Mechanisms of disease: roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis.

The discovery of osteoprotegerin, receptor activator of nuclear factor kappa B (RANK) and RANK ligand as critical molecular determinants of osteoclastogenesis and regulators of bone resorption, has revolutionized our understanding of the processes of normal and pathological bone biology. Altering the relative biological availabilities of these molecules has direct consequences for the regulation of both bone resorption and bone remodeling. Importantly, recent research suggests a pivotal role for these molecules in mediating cancer-induced bone destruction. This review summarizes the current evidence of osteoprotegerin, RANK ligand and RANK involvement in the pathophysiology of skeletal metastasis, and of therapeutic targeting of this process.