Denosumab: A promising drug for the prevention and treatment of osteoporosis

Abstract

Denosumab (formerly AMG 162) is a fully human monoclonal antibody with a high affinity and specificity for receptor activator of nuclear factor-κB ligand, a cytokine member of the tumor necrosis factor family that is the primary mediator of osteoclastic bone resorption. Increased bone resorption is a prominent feature in the pathogenesis of postmenopausal osteoporosis and other skeletal disorders. Denosumab inhibits the action of receptor activator of nuclear factor-κB ligand, thereby reducing the differentiation, activation and survival of osteoclasts, and slowing the rate of bone resorption. Postmenopausal women with low bone mineral density treated with denosumab have an increase in bone mineral density and a reduction of bone turnover markers that is rapid, sustained and reversible. In patients with multiple myeloma and bone metastases from breast cancer, denosumab reduces bone turnover to a similar magnitude but in a more sustained manner than intravenous pamidronate. Denosumab is well tolerated with adverse events similar to placebo. Denosumab is a promising investigational agent for the management of osteoporosis and other diseases associated with bone loss. ©2006 Future Medicine Ltd.