Osteoprotegerin and osteoprotegerin-ligand balance: a new paradigm in bonemetabolism providing new therapeutic targets

Osteoprotegerin-ligand, also called Osteoclast Differentiation Factor or RA NK-ligand, its receptor RANK and its decoy receptor Osteoprotegerin are key molecules regulating osteoclast differentiation and activation. In this vi ew we discuss structure and expression of these molecules, the genetic mode ls addressing their function and their role in in vivo models of osteoclast differentiation and activation. The new paradigm that has evolved from the se studies, is not only important in normal bone homeostasis but also appea rs to play a role in different diseases that affect the skeleton, such as o steoporosis, inflammatory joint disease and cancer. It has opened a new era in bone research by increasing our molecular knowledge and providing new t herapeutic targets in bone disease.