Clinical use of denosumab for the treatment for postmenopausal osteoporosis.

Denosumab is a fully human monoclonal antibody with high affinity and specificity for human receptor activator of nuclear factor kappa B ligand (RANKL), the principal regulator of osteoclastic bone resorption. By binding to RANKL, denosumab prevents it from binding to its receptor on the cell surface of pre-osteoclasts and mature osteoclasts, thereby reducing the formation, activity, and survival of osteoclasts and inhibiting osteoclastic bone resorption. In a large, randomized, placebo-controlled clinical trial in postmenopausal women with osteoporosis, denosumab 60 mg administered subcutaneously every 6 months reduced levels of bone turnover markers, increased bone mineral density, and reduced the risk of vertebral fractures, hip fractures, and non-vertebral fractures. There was no significant difference between denosumab and placebo in the overall risk of adverse events or serious adverse events. Denosumab was associated with a significant increase in the risk of eczema and cellulitis, and a significant decrease in the risk of falling and concussions. Denosumab recently received regulatory approval for the treatment of postmenopausal women with osteoporosis at high risk for fracture, with no dose adjustment in patients with renal impairment. Denosumab is a new therapeutic option to reduce fracture risk in women with postmenopausal osteoporosis, especially for those with impaired renal function or with intolerance or poor response to oral therapy.