title: Growth factors and bone formation in osteoporosis: roles for IGF-I and TGF-beta.
abstract: The cellular mechanisms involved in osteoblast function and bone formation alterations in osteoporosis have been partly elucidated. Recent studies have shown that bone formation abnormalities in various forms of osteopenia result mainly from defective recruitment of osteoblastic cells. These abnormalities in osteoblast function and bone formation are associated with alterations in the expression or production of several growth factors, such as IGFs and TGF-beta, which modulate the proliferation and activity of bone-forming cells. Bone loss related to aging or unloading is characterized by diminished osteoblast proliferation and reduced local concentrations of IGFs and TGF beta. In contrast, estrogen deficiency increases osteoblast proliferation and IGF-I production. These data suggest that alterations in the production of and/or in cell responsiveness to local growth factors may contribute to the bone formation abnormalities seen in these osteopenic disorders. This suggests that preventive or curative treatment with growth factors may be beneficial in osteopenia due predominantly to decreased bone formation. Low doses of IGF-I or TGF-beta have been reported to increase osteoblast recruitment and differentiation, leading to enhanced trabecular bone formation and decreased bone loss in models of osteopenia induced by aging, estrogen deficiency and unloading. A few clinical trials also suggest that low doses of growth factors may stimulate bone formation. Although these findings open up new prospects for the prevention and treatment of osteopenic disorders, progress in this direction awaits the development of factors or analogs that are capable of locally and specifically increasing osteoblast recruitment and differentiation without including side-effects.
authors.affiliation: INSERM_Unité 349, Lariboisière Hospital, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Marie
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology; D000818:Animals; D002986:Clinical Trials as Topic; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D010006:Osteoblasts / Q000378:metabolism; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D015663:Osteoporosis, Postmenopausal / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D011379:Prognosis; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D004967:Estrogens; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I