Relationships between bone mass and circulating leptin concentrations in Hutterites

Abstract

A limited number of previous studies have shown inverse associations between bone mass or density and circulating leptin in humans. Relationships between bone mass and circulating leptin in Hutterites, who have elevated bone density, are unknown. Knowledge gained from studies in mice suggests that Hutterites exhibit traits consistent with a deficiency in circulating leptin or in leptin signaling. We examined relationships between whole body (WB) and regional (lumbar, total hip, femoral neck, trochanter) bone mineral content (BMC) by dual energy X-ray absorptiometry and circulating leptin in 249 Hutterites (137 female) ages 20–55 years and 72 similarly aged non-Hutterites (37 female). We tested the hypothesis that (1) Hutterites will have low circulating leptin concentrations for a given amount of body fat compared to non-Hutterites, and (2) controlling for body fat, there will be an inverse relationship between BMC and circulating leptin among Hutterites. Hutterites had higher BMC than non-Hutterites at all skeletal sites after adjusting for site-specific bone area, age, and sex ( P ≤ 0.02). Hutterite females had higher leptin concentrations than non-Hutterite females [geometric mean and 95% confidence interval (CI): 18.38 (17.18, 19.67) vs. 14.30 (12.55, 16.28), P ≤ 0.001) after adjusting for WB fat mass. Hutterite males also had higher leptin concentrations than non-Hutterite males [geometric mean and 95% CI: 6.53 (6.11, 6.98) vs. 5.62 (4.98, 6.35), P = 0.03) after adjusting for WB fat mass. We used backward stepwise regression to determine significant ( P ≤ 0.10) covariates to include in models predicting WB and regional BMC among Hutterites (separately by sex). Subsequently, we entered leptin (log-transformed) to models to test for significance ( P ≤ 0.05). After adjusting for covariates, leptin concentration was not a significant predictor of BMC at any site, in either sex, among Hutterites. It is possible that genetic influences that interfere with hypothalamic leptin signaling, in a manner unrelated to adipocyte leptin production, contribute to elevated Hutterite bone density.