Insulin-like growth factors and bone: the osteoporosis connection revisited.
Tremendous advances have been made in knowledge about the pathogenesis and treatment of osteoporosis, a disease that affects more than 25 million Americans. In particular, it has been determined that two major processes are responsible for osteoporotic fractures. These are: 1) bone mass acquisition during adolescence; and 2) bone loss beyond the sixth decade. The former, and possibly the latter, are regulated by genetic and environmental factors. Insulin-like growth factor-I (IGF-I), a ubiquitous polypeptide, assumes a critical role in both of these processes. Very recent studies have elucidated a complex multifaceted IGF regulatory system in bone and have allowed investigators to consider site-directed approaches to therapy. Even more exciting is the prospect that the genetic regulation of peak bone mass may be controlled by components of the IGF regulatory system. Within the last half decade, tremendous strides have been made in defining the regulatory circuits that determine the expression of skeletal and serum IGF-I. These heritable modulators may be similar or identical to regulators of bone mineral density, thereby joining two distinct phenotypes. This minireview highlights some of the new investigations into the role IGF-I plays in the pathogenesis of osteoporosis. Although recent clinical trials with growth hormone and IGF-I in this disease have been relatively disappointing, advances on other fronts have generated considerable excitement, and these promise new and innovative approaches to this crippling disease.
Rosen
C J
CJ
Maine Center for Osteoporosis Research and Education, St. Joseph Hospital, Bangor 04401, USA. crosen@maine.maine.edu
Donahue
L R
LR
D000293:Adolescent; D000368:Aged; D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling / Q000502:physiology; D001842:Bone and Bones / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000209:etiology* / Q000378:metabolism / Q000628:therapy
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone