Objective: To examine the hypothesis of an influence of leptin on growth factors and on biochemical markers of bone turnover of prepubertal overweight children. Design and Methods: 395 prepubertal children, 6 - 13 years of age, were selected and the relationships between circulating serum levels of leptin and insulin-like growth factor I (IGF-I), insulin growth factor binding protein-3 (IGFBP-3) and some biochemical markers of bone turnover ( osteocalcin, OC; carboxyterminal propeptide of type I procollagen, PICP, and carboxyterminal propeptide of type I collagen, ICTP) were analyzed. The subjects were subdivided into normal weight ( NW, n = 163) and weight excess ( WE, n = 232) subjects. Results and Conclusions: Significant differences between the two groups were found for leptin ( p < 0.01), IGF-I (p < 0.01) and IGFBP-3 ( p < 0.01), with higher values in WEs, and for OC p < 0.01) with higher values in NWs. A significant reduction of leptin ( p < 0.01) and IGFBP-3 ( p < 0.01) serum values and an increase of those of OC ( p < 0.01) and PICP ( p < 0.05), but not of ICTP, were registered in 103 WEs who showed a drop in weight excess during a weight-excess reduction program. No variations were observed in 26 non-responsive subjects. In a multivariate analysis in which leptin, corrected by BMI and sex, was the independent variable, a significant negative correlation was found with PICP (beta = - 0.235, p < 0.01), IGF-I (beta = - 0.180, p < 0.01) and height velocity (beta = - 0.155, p < 0.01). There was no correlation with OC, ICTP and IGFBP-3. The results demonstrate that nutritional status and leptin levels are involved in the regulation of growth factors and biochemical markers of bone formation. Copyright (C) 2004 S. Karger AG, Basel.