RANKL, a necessary chance for clinical application to osteoporosis and cancer-related bone diseases

Core Tip

Core tip: This review describes a success story from discovery of osteoprotegerin/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK) to clinical application of a fully human anti-RANKL monoclonal antibody to the treatment of osteoporosis and cancer-related bone disorders. RANKL is a key molecule for osteoclast differentiation and activation. Inhibition of RANKL activity with anti-RANKL antibody reduces osteoclastogenesis, resulting in inhibition of bone resorption. Three animal disease models of osteoporosis, hypercalcemia, and osteopetrosis by treating normal mice with soluble RANKL (sRANKL), adenovirus expressing sRANKL, and anti-mouse RANKL neutralizing antibody, respectively, can be established in 2-14 d and the establishment of these animal models could help accelerate research on bone metabolism.