Serum leptin as a determinant of bone resorption in healthy postmenopausal women

To examine the relationships between serum leptin and bone metabolism, we measured bone mineral density (BMD) at the spine and the hip, fasting serum leptin, and osteocalcin and urinary excretion of C-terminal crosslinking telopeptide of type I collagen (CTX), as markers of bone formation and resorption, respectively, in 121 postmenopausal women aged 54 +/- 5 years. These parameters were also assessed at 6 months and 2 years of treatment with either 2.5 mg tibolone (n = 34), 1.25 mg tibolone (n = 45), or 2 mg estradiol plus 1 mg norethindrone acetate (n = 42). At baseline, serum leptin correlated positively with spine (r = 0.21, P = 0.02) and total hip (r = 0.26, P = 0.0044) BMD and negatively with CTX (r = -0.38, P < 0.0001) and osteocalcin (r = 0.21, P = 0.025). After adjustment for BMI and for fat mass, the association between serum leptin and CTX persisted with a partial correlation coefficient of -0.18 (P = 0.046) and of -0.22 (P = 0.03), respectively. Women in the highest quartile of leptin levels had 11% higher total hip (P = 0.0039) and lumbar spine BMD (P = 0.016), 21% lower osteocalcin (P = 0.01), and 38% lower CTX (P = 0.0005) than women in the lowest quartile (P < 0.05). During treatment, serum leptin levels increased (+14.7 +/- 47.3%, P = 0.019), without significant difference between the groups. This increase correlated with the increase in body weight (r = 0.46, P < 10(-4)). No correlation was found between the changes in leptin and the changes in bone parameters. In conclusion, leptin may play a role as a determinant of bone resorption in healthy, untreated postmenopausal women, but the effect of estradiol or tibolone on bone are not mediated by leptin.