Bone loss - Factors that regulate osteoclast differentiation: an update

Osteoclast activation is a critical cellular process for pathological bone resorption, such as erosions in rheumatoid arthritis (RA) or generalized bo ne loss. Among many factors triggering excessive osteoclast activity, cytok ines such as IL-1 or tumour necrosis factor (TNF)-alpha play a central role . New members of the TNF receptor ligand family (namely receptor activator of nuclear factor-kappaB [RANK] and RANK ligand [RANKL]) have been discover ed whose cross-interaction is mandatory for the differentiation of osteocla sts from hemopoietic precursors, in both physiological and pathological sit uations. Osteoprotegerin, a decoy receptor which blocks this interaction, d ecreases osteoclast activity and could have a fascinating therapeutic poten tial in conditions associated with upregulated bone resorption.