Emerging anti-osteoclast therapy for rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder characterized by progressive destruction of affected synovial joints. Recently, it was demonstrated that osteoclasts play critical roles in bone destruction in RA. Receptor activator of NF-κB ligand (RANKL), which belongs to the tumor necrosis factor superfamily, is indispensable for osteoclast differentiation and bone destruction in RA. Denosumab, a monoclonal antibody against human RANKL, not only increased bone mineral density, but also efficiently suppressed the progression of bone erosion in RA patients in a randomized controlled study. However, denosumab did not reduce the cartilage destruction or disease activity in RA, and further investigation is required to establish the appropriate positioning of denosumab in the treatment strategy of RA.