Bone mineral density directly correlates with elevated serum leptin in haemodialysis patients

Background. Experimentally, leptin has a positive effect on bone mass when infused intravenously, but a negative one after intracerebroventricular administration. Renal failure increases its serum level above the concentration beyond which its transport to the brain may be saturated. Thus, we tested, in a chronic haemodialysis population, the hypothesis of a positive relationship between serum leptin and bone mineral density (BMD) when serum levels are above this threshold. Methods. Serum leptin (using a two-site RIA), and BMD at the femoral neck, midshaft, and ultradistal radius, as measured by DEXA, were assessed in 17 female and 16 male chronic dialysis patients, with comparable calcium and phosphate metabolism, age and dialysis duration. Results. Polynomial regression analysis showed a U-shaped correlation between BMD Z-score, with an inflexion point, which may correspond to the concentration threshold at which leptin blood-brain carrier is saturated. Linear regression analysis showed no correlation between BMD and serum leptin levels below these points but a significant positive correlation between BMD at the two radius sites and leptin levels above these points. The correlation remained significant after adjustment for BMI, serum PTH and duration of dialysis. Leptin levels were twice as high in female patients and associated with higher BMD Z-scores close to zero. Conclusions. This study suggests a bone-sparing effect of serum leptin in haemodialysis patients only when the serum levels of leptin were higher than the presumed threshold of blood-brain transport saturation. Higher leptin levels in post-menopausal female haemodialysis patients than in male patients may account for their slower bone loss with ageing.