Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 92, Issue 11, Pages 4380-4386Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2007-0932
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Objective: The contribution of leptin to bone mass acquisition in humans remains unclear. We investigated the association of the Gln223Arg polymorphism in the leptin receptor gene ( LEPR) with bone mineral content ( BMC) and areal bone mineral density ( aBMD) in prepubertal boys and LEPR interaction with vitamin D receptor ( VDR) genotypes ( Bsm1 and Fok1). Design: In a cross-sectional design with a longitudinal follow-up, dual-energy x-ray absorptiometry measurements at the lumbar spine, hip, femoral diaphysis, and radius were performed at baseline ( mean age 7.4 +/- 0.4 yr) and 2 yr later in 222 healthy Caucasian males. Results: LEPR genotypes were significantly associated with baseline BMC at the hip ( P = 0.017), femur diaphysis ( P = 0.019), and radius ( P = 0.007) and with height ( P = 0.041) as well as with physical activity ( P = 0.016). Associations with height and BMC at femur diaphysis and radius remained significant after 2 yr. Significant differences in 2-yr bone mass gain at the spine and femur neck were also found among LEPR genotypes. In contrast, adjusting BMC for projected bone area ( aBMD) and/or weight, height, and physical activity resulted in a weak association only at the femur ( P = 0.014-0.054). VDR polymorphisms were not associated with BMC or aBMD, but significant interactions occurred between VDR Fok1 and LEPR genotypes. Conclusions: The LEPR Gln223Arg polymorphism was associated with bone mass in growing boys. The association, however, was markedly dependent on bone area, body size, and physical activity, in addition to VDR genetic variation, suggesting that the leptin system may modulate bone mass in humans mostly through indirect mechanisms.
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