Objective: The purpose of this study was to investigate the effect of raloxifene on leptin and insulin-like growth factor-I levels and their relation with the biochemical markers of bone metabolism in postmenopausal women. Study design: Sixty-four women were given 60 mg/d raloxifene for 6 months. Serum leptin, insulin-like growth factor-I, alkaline phosphatase, calcium, osteocalcin, and collagen type I cross-link C-telopeptide levels were measured before and after the treatment. The patients were grouped as obese (body mass index, >= 25 kg/m(2)) or non-obese (body mass index, < 25 kg/m(2)). Results: The mean basal leptin level was significantly higher (P < .001), and the mean cross-link C-telopeptide level was significantly lower (P = .001) in obese patients. Raloxifene therapy increased leptin levels (P < .001) and decreased insulin-like growth factor-I, alkaline phosphatase, and cross-link C-telopeptide levels significantly (P < .001). There was a strong negative correlation between leptin and cross-link C-telopeptide (r = -0.703; P < .001). Insulinlike growth factor-I was not correlated with any parameter. Conclusion: Raloxifene increases serum leptin levels while decreasing bone resorption in postmenopausal women. (c) 2005 Elsevier Inc. All rights reserved.