compression fractures may demonstrate a thoracic kyphosis with an exaggerated cervical lordosis (dowager hump). This is followed by a loss of lumbar lordosis. After each episode of vertebral compression fracture and progressive kyphosis, the patient's height may decrease by 2-3 cm.

Patients with acute vertebral fractures may have point tenderness over the involved vertebrae. Palpation of the spinous processes often does not aid the examiner in localizing point tenderness, but percussion may be helpful in acute or subacute vertebral compression fractures.

Patients with hip fractures may have severe pain with ambulation. A FABER (flexion in abduction and external rotation) hip joint test may reveal limited ROM with end-range pain. Patients with hip fractures may show decreased weight-bearing on the fractured side or an antalgic gait pattern.

Patients with pubic and sacral fractures may report marked pain with ambulation and tenderness to palpation, percussion, or both. Furthermore, patients with sacral fractures may have pain with physical examination techniques used to assess the sacroiliac joint, such as the FABER, Gaenslen, or squish test.

Fractures in other parts of the body, including the distal radius and humerus, are typically painful and result in limited range of motion of the involved joint.

Signs of collagen defects

Patients with osteoporosis may have physical findings consistent with subtle collagen defects. These include a short fifth digit, dentinogenesis imperfecta, hyperlaxity, hearing loss, pes planus, bunions, and blue sclerae.

Balance difficulties

Patients with osteoporosis are known to have decreased balance, possibly secondary to differences in balance control strategies and sway amplitude. Patients may have difficulty performing tandem gait and performing single limb stance. Poor balance may be noted particularly in patients with severe kyphosis resulting from vertebral compression fractures because their altered center of gravity makes ambulation with a stable base of support difficult for them.^[3]

Fractures are the most common and serious complication of osteoporosis. Patients with osteoporosis are at high risk for recurrent fractures of the hips, vertebrae, ribs, and wrists.

Screening in Men

Although routinely screening men for osteoporosis is not as widespread a practice as that of screening in women, the US Preventive Services Task Force (USPSTF) indicates that using bone measurement tests in men may not only help to detect this disease but also prevent its associated burden of fractures and fracture-related illness.^[109] Approximately 30% of all hip fractures occur in men and the mortality is higher in men than in women.

In weighing the risk versus benefit of screening men, clinicians should consider that osteoporosis is a preventable condition and that the potential harm in screening is likely to be small and mostly due to cost, such as that required to increase the number of dual-energy x-ray absorptiometry (DXA) scanners available for screening.^[109]In addition, assuming that the risk versus benefit of therapy for osteoporosis is similar for men and women, the men who are most likely to benefit from screening would be those with a 10-year risk for osteoporotic fracture that is equal to or greater than that for 65-year-old white women who have no additional risk factors.^[109]It is important to note, however, that there is insufficient current evidence for assessing the risk versus benefit of screening for osteoporosis in men.

The American College of Physicians (ACP) has similar recommendations for screening of osteoporosis in men, including periodic evaluation of risk factors in older men before age 65 years (particularly men who do not choose to be screened) and obtaining DXA for men at increased risk for the disease who are candidates for drug therapy.^[110]Risk factors for osteoporosis in men include the following^[110]:

Age older than 70 years
Low body weight (body mass index [BMI] < 20 to 25 kg/m ²)
Greater than 10% weight loss (relative to the usual young or adult weight or weight loss in recent years)
Physical inactivity
Corticosteroid use
Androgen deprivation therapy
Previous fragility fracture

Like the USPSTF, the ACP recommends further research to assess osteoporosis screening tests in men, to determine whether risk factors for osteoporosis in women also apply to men.^[110]

Osteoporosis in men should be treated. However, there has been less drug study for osteoporosis in men compared with that of women.^[111]Only zoledronic acid has been studied and has shown a risk reduction of new fractures. In a study of 1199 men with osteoporosis, treatment with zoledronic acid resulted in a 67% reduction in the risk of new vertebral fractures.^[111] Other medications use in the treatment of osteoporosis in men include risedronate, strontium ranelate, teriparatide, and denosumab.^[111]

Complications

Vertebral fractures from osteoporosis may lead to prolonged immobilization and medication use, which carry a range of complications.^[112]

Complications of prolonged immobilization include the following:

Deep venous thrombosis/pulmonary embolism
Infections
Pressure sores
Decreased muscle strength, 10-15% per week
Decreased bone mass
Cardiac effects - postural hypotension, decreased cardiac function
Gastrointestinal effects - constipation, fecal impaction
Neurosensory side effects - restlessness, anxiety, depression, fear, rapid mood changes, insomnia, hostility, pain intolerance, impaired intellectual and perceptual functioning

Complications of the medications used to relieve symptoms of vertebral fractures include the following:

Narcotics - constipation, somnolence, dependence
Nonsteroidal anti-inflammatory drugs (NSAIDs) - peptic ulcer disease, cardiovascular effects, kidney and liver effects, aspirin-exacerbated respiratory effects
Muscle relaxants - somnolence, dizziness, anticholinergic effects, weakness

Differential Diagnoses

Porter JL, Varacallo M. Osteoporosis. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].
Johnston CB, Dagar M. Osteoporosis in Older Adults. Med Clin North Am. 2020 Sep. 104 (5):873-884. [QxMD MEDLINE Link].
Lynn SG, Sinaki M, Westerlind KC. Balance characteristics of persons with osteoporosis. Arch Phys Med Rehabil. 1997 Mar. 78(3):273-7. [QxMD MEDLINE Link].
[Guideline] Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, et al. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014 Oct. 25 (10):2359-81. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Schousboe JT, Shepherd JA, Bilezikian JP, Baim S. Executive summary of the 2013 International Society for Clinical Densitometry Position Development Conference on bone densitometry. J Clin Densitom. 2013 Oct-Dec. 16(4):455-66. [QxMD MEDLINE Link].
Gosfield E 3rd, Bonner FJ Jr. Evaluating bone mineral density in osteoporosis. Am J Phys Med Rehabil. 2000 May-Jun. 79(3):283-91. [QxMD MEDLINE Link].
Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ 3rd, Khaltaev N. A reference standard for the description of osteoporosis. Bone. 2008 Mar. 42(3):467-75. [QxMD MEDLINE Link].
Silverman SL. Selecting patients for osteoporosis therapy. Ann N Y Acad Sci. 2007 Nov. 1117:264-72. [QxMD MEDLINE Link].
Czerwinski E, Badurski JE, Marcinowska-Suchowierska E, Osieleniec J. Current understanding of osteoporosis according to the position of the World Health Organization (WHO) and International Osteoporosis Foundation. Ortop Traumatol Rehabil. 2007 Jul-Aug. 9(4):337-56. [QxMD MEDLINE Link].
Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int. 1994 Nov. 4(6):368-81. [QxMD MEDLINE Link].
[Guideline] Camacho PM, Petak SM, Binkley N, Diab DL, Eldeiry LS, Farooki A, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis-2020 Update. Endocr Pract. 2020 May. 26 (Suppl 1):1-46. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Buckley L, Guyatt G, Fink HA, Cannon M, Grossman J, Hansen KE, et al. 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Care Res (Hoboken). 2017 Aug. 69 (8):1095-1110. [QxMD MEDLINE Link]. [Full Text].
Al Saedi A, Stupka N, Duque G. Pathogenesis of Osteoporosis. Handb Exp Pharmacol. 2020 Apr 16. 115(12):3318-25. [QxMD MEDLINE Link].
Majumdar SR, Lier DA, Beaupre LA, Hanley DA, Maksymowych WP, Juby AG, et al. Osteoporosis case manager for patients with hip fractures: results of a cost-effectiveness analysis conducted alongside a randomized trial. Arch Intern Med. 2009 Jan 12. 169(1):25-31. [QxMD MEDLINE Link].
Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, et al. Clinician's Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int. 2014 Oct. 25 (10):2359-81. [QxMD MEDLINE Link].
Maybury K. Strengthening Communication on Bone Health. Gallup. Available at http://www.gallup.com/poll/5851/Strengthening-Communication-Bone-Health.aspx?g_source=osteoporosis&g_medium=search&g_campaign=tiles. April 23, 2002; Accessed: December 20, 2022.
Haas AV, LeBoff MS. Osteoanabolic Agents for Osteoporosis. J Endocr Soc. 2018 Aug 1. 2 (8):922-932. [QxMD MEDLINE Link].
World Health Organization. WHO scientific group on the assessment of osteoporosis at primary health care level: summary meeting report. Available at http://www.who.int/chp/topics/Osteoporosis.pdf. 2007; Accessed: January 21, 2021.
Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. 2008 Nov. 3 Suppl 3:S131-9. [QxMD MEDLINE Link].
Bono CM, Einhorn TA. Overview of osteoporosis: pathophysiology and determinants of bone strength. Eur Spine J. 2003 Oct. 12 Suppl 2:S90-6. [QxMD MEDLINE Link].
Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med. 2006 May 25. 354(21):2250-61. [QxMD MEDLINE Link].
S Tanaka, K Nakamura, N Takahas. Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system. Immunol Rev. 2005. 208:30-49. [Full Text].
Mora S, Gilsanz V. Establishment of peak bone mass. Endocrinol Metab Clin North Am. 2003 Mar. 32(1):39-63. [QxMD MEDLINE Link].
Föger-Samwald U, Dovjak P, Azizi-Semrad U, Kerschan-Schindl K, Pietschmann P. Osteoporosis: Pathophysiology and therapeutic options. EXCLI J. 2020. 19:1017-1037. [QxMD MEDLINE Link].
Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. 2005 Dec. 115 (12):3318-25. [QxMD MEDLINE Link].
Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, et al. Increased osteoclast development after estrogen loss: mediation by interleukin-6. Science. 1992 Jul 3. 257(5066):88-91. [QxMD MEDLINE Link].
Föger-Samwald U, Dovjak P, Azizi-Semrad U, Kerschan-Schindl K, Pietschmann P. Osteoporosis: Pathophysiology and therapeutic options. EXCLI J. 2020. 19:1017-1037. [QxMD MEDLINE Link].
Cline-Smith A, Axelbaum A, Shashkova E, Chakraborty M, Sanford J, Panesar P, et al. Ovariectomy Activates Chronic Low-Grade Inflammation Mediated by Memory T Cells, Which Promotes Osteoporosis in Mice. J Bone Miner Res. 2020 Jun. 35 (6):1174-1187. [QxMD MEDLINE Link].
Demontiero O, Vidal C, Duque G. Aging and bone loss: new insights for the clinician. Ther Adv Musculoskelet Dis. 2012 Apr. 4 (2):61-76. [QxMD MEDLINE Link].
Warriner AH, Patkar NM, Curtis JR, Delzell E, Gary L, Kilgore M, et al. Which fractures are most attributable to osteoporosis?. J Clin Epidemiol. 2011 Jan. 64 (1):46-53. [QxMD MEDLINE Link].
Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002 May 18. 359(9319):1761-7. [QxMD MEDLINE Link].
Rosen CJ, Tenenhouse A. Biochemical markers of bone turnover. A look at laboratory tests that reflect bone status. Postgrad Med. Oct 1998. 104(4):101-2, 107-10.
Nusse R. Wnt signaling in disease and in development. Cell Res. 2005 Jan. 15(1):28-32. [QxMD MEDLINE Link].
Ling L, Nurcombe V, Cool SM. Wnt signaling controls the fate of mesenchymal stem cells. Gene. 2009 Mar 15. 433(1-2):1-7. [QxMD MEDLINE Link].
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2. 284(5411):143-7. [QxMD MEDLINE Link].
Rao TP, Kühl M. An updated overview on Wnt signaling pathways: a prelude for more. Circ Res. 2010 Jun 25. 106(12):1798-806. [QxMD MEDLINE Link].
Clevers H, Nusse R. Wnt/ß-catenin signaling and disease. Cell. 2012 Jun 8. 149(6):1192-205. [QxMD MEDLINE Link].
Krishnan V, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. 2006 May. 116(5):1202-9. [QxMD MEDLINE Link]. [Full Text].
Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, et al. High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med. 2002 May 16. 346(20):1513-21. [QxMD MEDLINE Link].
Van Wesenbeeck L, Cleiren E, Gram J, Beals RK, Bénichou O, Scopelliti D, et al. Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet. 2003 Mar. 72(3):763-71. [QxMD MEDLINE Link]. [Full Text].
Levasseur R, Lacombe D, de Vernejoul MC. LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. Joint Bone Spine. 2005 May. 72(3):207-14. [QxMD MEDLINE Link].
Zhu Y, Sun Z, Han Q, Liao L, Wang J, Bian C, et al. Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia. 2009 May. 23(5):925-33. [QxMD MEDLINE Link].
Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci. 2003 Jul 1. 116:2627-34. [QxMD MEDLINE Link].
Kaiser M, Mieth M, Liebisch P, Oberländer R, Rademacher J, Jakob C, et al. Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma. Eur J Haematol. 2008 Jun. 80(6):490-4. [QxMD MEDLINE Link].
Tai N, Inoue D. [Anti-Dickkopf1 (Dkk1) antibody as a bone anabolic agent for the treatment of osteoporosis]. Clin Calcium. 2014 Jan. 24 (1):75-83. [QxMD MEDLINE Link].
Bonewald LF. The amazing osteocyte. J Bone Miner Res. 2011 Feb. 26(2):229-38. [QxMD MEDLINE Link]. [Full Text].
Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem. 2005 May 20. 280(20):19883-7. [QxMD MEDLINE Link].
FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture. U.S. Food & Drug Administration. Available at https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-osteoporosis-postmenopausal-women-high-risk-fracture. April 09, 2019; Accessed: January 21, 2021.
Ringe JD, Farahmand P. Advances in the management of corticosteroid-induced osteoporosis with bisphosphonates. Clin Rheumatol. 2007 Apr. 26(4):474-84. [QxMD MEDLINE Link].
Dennison EM, Syddall HE, Sayer AA, Gilbody HJ, Cooper C. Birth weight and weight at 1 year are independent determinants of bone mass in the seventh decade: the Hertfordshire cohort study. Pediatr Res. 2005 Apr. 57(4):582-6. [QxMD MEDLINE Link].
Fall C, Hindmarsh P, Dennison E, Kellingray S, Barker D, Cooper C. Programming of growth hormone secretion and bone mineral density in elderly men: a hypothesis. J Clin Endocrinol Metab. 1998 Jan. 83(1):135-9. [QxMD MEDLINE Link].
Marini F, Cianferotti L, Brandi ML. Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?. Int J Mol Sci. 2016 Aug 12. 17 (8):[QxMD MEDLINE Link].
Colangelo L, Biamonte F, Pepe J, Cipriani C, Minisola S. Understanding and managing secondary osteoporosis. Expert Rev Endocrinol Metab. 2019 Mar. 14 (2):111-122. [QxMD MEDLINE Link].
Kelman A, Lane NE. The management of secondary osteoporosis. Best Pract Res Clin Rheumatol. 2005 Dec. 19(6):1021-37. [QxMD MEDLINE Link].
Adams JS, Song CF, Kantorovich V. Rapid recovery of bone mass in hypercalciuric, osteoporotic men treated with hydrochlorothiazide. Ann Intern Med. 1999 Apr 20. 130(8):658-60. [QxMD MEDLINE Link].
Mann GB, Kang YC, Brand C, Ebeling PR, Miller JA. Secondary causes of low bone mass in patients with breast cancer: a need for greater vigilance. J Clin Oncol. 2009 Aug 1. 27(22):3605-10. [QxMD MEDLINE Link].
Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19. 357(3):266-81. [QxMD MEDLINE Link].
di Munno O, Mazzantini M, Sinigaglia L, Bianchi G, Minisola G, Muratore M, et al. Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter cross-sectional study. J Rheumatol. 2004 Jul. 31(7):1305-9. [QxMD MEDLINE Link].
Migliaccio S, Brama M, Malavolta N. Management of glucocorticoids-induced osteoporosis: role of teriparatide. Ther Clin Risk Manag. 2009 Apr. 5(2):305-10. [QxMD MEDLINE Link]. [Full Text].
van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002 Oct. 13(10):777-87. [QxMD MEDLINE Link].
Licata AA. Challenges of Estimating Fracture Risk with DXA: Changing Concepts About Bone Strength and Bone Density. Aerosp Med Hum Perform. 2015 Jul. 86 (7):628-32. [QxMD MEDLINE Link].
Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994. 843:1-129. [QxMD MEDLINE Link].
Lyles KW, Schenck AP, Colón-Emeric CS. Hip and other osteoporotic fractures increase the risk of subsequent fractures in nursing home residents. Osteoporos Int. 2008 Aug. 19(8):1225-33. [QxMD MEDLINE Link]. [Full Text].
Fink HA, Kuskowski MA, Taylor BC, Schousboe JT, Orwoll ES, Ensrud KE. Association of Parkinson's disease with accelerated bone loss, fractures and mortality in older men: the Osteoporotic Fractures in Men (MrOS) study. Osteoporos Int. 2008 Sep. 19(9):1277-82. [QxMD MEDLINE Link].
Sinaki M. Exercise and osteoporosis. Arch Phys Med Rehabil. 1989 Mar. 70(3):220-9. [QxMD MEDLINE Link].
Yaturu S, DjeDjos S, Alferos G, Deprisco C. Bone mineral density changes on androgen deprivation therapy for prostate cancer and response to antiresorptive therapy. Prostate Cancer Prostatic Dis. 2006. 9(1):35-8. [QxMD MEDLINE Link].
Busko M. Chemical in Toothpaste Tied to Osteoporosis in Women. Medscape Medical News. Available at https://www.medscape.com/viewarticle/914888. June 26, 2019; Accessed: June 27, 2019.
Hansen D, Bazell C, Pelizzari P, Pyenson B. Medicare cost of osteoporotic fractures: The clinical and cost burden of an important consequence of osteoporosis. Available at https://static1.squarespace.com/static/5c0860aff793924efe2230f3/t/5d76b949deb7e9086ee3d7dd/1568061771769/Medicare+Cost+of+Osteoporotic+Fractures+20190827.pdf. August 2019; Accessed: January 21, 2021.
Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992 Nov. 2(6):285-9. [QxMD MEDLINE Link].
Who are candidates for prevention and treatment for osteoporosis?. Osteoporos Int. 1997. 7(1):1-6. [QxMD MEDLINE Link].
Jensen GF, Christiansen C, Boesen J, Hegedüs V, Transbøl I. Epidemiology of postmenopausal spinal and long bone fractures. A unifying approach to postmenopausal osteoporosis. Clin Orthop Relat Res. 1982 Jun. 75-81. [QxMD MEDLINE Link].
Melton LJ 3rd, Kan SH, Frye MA, Wahner HW, O'Fallon WM, Riggs BL. Epidemiology of vertebral fractures in women. Am J Epidemiol. 1989 May. 129(5):1000-11. [QxMD MEDLINE Link].
Smith R, Wordsworth P. Osteoporosis. Clinical and Biochemical Disorders of the Skeleton. 2005. 123.
Chon KS, Sartoris DJ, Brown SA, Clopton P. Alcoholism-associated spinal and femoral bone loss in abstinent male alcoholics, as measured by dual X-ray absorptiometry. Skeletal Radiol. 1992. 21(7):431-6. [QxMD MEDLINE Link].
Robbins J, Aragaki AK, Kooperberg C, Watts N, Wactawski-Wende J, Jackson RD, et al. Factors associated with 5-year risk of hip fracture in postmenopausal women. JAMA. 2007 Nov 28. 298(20):2389-98. [QxMD MEDLINE Link].
Bass MA, Sharma A, Nahar VK, Chelf S, Zeller B, Pham L, et al. Bone Mineral Density Among Men and Women Aged 35 to 50 Years. J Am Osteopath Assoc. 2019 Jun 1. 119 (6):357-363. [QxMD MEDLINE Link]. [Full Text].
Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ. 2003. 81(9):646-56. [QxMD MEDLINE Link]. [Full Text].
Balfour F. China’s "Demographic Tsunami." Bloomberg Businessweek. January 5, 2012. Available at http://www.businessweek.com/magazine/chinas-demographic-tsunami-01052012.html. Accessed: February 16, 2012.
Morin SN, Lix LM, Majumdar SR, Leslie WD. Temporal trends in the incidence of osteoporotic fractures. Curr Osteoporos Rep. 2013 Dec. 11(4):263-9. [QxMD MEDLINE Link].
Melton LJ 3rd, Sampson JM, Morrey BF, Ilstrup DM. Epidemiologic features of pelvic fractures. Clin Orthop Relat Res. 1981 Mar-Apr. 43-7. [QxMD MEDLINE Link].
Cauley JA, Lui LY, Ensrud KE, Zmuda JM, Stone KL, Hochberg MC, et al. Bone mineral density and the risk of incident nonspinal fractures in black and white women. JAMA. 2005 May 4. 293(17):2102-8. [QxMD MEDLINE Link].
Bone Health and Osteoporosis: A Report of the Surgeon General. Washington, DC: Department of Health and Human Services; 2004. [Full Text].
Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007 Mar. 22(3):465-75. [QxMD MEDLINE Link].
Ensrud KE, Kats AM, Boyd CM, Diem SJ, Schousboe JT, Taylor BC, et al. Association of Disease Definition, Comorbidity Burden, and Prognosis With Hip Fracture Probability Among Late-Life Women. JAMA Intern Med. 2019 Jun 17. [QxMD MEDLINE Link].
Sharon Chou, MD, Anjali Grover, MD, and Meryl S LeBoff, MD. New Osteoporotic/Vertebral Compression Fractures. Available at https://www.ncbi.nlm.nih.gov/books/NBK279035/. 09/19/18; Accessed: December 9 , 2022.
Cooper C, Atkinson EJ, Jacobsen SJ, et al. Population-based study of survival after osteoporotic fractures. Am J Epidemiol. 1993 May 1. 137(9):1001-5. [QxMD MEDLINE Link].
Kado DM, Browner WS, Palermo L, Nevitt MC, Genant HK, Cummings SR. Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med. 1999 Jun 14. 159(11):1215-20. [QxMD MEDLINE Link].
Vestergaard P, Rejnmark L, Mosekilde L. Increased mortality in patients with a hip fracture-effect of pre-morbid conditions and post-fracture complications. Osteoporos Int. 2007 Dec. 18(12):1583-93. [QxMD MEDLINE Link].
Trombetti A, Herrmann F, Hoffmeyer P, Schurch MA, Bonjour JP, Rizzoli R. Survival and potential years of life lost after hip fracture in men and age-matched women. Osteoporos Int. 2002 Sep. 13(9):731-7. [QxMD MEDLINE Link].
Michel JP, Hoffmeyer P, Klopfenstein C, et al. Prognosis of functional recovery 1 year after hip fracture: typical patient profiles through cluster analysis. J Gerontol A Biol Sci Med Sci. 2000 Sep. 55(9):M508-15. [QxMD MEDLINE Link].
Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA. 2001 Jan 17. 285(3):320-3. [QxMD MEDLINE Link].
Klotzbuecher CM, Ross PD, Landsman PB, et al. Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res. 2000 Apr. 15(4):721-39. [QxMD MEDLINE Link].
Morin SN, Lix LM, Leslie WD. The importance of previous fracture site on osteoporosis diagnosis and incident fractures in women. J Bone Miner Res. 2014 Jul. 29(7):1675-80. [QxMD MEDLINE Link].
FRAX Fracture Risk Assessment Tool. Available at http://www.shef.ac.uk/FRAX/. Accessed: December 9, 2022.
Leslie WD, Morin S, Lix LM. Before-and-After Study of Fracture Risk Reporting and Osteoporosis Treatment Initiation. Ann Intern Med. Nov 2 2010. 153(9):580-6.
Schwartz AV, Vittinghoff E, Bauer DC, et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA. 2011 Jun 1. 305(21):2184-92. [QxMD MEDLINE Link].
Tremollieres FA, Pouilles JM, Drewniak N, Laparra J, Ribot CA, Dargent-Molina P. Fracture risk prediction using BMD and clinical risk factors in early postmenopausal women: sensitivity of the WHO FRAX tool. J Bone Miner Res. 2010 May. 25(5):1002-9. [QxMD MEDLINE Link]. [Full Text].
Grisso JA, Kelsey JL, Strom BL, Chiu GY, Maislin G, O'Brien LA, et al. Risk factors for falls as a cause of hip fracture in women. The Northeast Hip Fracture Study Group. N Engl J Med. 1991 May 9. 324(19):1326-31. [QxMD MEDLINE Link].
Nellans KW, Kowalski E, Chung KC. The epidemiology of distal radius fractures. Hand Clin. 2012 May. 28(2):113-25. [QxMD MEDLINE Link]. [Full Text].
Sandhu SK, Nguyen ND, Center JR, Pocock NA, Eisman JA, Nguyen TV. Prognosis of fracture: evaluation of predictive accuracy of the FRAX algorithm and Garvan nomogram. Osteoporos Int. 2010 May. 21(5):863-71. [QxMD MEDLINE Link].
Kanis JA, Harvey NC, Johansson H, Odén A, McCloskey EV, Leslie WD. Overview of Fracture Prediction Tools. J Clin Densitom. 2017 Jul - Sep. 20 (3):444-450. [QxMD MEDLINE Link].
Cooper C, Atkinson EJ, O'Fallon WM, et al. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985-1989. J Bone Miner Res. 1992 Feb. 7(2):221-7. [QxMD MEDLINE Link].
Cook DJ, Guyatt GH, Adachi JD, Clifton J, Griffith LE, Epstein RS, et al. Quality of life issues in women with vertebral fractures due to osteoporosis. Arthritis Rheum. 1993 Jun. 36(6):750-6. [QxMD MEDLINE Link].
Schnatz PF, Marakovits KA, Dubois M, O'Sullivan DM. Osteoporosis screening and treatment guidelines: are they being followed?. Menopause. 2011 Oct. 18(10):1072-8. [QxMD MEDLINE Link].
Geusens P, Dumitrescu B, van Geel T, van Helden S, Vanhoof J, Dinant GJ. Impact of systematic implementation of a clinical case finding strategy on diagnosis and therapy of postmenopausal osteoporosis. J Bone Miner Res. 2008 Jun. 23(6):812-8. [QxMD MEDLINE Link].
[Guideline] Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med. 2011 Mar 1. 154(5):356-64. [QxMD MEDLINE Link].
Bone Health and Osteoporosis: A Report of the Surgeon General. [Full Text].
Zhu K, Devine A, Lewis JR, Dhaliwal SS, Prince RL. Timed up and go test and bone mineral density measurement for fracture prediction. Arch Intern Med. 2011 Oct 10. 171(18):1655-61. [QxMD MEDLINE Link].
Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women. Ann Intern Med. 2011 Dec 6. 155(11):751-61. [QxMD MEDLINE Link].
[Guideline] Liu H, Paige NM, Goldzweig CL, Wong E, Zhou A, Suttorp MJ, et al. Screening for osteoporosis in men: a systematic review for an American College of Physicians guideline. Ann Intern Med. 2008 May 6. 148(9):685-701. [QxMD MEDLINE Link]. [Full Text].
Spiegel R, Nawroth PP, Kasperk C. The effect of zoledronic acid on the fracture risk in men with osteoporosis. J Endocrinol Invest. 2014 Mar. 37 (3):229-32. [QxMD MEDLINE Link].
Dittmer DK, Teasell R. Complications of immobilization and bed rest. Part 1: Musculoskeletal and cardiovascular complications. Can Fam Physician. 1993 Jun. 39:1428-32, 1435-7. [QxMD MEDLINE Link].
Guglielmi G, Muscarella S, Bazzocchi A. Integrated imaging approach to osteoporosis: state-of-the-art review and update. Radiographics. 2011 Sep-Oct. 31(5):1343-64. [QxMD MEDLINE Link].
Khoo BC, Brown K, Cann C, et al. Comparison of QCT-derived and DXA-derived areal bone mineral density and T scores. Osteoporos Int. 2009 Sep. 20(9):1539-45. [QxMD MEDLINE Link].
Link TM. Axial and peripheral QCT. Guglielmi G, ed. Osteoporosis and Bone Densitometry Measurements. New York, NY: Springer Heidelberg; 2013. 123-32.
Beaudoin C, Moore L, Gagné M, Bessette L, Ste-Marie LG, Brown JP, et al. Performance of predictive tools to identify individuals at risk of non-traumatic fracture: a systematic review, meta-analysis, and meta-regression. Osteoporos Int. 2019 Apr. 30 (4):721-740. [QxMD MEDLINE Link].
Paunier L. Effect of magnesium on phosphorus and calcium metabolism. Monatsschr Kinderheilkd. 1992 Sep. 140(9 Suppl 1):S17-20. [QxMD MEDLINE Link].
Lee WY, Oh KW, Rhee EJ, Jung CH, Kim SW, Yun EJ, et al. Relationship between subclinical thyroid dysfunction and femoral neck bone mineral density in women. Arch Med Res. 2006 May. 37(4):511-6. [QxMD MEDLINE Link].
Tannenbaum C, Clark J, Schwartzman K, Wallenstein S, Lapinski R, Meier D. Yield of laboratory testing to identify secondary contributors to osteoporosis in otherwise healthy women. J Clin Endocrinol Metab. 2002 Oct. 87(10):4431-7. [QxMD MEDLINE Link].
Liu JM, Zhao HY, Ning G, Chen Y, Zhang LZ, Sun LH, et al. IGF-1 as an early marker for low bone mass or osteoporosis in premenopausal and postmenopausal women. J Bone Miner Metab. 2008. 26(2):159-64. [QxMD MEDLINE Link].
Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med. 2011 Aug. 49 (8):1271-4. [QxMD MEDLINE Link].
Resnick D, Kransdorf M. Osteoporosis. Bone and Joint Imaging. Third Edition. 2005. 551.
Hillier TA, Stone KL, Bauer DC, Rizzo JH, Pedula KL, Cauley JA, et al. Evaluating the value of repeat bone mineral density measurement and prediction of fractures in older women: the study of osteoporotic fractures. Arch Intern Med. 2007 Jan 22. 167(2):155-60. [QxMD MEDLINE Link].
Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women. Ann Intern Med. 2011 Dec 6. 155(11):751-61. [QxMD MEDLINE Link]. [Full Text].
Lin JT, Lane JM. Bisphosphonates. J Am Acad Orthop Surg. 2003 Jan-Feb. 11(1):1-4. [QxMD MEDLINE Link].
Faulkner KG, Wacker WK, Barden HS, Simonelli C, Burke PK, Ragi S, et al. Femur strength index predicts hip fracture independent of bone density and hip axis length. Osteoporos Int. 2006. 17(4):593-9. [QxMD MEDLINE Link].
Prevrhal S, Shepherd JA, Faulkner KG, Gaither KW, Black DM, Lang TF. Comparison of DXA hip structural analysis with volumetric QCT. J Clin Densitom. 2008 Apr-Jun. 11(2):232-6. [QxMD MEDLINE Link].
Kaptoge S, Beck TJ, Reeve J, Stone KL, Hillier TA, Cauley JA, et al. Prediction of incident hip fracture risk by femur geometry variables measured by hip structural analysis in the study of osteoporotic fractures. J Bone Miner Res. 2008 Dec. 23(12):1892-904. [QxMD MEDLINE Link]. [Full Text].
Beck TJ. Extending DXA beyond bone mineral density: understanding hip structure analysis. Curr Osteoporos Rep. 2007 Jun. 5(2):49-55. [QxMD MEDLINE Link].
Hans D, Barthe N, Boutroy S, Pothuaud L, Winzenrieth R, Krieg MA. Correlations between trabecular bone score, measured using anteroposterior dual-energy X-ray absorptiometry acquisition, and 3-dimensional parameters of bone microarchitecture: an experimental study on human cadaver vertebrae. J Clin Densitom. 2011 Jul-Sep. 14(3):302-12. [QxMD MEDLINE Link].
Pothuaud L, Barthe N, Krieg MA, Mehsen N, Carceller P, Hans D. Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study. J Clin Densitom. 2009 Apr-Jun. 12(2):170-6. [QxMD MEDLINE Link].
Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N, et al. Trabecular bone score: a noninvasive analytical method based upon the DXA image. J Bone Miner Res. 2014 Mar. 29(3):518-30. [QxMD MEDLINE Link].
Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, et al. Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone. 2004 Jan. 34(1):195-202. [QxMD MEDLINE Link].
Imai K. Recent methods for assessing osteoporosis and fracture risk. Recent Pat Endocr Metab Immune Drug Discov. 2014 Jan. 8(1):48-59. [QxMD MEDLINE Link].
Yang L, Palermo L, Black DM, Eastell R. Prediction of incident hip fracture with the estimated femoral strength by finite element analysis of DXA Scans in the study of osteoporotic fractures. J Bone Miner Res. 2014 Dec. 29(12):2594-600. [QxMD MEDLINE Link].
Torres-del-Pliego E, Vilaplana L, Güerri-Fernández R, Diez-Pérez A. Measuring bone quality. Curr Rheumatol Rep. 2013 Nov. 15(11):373. [QxMD MEDLINE Link].
Kulkarni AG, Thonangi Y, Pathan S, Gunjotikar S, Goparaju P, Talwar I, et al. Should Q-CT Be the Gold Standard for Detecting Spinal Osteoporosis?. Spine (Phila Pa 1976). 2022 Mar 15. 47 (6):E258-E264. [QxMD MEDLINE Link].
Prior JC, Vigna YM, Wark JD, et al. Premenopausal ovariectomy-related bone loss: a randomized, double-blind, one-year trial of conjugated estrogen or medroxyprogesterone acetate. J Bone Miner Res. 1997 Nov. 12(11):1851-63. [QxMD MEDLINE Link].
Henzell S, Dhaliwal S, Pontifex R, et al. Precision error of fan-beam dual X-ray absorptiometry scans at the spine, hip, and forearm. J Clin Densitom. 2000 Winter. 3(4):359-64. [QxMD MEDLINE Link].
White J, Harris SS, Dallal GE, Dawson-Hughes B. Precision of single vs bilateral hip bone mineral density scans. J Clin Densitom. 2003 Summer. 6(2):159-62. [QxMD MEDLINE Link].
Bauer JS, Henning TD, Müeller D, Lu Y, Majumdar S, Link TM. Volumetric quantitative CT of the spine and hip derived from contrast-enhanced MDCT: conversion factors. AJR Am J Roentgenol. 2007 May. 188(5):1294-301. [QxMD MEDLINE Link].
Engelke K, Adams JE, Armbrecht G, et al. Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD Official Positions. J Clin Densitom. 2008 Jan-Mar. 11(1):123-62. [QxMD MEDLINE Link].
Liu G, Peacock M, Eilam O, Dorulla G, Braunstein E, Johnston CC. Effect of osteoarthritis in the lumbar spine and hip on bone mineral density and diagnosis of osteoporosis in elderly men and women. Osteoporos Int. 1997. 7(6):564-9. [QxMD MEDLINE Link].
[Guideline] Qaseem A, Forciea MA, McLean RM, Denberg TD, for the Clinical Guidelines Committee of the American College of Physicians. 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. Ann Intern Med. 9 May 2017. [Full Text].
Fribourg D, Tang C, Sra P, Delamarter R, Bae H. Incidence of subsequent vertebral fracture after kyphoplasty. Spine (Phila Pa 1976). 2004 Oct 15. 29(20):2270-6; discussion 2277. [QxMD MEDLINE Link].
Movrin I, Vengust R, Komadina R. Adjacent vertebral fractures after percutaneous vertebral augmentation of osteoporotic vertebral compression fracture: a comparison of balloon kyphoplasty and vertebroplasty. Arch Orthop Trauma Surg. 2010 Sep. 130(9):1157-66. [QxMD MEDLINE Link].
Kastner M, Straus SE. Clinical decision support tools for osteoporosis disease management: a systematic review of randomized controlled trials. J Gen Intern Med. 2008 Dec. 23(12):2095-105. [QxMD MEDLINE Link]. [Full Text].
Knopp JA, Diner BM, Blitz M, Lyritis GP, Rowe BH. Calcitonin for treating acute pain of osteoporotic vertebral compression fractures: a systematic review of randomized, controlled trials. Osteoporos Int. 2005 Oct. 16 (10):1281-90. [QxMD MEDLINE Link].
Kirshblum SC. Rehabilitation Medicine: Principles and Practice. DeLisa JA, Gans BM. Spinal and upper extremity orthotics. 3rd. Philadelphia, Pa: Lippincott-Raven; 1998. 635-50.
Stillo JV. Low back orthoses. Phys Med Rehab Clin North Am. 1992. 3:57-94.
[Guideline] Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019 May 1. 104 (5):1595-1622. [QxMD MEDLINE Link].
Gertz BJ, Holland SD, Kline WF, Matuszewski BK, Freeman A, Quan H, et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther. 1995 Sep. 58 (3):288-98. [QxMD MEDLINE Link].
Abrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med. 2011 Jun 13. 171(11):998-1004. [QxMD MEDLINE Link].
Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA. 1999 Oct 13. 282 (14):1344-52. [QxMD MEDLINE Link]. [Full Text].
Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007 May 3. 356(18):1809-22. [QxMD MEDLINE Link].
Boonen S, Reginster JY, Kaufman JM, Lippuner K, Zanchetta J, Langdahl B, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012 Nov. 367(18):1714-23. [QxMD MEDLINE Link].
Boonen S, Orwoll E, Magaziner J, Colón-Emeric CS, Adachi JD, Bucci-Rechtweg C, et al. Once-yearly zoledronic acid in older men compared with women with recent hip fracture. J Am Geriatr Soc. 2011 Nov. 59(11):2084-90. [QxMD MEDLINE Link].
Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005 Mar. 90(3):1294-301. [QxMD MEDLINE Link].
Halasy-Nagy JM, Rodan GA, Reszka AA. Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis. Bone. 2001 Dec. 29(6):553-9. [QxMD MEDLINE Link].
US Food and Drug Administration. FDA drug safety communication: New contraindication and updated warning on kidney impairment for Reclast (zoledronic acid). Available at http://www.fda.gov/Drugs/DrugSafety/ucm270199.htm. September 1, 2011; Accessed: June 19, 2019.
Safety Information: Zometa (zoledronic acid) for injection. U.S. Food and Drug Administration. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021817s022lbl.pdf. April 2016; Accessed: June 15, 2019.
Khan AA, Morrison A, Hanley DA, Felsenberg D, McCauley LK, et al, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015 Jan. 30 (1):3-23. [QxMD MEDLINE Link].
Strampel W, Emkey R, Civitelli R. Safety considerations with bisphosphonates for the treatment of osteoporosis. Drug Saf. 2007. 30(9):755-63. [QxMD MEDLINE Link].
Zebic L, Patel V. Preventing medication-related osteonecrosis of the jaw. BMJ. 2019 May 8. 365:l1733. [QxMD MEDLINE Link].
Park-Wyllie LY, Mamdani MM, Juurlink DN, Hawker GA, Gunraj N, Austin PC, et al. Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women. JAMA. 2011 Feb 23. 305(8):783-9. [QxMD MEDLINE Link].
Lo JC, Neugebauer RS, Ettinger B, Chandra M, Hui RL, Ott SM, et al. Risk of complete atypical femur fracture with Oral bisphosphonate exposure beyond three years. BMC Musculoskelet Disord. 2020 Dec 3. 21 (1):801. [QxMD MEDLINE Link].
Geusens P. Bisphosphonates for postmenopausal osteoporosis: determining duration of treatment. Curr Osteoporos Rep. 2009 Mar. 7(1):12-7. [QxMD MEDLINE Link].
[Guideline] Adler RA, El-Hajj Fuleihan G, Bauer DC, Camacho PM, Clarke BL, Clines GA, et al. Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016 Jan. 31 (1):16-35. [QxMD MEDLINE Link]. [Full Text].
Grady D, Cauley JA, Stock JL, Cox DA, Mitlak BH, Song J, et al. Effect of Raloxifene on all-cause mortality. Am J Med. 2010 May. 123(5):469.e1-7. [QxMD MEDLINE Link].
Lindsay R, Gallagher JC, Kagan R, Pickar JH, Constantine G. Efficacy of tissue-selective estrogen complex of bazedoxifene/conjugated estrogens for osteoporosis prevention in at-risk postmenopausal women. Fertil Steril. 2009 Sep. 92(3):1045-52. [QxMD MEDLINE Link].
Gilsenan A, Harris D, Reynolds M, McSorley D, Midkiff K, Jackson L, et al. Long-term cancer surveillance: results from the Forteo Patient Registry Surveillance Study. Osteoporos Int. 2020 Nov 5. [QxMD MEDLINE Link].
Quattrocchi E, Kourlas H. Teriparatide: a review. Clin Ther. 2004 Jun. 26(6):841-54. [QxMD MEDLINE Link].
Koski AM, Sikiö A, Forslund T. Teriparatide treatment complicated by malignant myeloma. BMJ Case Rep. 2010 Aug 13. 2010:[QxMD MEDLINE Link]. [Full Text].
Body JJ, Gaich GA, Scheele WH, Kulkarni PM, Miller PD, Peretz A. A randomized double-blind trial to compare the efficacy of teriparatide [recombinant human parathyroid hormone (1-34)] with alendronate in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2002 Oct. 87(10):4528-35. [QxMD MEDLINE Link].
Dempster DW, Cosman F, Kurland ES, Zhou H, Nieves J, Woelfert L, et al. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J Bone Miner Res. 2001 Oct. 16(10):1846-53. [QxMD MEDLINE Link].
Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10. 344(19):1434-41. [QxMD MEDLINE Link].
Kurland ES, Heller SL, Diamond B, McMahon DJ, Cosman F, Bilezikian JP. The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1-34)]. Osteoporos Int. 2004 Dec. 15(12):992-7. [QxMD MEDLINE Link].
Finkelstein JS, Hayes A, Hunzelman JL, Wyland JJ, Lee H, Neer RM. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med. 2003 Sep 25. 349(13):1216-26. [QxMD MEDLINE Link].
Cosman F, Nieves J, Zion M, Woelfert L, Luckey M, Lindsay R. Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med. 2005 Aug 11. 353(6):566-75. [QxMD MEDLINE Link].
Deal C, Omizo M, Schwartz EN, Eriksen EF, Cantor P, Wang J, et al. Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial. J Bone Miner Res. 2005 Nov. 20(11):1905-11. [QxMD MEDLINE Link].
Ste-Marie LG, Schwartz SL, Hossain A, Desaiah D, Gaich GA. Effect of teriparatide [rhPTH(1-34)] on BMD when given to postmenopausal women receiving hormone replacement therapy. J Bone Miner Res. 2006 Feb. 21(2):283-91. [QxMD MEDLINE Link].
Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet. 2013 Jul 6. 382(9886):50-6. [QxMD MEDLINE Link].
Leder BZ, Tsai JN, Uihlein AV, Wallace PM, Lee H, Neer RM, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. 2015 Sep 19. 386 (9999):1147-55. [QxMD MEDLINE Link].
Bouxsein ML, Chen P, Glass EV, Kallmes DF, Delmas PD, Mitlak BH. Teriparatide and raloxifene reduce the risk of new adjacent vertebral fractures in postmenopausal women with osteoporosis. Results from two randomized controlled trials. J Bone Joint Surg Am. 2009 Jun. 91(6):1329-38. [QxMD MEDLINE Link].
Kendler DL, Marin F, Zerbini CAF, Russo LA, Greenspan SL, Zikan V, et al. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet. 2017 Nov 9. [QxMD MEDLINE Link].
Gomberg SJ, Wustrack RL, Napoli N, Arnaud CD, Black DM. Teriparatide, vitamin D, and calcium healed bilateral subtrochanteric stress fractures in a postmenopausal woman with a 13-year history of continuous alendronate therapy. J Clin Endocrinol Metab. 2011 Jun. 96(6):1627-32. [QxMD MEDLINE Link].
Saleh A, Hegde VV, Potty AG, Schneider R, Cornell CN, Lane JM. Management strategy for symptomatic bisphosphonate-associated incomplete atypical femoral fractures. HSS J. 2012 Jul. 8(2):103-10. [QxMD MEDLINE Link]. [Full Text].
Lau AN, Adachi JD. Resolution of osteonecrosis of the jaw after teriparatide [recombinant human PTH-(1-34)] therapy. J Rheumatol. 2009 Aug. 36(8):1835-7. [QxMD MEDLINE Link].
Cheung A, Seeman E. Teriparatide therapy for alendronate-associated osteonecrosis of the jaw. N Engl J Med. 2010 Dec 16. 363(25):2473-4. [QxMD MEDLINE Link].
Narongroeknawin P, Danila MI, Humphreys LG Jr, Barasch A, Curtis JR. Bisphosphonate-associated osteonecrosis of the jaw, with healing after teriparatide: a review of the literature and a case report. Spec Care Dentist. 2010 Mar-Apr. 30(2):77-82. [QxMD MEDLINE Link]. [Full Text].
Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016 Aug 16. 316 (7):722-33. [QxMD MEDLINE Link]. [Full Text].
Cosman F, Miller PD, Williams GC, Hattersley G, Hu MY, Valter I, et al. Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend Trial. Mayo Clin Proc. 2017 Feb. 92 (2):200-210. [QxMD MEDLINE Link]. [Full Text].
Czerwinski E, Cardona J, Plebanski R, Recknor C, Vokes T, Saag KG, et al. The Efficacy and Safety of Abaloparatide-SC in Men With Osteoporosis: A Randomized Clinical Trial. J Bone Miner Res. 2022 Dec. 37 (12):2435-2442. [QxMD MEDLINE Link]. [Full Text].
Peichl P, Holzer LA, Maier R, Holzer G. Parathyroid hormone 1-84 accelerates fracture-healing in pubic bones of elderly osteoporotic women. J Bone Joint Surg Am. 2011 Sep 7. 93(17):1583-7. [QxMD MEDLINE Link].
Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016 Sep 18. [QxMD MEDLINE Link]. [Full Text].
Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12. 377 (15):1417-1427. [QxMD MEDLINE Link]. [Full Text].
Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, Ebeling PR, Adachi JD, Miyauchi A, et al. One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study. J Bone Miner Res. 2019 Mar. 34 (3):419-428. [QxMD MEDLINE Link].
Lewiecki EM, Blicharski T, Goemaere S, Lippuner K, Meisner PD, Miller PD, et al. A Phase III Randomized Placebo-Controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis. J Clin Endocrinol Metab. 2018 Sep 1. 103 (9):3183-3193. [QxMD MEDLINE Link].
Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12. 377 (15):1417-1427. [QxMD MEDLINE Link].
Body JJ, Facon T, Coleman RE, Lipton A, Geurs F, Fan M, et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res. 2006 Feb 15. 12(4):1221-8. [QxMD MEDLINE Link].
McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006 Feb 23. 354(8):821-31. [QxMD MEDLINE Link].
Orwoll E, Teglbjærg CS, Langdahl BL, Chapurlat R, Czerwinski E, Kendler DL, et al. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab. 2012 Sep. 97(9):3161-9. [QxMD MEDLINE Link].
Block GA, Bone HG, Fang L, Lee E, Padhi D. A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res. 2012 Jul. 27(7):1471-9. [QxMD MEDLINE Link]. [Full Text].
Saag KG, Wagman RB, Geusens P, Adachi JD, Messina OD, Emkey R, et al. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. 2018 Apr 6. [QxMD MEDLINE Link].
Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20. 361(8):756-65. [QxMD MEDLINE Link].
Smith MR, Egerdie B, Hernández Toriz N, Feldman R, Tammela TL, Saad F, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009 Aug 20. 361(8):745-55. [QxMD MEDLINE Link].
Lyu H, Jundi B, Xu C, Tedeschi SK, Yoshida K, Zhao S, et al. Comparison of Denosumab and Bisphosphonates in Patients With Osteoporosis: A Meta-Analysis of Randomized Controlled Trials. J Clin Endocrinol Metab. 2019 May 1. 104 (5):1753-1765. [QxMD MEDLINE Link].
Schwarz EM, Ritchlin CT. Clinical development of anti-RANKL therapy. Arthritis Res Ther. 2007. 9 Suppl 1:S7. [QxMD MEDLINE Link]. [Full Text].
Tsai JN, Uihlein AV, Lee H, Kumbhani R, Siwila-Sackman E, McKay EA, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet. 2013 May 14. [QxMD MEDLINE Link].
Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O. Clinical Features of 24 Patients With Rebound-Associated Vertebral Fractures After Denosumab Discontinuation: Systematic Review and Additional Cases. J Bone Miner Res. 2017 Jun. 32 (6):1291-1296. [QxMD MEDLINE Link].
Postmarket Drug Safety Information for Patients and Providers-Questions and Answers: Changes to the Indicated Population for Miacalcin (calcitonin-salmon). U.S. Food and Drug Administration. Available at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm388641.htm. September 1, 2015; Accessed: January 21, 2021.
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002 Jul 17. 288(3):321-33. [QxMD MEDLINE Link].
Blake GM, Fogelman I. Long-term effect of strontium ranelate treatment on BMD. J Bone Miner Res. 2005 Nov. 20(11):1901-4. [QxMD MEDLINE Link].
Burlet N, Reginster JY. Strontium ranelate: the first dual acting treatment for postmenopausal osteoporosis. Clin Orthop Relat Res. 2006 Feb. 443:55-60. [QxMD MEDLINE Link].
Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, et al. Effect of Vitamin D on falls: a meta-analysis. JAMA. 2004 Apr 28. 291(16):1999-2006. [QxMD MEDLINE Link].
Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011 Jan. 96(1):53-8. [QxMD MEDLINE Link]. [Full Text].
Bruni V, Dei M, Filicetti MF, Balzi D, Pasqua A. Predictors of bone loss in young women with restrictive eating disorders. Pediatr Endocrinol Rev. 2006 Jan. 3 Suppl 1:219-21. [QxMD MEDLINE Link].
Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007 Aug 25. 370(9588):657-66. [QxMD MEDLINE Link].
Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009 Mar 23. 169(6):551-61. [QxMD MEDLINE Link].
Warensjö E, Byberg L, Melhus H, et al. Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study. BMJ. 2011 May 24. 342:d1473. [QxMD MEDLINE Link]. [Full Text].
DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ. 2010 Jan 12. 340:b5463. [QxMD MEDLINE Link]. [Full Text].
Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart. 2012 Jun. 98(12):920-5. [QxMD MEDLINE Link].
Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med. 1997 Apr 1. 126(7):497-504. [QxMD MEDLINE Link].
Candelas G, Martinez-Lopez JA, Rosario MP, Carmona L, Loza E. Calcium supplementation and kidney stone risk in osteoporosis: a systematic literature review. Clin Exp Rheumatol. 2012 Nov-Dec. 30(6):954-61. [QxMD MEDLINE Link].
Favus MJ. The risk of kidney stone formation: the form of calcium matters. Am J Clin Nutr. 2011 Jul. 94(1):5-6. [QxMD MEDLINE Link].
Sinaki M. Postmenopausal spinal osteoporosis: physical therapy and rehabilitation principles. Mayo Clin Proc. 1982 Nov. 57(11):699-703. [QxMD MEDLINE Link].
Tinetti ME, Speechley M. Prevention of falls among the elderly. N Engl J Med. 1989 Apr 20. 320(16):1055-9. [QxMD MEDLINE Link].
Sinaki M, Mikkelsen BA. Postmenopausal spinal osteoporosis: flexion versus extension exercises. Arch Phys Med Rehabil. 1984 Oct. 65(10):593-6. [QxMD MEDLINE Link].
Sinaki M, Itoi E, Wahner HW, Wollan P, Gelzcer R, Mullan BP, et al. Stronger back muscles reduce the incidence of vertebral fractures: a prospective 10 year follow-up of postmenopausal women. Bone. 2002 Jun. 30(6):836-41. [QxMD MEDLINE Link].
Sinaki M, Itoi E, Rogers JW, Bergstralh EJ, Wahner HW. Correlation of back extensor strength with thoracic kyphosis and lumbar lordosis in estrogen-deficient women. Am J Phys Med Rehabil. 1996 Sep-Oct. 75(5):370-4. [QxMD MEDLINE Link].
Chien MY, Wu YT, Hsu AT, Yang RS, Lai JS. Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal women. Calcif Tissue Int. 2000 Dec. 67(6):443-8. [QxMD MEDLINE Link].
Snow CM, Shaw JM, Winters KM, Witzke KA. Long-term exercise using weighted vests prevents hip bone loss in postmenopausal women. J Gerontol A Biol Sci Med Sci. 2000 Sep. 55(9):M489-91. [QxMD MEDLINE Link].
Howe TE, Shea B, Dawson LJ, et al. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev. 2011 Jul 6. CD000333. [QxMD MEDLINE Link].
Iwamoto J, Takeda T, Ichimura S. Effect of exercise training and detraining on bone mineral density in postmenopausal women with osteoporosis. J Orthop Sci. 2001. 6(2):128-32. [QxMD MEDLINE Link].
Kerschan-Shindl K, Uher E, Kainberger F, Kaider A, Ghanem AH, Preisinger E. Long-term home exercise program: effect in women at high risk of fracture. Arch Phys Med Rehabil. 2000 Mar. 81(3):319-23. [QxMD MEDLINE Link].
Robertson MC, Devlin N, Gardner MM, Campbell AJ. Effectiveness and economic evaluation of a nurse delivered home exercise programme to prevent falls. 1: Randomised controlled trial. BMJ. 2001 Mar 24. 322(7288):697-701. [QxMD MEDLINE Link]. [Full Text].
Walker M, Klentrou P, Chow R, Plyley M. Longitudinal evaluation of supervised versus unsupervised exercise programs for the treatment of osteoporosis. Eur J Appl Physiol. 2000 Nov. 83(4 -5):349-55. [QxMD MEDLINE Link].
Wolf SL, Barnhart HX, Kutner NG, McNeely E, Coogler C, Xu T. Reducing frailty and falls in older persons: an investigation of Tai Chi and computerized balance training. Atlanta FICSIT Group. Frailty and Injuries: Cooperative Studies of Intervention Techniques. J Am Geriatr Soc. 1996 May. 44(5):489-97. [QxMD MEDLINE Link].
Carter ND, Khan KM, Petit MA, Heinonen A, Waterman C, Donaldson MG, et al. Results of a 10 week community based strength and balance training programme to reduce fall risk factors: a randomised controlled trial in 65-75 year old women with osteoporosis. Br J Sports Med. 2001 Oct. 35(5):348-51. [QxMD MEDLINE Link]. [Full Text].
Riggs BL, Melton LJ 3rd. The prevention and treatment of osteoporosis. N Engl J Med. 1992 Aug 27. 327(9):620-7. [QxMD MEDLINE Link].
Iwamoto J, Sato Y, Uzawa M, Takeda T, Matsumoto H. Comparison of effects of alendronate and raloxifene on lumbar bone mineral density, bone turnover, and lipid metabolism in elderly women with osteoporosis. Yonsei Med J. 2008 Feb 29. 49(1):119-28. [QxMD MEDLINE Link]. [Full Text].
Gourlay ML, Fine JP, Preisser JS, May RC, Li C, Lui LY, et al. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012 Jan 19. 366(3):225-33. [QxMD MEDLINE Link]. [Full Text].
Schwab P, Klein RF. Nonpharmacological approaches to improve bone health and reduce osteoporosis. Curr Opin Rheumatol. 2008 Mar. 20(2):213-7. [QxMD MEDLINE Link].
Lin JT, Lane JM. Nonmedical management of osteoporosis. Curr Opin Rheumatol. 2002 Jul. 14(4):441-6. [QxMD MEDLINE Link].
Gourlay ML, Fine JP, Preisser JS, May RC, Li C, Lui LY, et al. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012 Jan 19. 366(3):225-33. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Viswanathan M, Reddy S, Berkman N, Cullen K, Middleton JC, Nicholson WK, et al. Screening to Prevent Osteoporotic Fractures: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018 Jun 26. 319 (24):2532-2551. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Updates to the Clinician’s Guide to the Prevention and Treatment of Osteoporosis. National Osteoporosis Foundation. Available at https://my.nof.org/bone-source/Incorporation-of-diagnostic-criteria-to-be-used-to-establish-a-clinical-diagnosis-of-osteoporosis. November 11, 2015; Accessed: January 21, 2021.
[Guideline] Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019 Mar 25. [QxMD MEDLINE Link]. [Full Text].
NIH Consensus conference. Optimal calcium intake. NIH Consensus Development Panel on Optimal Calcium Intake. JAMA. 1994 Dec 28. 272(24):1942-8. [QxMD MEDLINE Link].

Media Gallery

Osteoporosis. Lateral radiograph demonstrates multiple osteoporotic vertebral compression fractures. Kyphoplasty has been performed at one level.
Osteoporosis. Lateral radiograph of the patient seen in the previous image following kyphoplasty performed at 3 additional levels.
Osteoporosis of the spine. Observe the considerable reduction in overall vertebral bone density and note the lateral wedge fracture of L2.
Osteoporosis of the spine. Note the lateral wedge fracture in L3 and the central burst fracture in L5. The patient had suffered a recent fall.
Normal femoral anatomy.
Stable intertrochanteric fracture of the femur.
Percutaneous vertebroplasty, transpedicular approach.
Asymmetric loss in vertebral body height, without evidence of an acute fracture, can develop in patients with osteoporosis. These patients become progressively kyphotic (as shown) over time, and the characteristic hunched-over posture of severe osteoporosis develops eventually.
In kyphoplasty, a KyphX inflatable bone tamp is percutaneously advanced into the collapsed vertebral body (A). It is then inflated, (B) elevating the depressed endplate, creating a central cavity, and compacting the remaining trabeculae to the periphery. Once the balloon tamp is deflated and withdrawn, the cavity (C) is filled under low pressure with a viscous preparation of methylmethacrylate (D).
Osteoporosis is defined as a loss of bone mass below the threshold of fracture. This slide (methylmethacrylate embedded and stained with Masson's trichrome) demonstrates the loss of connected trabecular bone.
The bone loss of osteoporosis can be severe enough to create separate bone "buttons" with no connection to the surrounding bone. This easily leads to insufficiency fractures.
Inactive osteoporosis is the most common form and manifests itself without active osteoid formation.
Osteoporosis that is active contains osteoid seams (red here in the Masson's trichrome).
Woven bone arising directly from surrounding mesenchymal tissue.
This image depicts bone remodeling with osteoclasts resorbing one side of a bony trabecula and osteoblasts depositing new bone on the other side.
Osteoclast, with bone below it. This image shows typical distinguishing characteristics of an osteoclast: a large cell with multiple nuclei and a "foamy" cytosol.
In this image, several osteoblasts display a prominent Golgi apparatus and are actively synthesizing osteoid. Two osteocytes can also be seen.
Severe osteoporosis. This radiograph shows multiple vertebral crush fractures. Source: Government of Western Australia Department of Health.
Lateral spine radiograph depicting osteoporotic wedge fractures of L1-L2. Source: Wikimedia Commons.
Dual-energy computed tomography (CT) scan in a patient with involutional osteoporosis. Insufficiency fractures of the sacrum and the pubic rami are seen on an isotopic bone scan as a characteristic H, or Honda, sign (arrows), which appears as intense radiopharmaceutical uptake at the fracture sites.
Schematic example of an early bone densitometer: the QDR-1000 System (spine scan). (From: Third National Health and Nutrition Examination Survey Bone Densitometry Manual. Rockville, Md: Westat, Inc; 1989 [revised].)
Bone density scanner. This machine measures bone density to check for osteoporosis in the elderly and other vulnerable subjects. Source: Wikimedia Commons.
Example of a dual energy x-ray absorption (DXA) scan. This image is of the left hip bone. Source: Government of Western Australia Department of Health.
Example of a dual energy x-ray absorption (DXA) scan. This image is of the lumbar spine. Source: Government of Western Australia Department of Health.

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Table 1. WHO Definition of Osteoporosis Based on BMD Measurements by DXA

Definition	Bone Mineral Density Measurement	T-Score
Normal	BMD within 1 SD of the mean bone density for young adult women	T-score ≥ –1
Low bone mass (osteopenia)	BMD 1–2.5 SD below the mean for young adult women	T-score between –1 and –2.5
Osteoporosis	BMD ≥2.5 SD below the normal mean for young-adult women	T-score ≤ –2.5
Severe or “established” osteoporosis	BMD ≥2.5 SD below the normal mean for young-adult women in a patient who has already experienced ≥1 fracture	T-score ≤ –2.5 (with fragility fracture[s])
Sources: (1) World Health Organization (WHO). WHO scientific group on the assessment of osteoporosis at primary health care level: summary meeting report. Available at: https://www.who.int/chp/topics/Osteoporosis.pdf. Accessed August 21, 2020^[18] (2) Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int. Nov 1994;4(6):368-81.^[10] (3) Czerwinski E, Badurski JE, Marcinowska-Suchowierska E, Osieleniec J. Current understanding of osteoporosis according to the position of the World Health Organization (WHO) and International Osteoporosis Foundation. Ortop Traumatol Rehabil. Jul-Aug 2007;9(4):337-56.^[9] BMD = bone mineral density; DXA = dual x-ray absorptiometry; SD = standard deviation; T-score = a measurement expressed in SD units from a given mean that is equal to a patient's BMD measured by DXA minus the value in a young healthy person, divided by the SD measurement in the population.

Table 2. Types of Primary Osteoporosis

Type of Primary Osteoporosis	Characteristics
Juvenile osteoporosis	Usually occurs in children or young adults of both sexes Normal gonadal function Age of onset: usually 8-14 years Hallmark characteristic: abrupt bone pain and/or a fracture following trauma
Idiopathic osteoporosis
Postmenopausal osteoporosis (type I osteoporosis)	Occurs in women with estrogen deficiency Characterized by a phase of accelerated bone loss, primarily from trabecular bone Fractures of the distal forearm and vertebral bodies common
Age-associated or senile osteoporosis (type II osteoporosis)	Occurs in women and men as BMD gradually declines with aging Represents bone loss associated with aging Fractures occur in cortical and trabecular bone Wrist, vertebral, and hip fractures often seen

Table 3. Causes of Secondary Osteoporosis in Adults

Cause	Examples
Genetic/congenital	Renal hypercalciuria – one of the most important secondary causes of osteoporosis; can be treated with thiazide diuretics Cystic fibrosis Ehlers-Danlos syndrome Glycogen storage disease Gaucher disease Marfan syndrome Menkes steely hair syndrome Riley-Day syndrome Osteogenesis imperfecta Hemochromatosis Homocystinuria Idiopathic hypercalciuria Hypogonadal states
Hypogonadal states	Androgen insensitivity Anorexia nervosa/bulimia nervosa Female athlete triad Hyperprolactinemia Panhypopituitarism Premature menopause Turner syndrome Klinefelter syndrome
Endocrine disorders^[56]	Cushing syndrome Diabetes mellitus Acromegaly Adrenal insufficiency Estrogen deficiency Growth hormone deficiency Hypercortisolism Hyperparathyroidism Hyperthyroidism Hypogonadism Hypophosphatasia Pregnancy Porphyria Prolactinoma
Deficiency states and malabsorption syndromes	Alcoholism Anorexia nervosa Calcium deficiency Magnesium deficiency Protein deficiency Vitamin D deficiency^{[56, 57]} Bariatric surgery Celiac disease Cystic fibrosis Gastrectomy Malnutrition Parenteral nutrition Chronic liver disease
Inflammatory diseases	Inflammatory bowel disease/Crohn disease Ankylosing spondylitis Rheumatoid arthritis Systemic lupus erythematosus
Hematologic and neoplastic disorders	Hemochromatosis Hemophilia Leukemia Lymphoma Multiple myeloma Sickle cell anemia Systemic mastocytosis Thalassemia Metastatic disease
Medications	Anticonvulsants Antipsychotic drugs Antiretroviral drugs Aromatase inhibitors Chemotherapeutic/transplant drugs: cyclosporine, tacrolimus, platinum compounds, cyclophosphamide, ifosfamide, high-dose methotrexate^[58] Furosemide Glucocorticoids and corticotropin^[59]: prednisone (≥5 mg/day for ≥3 mo)^[60] Heparin (long term) Hormonal/endocrine therapies: gonadotropin-releasing hormone (GnRH) agonists, luteinizing hormone-releasing hormone (LHRH) analogues, depomedroxyprogesterone, excessive thyroxine Lithium Proton pump inhibitors Selective serotonin reuptake inhibitors (SSRIs) SGLT2- inhibitors Thiazolidinediones
Miscellaneous	Amyloidosis Chronic metabolic acidosis Chronic heart failure Chronic obstructive pulmonary disease (COPD) Chronic or end-stage renal disease HIV/AIDS Idiopathic scoliosis Immobility Major Depression Multiple sclerosis Ochronosis Organ transplantation Renal insufficiency/ failure Renal tubular acidosis Sarcoidosis Weightlessness^[61]
Sources: (1) American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2020 update. Endocr Pract. May2020; 26(Suppl 1):1-46.^[11] (2) Kelman A, Lane NE. The management of secondary osteoporosis. Best Pract Res Clin Rheumatol. Dec 2005;19(6):1021-37.^[54]

Table 4. Prevalence of Osteoporosis Among Racial and Ethnic Groups

Race/Ethnicity	Sex (age ≥50 y)	% Estimated to have osteoporosis	% Estimated to have low bone mass
Non-Hispanic white; Asian	Women	15.8	52.6
Non-Hispanic white; Asian	Men	3.9	36
Non-Hispanic black	Women	7.7	36.2
Non-Hispanic black	Men	1.3	21.3
Hispanic	Women	20.4	47.8
Hispanic	Men	5.9	38.3
Source: Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res. Nov 2014;29(11):2520-6. [QxMD MEDLINE Link].

Table 5. Baseline Laboratory Studies for Underlying Disorders in Osteoporosis

Baseline test	Disorder
Complete blood count (CBC)	CBC results may reveal anemia, as in sickle cell disease (patients with anemia, particularly those older than 60 years, should also be evaluated for multiple myeloma), and may raise the suspicion for alcohol abuse (in conjunction with results from serum chemistry tests and liver function tests)
Serum chemistry levels	Calcium levels can reflect underlying disease states (eg, severe hypercalcemia may reflect underlying malignancy or hyperparathyroidism; hypocalcemia can contribute to osteoporosis) Levels of serum calcium, phosphate, and alkaline phosphatase are usually normal in persons with primary osteoporosis, although alkaline phosphatase levels may be elevated for several months after a fracture Levels of serum calcium, phosphate, and alkaline phosphatase may be obtained to assess osteomalacia Creatinine levels may decrease with increasing parathyroid hormone (PTH) levels or may be elevated in patients with multiple myeloma Creatinine levels are also used to estimate creatinine clearance, which may indicate reduced renal function in elderly patients Magnesium is very important in calcium homeostasis^[117]; decreased levels of magnesium may affect calcium absorption and metabolism
Liver function tests	Increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), bilirubin, and alkaline phosphatase may indicate alcohol abuse An elevated level of alkaline phosphatase in combination with normal calcium, phosphate, and aminotransferase should prompt consideration of Paget disease
Thyroid-stimulating hormone (TSH) level	Thyroid dysfunction has been associated with osteoporosis and should therefore be ruled out^[118]
25-Hydroxyvitamin D level	This test assesses for vitamin D insufficiency; inadequate vitamin D levels can predispose persons to osteoporosis through a mechanism of secondary hyperparathyroidism If vitamin D insufficiency and bone pain are present, consider the alternative diagnosis of osteomalacia

Table 6. Tests for Secondary Causes of Osteoporosis

Tests for Secondary Causes of Osteoporosis	Disorder
24-Hour urine calcium level	This study assesses for hypercalciuria and hypocalciuria
Parathyroid hormone (PTH) level	An intact PTH result is essential in ruling out hyperparathyroidism; an elevated PTH level may be present in benign familial hypocalciuric hypercalcemia
Thyrotropin level (if on thyroid replacement)	Experts are divided on whether to include thyrotropin testing, regardless of a history of thyroid disease or replacement; however, one study showed reduced femoral neck bone mineral density (BMD) in women with subclinical hypothyroidism and hyperthyroidism^[118]
Testosterone and gonadotropin levels in younger men with low bone densities	These tests may help evaluate a sex hormone deficiency as a secondary cause of osteoporosis
Urinary free cortisol level and tests for adrenal hypersecretion	These tests are used to exclude Cushing syndrome, which, although uncommon, can lead to rapidly progressive osteoporosis when the condition is present; a urine free cortisol value or overnight dexamethasone suppression test should be ordered in suspected cases
Serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP)	These are used to identify multiple myeloma
Antigliadin, antiendomysial, and anti-tissue transglutaminase (TTG) IgA antibodies	These tests can help identify celiac disease. A concomitant total IgA level is needed for interpretation, in case of IgA deficiency.
Serum tryptase and urine N-methylhistamine	These tests help identify mastocytosis
Bone marrow biopsy	This study is obtained when a hematologic disorder is suspected

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Author

Rachel Elizabeth Whitaker Elam, MD, MSc Fellow, Department of Rheumatology, Medical College of Georgia at Augusta University

Rachel Elizabeth Whitaker Elam, MD, MSc is a member of the following medical societies: Alpha Omega Alpha, American College of Rheumatology, Georgia Society of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

Nicola Natasha Jackson, MBBS Resident Physician, Department of Internal Medicine, Piedmont Athens Regional Medical Center

Disclosure: Nothing to disclose.

Wambui Machua, MD Rheumatologist, Piedmont Hospital

Wambui Machua, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, Atlanta Medical Association, Georgia Society of Rheumatology, International Society for Clinical Densitometry, Medical Association of Atlanta, Medical Association of Georgia

Disclosure: Nothing to disclose.

Laura D Carbone, MD, MS, FACP Professor, Department of Internal Medicine, Section Chief of Rheumatology, Medical College of Georgia at Augusta University and Charlie Norwood Veterans Affairs Medical Center

Laura D Carbone, MD, MS, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Women's Association, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD Visiting Professor of Medicine, Division of Rheumatology, State University of New York Downstate Medical Center; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital

Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, Phi Beta Kappa

Disclosure: Nothing to disclose.

Additional Contributors

Kristine M Lohr, MD, MS Professor, Department of Internal Medicine, Interim Chief, Division of Rheumatology, Director, Rheumatology Training Program, University of Kentucky College of Medicine

Kristine M Lohr, MD, MS is a member of the following medical societies: American College of Physicians, American College of Rheumatology

Disclosure: Nothing to disclose.

Monique Bethel, MD Resident Physician, Department of Internal Medicine, Medical College of Georgia at Augusta University

Disclosure: Nothing to disclose.

Acknowledgements

Michael T Andary, MD, MS Professor, Residency Program Director, Department of Physical Medicine and Rehabilitation, Michigan State University College of Osteopathic Medicine

Michael T Andary, MD, MS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, and Association of Academic Physiatrists

Disclosure: Allergan Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard M Miller School of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society