Growth Hormone, Insulin-Like Growth Factors, and the Skeleton
GH and IGF-I are important regulators of bone homeostasis and are central to the achievement of normal longitudinal bone growth and bone mass. Although GH may act directly on skeletal cells, most of its effects are mediated by IGF-I, which is present in the systemic circulation and is synthesized by peripheral tissues. The availability of IGF-I is regulated by IGF binding proteins. IGF-I enhances the differentiated function of the osteoblast and bone formation. Adult GH deficiency causes low bone turnover osteoporosis with high risk of ver-tebral and nonvertebral fractures, and the low bone mass can be partially reversed by GH replacement. Acromegaly is characterized by high bone turnover, which can lead to bone loss and vertebral fractures, particularly in patients with coexistent hypogonadism. GH and IGF-I secretion are decreased in aging individuals, and abnormalities in the GH/IGF-I axis play a role in the pathogenesis of the osteoporosis of anorexia nervosa and after glucocorticoid exposure. (Endocrine Reviews 29: 535-559, 2008) I. Introduction II. The Growth Hormone (GH)/Insulin-Like Growth Factor-I (IGF-I) Axis III. Mechanisms of GH and IGF-I Action in Bone A. GH B. IGF-I C. IGF binding proteins (IGFBPs) IV. Skeletal Manifestations of GH Deficiency and Excess in Humans A. Adult growth hormone deficiency (GHD) B. Skeletal effects of recombinant human GH (rhGH) in adult-onset GHD C. Skeletal manifestations of acromegaly V. Skeletal Manifestations of Selected Diseases with Abnormal GH/IGF-I Axis A. Postmenopausal and senile osteoporosis B. Anorexia nervosa C. Glucocorticoid-induced osteoporosis VI. Conclusions