IGF-I and osteoporosis.

Serum IGF-I is controlled by several different regulatory factors. The final adult level represents the sum of the inert circulating depot, newly derived IGF-I synthesized from various tissues including liver, heart, kidney, bone, and others, and the departure from the circulation of IGF-I through mechanisms including receptor internalization and proteolysis of several IGFBPs. Although there is a numerical relationship between measurable IGF-I and bone mass, or risk of fractures, it is not clear that it is causal. Certainly, in situations like chronic undernutrition, which can lead to musculoskeletal instability and fractures, hepatic IGF-I expression is impaired. Yet, it is uncertain whether low levels of circulating IGF-I actually cause osteoporosis. Moreover, it has not been proved that serum levels of this peptide always reflect tissue concentrations. Caution must be undertaken in deciphering the results of a low, normal, or high IGF-I in relation to osteoporosis. Future studies should help define more clearly the possible pathogenic relationship between IGF-I and bone mass.