Current and emerging pharmacologic therapies for the management of postmenopausal osteoporosis

Postmenopausal osteoporosis is an asymptomatic skeletal disease that is often underdiagnosed and undertreated. Osteoporotic fractures are associated with substantial morbidity and mortality and impaired quality of life-socially, emotionally, and financially. Considering the growing burden of osteoporotic fractures worldwide, there remains an ongoing need for progress in the diagnosis of osteoporosis, identification of individuals at high fracture risk, and treatment to prevent fractures. Adequate intake of calcium and vitamin D is recommended as baseline therapy for osteoporosis prevention and treatment. Available pharmacological agents for the management of postmenopausal osteoporosis may not be appropriate for all women. Oral bisphosphonates are generally considered first-line therapy for patients with osteoporosis, but their use may be limited by gastrointestinal side effects. Other agents include hormone therapy, the selective estrogen receptor modulator (SERM) raloxifene, salmon calcitonin, teriparatide (human recombinant parathyroid hormone), and strontium ranelate (in some countries). Factors that may contribute to poor compliance and persistence with current osteoporosis therapies include drug intolerance, complexity of dosing regimens, and poor understanding of the relative benefit and risk with treatment. Emerging therapies for postmenopausal osteoporosis include novel SERMs (bazedoxifene, lasofoxifene, ospemifene, arzoxifene) and denosumab. Because SERMs can display mixed functional estrogen receptor agonist or antagonist activity depending on the target tissue, they may confer beneficial effects on bone with limited stimulation of other tissues (e.g., breast, endometrium). Clinical investigation of these promising new agents is ongoing to evaluate efficacy and safety, with the goal of developing effective strategies to maximize long-term tolerance, compliance, and persistence with therapy.