Denosumab (Dmab) was the first monoclonal antibody (mAb) approved for the treatment of osteoporosis . It blocks the receptor activator for nuclear factor κB ligand (RANKL) and acts as a potent antiresorptive agent . In contrast to classic antiresorptive agents, Dmab treatment leads to a progressive increase in bone mass, but the mechanisms remain controversial . Recently, RANKL signaling in osteoblastogenesis and bone formation and RANKL reverse signaling in coupling bone resorption and formation were demonstrated . Thus, here we discuss the roles of RANKL signaling and RANKL reverse signaling in the bone-forming effects of Dmab.