Influence of RANKL inhibition on immune system in the treatment of bone diseases

Receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast differentiation, activation and survival. Recently, denosumab, a human monoclonal antibody to RANKL, has been tested in the treatment of osteoporosis. But the interactions between RANKL, receptor activator of nuclear factor-κB (RANK) and osteoprotegerin (OPG) are also involved in immune regulations in addition to bone metabolism. So, blocking RANKL could interplay with immune cells and have systemic effects. Here, we review biological data regarding potential consequences of RANKL blocking on the immune system.