Gender Differences in the Genetic Factors Responsible for Variation in Bone Density and Ultrasound

Abstract Although genetic factors are thought to explain a large proportion of the variation in bone density in women, few studies have been conducted in men. Therefore, it is unclear whether the individual differences in bone strength between men and women are a reflection of gender differences in the relative influence of genetic and environmental factors on bone density variance. The aim of this study was to determine if there were gender differences in the genetic components of variance for bone density and ultrasound. In addition, the study aimed to explore the hypothesis that there are unique gender-specific genetic determinants of these traits. Bone mineral density (BMD) of the hip, distal forearm, and lumbar spine were measured by dual-energy X-ray absorptiometry (DXA) as well as quantitative ultrasound (QUS) at the calcaneus in healthy female twin pairs (286 identical [MZ] and 265 nonidentical [DZ]), male twin pairs (72 MZ and 65 DZ), and 82 opposite-sex (OS) pairs aged between 18 and 80 years. For hip BMD, distal forearm, and QUS measurements, the differences between MZ correlations and like-sex DZ correlations were similar for both sexes, suggesting little difference in the component of total variance explained by genetic factors between male and female twin pairs. However, correlations between OS twin pairs were lower than that of like-sex twin pairs, suggesting the possibility of unique gender-specific genetic effects. At the forearm, model fitting suggested a small gender difference in the magnitude of genetic variance as well as the presence of a unique gender-specific genetic variance component. Hip, lumbar spine, and QUS measurements were better explained by models that assumed no gender differences in genetic variance between the sexes, but the study had insufficient power to detect small differences in the genetic components of variance. The results of this study suggest that the proportion of bone strength variance explained by genetic factors is similar for men and women. However, at some regions there is evidence to suggest a gender-specific genetic component to the overall genetic variance.