Leptin and biochemical markers of bone turnover in dialysis patients

The adipose tissue cytokine leptin is suggested to interfere with bone turnover mechanisms because, in rats with leptin deficiency, intra-cerebroventricular administration of this cytokine causes a reduction in bone mass. We studied the relationship between plasma leptin and biochemical bone turnover indicators in 161 hemodialysis (HD) patients.

Plasma leptin was sex-dependent, being significantly higher (p<0.001 ) in female dialysis patients than in male dialysis patients, and it related directly to body mass index (BMI). In males, plasma leptin related inversely to serum intact parathyroid (PTH) (partial r= -0.34), serum PTH(1-84) (r= -0.36), carboxyterminal PTH (C-PTH) fragment (r= -0.31) and serum PTH(1-84)/C-PTH fragment ratio (r= -0.22), while no such relationships were found in females. Of 93 male dialysis patients, 44 had a serum intact PTH <100 pg/mL and 14 had a serum PTH(1-84)/C-PTH fragment ratio <1. In a multiple logistic regression analysis in males, for each 1 ng/mL increase in plasma leptin there was an 11% excess risk of serum intact PTH <100 pg/mL (odds ratio (OR) 1.11, 95% confidence interval (95% CI): 1.02-1.20, p=0.01) and a similar OR was found when low bone turnover was defined based on a serum PTH(1-84)/C-PTH fragment ratio <1 (p=0.01). In addition, plasma leptin related inversely to skeletal alkaline phosphatase and again this relationship was found in male but not in female dialysis patients.

Our data support the theory that leptin reduces bone turnover in male dialysis patients. Whether this link underlies a noxious or a protective mechanism, i.e. if it can serve to limit high bone turnover due to hyperparathyroidism, remains to be established in prospective studies based on solid outcome measures like the risk of fractures.