The receptor activator of NF-kappa B ligand (RANKL) is a member of the
TNF receptor superfamily, essential for osteoclastogenesis. It binds to
its receptor activator of NF-kappa B on the surface of osteoclast
precursors and enhances their differentiation, survival and fusion,
while it activates mature osteoclasts and inhibits their apoptosis. The
effects of RANKL are counteracted by osteoprotegerin (OPG), a
neutralizing decoy receptor. Derangement of the balance in RANKL/OPG
action is implicated in the pathophysiology of metabolic bone diseases,
including osteoporosis. Current therapies used to prevent or treat
metabolic bone diseases are thought to act, at least in part, through
modification of the RANKL/OPG dipole. The idea of using a molecule that
could specifically bind and neutralize RANKL to decrease bone resorption
and subsequent bone loss is appealing. Recombinant OPG was initially
tested. Denosumab, a fully human monoclonal antibody against RANKL, is a
promising antiresorptive agent under investigation. it rapidly decreases
bone turnover markers resulting in a significant increase in bone
mineral density and reduction in fracture risk. However, because
receptor activator of NF-kappa B activation by RANKL is also essential
for T-cell growth and dendritic-cell function, inhibition of its action
could simultaneously affect the immune system, leading to susceptibility
in infections or malignancies