Skeletal effects of growth hormone and insulin-like growth factor-I therapy

Abstract

The growth hormone/insulin-like growth factor (GH/IGF) axis is critically important for the regulation of bone formation, and deficiencies in this system have been shown to contribute to the development of osteoporosis and other diseases of low bone mass. The GH/IGF axis is regulated by a complex set of hormonal and local factors which can act to regulate this system at the level of the ligands, receptors, IGF binding proteins (IGFBPs), or IGFBP proteases. A combination of in vitro studies, transgenic animal models, and clinical human investigations has provided ample evidence of the importance of the endocrine and local actions of both GH and IGF-I, the two major components of the GH/IGF axis, in skeletal growth and maintenance. GH- and IGF-based therapies provide a useful avenue of approach for the prevention and treatment of diseases such as osteoporosis.

Keywords: Growth hormone (GH); IGF binding proteins (IGFBPs); Insulin-like growth factors (IGFs); Osteoporosis; Skeletal development.

Fig. 1

Model overview of GH/IGF-I regulation of skeletal growth, including both endocrine and local actions of IGF-I. GH acts by increasing hepatic IGF-I production, by increasing local skeletal IGF-I production, and by influencing the bone directly, independent of IGF-I. Hepatic IGF-I acts in an endocrine manner, circulating in the blood primarily as a ternary complex with acid-labile subunit (ALS) and IGF binding protein (IGFBP)-3, although IGF-I can also complex with other IGFBPs. Only a small amount circulates as free IGF-I. Locally produced IGF-I acts on the bone in an autocrine/paracrine manner.