Leptin predicts BMD and bone resorption in older women but not older men: the Rancho Bernardo study

We studied the relation of leptin to bone, bone loss, and bone turnover in community-dwelling men and women. Leptin predicted higher BMD and lower bone turnover only in women. Leptin was not associated with 4-year bone loss in either sex.

Leptin, the protein product of the obesity (OB) gene produced in fat tissue, was originally thought to be involved only in the regulation of food intake and energy balance. Recent evidence suggests that leptin may play a role in the pathophysiology of several chronic diseases. Studies of the association between leptin and bone have been numerous yet inconclusive. Only one previous longitudinal study has been reported, which showed no association of leptin with BMD after adjusting for body size.

We report the association of serum leptin with BMD at the hip, spine, and midshaft radius in community-dwelling men (n = 498) and nonestrogen-using postmenopausal women (n = 411) 45-92 years of age. Serum leptin was measured in blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA; at the same visit, height, weight, and body fat (by bioelectrical impedance analysis) were measured, and bone resorption was assessed in a subset of men (n = 286) and women (n = 241) using urine N-telopeptide (NTX). Four years later, axial BMD was remeasured in 536 participants. Sex-specific associations of leptin with BMD, NTX, and bone loss were tested using regression analysis.

In unadjusted analyses, leptin was associated with BMD at the femoral neck, total hip, lumbar spine, and midshaft radius in both sexes (p < 0.01). In multiple regression analyses, adjusted for age, BMI, and other bone-related factors, only women showed a graded stepwise positive association between serum leptin and BMD at all sites and a negative stepwise association with NTX (all p for trend < 0.01). Baseline leptin levels did not predict 4-year bone loss in either sex.

A favorable dose-dependent leptin-BMD association unexplained by obesity was observed only in women. The reason for the sex difference is unknown.