Growth hormone, insulin-like growth factors, and the skeleton

Abstract

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 vertebral 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.

Figure 1

Effects of GH and IGF-I on bone. ---> not consistently demonstrated effect; > minor stimulating effect; > major stimulating effect. FGF, Fibroblast growth factor; E2, estradiol; OPG, osteoprotegerin.

Figure 2

Scatter plots of BMD T-scores in patients with GHD (A) or acromegaly (B), with and without fractures. NS, Not significant. [Adapted from G. Mazziotti et al.: J Bone Miner Res 21:520–528, 2006 (234); and S. Bonadonna et al.: J Bone Miner Res 20:1837–1844, 2005 (276), with permission of the American Society for Bone and Mineral Research.]

Figure 3

Prevalence of fractures in adult-onset GHD, untreated and treated (early and late in the course of the disease) with rhGH. *, P < 0.05 untreated vs. late treated or untreated GHD. [Adapted from G. Mazziotti et al.: J Bone Miner Res 21:520–528, 2006 (234) with permission of the American Society for Bone and Mineral Research.]

Figure 4

Differences in fracture rates and BMD between patients with active acromegaly and those with controlled acromegaly. *, P < 0.05 controlled vs. active acromegaly. [Modified from S. Bonadonna et al.: J Bone Miner Res 20:1837–1844, 2005 (276), with permission of the American Society for Bone and Mineral Research.]