Genetic influence on the association between bone mineral density and testosterone in Korean men.

Abstract

Low bone mineral density (BMD) leads to an increased risk of osteoporotic fracture. Total testosterone and free testosterone were positively associated with BMD, which was significantly influenced by the additive genetic effects. This cross-sectional study aimed to evaluate an association between testosterone and BMD and the influence of genetic factors on the association. Study subjects were 1070 Korean men including 144 pairs of monozygotic twins and their family members. Levels of serum total testosterone and sex hormone binding globulin (SHBG) were measured by chemiluminescence immunoassay. Calculated free testosterone (cFT) was then determined using Vermeulen's method. BMDs of the whole body and specific regions were measured using dual-energy X-ray absorptiometry. Linear mixed regression analyses showed that total testosterone and cFT were positively associated with BMD at most regions, after considering intra-familial relationship and covariates including fat mass, lean mass, and SHBG. SHBG had an inverse association with BMD at the pelvis but not with the BMD at other regions after adjusting for all covariates and cFT. Co-twin control analysis in monozygotic twins found no association between pairwise difference of testosterone and pairwise difference of BMD. Bivariate variance component analysis showed that both total testosterone and cFT had a significant positive additive genetic correlation with BMD at rib, spine, and arm, whereas SHBG had no significant genetic correlation with BMD. Inverse environmental correlations were seen between total testosterone and BMDs at the lumbar spine and arm. This Korean twin and family study showed that both total testosterone and free testosterone were positively associated with BMD and that genetic effects were significant on the association between testosterone and BMD.