Bone metabolism in relation to alterations in systemic growth hormone.

Growth hormone (GH) has a major role in the maintenance of bone mass in adults by regulating bone remodeling through a complex interaction of circulating GH, insulin-like growth factors (IGFs), IGF binding protein (IGFBPs), and locally produced IGFs and IGFBPs, acting in an autocrine and paracrine way. In vitro data has greatly increased our understanding of GH and IGFs effects and regulation in bone cells under controlled conditions, and especially the molecular pathways involved. However, the GH-and type I IGF-receptor are present in many tissues and various systemic factors may potentially regulate local expression of IGFs and IGFBPs in the intact organism. The use of genetically altered mice has changed this and had a major impact on defining the role of IGFs in skeletal homeostasis, and especially the role of systemic IGF-I in the development and maintenance of the adult skeleton. The focus of this review is to describe recent work on the effect of GH/IGF on remodeling in the adult skeleton emphasizing on data obtained in patient populations (i.e. acromegaly, GH deficiency, postmenopausal osteoporosis) and experimental models (i.e. animals with genetically altered expression of different GH and IGF family members) characterized by different systemic levels of these proteins. The role of IGF-I as a coupling agent between resorption and bone formation through effects on osteoprotegerin (OPG) and receptor activator of NFkappaB ligand (RANKL) are also discussed.