AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation and synovitis which evolve into joint destruction and deformity. Bone abnormalities are represented by marginal bone erosions and iuxta-articular and generalized osteoporosis. Overactivation of osteoclasts along with dysregulation of osteoblasts are the key events. Bone resorption is mediated by the receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANK-L), responsible for the differentiation, proliferation, and activation of osteoclasts. RANK-L binds its receptor RANK, localized on the surface of preosteoclasts and mature osteoclasts promoting osteoclastogenesis. High levels of RANK-L were demonstrated in active RA patients. Denosumab, a fully human monoclonal antibody, binds RANK-L and suppresses the RANK–RANK-L signaling pathway leading to the inhibition of osteoclastogenesis. A retrospective analysis of published studies such as clinical trials evidenced the efficacy of denosumab in preventing bone erosion progression in RA patients.