What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis?

Abstract

Pharmacologic osteoporosis therapy, particularly anti-resorptives, is recommended in postmenopausal women with clinical risk factors for fracture. Treatment decisions should be made based on the relative benefit-risk profile in different patient populations. Emerging options [e.g., selective estrogen receptor modulators (SERMs) and denosumab] may hold promise for providing protection from bone loss and for fracture risk reduction.Osteoporosis, the most common clinical disorder of bone metabolism, is characterized by low bone mineral density, deterioration of microarchitecture, and a consequent increase in bone fragility and risk of fracture. Pharmacologic therapy is recommended in postmenopausal women with clinical risk factors for fracture and includes anti-resorptive agents such as bisphosphonates, hormone therapy, SERMs, and calcitonin. The anabolic agent teriparatide (parathyroid hormone) is usually reserved for high-risk patients or those with glucocorticoid-induced osteoporosis. Strontium ranelate, available outside the USA, has both anti-resorptive and anabolic properties. Supplementation with calcium and vitamin D is recommended for all women aged 50 years and older. Bisphosphonates are often considered first-line therapy for osteoporosis and have the largest base of clinical trial data showing efficacy for global fracture risk reduction. Low-dose hormone therapy is appropriate for younger women who are experiencing other menopausal symptoms. In women for whom bisphosphonates are not appropriate or not tolerated or in younger postmenopausal women who have a low risk for hip fracture, SERMs are a suitable treatment option. Calcitonin is designated for patients who are unable or unwilling to tolerate other osteoporosis agents. Emerging options, including newer SERMs (e.g., bazedoxifene and lasofoxifene) and the monoclonal antibody denosumab, may hold promise for providing protection from bone loss and for fracture risk reduction. Because no single agent is appropriate for all patients, treatment decisions should be made on an individual basis, taking into account the relative benefits and risks in different patient populations.

Combined treatment with dexamethasone and raloxifene totally abrogates osteoporosis and joint destruction in experimental postmenopausal arthritis

“…Numerous new SERMs are currently undergoing clinical development for the prevention and/or treatment of postmenopausal osteoporosis [48]. For example, lasofoxifene was recently described to be associated with reduced risks of fractures, ER-positive breast cancer, coronary heart disease, and stroke in postmenopausal patients with osteoporosis [49].…”

Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled study

“…Many pharmacologic agents are available for postmenopausal osteoporosis, including bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid), hormone therapy, calcitonin, parathyroid hormone (1-34 and 1-84), and the selective estrogen receptor modulator (SERM; also referred to as estrogen receptor agonist/antagonist) raloxifene. Although these therapies are effective in preventing bone loss and/or reducing fracture risk [4,9,10], available options may not be appropriate for all women based on individual benefitrisk profiles. Because of the considerable and growing health and economic impact of postmenopausal osteoporosis and related fractures, the continued development of therapeutic alternatives is essential to ensure that the needs of women are met.…”

Development of Cell-Based High-Throughput Assays for the Identification of Inhibitors of Receptor Activator of Nuclear Factor-Kappa B Signaling

“…6 Four major antiresorptive drugs (agents capable of inhibiting osteoclast formation and/or function) are currently available on the market: estrogen, selective estrogen receptor modulators, bisphosphonates, and calcitonin. [7][8][9][10][11] Nonetheless, these drugs either offer only modest efficacy or may cause adverse side effects in clinical management of various bone disorders. [11][12][13][14] Thus, there is a need for development of more efficacious and safer antiresorptive drugs.…”

“…[7][8][9][10][11] Nonetheless, these drugs either offer only modest efficacy or may cause adverse side effects in clinical management of various bone disorders. [11][12][13][14] Thus, there is a need for development of more efficacious and safer antiresorptive drugs. Currently, the most attractive target for antiresorptive therapy is the receptor activator of nuclear factor-kappa B ligand (RANKL)/ receptor activator of nuclear factor-kappa B (RANK) system.…”