Denosumab (RANKL Inhibitor): A Potent Anti-Resorptive Agent

ABSTRACT

Denosumab, a fully human monoclonal antibody to the receptor activator of nuclear factor-kappa B ligand, was introduced and used as an anti-osteoporotic agent. Denosumab prevents bone resorption by inhibiting the differentiation and action of osteoclasts, resulting in an increase of bone mineral density and broad-spectrum anti-fracture efficacy. Clinical studies, including FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every Six Months) and its extension up to 10 years, FREEDOM Extension, demonstrated its long-term efficacy and safety in postmenopausal osteoporosis. In addition, the efficacy and safety of denosumab were confirmed in male osteoporosis and glucocorticoid- induced osteoporosis. Therefore, recent clinical guidelines recommend denosumab as an initial treatment. This review summarizes the mechanism of action, pharmacological characteristics, efficacy, and safety issue of denosumab.