Osteoporosis Medication

Updated: Jun 27, 2019
  • Author: Monique Bethel, MD; Chief Editor: Herbert S Diamond, MD  more...
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Medication

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, romosozumab, and denosumab. In addition, there are parathyroid hormone analogues that promote bone formation in patients with osteoporosis (eg, teriparatide, abaloparatide). 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. [229]

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 Analogs

Class Summary

Parathyroid hormone (PTH) is the primary regulator of calcium and phosphate metabolism in bone and kidneys.

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.

Abaloparatide (Tymlos)

Synthetic peptide analog of human parathyroid hormone-related protein (hPTHrP); hPTHrP is a naturally occurring hormone that, among other functions, regulates bone formation. It elicits anabolic effect on bone, demonstrated by increases in bone mineral density and content that correlated with increases in bone strength at vertebral and/or nonvertebral sites. Daily SC administration for 18 mo was associated with significant reductions in the relative risk for new vertebral fractures (86% reduction) and nonvertebral fractures (43% reduction) compared with placebo. The absolute risk reductions were 3.6% and 2.0%, respectively.

It is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.

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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. Another monoclonal antibody, romosozumab, binds sclerostin, a regulatory factor in bone metabolism.

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. Additionally, it is indicated for glucocorticoid-induced osteoporosis in men and women at high risk of fracture. 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.

Romosozumab (Evenity)

Monoclonal antibody (IgG2) that binds sclerostin, a regulatory factor in bone metabolism. Sclerostin inhibition increases bone formation and, to a lesser extent, decreases bone resorption. It is indicated for osteoporosis treatment in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture or multiple risk factors for fracture. It is also indicated for patients who have failed or are intolerant to other available osteoporosis therapy.

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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. [230] 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. [231] 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. [231] 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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