In the adult skeleton, bone formation is regulated by an event referred to as the coupling of bone formation to resorption (i.e. formation is quantitatively linked to resorption), which is thought to be mediated in part by osteogenic growth factor molecules produced by bone cells. Of the various osteogenic growth factors identified in bone, there is sufficient evidence to document an important role for the insulin-like growth factor (IGF) system in mediating this coupling process. Studies on the basic aspects of the IGF system reveal that it is complex and involves a number of components which include the inhibitory IGF binding protein (IGFBP)-4 and stimulatory IGFBP-5 and their corresponding proteases. This complex regulatory scheme of the IGF component system, together with the finding that all of the IGF system components are regulated in bone cells by both local and systemic effectors of bone metabolism, underscores the importance of the IGFs in mediating coupling of bone formation to resorption. In addition, a number of in vitro and in vivo findings also suggest that the IGF system could play a role in the positive (net gain of bone) or negative (net loss of bone) uncoupling of bone formation to resorption.

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