IGF-1 and Osteoporosis: Lessons from Mice and Men

Abstract

The insulin-like growth factors (IGF-1 and -2) are ubiquitous polypeptides that mediate the activity of growth hormone. In many tissues they serve as paracrine or autocrine factors (1). Second only to the liver, the skeleton is an exceptionally rich source of IGF-1 where it is both synthesized and stored. During bone remodeling, both systemic and skeletal IGF-1 play a major role in the recruitment and differentiation of osteoblasts (2, 3). In the course of bone resorption, the initiating bone remodeling event, matrix-bound IGFs are released and become critical coupling agents linking the processes of bone resorption and bone formation (2). Efforts to establish a relationship between synthesis of rapid bone loss or impaired bone formation and changes in the skeletal or circulatory IGF system have led to several hypotheses suggesting that IGF-1 is of pathophysiologic significance (2). Two recent studies, one showing an age-associated decline in skeletal IGF-1, and the other relating serum IGF-1 to bone density, have strengthened the view that the skeletal IGF regulatory system is important in states of impaired bone remodeling (4, 5). Two additional studies have demonstrated a strong relationship between serum IGF-1 and bone mineral density in men with idiopathic osteoporosis (6, 7). Based on these lines of evidence and the concept that bone density at any age is strongly dependent on peak bone mass, our group has considered IGF-1 to be a key factor in the acquisition of peak bone mass. In this paper, data will be presented which suggest that in several inbred strains of mice and in humans, osteoporotic male idiopathic IGF-1 is an important determinant of bone mineral density (BMD).