This study examines the influence of circulating insulin-like growth factor-1 (IGF-1) and serum leptin on bone mass as well as modulation of bone mass during skeletal development. Moreover, an inverse relationship between IGF-1 and leptin is reported. To evaluate the effects of serum IGF-1 and serum leptin on bone mass in healthy postmenopausal women, and the possible role of IGF-1 in leptin production, we studied a population of 123 women, aged 39-82 years. Bone mineral density (BMD) was determined by whole-body dual-energy X ray absorptiometry, which also enables measurement of body composition. Bone metabolism was assessed by measuring serum total alkaline phosphatase (TAP) and urinary hydroxyproline/creatinine (HP/Cr) excretion. IGF-1 correlated significantly with age (r = -0.28, p < 0.01) and years since menopause (r = -0.24, p < 0.01). A negative correlation was also found with weight and body mass index (r = -0.15, p < 0.05 and r = -0.19, p < 0.05, respectively). Leptin values were strongly correlated with weight (r = 0.7, p < 0.01), BMI (r = 0.7, p < 0.01), fat mass (r = 0.77, p < 0.01), and lean mass (r = 0.39, p < 0.01); a significant correlation was found with total body BMD (r = 0.29, p < 0.01), TAP (r = 0.15, p < 0.05), and HP/Cr (r = 0.18, p < 0.05). After adjustment for BMI, the significance of these relationships disappeared, demonstrating the lack of effect of serum leptin on BMD and bone turnover independent of body weight. On the other hand, the relationship between BMD and fat mass remained statistically significant after adjusting for serum leptin (r = 0.15, p < 0.05). Controlling for BMI eliminated the significant inverse correlation between IGF-1 and leptin; significant differences in leptin levels were found among women in the lower and higher quartile of IGF-1, suggesting that leptin production may be inhibited only at high values of serum IGF-1. We conclude that serum IGF-1 and serum leptin have no direct effect on bone mass and bone turnover.