[Advances in ostheochlast biology: the osteoprotegerin-RANK ligand system]

The differentiation and activation of osteoclasts specialized cells that degrade the bone matrix are decisively regulated by the osteoprotegerin (OPG)-RANK ligand (RANKL) paracrine system. The OPG is a soluble protein, similar to other members of the tumor necrosis factor receptor superfamily, which works as a decoy receptor of RANKL. The biologic activity of OPG counteracts the effects of RANKL by competing with the receptor activator of the nuclear factor *B (RANK); subsequently, the differentiation and activation of osteoclasts is inhibited and bone resorption reduced. The critical role of this pathway in the regulation of bone metabolism has been signalled by the finding of extreme phenotypes (osteoporosis vs. osteopetrosis) in animal models. Further studies with these factors will provide the development of drugs to treat osteoporosis and other metabolic bone diseases.