Osteoporosis Medication

  • Author: Dana Jacobs-Kosmin, MD; Chief Editor: Herbert S Diamond, MD   more...
 
Updated: Apr 19, 2012
 

Medication Summary

Antiresorptive agents decrease bone resorption, including bisphosphonates, the selective estrogen-receptor modulator (SERM) raloxifene, calcitonin, and denosumab. In addition, there are anabolic steroids that promote bone formation in patients with osteoporosis, such as teriparatide. All therapies should be given with calcium and vitamin D supplementation.

Next

Calcium Metabolism Modifiers

Class Summary

Calcium metabolism modifiers such as bisphosphonates are stable analogues of inorganic pyrophosphate. Bisphosphonates have a high affinity for hydroxyapatite crystals, and by binding at sites of active bone resorption, these agents can inhibit osteoclastic resorption. All oral bisphosphonates have poor absorption and have a bioavailability of less than 5%. Bone uptake is 20-80%, with the remainder being rapidly excreted through the kidneys.[68]

Bisphosphonates are approved in the United States for the prevention and treatment of postmenopausal osteoporosis, osteoporosis in males, and glucocorticoid-induced osteoporosis. Their major pharmacologic action is the inhibition of bone resorption.

View full drug information

Alendronate (Fosamax); alendronate sodium/cholecalciferol (Fosamax Plus D)

 

Alendronate inhibits osteoclast activity and bone resorption. By binding to calcium salts, alendronate blocks the transformation of calcium phosphate into hydroxyapatite and inhibits the formation, aggregation, and dissolution of hydroxyapatite crystals in bone. Alendronate increases bone mineral density (BMD) at the spine by 8% and the hip by 3.5%. It reduces the incidence of vertebral fractures by 47% and nonvertebral fractures by 50% over 3 years. Alendronate is approved for the treatment and prevention of postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis.

View full drug information

Risedronate (Actonel, Atelvia)

 

Risedronate is a potent antiresorptive agent that does not affect bone mineralization. The inclusion of an amino group within the heterocyclic ring makes risedronate one of the most potent antiresorptive bisphosphonates. As with other bisphosphonates, risedronate inhibits osteoclast formation and activity. Risedronate increases BMD at the spine by 5.4% and the hip by 1.6%. It reduces vertebral fractures by 41% and nonvertebral fractures by 39% over 3 years. It is approved for the treatment and prevention of postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis.

View full drug information

Calcitonin salmon (Miacalcin, Fortical)

 

Calcitonin is used for the treatment of postmenopausal osteoporosis in women more than 5 years post menopause with low bone mass relative to healthy premenopausal females. Calcitonin-salmon injection should be reserved for patients who refuse or cannot tolerate estrogens or in whom estrogens are contraindicated. Use of calcitonin-salmon injection is recommended in conjunction with adequate calcium and vitamin D intake to prevent the progressive loss of bone mass. It inhibits osteoclastic bone resorption and has some analgesic effects in patients with fractures.

Although no research data support the idea that the use of intranasal calcitonin reduces the incidence of fractures, studies do show an increase in BMD with the use of calcitonin. Calcitonin increases BMD at the lumbar spine by 1-1.5%. It reduces the incidence of spine fracture by 33% in groups receiving 200 IU/day. It is available in parenteral and intranasal forms; however, the intranasal form is more convenient and better tolerated.

View full drug information

Ibandronate (Boniva)

 

Ibandronate increases BMD and reduces the incidence of vertebral fractures. Ibandronate increases BMD at the spine by 5.7-6.5% and the hip by 2.4-2.8%. It reduces vertebral fractures by 50% with intermittent (nondaily) dosing over 3 years; it has no effects on reduction of nonvertebral fractures. Ibandronate is approved for the treatment and prevention of postmenopausal osteoporosis. It is available as a 150-mg oral tablet and intravenous solution.

View full drug information

Zoledronic acid (Reclast)

 

Zoledronic acid inhibits bone resorption by altering osteoclast activity and by inhibiting normal endogenous, as well as tumor induced, mediators of bone degradation. Like other bisphosphonates, zoledronic acid binds to hydroxyapatite crystals in mineralized bone matrix. The binding to calcium phosphates slows the dissolution of hydroxyapatite crystals, as well as inhibits the formation and aggregation of these crystals. It increases BMD at the spine by 4.3-5.1% and at the hip by 3.1-3.5%, as compared with placebo. It reduces the incidence of spine fractures by 70%, hip fractures by 41%, and nonvertebral fractures by 25% over 3 years. Zoledronic acid is approved for the treatment and prevention of postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, osteoporosis in men, and Paget disease of bone. It is contraindicated in patients with severe renal failure.

Previous
Next

Parathyroid Hormone Analogues

Class Summary

Parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidneys. Teriparatide is a recombinant amino terminal fragment of PTH composed of the first 34 amino acids of PTH, which produce most of its chief biologic effects.

View full drug information

Teriparatide (Forteo)

 

Teriparatide is recombinant human PTH 1-34, which has identical sequence to the 34 N-terminal amino acids (the biologically active region) of 84-amino acid human PTH. This anabolic agent acts as endogenous PTH, thus regulating calcium and phosphate metabolism in bone and kidneys. It works primarily to stimulate new bone by increasing number and activity of osteoblasts (bone-forming cells).

Additional physiological actions include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. Teriparatide increases BMD at the lumbar spine by 9-13% and the hip by 3-6% compared with placebo. When given intermittently, PTH increases bone remodeling with the net effect of increased bone mass and improved skeletal microarchitecture. (This is in contrast to continuous exposure to PTH, which increases bone resorption with a net effect of decreased trabecular bone volume). PTH promotes new bone formation, leading to increased BMD. It reduces the risk of spine fractures by 65% and nonspinal fractures by 54% in patients after an average of 18 mo of therapy. Teriparatide is approved for men or women at high risk of fracture due to primary or hypogonadal osteoporosis or postmenopausal osteoporosis, respectively.[27]

Previous
Next

Selective Estrogen Receptor Modulator

Class Summary

Selective estrogen receptor modulators (SERMs) affect some of the receptors stimulated by estrogen but can selectively act as an antagonist or agonist, depending on the organ system. Like estrogen, these are antiresorptive agents. However, because of their selective receptor-modulating property, they provide the beneficial effects of estrogens without the adverse effects.

View full drug information

Raloxifene (Evista)

 

The biological actions of raloxifene are largely mediated through binding to estrogen receptors, which results in activation of estrogenic pathways in some tissues (agonism) and blockade of estrogenic pathways in others (antagonism). Raloxifene increases BMD at the spine and the hip. It reduces the incidence of spine fractures by 30-55% over 3 years. Raloxifene is approved for the prevention and treatment of postmenopausal osteoporosis in women. It is available as 60 mg tablets that are given orally daily. Adverse reactions commonly seen include hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, and sweating.

Previous
Next

Monoclonal Antibodies, Endocrine

Class Summary

Monoclonal antibodies such as denosumab (Prolia) inhibit osteoclast formation, decrease bone resorption, increase BMD, and reduce the risk of fracture.

View full drug information

Denosumab (Prolia)

 

Denosumab binds to the receptor activator of nuclear factor-kappa B ligand (RANKL), a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, which are the cells that are responsible for bone resorption. It is indicated for the treatment of osteoporosis in postmenopausal women and is used to increase bone mass in both men and women at high risk for fracture. The general dosage is 60 mg every 6 months as a subcutaneous injection in the upper arm, upper thigh, or abdomen. Patients should be instructed to take 1000 mg of calcium daily and at least 400 IU of vitamin D daily.

Previous
Next

Calcium Salts

Class Summary

Calcium and vitamin D are essential to increase bone density. Vitamin D repletion is essential for calcium absorption. Calcium supplements are used to increase calcium levels.[141] Adequate calcium intake is essential to attain peak bone mass and for continued maintenance of bone health.

View full drug information

Calcium citrate (Cal-Citrate, Cal-Cee, Cal-C-Caps)

 

Calcium is the primary component of skeletal tissue, providing structural integrity and support for individual growth. Bone undergoes constant remodeling and turnover. A combination of supplemental calcium and vitamin D can potentially lower the incidence of fractures. Calcium citrate is absorbed equally well when taken with or without food.

View full drug information

Calcium carbonate (Caltrate 600, Calcarb 600, Oysco 500, Super Calcium 600, Tums Ultra)

 

Calcium intake is essential in the prevention and treatment of osteoporosis. Calcium carbonate is generally more inexpensive and requires fewer tablets. Because of its dependence on stomach acid for absorption, calcium carbonate is absorbed most efficiently when taken with food.

Previous
Next

Estrogen Derivatives

Class Summary

Estrogen derivatives are approved for the prevention of osteoporosis and relief of menopause-associated vasomotor symptoms and vulvovaginal atrophy. They are used to increase the serum estrogen level, which, in turn, decreases the rate of bone resorption.[142] The lowest effective dose at the shortest duration necessary should be used. Estrogen therapy reduces bone resorption and retards or halts postmenopausal bone loss. Estrogen therapy is no longer a first-line approach for the treatment of osteoporosis in postmenopausal women because of increased risk of breast cancer, stroke, venous thromboembolism, and coronary disease. The FDA recommends that other approved nonestrogen treatments be considered first for osteoporosis prevention.

View full drug information

Conjugated estrogens (Premarin)

 

Conjugated estrogens (Premarin)

Estrogens can directly affect bone mass through estrogen receptors in bone, reducing bone turnover and bone loss. Estrogens can also indirectly increase intestinal calcium absorption and renal calcium conservation and, therefore, improve calcium balance. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should be considered only for women at significant risk of osteoporosis and for whom nonestrogen medications need to be carefully considered.

View full drug information

Estradiol (Estrace, Estraderm, Menostar, Vivelle-Dot, Climara, Estraderm, Alora)

 

Estradiol restores estrogen levels to concentrations that induce negative feedback at gonadotropic regulatory centers; this, in turn, reduces the release of gonadotropins from the pituitary. Estradiol increases the synthesis of DNA, RNA, and many proteins in target tissues; it also inhibits osteoclastic activity and delays bone loss. In addition, evidence suggests a reduced incidence of fractures.

View full drug information

Estropipate

 

Estropipate is indicated for the prevention of osteoporosis. The results of a double-blind, placebo-controlled 2-year study have shown that treatment with 1 tablet of estropipate, 0.75 mg daily for 25 days (of a 31-day cycle per month), prevents vertebral bone mass loss in postmenopausal women. When estrogen therapy is discontinued, bone mass declines at a rate comparable to that of the immediate postmenopausal period. There is no evidence that estrogen replacement therapy restores bone mass to premenopausal levels.

Previous
Next

Vitamins, Fat-Soluble

Class Summary

Vitamin D is a fat-soluble sterol compound that includes ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). It can be obtained from food and produced by skin when exposed to sunlight of sufficient intensity. When activated in the liver and then the kidney, vitamin D promotes calcium absorption and bone mass. Vitamin D replacement also increases muscle strength and lowers the risk of falling.

View full drug information

Vitamin D (Calciferol, Drisdol)

 

Vitamin D refers to both ergocalciferol (D2) and cholecalciferol (D3). Following exposure to UV light, 7-dehydrocholesterol (provitamin D3) is converted to cholecalciferol, which is then converted by the liver to calcifediol and then again by the kidney to calcitriol. Vitamin D is available in various forms, including tablets, oral liquid, and capsules. It is commonly coadministered with calcium supplements in patients with osteoporosis.

Previous
Next

Estrogens/Progestins

Class Summary

Estrogen derivatives are approved for the prevention of osteoporosis and relief of menopause-associated vasomotor symptoms and vulvovaginal atrophy. They are used to increase the serum estrogen level, which, in turn, decreases the rate of bone resorption.[142] The lowest effective dose at the shortest duration necessary should be used. Estrogen therapy reduces bone resorption and retards or halts postmenopausal bone loss. Estrogen therapy is no longer a first-line approach for the treatment of osteoporosis in postmenopausal women because of increased risk of breast cancer, stroke, venous thromboembolism, and coronary disease. The FDA recommends that other approved nonestrogen treatments be considered first for osteoporosis prevention.

View full drug information

Norethindrone/ethinylestradiol (Femhrt)

 

Ethinyl estradiol with norethindrone is used to prevent osteoporosis associated with menopause. When prescribing it solely for the prevention of postmenopausal osteoporosis, therapy should be considered only for women at significant risk of osteoporosis.

View full drug information

Estradiol/norethindrone acetate (Activella, Mimvey, CombiPatch)

 

Ethinyl estradiol with norethindrone is used to prevent osteoporosis associated with menopause. When prescribing it solely for the prevention of postmenopausal osteoporosis, therapy should be considered only for women at significant risk of osteoporosis.

Previous
Next

Estrogens/Progestins-HRT

Class Summary

The combination of conjugated estrogens and medroxyprogesterone reduces bone resorption and retards or halts postmenopausal bone loss.

View full drug information

Conjugated estrogens/medroxyprogesterone acetate (Prempro, Premphase)

 

The combination of conjugated estrogens and medroxyprogesterone reduces bone resorption and retards or halts postmenopausal bone loss.

View full drug information

Estradiol/levonorgestrel (Climara Pro)

 

Estradiol/levonorgestrel transdermal system releases both estradiol and levonorgestrel continuously upon application to skin. It is approved for the prevention of postmenopausal osteoporosis.

View full drug information

Estradiol/norgestimate (Prefest)

 

Estradiol/norgestimate is approved for the prevention of postmenopausal osteoporosis. It is available as a combination of estradiol 1 mg/norgestimate 0.09 mg.

Previous
 
Contributor Information and Disclosures
Author

Dana Jacobs-Kosmin, MD  Attending Physician, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center; Clinical Assistant Professor of Medicine, Jefferson Medical College

Dana Jacobs-Kosmin, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology

Disclosure: Nothing to disclose.

Coauthor(s)

Sucharitha Shanmugam, MD  Consulting Physician, PMA Medical Specialists, Limerick, PA

Sucharitha Shanmugam, MD is a member of the following medical societies: American College of Rheumatology

Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD  Adjunct Professor of Medicine, Division of Rheumatology, University of Pittsburgh School of Medicine; 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, and Phi Beta Kappa

Disclosure: Merck Ownership interest Other; Smith Kline Ownership interest Other; Zimmer Ownership interest Other

Additional Contributors

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

Disclosure: Nothing to disclose.

Elliot Goldberg, MD Dean of the Western Pennsylvania Clinical Campus, Professor, Department of Medicine, Temple University School of Medicine

Elliot Goldberg, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, and American College of Rheumatology

Disclosure: Nothing to disclose.

Coburn Hobar, MD Clinician in Rheumatology, Hobar Health and Wellness, and Anti-Aging & Wellness Center of Sarasota

Coburn Hobar, MD is a member of the following medical societies: American Academy of Anti-Aging Medicine and American College of Rheumatology

Disclosure: Nothing to disclose.

Robert J Kaplan, MD James E Van Zandt VA Medical Center, Staff Physician, Department of Rehabilitation Medicine

Robert J Kaplan, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation

Disclosure: Nothing to disclose.

Joseph M Lane, MD  Professor of Orthopedic Surgery, Weill Medical College of Cornell University; Chief, Metabolic Bone Disease Service, Hospital for Special Surgery

Joseph M Lane, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Association of University Professors, American Federation for Aging Research, American Orthopaedic Association, American Society for Bone and Mineral Research, Association of Bone and Joint Surgeons, Medical Society of the State of New York, Musculoskeletal Tumor Society, National Osteoporosis Foundation, North American Spine Society, and Orthopaedic Research Society

Disclosure: Lilly; Aventis; Novartis; Warner Chilcott; Biomimetics; Zimmer; DFine; Innovative Solutions; Honoraria Speaking and teaching; Graftys; Bone Technologies SA; CollPlant Consulting fee Consulting

David Lenrow, MD Vice Chair of Clinical Services, Medical Director, Erdman Clinic; Associate Professor, Department of Rehabilitation Medicine, University of Pennsylvania at Philadelphia

David Lenrow, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation and American Medical Assocation

Disclosure: Nothing to disclose.

Julie Lin, MD Assistant Professor, Department of Rehabilitation Medicine, Weill Medical College of Cornell University; Assistant Attending Physiatrist, Physiatry Department, Hospital for Special Surgery

Julie Lin, MD 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, North American Spine Society, and Physiatric Association of Spine, Sports and Occupational Rehabilitation

Disclosure: Nothing to disclose.

Elizabeth A Moberg-Wolff, MD Associate Professor, Department of Physical Medicine and Rehabilitation, Children's Hospital of Wisconsin, Medical College of Wisconsin

Elizabeth A Moberg-Wolff, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine and American Academy of Physical Medicine and Rehabilitation

Disclosure: Medtronic Neurological Grant/research funds Speaking and teaching

Srinivas R Nalamachu, MD Clinical Assistant Professor, Department of Internal Medicine, Kansas City University of Medicine and Biosciences; President and Medical Director, Internation Clinical Research Institute, Inc; Medical Director, Pain Management Institute

Srinivas R Nalamachu, MD is a member of the following medical societies: International Association for the Study of Pain

Disclosure: Nothing to disclose.

Richard Salcido, MD Chairman, Erdman Professor of Rehabilitation, Department of Physical Medicine and Rehabilitation, University of Pennsylvania School of Medicine

Richard Salcido, MD is a member of the following medical societies: American Academy of Pain Medicine, American Academy of Physical Medicine and Rehabilitation, American College of Physician Executives, American Medical Association, and American Paraplegia Society

Disclosure: Nothing to disclose.

Miguel A Schmitz, MD Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic

Miguel A Schmitz, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, Arthroscopy Association of North America, and North American Spine Society

Disclosure: Nothing to disclose.

Alana C Serota, MD Fellow in Metabolic Bone Disease and Osteoporosis, Department of Orthopedics, Hospital for Special Surgery

Alana C Serota, MD is a member of the following medical societies: American Academy of Family Physicians

Disclosure: Nothing to disclose.

Curtis W Slipman, MD Director, University of Pennsylvania Spine Center; Associate Professor, Department of Physical Medicine and Rehabilitation, University of Pennsylvania Medical Center

Curtis W Slipman, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists, International Association for the Study of Pain, and North American Spine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Shireesha Vuppalanchi, MD Consulting Staff, Methodist Hospital, Indianapolis; Hospitalist, Respiratory and Critical Care Consultants, PC

Disclosure: Nothing to disclose.

William S Whyte II, MD Director of Interventional Spine and Pain Management, Louisiana Pain Physicians

William S Whyte II, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Medical Association, Association of Academic Physiatrists, North American Spine Society, Physiatric Association of Spine, Sports and Occupational Rehabilitation, and Southern Medical Association

Disclosure: Nothing to disclose.

Jerome D Wiedel, MD Chair, Professor, Department of Orthopedics, University of Colorado Health Sciences Center

Disclosure: Nothing to disclose.

References

  1. Ahmed SF, Elmantaser M. Secondary osteoporosis. Endocr Dev. 2009;16:170-90. [Medline].

  2. [Best Evidence] 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. Jan 12 2009;169(1):25-31. [Medline].

  3. National Osteoporosis Foundation. Gallup survey: women's knowledge of osteoporosis. Am Fam Physician. 1991;44:1052.

  4. Kanis JA, McCloskey EV, Johansson H, Oden A, Melton LJ 3rd, Khaltaev N. A reference standard for the description of osteoporosis. Bone. Mar 2008;42(3):467-75. [Medline].

  5. Silverman SL. Selecting patients for osteoporosis therapy. Ann N Y Acad Sci. Nov 2007;1117:264-72. [Medline].

  6. 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. [Medline].

  7. 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. [Medline].

  8. 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. Accessed February 6, 2012.

  9. WebMD. Medical dictionary: T-score. Available at http://dictionary.webmd.com/terms/t-score. Accessed February 6, 2012.

  10. Bono CM, Einhorn TA. Overview of osteoporosis: pathophysiology and determinants of bone strength. Eur Spine J. Oct 2003;12 Suppl 2:S90-6. [Medline].

  11. Raisz LG. Pathogenesis of osteoporosis: concepts, conflicts, and prospects. J Clin Invest. Dec 2005;115(12):3318-25. [Medline].

  12. Seeman E, Delmas PD. Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med. May 25 2006;354(21):2250-61. [Medline].

  13. Mora S, Gilsanz V. Establishment of peak bone mass. Endocrinol Metab Clin North Am. Mar 2003;32(1):39-63. [Medline].

  14. Sandhu SK, Hampson G. The pathogenesis, diagnosis, investigation and management of osteoporosis. J Clin Pathol. Dec 2011;64(12):1042-50. [Medline].

  15. 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. Jul 3 1992;257(5066):88-91. [Medline].

  16. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. May 18 2002;359(9319):1761-7. [Medline].

  17. 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.

  18. Ringe JD, Farahmand P. Advances in the management of corticosteroid-induced osteoporosis with bisphosphonates. Clin Rheumatol. Apr 2007;26(4):474-84. [Medline].

  19. 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. Apr 2005;57(4):582-6. [Medline].

  20. 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. Jan 1998;83(1):135-9. [Medline].

  21. [Guideline] American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Endocr Pract. Nov-Dec 2003;9(6):544-64. [Medline].

  22. Kelman A, Lane NE. The management of secondary osteoporosis. Best Pract Res Clin Rheumatol. Dec 2005;19(6):1021-37. [Medline].

  23. Adams JS, Song CF, Kantorovich V. Rapid recovery of bone mass in hypercalciuric, osteoporotic men treated with hydrochlorothiazide. Ann Intern Med. Apr 20 1999;130(8):658-60. [Medline].

  24. 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. Aug 1 2009;27(22):3605-10. [Medline].

  25. Holick MF. Vitamin D deficiency. N Engl J Med. Jul 19 2007;357(3):266-81. [Medline].

  26. 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. Jul 2004;31(7):1305-9. [Medline].

  27. Migliaccio S, Brama M, Malavolta N. Management of glucocorticoids-induced osteoporosis: role of teriparatide. Ther Clin Risk Manag. Apr 2009;5(2):305-10. [Medline]. [Full Text].

  28. van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. Oct 2002;13(10):777-87. [Medline].

  29. 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. [Medline].

  30. Lyles KW, Schenck AP, Colón-Emeric CS. Hip and other osteoporotic fractures increase the risk of subsequent fractures in nursing home residents. Osteoporos Int. Aug 2008;19(8):1225-33. [Medline]. [Full Text].

  31. 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. Sep 2008;19(9):1277-82. [Medline].

  32. Sinaki M. Exercise and osteoporosis. Arch Phys Med Rehabil. Mar 1989;70(3):220-9. [Medline].

  33. 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. [Medline].

  34. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med. Mar 23 1995;332(12):767-73. [Medline].

  35. National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Available at http://www.nof.org/professionals/clinical-guidelines. Accessed January 13, 2011.

  36. Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. Nov 1992;2(6):285-9. [Medline].

  37. Who are candidates for prevention and treatment for osteoporosis?. Osteoporos Int. 1997;7(1):1-6. [Medline].

  38. Gullberg B, Johnell O, Kanis JA. World-wide projections for hip fracture. Osteoporos Int. 1997;7(5):407-13. [Medline].

  39. 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. Jun 1982;75-81. [Medline].

  40. Melton LJ 3rd, Kan SH, Frye MA, Wahner HW, O'Fallon WM, Riggs BL. Epidemiology of vertebral fractures in women. Am J Epidemiol. May 1989;129(5):1000-11. [Medline].

  41. Smith R, Wordsworth P. Osteoporosis. In: Clinical and Biochemical Disorders of the Skeleton. 2005:123.

  42. National Osteoporosis Foundation. Fast facts. Available at http://www.nof.org/node/40. Accessed February 16, 2012.

  43. 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.

  44. Melton LJ 3rd, Sampson JM, Morrey BF, Ilstrup DM. Epidemiologic features of pelvic fractures. Clin Orthop Relat Res. Mar-Apr 1981;43-7. [Medline].

  45. 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. May 4 2005;293(17):2102-8. [Medline].

  46. Bone Health and Osteoporosis: A Report of the Surgeon General. Washington, DC: Department of Health and Human Services; 2004. [Full Text].

  47. 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. Mar 2007;22(3):465-75. [Medline].

  48. Cooper C, Atkinson EJ, Jacobsen SJ, et al. Population-based study of survival after osteoporotic fractures. Am J Epidemiol. May 1 1993;137(9):1001-5. [Medline].

  49. 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. Jun 14 1999;159(11):1215-20. [Medline].

  50. 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. Feb 1992;7(2):221-7. [Medline].

  51. 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. Dec 2007;18(12):1583-93. [Medline].

  52. 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. Sep 2002;13(9):731-7. [Medline].

  53. 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. Sep 2000;55(9):M508-15. [Medline].

  54. Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA. Jan 17 2001;285(3):320-3. [Medline].

  55. 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. Apr 2000;15(4):721-39. [Medline].

  56. The World Health Organization Fracture Risk Assessment Tool. Available at http://www.shef.ac.uk/FRAX/. Accessed May 5, 2008.

  57. 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.

  58. 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. Jun 1 2011;305(21):2184-92. [Medline].

  59. 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. Jun 1993;36(6):750-6. [Medline].

  60. Schnatz PF, Marakovits KA, Dubois M, O'Sullivan DM. Osteoporosis screening and treatment guidelines: are they being followed?. Menopause. Oct 2011;18(10):1072-8. [Medline].

  61. 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. [Medline].

  62. 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. Jun 2008;23(6):812-8. [Medline].

  63. U.S. Preventive Services Task Force. Screening for Osteoporosis: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. Jan 17 2011;[Medline].

  64. 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. Oct 10 2011;171(18):1655-61. [Medline].

  65. Lynn SG, Sinaki M, Westerlind KC. Balance characteristics of persons with osteoporosis. Arch Phys Med Rehabil. Mar 1997;78(3):273-7. [Medline].

  66. Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women. Ann Intern Med. Dec 6 2011;155(11):751-61. [Medline].

  67. [Guideline] Qaseem A, Snow V, Shekelle P, Hopkins R Jr, Forciea MA, Owens DK. Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: a clinical practice guideline from the American College of Physicians. Ann Intern Med. Sep 16 2008;149(6):404-15. [Medline].

  68. Keen R. Osteoporosis: strategies for prevention and management. Best Pract Res Clin Rheumatol. Feb 2007;21(1):109-22. [Medline].

  69. Guglielmi G, Muscarella S, Bazzocchi A. Integrated imaging approach to osteoporosis: state-of-the-art review and update. Radiographics. Sep-Oct 2011;31(5):1343-64. [Medline].

  70. The International Society for Clinical Densitometry. 2007 ISCD Official Positions Brochure. Available at http://www.iscd.org/Visitors/positions/OfficialPositionsText.cfm. Accessed May 5, 2008.

  71. Paunier L. Effect of magnesium on phosphorus and calcium metabolism. Monatsschr Kinderheilkd. Sep 1992;140(9 Suppl 1):S17-20. [Medline].

  72. 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. May 2006;37(4):511-6. [Medline].

  73. 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. Oct 2002;87(10):4431-7. [Medline].

  74. 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. [Medline].

  75. Resnick D, Kransdorf M. Osteoporosis. In: Bone and Joint Imaging. Third Edition. 2005:551.

  76. Gosfield E 3rd, Bonner FJ Jr. Evaluating bone mineral density in osteoporosis. Am J Phys Med Rehabil. May-Jun 2000;79(3):283-91. [Medline].

  77. Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women. Ann Intern Med. Dec 6 2011;155(11):751-61. [Medline]. [Full Text].

  78. Lin JT, Lane JM. Bisphosphonates. J Am Acad Orthop Surg. Jan-Feb 2003;11(1):1-4. [Medline].

  79. Kastner M, Straus SE. Clinical decision support tools for osteoporosis disease management: a systematic review of randomized controlled trials. J Gen Intern Med. Dec 2008;23(12):2095-105. [Medline]. [Full Text].

  80. Lecart MP, Reginster JY. Current options for the management of postmenopausal osteoporosis. Expert Opin Pharmacother. Nov 2011;12(16):2533-52. [Medline].

  81. Chaiamnuay S, Saag KG. Postmenopausal osteoporosis. What have we learned since the introduction of bisphosphonates?. Rev Endocr Metab Disord. Jun 2006;7(1-2):101-12. [Medline].

  82. Mulder JE, Kolatkar NS, LeBoff MS. Drug insight: Existing and emerging therapies for osteoporosis. Nat Clin Pract Endocrinol Metab. Dec 2006;2(12):670-80. [Medline].

  83. Watts NB, Bilezikian JP, Camacho PM, Greenspan SL, Harris ST, Hodgson SF, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract. Nov-Dec 2010;16 Suppl 3:1-37. [Medline]. [Full Text].

  84. Abrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med. Jun 13 2011;171(11):998-1004. [Medline].

  85. [Best Evidence] Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. May 3 2007;356(18):1809-22. [Medline].

  86. 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. Nov 2011;59(11):2084-90. [Medline].

  87. 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. Accessed September 1, 2011.

  88. 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. Mar 2005;90(3):1294-301. [Medline].

  89. Strampel W, Emkey R, Civitelli R. Safety considerations with bisphosphonates for the treatment of osteoporosis. Drug Saf. 2007;30(9):755-63. [Medline].

  90. 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. Feb 23 2011;305(8):783-9. [Medline].

  91. Geusens P. Bisphosphonates for postmenopausal osteoporosis: determining duration of treatment. Curr Osteoporos Rep. Mar 2009;7(1):12-7. [Medline].

  92. [Best Evidence] Grady D, Cauley JA, Stock JL, Cox DA, Mitlak BH, Song J, et al. Effect of Raloxifene on all-cause mortality. Am J Med. May 2010;123(5):469.e1-7. [Medline].

  93. 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. Oct 2002;87(10):4528-35. [Medline].

  94. 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. Oct 2001;16(10):1846-53. [Medline].

  95. 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. May 10 2001;344(19):1434-41. [Medline].

  96. 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. Dec 2004;15(12):992-7. [Medline].

  97. 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. Sep 25 2003;349(13):1216-26. [Medline].

  98. 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. Feb 2006;21(2):283-91. [Medline].

  99. 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. Nov 2005;20(11):1905-11. [Medline].

  100. [Best Evidence] 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. Jun 2009;91(6):1329-38. [Medline].

  101. 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. Sep 7 2011;93(17):1583-7. [Medline].

  102. 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. Feb 15 2006;12(4):1221-8. [Medline].

  103. 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. Feb 23 2006;354(8):821-31. [Medline].

  104. [Best Evidence] 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. Aug 20 2009;361(8):756-65. [Medline].

  105. [Best Evidence] 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. Aug 20 2009;361(8):745-55. [Medline].

  106. Schwarz EM, Ritchlin CT. Clinical development of anti-RANKL therapy. Arthritis Res Ther. 2007;9 Suppl 1:S7. [Medline]. [Full Text].

  107. 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. Jul 17 2002;288(3):321-33. [Medline].

  108. Blake GM, Fogelman I. Long-term effect of strontium ranelate treatment on BMD. J Bone Miner Res. Nov 2005;20(11):1901-4. [Medline].

  109. Burlet N, Reginster JY. Strontium ranelate: the first dual acting treatment for postmenopausal osteoporosis. Clin Orthop Relat Res. Feb 2006;443:55-60. [Medline].

  110. Jamal SA, Hamilton CJ, Eastell R, Cummings SR. Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: a randomized trial. JAMA. Feb 23 2011;305(8):800-7. [Medline].

  111. [Best Evidence] 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. Mar 23 2009;169(6):551-61. [Medline].

  112. Warensjö E, Byberg L, Melhus H, et al. Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study. BMJ. May 24 2011;342:d1473. [Medline]. [Full Text].

  113. Bruni V, Dei M, Filicetti MF, Balzi D, Pasqua A. Predictors of bone loss in young women with restrictive eating disorders. Pediatr Endocrinol Rev. Jan 2006;3 Suppl 1:219-21. [Medline].

  114. 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. Apr 28 2004;291(16):1999-2006. [Medline].

  115. [Best Evidence] 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. Aug 25 2007;370(9588):657-66. [Medline].

  116. [Best Evidence] 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. Jan 12 2010;340:b5463. [Medline].

  117. [Best Evidence] Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. Jul 29 2010;341:c3691. [Medline]. [Full Text].

  118. Sinaki M. Postmenopausal spinal osteoporosis: physical therapy and rehabilitation principles. Mayo Clin Proc. Nov 1982;57(11):699-703. [Medline].

  119. Tinetti ME, Speechley M. Prevention of falls among the elderly. N Engl J Med. Apr 20 1989;320(16):1055-9. [Medline].

  120. Sinaki M, Mikkelsen BA. Postmenopausal spinal osteoporosis: flexion versus extension exercises. Arch Phys Med Rehabil. Oct 1984;65(10):593-6. [Medline].

  121. 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. Jun 2002;30(6):836-41. [Medline].

  122. 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. Sep-Oct 1996;75(5):370-4. [Medline].

  123. 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. Dec 2000;67(6):443-8. [Medline].

  124. 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. Sep 2000;55(9):M489-91. [Medline].

  125. Howe TE, Shea B, Dawson LJ, et al. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev. Jul 6 2011;CD000333. [Medline].

  126. 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. [Medline].

  127. 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. Mar 2000;81(3):319-23. [Medline].

  128. 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. Mar 24 2001;322(7288):697-701. [Medline]. [Full Text].

  129. 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. Nov 2000;83(4 -5):349-55. [Medline].

  130. 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. May 1996;44(5):489-97. [Medline].

  131. 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. Oct 2001;35(5):348-51. [Medline]. [Full Text].

  132. Riggs BL, Melton LJ 3rd. The prevention and treatment of osteoporosis. N Engl J Med. Aug 27 1992;327(9):620-7. [Medline].

  133. 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. Feb 29 2008;49(1):119-28. [Medline]. [Full Text].

  134. Hosking D, Chilvers CE, Christiansen C, Ravn P, Wasnich R, Ross P, et al. Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group. N Engl J Med. Feb 19 1998;338(8):485-92. [Medline].

  135. Grossman JM, Gordon R, Ranganath VK, et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken). Nov 2010;62(11):1515-26.

  136. Schwab P, Klein RF. Nonpharmacological approaches to improve bone health and reduce osteoporosis. Curr Opin Rheumatol. Mar 2008;20(2):213-7. [Medline].

  137. Lin JT, Lane JM. Nonmedical management of osteoporosis. Curr Opin Rheumatol. Jul 2002;14(4):441-6. [Medline].

  138. 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. Jan 19 2012;366(3):225-33. [Medline]. [Full Text].

  139. Kirshblum SC. Rehabilitation Medicine: Principles and Practice. In: DeLisa JA, Gans BM. Spinal and upper extremity orthotics. 3rd. Philadelphia, Pa: Lippincott-Raven; 1998:635-50.

  140. Stillo JV. Low back orthoses. Phys Med Rehab Clin North Am. 1992;3:57-94.

  141. NIH Consensus conference. Optimal calcium intake. NIH Consensus Development Panel on Optimal Calcium Intake. JAMA. Dec 28 1994;272(24):1942-8. [Medline].

  142. Hulley SB, Grady D. The WHI estrogen-alone trial--do things look any better?. JAMA. Apr 14 2004;291(14):1769-71. [Medline].

  143. Aloia JF, Vaswani A, Yeh JK, Flaster E. Risk for osteoporosis in black women. Calcif Tissue Int. Dec 1996;59(6):415-23. [Medline].

  144. Boonen S, Orwoll E, Magaziner J, et al. Once-Yearly Zoledronic Acid in Older Men Compared with Women with Recent Hip Fracture. J Am Geriatr Soc. Nov 2011;59(11):2084-2090. [Medline].

  145. Canalis E. New treatments in osteoporosis. Bone. Sep 2001;29(3):296.

  146. Cohen A, Dempster DW, Recker RR, Stein EM, Lappe JM, Zhou H, et al. Abnormal bone microarchitecture and evidence of osteoblast dysfunction in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab. Oct 2011;96(10):3095-105. [Medline]. [Full Text].

  147. 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. Aug 11 2005;353(6):566-75. [Medline].

  148. Curtis JR, Carbone L, Cheng H, Hayes B, Laster A, Matthews R, et al. Longitudinal trends in use of bone mass measurement among older americans, 1999-2005. J Bone Miner Res. Jul 2008;23(7):1061-7. [Medline]. [Full Text].

  149. Jensen ME, Evans AJ, Mathis JM, Kallmes DF, Cloft HJ, Dion JE. Percutaneous polymethylmethacrylate vertebroplasty in the treatment of osteoporotic vertebral body compression fractures: technical aspects. AJNR Am J Neuroradiol. Nov-Dec 1997;18(10):1897-904. [Medline].

  150. Lau EM, Cooper C. The epidemiology of osteoporosis. The oriental perspective in a world context. Clin Orthop Relat Res. Feb 1996;65-74. [Medline].

  151. Lauderdale DS, Jacobsen SJ, Furner SE, Levy PS, Brody JA, Goldberg J. Hip fracture incidence among elderly Hispanics. Am J Public Health. Aug 1998;88(8):1245-7. [Medline]. [Full Text].

  152. Ledlie JT, Renfro M. Balloon kyphoplasty: one-year outcomes in vertebral body height restoration, chronic pain, and activity levels. J Neurosurg. Jan 2003;98(1 Suppl):36-42. [Medline].

 
Previous
Next
 
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).
Reduction in kyphotic angulation after kyphoplasty.
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. http://www.imagingpathways.health.wa.gov.au/includes/dipmenu/osteo/image.html.
This radiograph of the spine shows a lateral wedge fracture of L3 (yellow asterisk) and compression fracture of L5 (red asterisk) in an osteoporotic patient who suffered a recent fall. More detailed imaging, usually with computed tomography (CT) scanning, is often needed to better evaluate compression fractures and to determine the urgency of surgical interventions.
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. http://www.imagingpathways.health.wa.gov.au/includes/dipmenu/osteo/image.html.
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. http://www.imagingpathways.health.wa.gov.au/includes/dipmenu/osteo/image.html.
Table 1. WHO Definition of Osteoporosis Based on BMD Measurements by DXA
Definition Bone Mass Density Measurement T-Score
NormalBMD within 1 SD of the mean bone density for young adult womenT-score ≥ –1
Low bone mass (osteopenia)BMD 1–2.5 SD below the mean for young-adult womenT-score between –1 and –2.5
OsteoporosisBMD ≥2.5 SD below the normal mean for young-adult womenT-score ≤ –2.5
Severe or “established” osteoporosisBMD ≥2.5 SD below the normal mean for young-adult women in a patient who has already experienced ≥1 fracturesT-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: http://www.who.int/chp/topics/Osteoporosis.pdf. Accessed February 6, 2012.[8]



(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.[7]



(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.[6]



BMD = bone mass 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.[9] .



Table 2. Types of Primary Osteoporosis
Type of Primary OsteoporosisCharacteristics
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 aged 50-65 years
  • 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 older than 70 years
  • Represents bone loss associated with aging
  • Fractures occur in cortical and trabecular bone
  • Wrist, vertebral, and hip fractures often seen in patients with type II osteoporosis
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
  • Hypophosphatasia
  • Idiopathic hypercalciuria
  • Porphyria
  • Hypogonadal states
Hypogonadal states
  • Androgen insensitivity
  • Anorexia nervosa/bulimia nervosa
  • Female athlete triad
  • Hyperprolactinemia
  • Panhypopituitarism
  • Premature menopause
  • Turner syndrome
  • Klinefelter syndrome
Endocrine disorders[24]
  • Cushing syndrome
  • Diabetes mellitus
  • Acromegaly
  • Adrenal insufficiency
  • Estrogen deficiency
  • Hyperparathyroidism
  • Hyperthyroidism
  • Hypogonadism
  • Pregnancy
  • Prolactinoma
Deficiency states
  • Calcium deficiency
  • Magnesium deficiency
  • Protein deficiency
  • Vitamin D deficiency[24, 25]
  • Bariatric surgery
  • Celiac disease
  • Gastrectomy
  • Malabsorption
  • Malnutrition
  • Parenteral nutrition
  • Primary biliary cirrhosis
Inflammatory diseases
  • Inflammatory bowel 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: phenytoin, barbiturates, carbamazepine (these agents are associated with treatment-induced vitamin D deficiency)
  • Antipsychotic drugs
  • Antiretroviral drugs
  • Aromatase inhibitors: exemestane, anastrozole
  • Chemotherapeutic/transplant drugs: cyclosporine, tacrolimus, platinum compounds, cyclophosphamide, ifosfamide, high-dose methotrexate[26]
  • Furosemide
  • Glucocorticoids and corticotropin[27] : prednisone (≥5 mg/day for ≥3 mo)[28]
  • Heparin (long term)
  • Hormonal/endocrine therapies: gonadotropin-releasing hormone (GnRH) agonists, luteinizing hormone-releasing hormone (LHRH) analogues, depomedroxyprogesterone, excessive thyroxine
  • Lithium
  • Selective serotonin reuptake inhibitors (SSRIs)
Miscellaneous
  • Alcoholism
  • Amyloidosis
  • Chronic metabolic acidosis
  • Congestive heart failure
  • Depression
  • Emphysema
  • Chronic or end-stage renal disease
  • Chronic liver disease
  • HIV/AIDS
  • Idiopathic scoliosis
  • Immobility
  • Multiple sclerosis
  • Ochronosis
  • Organ transplantation
  • Pregnancy/lactation
  • Sarcoidosis
  • Weightlessness
Sources:



(1) American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Endocr Pract. Nov-Dec 2003;9(6):544-64.[21]



(2) Kelman A, Lane NE. The management of secondary osteoporosis. Best Pract Res Clin Rheumatol. Dec 2005;19(6):1021-37.[22]



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; AsianWomen2052
Men735
Non-Hispanic blackWomen5*
Men419
HispanicWomen1049
Men323
Source:  National Osteoporosis Foundation. Fast facts. Available at: http://www.nof.org/node/40. Accessed: February 16, 2012.[42]



* Low bone density is present in an additional 35% of black women, increasing their risk of developing osteoporosis.



Table 5. Comparison of Densitometry Techniques and Cost-Effectiveness
Single-photon absorptiometry Dual-photon absorptiometry Dual-energy x-ray absorptiometry Quantitative computed tomography
Time5-15 min20-30 min5-10 min10-30 min
Cost$50-150$150-300$100-200$150-300
Sites scannedRadius, forearm,



calcaneus



Spine, hip (anteroposterior)Spine (lateral), hip,



radius



Spine (lateral), hip,



radius



Source:  Nayak S, Roberts MS, Greenspan SL. Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women. Ann Intern Med. Dec 6 2011;155(11):751-61.[68]
Table 6. Baseline Studies for Baseline Conditions 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 levelsCalcium 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, alkaline phosphatase, and 25(OH) vitamin D 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[71] ; decreased levels of magnesium may affect calcium absorption and metabolism



Serum iron and ferritin levelsThese tests are helpful when malabsorption or hemochromatosis are suspected
Liver function testsIncreased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), bilirubin, and alkaline phosphatase may indicate alcohol abuse
Thyroid-stimulating hormone (TSH) levelThyroid dysfunction has been associated with osteoporosis and should therefore be ruled out[72]
25-Hydroxyvitamin D levelThis test assesses for vitamin D insufficiency; inadequate vitamin D levels can predispose persons to osteoporosis
Table 7. Tests for Secondary Causes of Osteoporosis
Tests for Secondary Causes of Osteoporosis Disorder
24-Hour urine calcium levelThis study assesses for hypercalciuria to help rule out benign familial hypocalciuric hypercalcemia (FHH), in which urinary calcium levels are low
Parathyroid hormone (PTH) levelAn intact PTH result is essential in ruling out hyperparathyroidism; an elevated PTH level may be present in benign FHH
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[72]
Testosterone and gonadotropin levels in younger men with low bone densitiesThese tests may help evaluate a sex hormone deficiency as a secondary cause of osteoporosis
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levelsSome practitioners include ESR and CRP values in the workup, although their utility in this setting has not been proven in an evidence-based manner
Urinary free cortisol level and tests for adrenal hypersecretionThese 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 and antiendomysial antibodiesThese tests can help identify celiac disease
Serum tryptase and urine N-methylhistamineThese tests help identify mastocytosis and are used to exclude the presence of multiple myeloma; serum tryptase may be performed to rule out plasma cell dyscrasias
Bone marrow biopsyThis study is obtained when a hematologic disorder is suspected
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.