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Osteoporosis Medication

  • Author: Monique Bethel, MD; Chief Editor: Herbert S Diamond, MD  more...
 
Updated: Jun 16, 2016
 

Medication Summary

Pharmacologic therapy for osteoporosis includes the use of antiresorptive agents to decrease bone resorption, such as 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.

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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.[211]

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.

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.

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.

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.

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.

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.

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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.

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.

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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.

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.

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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.

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 to increase bone mass in men and postmenopausal women with osteoporosis at high risk for fracture. It is also indicated for men at high risk for fracture who are receiving androgen deprivation therapy for nonmetastatic prostate cancer. The general dosage is 60 mg every 6 months as an SC 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.

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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.[212] Adequate calcium intake is essential to attain peak bone mass and for continued maintenance of bone health.

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.

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.

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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.[213] 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.

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.

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.

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.

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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.

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.

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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.[213] 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.

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.

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.

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Estrogens/Progestins-HRT

Class Summary

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

Conjugated estrogens/medroxyprogesterone acetate (Prempro, Premphase)

 

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

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.

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.

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Contributor Information and Disclosures
Author

Monique Bethel, MD Resident Physician, Department of Internal Medicine, Georgia Regents University

Disclosure: Nothing to disclose.

Coauthor(s)

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.

Laura D Carbone, MD, MS, FACP Professor, Department of Internal Medicine, Section Chief of Rheumatology, Georgia Regents 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 Womens Association, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, Society of General Internal Medicine

Disclosure: Nothing to disclose.

Wambui Machua, MD Fellow, Department of Internal Medicine, Division of Rheumatology, Georgia Regents University

Wambui Machua, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, National Medical Association, Georgia Society of Rheumatology

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.

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

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.

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

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

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 Association

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.

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.

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.

Authors' Disclaimer

This work does not reflect the views of the Veterans Health Administration or the United States government.

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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.
Table 1. WHO Definition of Osteoporosis Based on BMD Measurements by DXA
Definition Bone Mass 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 fractures 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: http://www.who.int/chp/topics/Osteoporosis.pdf. Accessed February 23, 2015.[16]



(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.[8]



(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.[7]



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.[17]



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 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[47]
  • 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 [47, 48]
  • 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
  • Antipsychotic drugs
  • Antiretroviral drugs
  • Aromatase inhibitors
  • Chemotherapeutic/transplant drugs: cyclosporine, tacrolimus, platinum compounds, cyclophosphamide, ifosfamide, high-dose methotrexate [49]
  • Furosemide
  • Glucocorticoids and corticotropin [50] : prednisone (≥5 mg/day for ≥3 mo) [51]
  • 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 [52]
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.[44]



(2) Kelman A, Lane NE. The management of secondary osteoporosis. Best Pract Res Clin Rheumatol. Dec 2005;19(6):1021-37.[45]



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
Men 3.9 36
Non-Hispanic black Women 7.7 36.2
Men 1.3 21.3
Hispanic Women 20.4 47.8
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. [Medline].
Table 5. 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 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, 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[98] ; 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
Thyroid-stimulating hormone (TSH) level Thyroid dysfunction has been associated with osteoporosis and should therefore be ruled out[99]
25-Hydroxyvitamin D level This test assesses for vitamin D insufficiency; inadequate vitamin D levels can predispose persons to osteoporosis
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[99]
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 and antiendomysial antibodies These tests can help identify celiac disease
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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