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Denosumab for treatment of osteoporosis in postmenopausal women

Ove Torring

Osteoporosis leads to fragility fractures that are associated with adverse health outcomes, including increased mortality, disability, psychological deterioration and impaired health-related quality of life. Denosumab is a human monoclonal antibody that specifically blocks bone resorption. Denosumab has recently been approved for treatment of postmenopausal osteoporosis. Its efficacy in reducing the risk of fracture has been shown in a large prospective, randomized multicenter study of 7868 postmenopausal women with osteoporosis – the FREEDOM trial. Denosumab 60 mg injected subcutaneously every 6 months for 3 years significantly increased the bone mineral density of the lumbar spine, hip and radius and reduced the relative risk of new vertebral fractures by 68%, hip fractures by 40% and of nonvertebral fractures by 20%, compared with a placebo-treated group. Bone biopsies showed normal trabecular and cortical microarchitecture, normal mineralization and no adverse effects on the formation of lamellar bone. Denosumab is cleared by the reticuloendothelial system and may have advantages for the treatment of osteoporosis in patients with renal impairment. This article summarizes the receptor activator of nuclear factor kB ligand–osteoprotegerin mechanism and a brief description of clinically relevant aspects of denosumab for treatment of osteoporosis in postmenopausal women. The results of the 3-year FREEDOM study are compared with the pivotal fracture data from other antiresorptive therapies for treatment of postmenopausal osteoporotic women (alendronic acid, risedronic acid, raloxifene, ibandronic acid and zoledronic acid). The properties of denosumab for treatment of osteoporosis in patients with renal impairment are discussed.

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