Regulation of bone mass by growth hormone

Growth hormone (GH) is a peptide hormone secreted from the pituitary gland under the control of the hypothalamus. It has a many actions in the body, including regulating a number of metabolic pathways. Some, but not all, of its effects are mediated through insulin-like growth factor-I (IGF-I). Both GH and IGF-I play significant roles in the regulation of growth and bone metabolism and hence are regulators of bone mass. Bone mass increases steadily through childhood, peaking in the mid 20s. Subsequently, there is a slow decline that accelerates in late life. During childhood, the accumulation in bone mass is a combination of bone growth and bone remodeling. Bone remodeling is the process of new bone formation by osteoblasts and bone resorption by osteoclasts. GH directly and through IGF-I stimulates osteoblast proliferation and activity, promoting bone formation. It also stimulates osteoclast differentiation and activity, promoting bone resorption. The result is an increase in the overall rate of bone remodeling, with a net effect of bone accumulation. The absence of GH results in a reduced rate of bone remodeling and a gradual loss of bone mineral density. Bone growth primarily occurs at the epiphyseal growth plates and is the result of the proliferation and differentiation of chondrocytes. GH has direct effects on these chondrocytes, but primarily regulates this function through IGF-I, which stimulates the proliferation of and matrix production by these cells. GH deficiency severely limits bone growth and hence the accumulation of bone mass. GH deficiency is not an uncommon complication in oncology and has long-term effects on bone health. (C) 2003 Wiley-Liss, Inc.