Skeletal actions of insulin-like growth factors

Insulin-like growth factors (IGFs) promote longitudinal growth and display anabolic effects in adult bone by acting through endocrine and autocrine/paracrine mechanisms. Binding of IGF-I to its specific tyrosine-kinase receptor leads to interaction with the intracellular proteins, insulin receptor substrate-1 and -2, and the activation of distinct intracellular signaling pathways. In cartilage, IGF-I regulates the differentiation of chondrocytes and stimulates the synthesis of components of the extracellular matrix. In bone tissue, IGF-I increases the function of the differentiated osteoblasts and mediates selected anabolic actions of parathyroid hormone. Genetically modified mice, in which selected components of the IGF system were targeted in a tissue-specific fashion, have documented that circulating IGF-I is essential for physiological skeletal growth and adult bone remodeling and that local autocrine/paracrine IGF-I activities are required for optimal trabecular bone mass and mineralization. Studies in humans have indicated a correlation between serum IGF-I levels and bone mineral density. However, there is little information on the use of IGF-I in patients with metabolic bone disease.