The anabolic effects of GH/IGF systems on bone

Osteoporosis is the result of imbalance in bone remodeling caused by increased bone resorption and decreased bone formation. In terms of the mechanisms for the age-related impairment in bone formation, a deficiency in growth hormone (GH)/insulin-like growth factor (IGF) system that occurs with age has been proposed to play a major role. The potential causes for age-related decline in GH secretion are under active investigation and may involve multiple mechanisms including GH secretagogues, sex hormones, nutritional status and physical activity. Although a number of animal and clinical studies have provided experimental evidence for potential use of GH/IGF system components to increase bone mass, the clinical utility of GH/IGF system components for treatment of osteoporosis has not come to fruition because of our incomplete understanding of the regulation of production and actions of GH/IGF system components. Regarding the actions of GH in target tissues, there is evidence that IGF system plays a major role in mediating the GH effects. In addition, GH may also exert effects on certain target tissues independent of IGFs. It is also known that GH effects on target tissue involve multiple components of the IGF system including the ligands, receptors, IGF binding proteins (IGFBP), IGFBP proteases and activators and inhibitors of IGFBP proteases. Future studies on the mechanisms that contribute to age-related impairment in GH/IGF axis and the molecular pathways that contribute to the bone forming effects of GH/IGF axis may provide a foundation for the development of safe and effective therapies involving one or more IGF system components to correct bone formation deficit in the elderly subjects.