BACKGROUND: The obese are usually protected against osteoporosis and have increased bone mineral density and plasma leptin concentrations. A recent in vitro study demonstrated that leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts, suggesting an influence of leptin on bone mass. However, little is known about the relationship between plasma leptin and bone mass in postmenopausal women with osteoporosis. OBJECTIVE: To investigate plasma leptin concentrations in postmenopausal women with osteoporosis to improve the understanding of the role of leptin in determining bone mass. METHODS: Fifty postmenopausal women with osteoporosis (ages 61.18+/-6.51 years; body mass index (BMI) 28. 91+/-3.44kg/m(2), mean+/-s.d.) and 30 age- and BMI-matched healthy postmenopausal women were included in the study. Bone mineral densities (BMD) were measured by dual energy X-ray absorptiometry. Plasma leptin concentrations were determined using an immunoradiometric assay. RESULTS: The median spine BMD value in the patient group (0.695+/-8.26g/cm(2), median+/-s.e.m.) was significantly lower than that in the control group (1.006+/-1. 29g/cm(2), median+/-s.e.m.; z=-7.454, P<0.001). The median plasma leptin concentration in the patient group (18.70+/-1.78ng/ml, median+/-s.e.m.) was not significantly different from that in the control group (22.35+/-2.20ng/ml, median+/-s.e.m.; z=-1.630, P=0. 103). Plasma leptin concentrations were correlated with BMI in both groups (r(s)=0.394, P=0.031 in controls and r(s)=0.404, P=0.004 in the patient group). There was no correlation between plasma leptin concentrations and BMD values in controls (r(s)=-0.107, P=0.575) but a weak correlation was observed in the patient group (r(s)=0.285, P=0.045). CONCLUSION: Our data suggest that circulating plasma leptin does not have a significant direct influence on bone mass in postmenopausal women.