From mouse to man: Redefining the role of insulin-like growth factor-I in the acquisition of bone mass

Shoshana Yakar, Clifford J. Rosen

Research output: Contribution to journalShort surveypeer-review


The insulin-like growth factor system (IGF) has been linked to the process of bone acquisition through epidemiologic analyses of large cohorts and in vitro studies of bone cells. But the exact relationship between expression of IGF-I in bone and skeletal homeostasis or pathologic conditions, such as osteoporosis, remains poorly defined. Recent advances in genomic engineering have resulted in the development of better in vivo models to test the role of IGF-I during development and maintenance of the adult skeleton. It is now established that skeletal expression of IGF-I is critical for differentiative bone cell function. It may also be essential for the full anabolic effects of parathyroid hormone on trabecular bone and for some component of biomineralization. Evidence from conditional mutagenesis studies suggests that serum IGF-I may represent more than a storage depot or permissive factor during the final phase of skeletal acquisition. This work re-examines the original tenets of the "somatomedin hypothesis" in light of these newer mouse models and their remarkable skeletal phenotypes. The implications 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.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalExperimental Biology and Medicine
Issue number3
StatePublished - Mar 2003


  • Bone volume
  • Conditional mutagenesis
  • IGF-I
  • Osteoblasts
  • Periosteum

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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