Insulin-like growth factor I and bone mineral density: experience from animal models and human observational studies

The insulin-like growth factor (IGF) system has been linked to the process of bone acquisition through epidemiological analyses of large cohorts and in vitro studies of bone cells. However, the precise relationship between the expression of IGF-I in bone and skeletal homeostasis or pathological conditions such as osteoporosis, remains poorly defined. Recent advances in genomic engineering have resulted in the development of better in vivo models for testing the role of IGF-I during development and the maintenance of the adult skeleton. Evidence from conditional mutagenesis studies of IGF-I has opened up a new area of in vivo analysis. These studies suggest that serum IGF-I levels may represent more than a storage depot or permissive factor during skeletal acquisition and that tissue IGF-I is essential for normal bone formation. The implications from these animal models are far-reaching and suggest that newer approaches for manipulating the IGF regulatory system may one day be useful as therapeutic adjuncts for the treatment of osteoporosis.