Abstract
Fifteen years have passed since discovery of RANKL (receptor activator of NF-κB ligand), resulting in identification of the mechanisms regulating osteoclast differentiation and function. The discovery of RANKL contributed to development of a fully human anti-RANKL monoclonal neutralizing antibody (denosumab). Denosumab has been clinically available for treatment of osteoporosis and cancer-induced bone diseases in the US, Europe and many countries since 2010. In Japan denosumab has been clinically available for treatment of cancer-induced bone diseases since 2012 and it was approved for the treatment of osteoporosis in March 2013. Because RANKL is the absolute factor for osteoclast differentiation, anti-RANKL antibody is very effective and its application is good news for many patients. In this review I described the mechanisms regulating osteoclast differentiation and the strong increase of bone mass in normal mice with anti-mouse RANKL antibody. The single injection of the antibody markedly reduced the number of osteoclasts, inhibited bone resorption, and increased bone mass within several days.
