Effects of Genes, Sex, Age, and Activity on BMC, Bone Size, and Areal and Volumetric BMD

Quantitative genetic analyses of bone data for 710 inter‐related individuals 8–85 yr of age found high heritability estimates for BMC, bone area, and areal and volumetric BMD that varied across bone sites. Activity levels, especially time in moderate plus vigorous activity, had notable effects on bone. In some cases, these effects were age and sex specific. Introduction: Genetic and environmental factors play a complex role in determining BMC, bone size, and BMD. This study assessed the heritability of bone measures; characterized the effects of age, sex, and physical activity on bone; and tested for age‐ and sex‐specific bone effects of activity. Materials and Methods: Measures of bone size and areal and volumetric density (aBMD and vBMD, respectively) were obtained by DXA and pQCT on 710 related individuals (466 women) 8–85 yr of age. Measures of activity included percent time in moderate + vigorous activity (%ModVig), stair flights climbed per day, and miles walked per day. Quantitative genetic analyses were conducted to model the effects of activity and covariates on bone outcomes. Results: Accounting for effects of age, sex, and activity levels, genes explained 40–62% of the residual variation in BMC and BMD and 27–75% in bone size (all p < 0.001). Decline in femoral neck (FN), hip, and spine aBMD with advancing age was greater among women than men (age‐by‐sex interaction; all p ≤ 0.05). %ModVig had the most notable effect on bone; high activity was associated with higher aBMD at all sites, but the magnitude of this effect varied. Activity among men was associated with higher FN BMC and cross‐sectional area (CSA) at the 4% radius, but this was not observed among women (sex‐by‐activity interaction, both p ≤ 0.05). Younger women had greater cortical vBMD (Cort‐vBMD) than younger men, with minimal difference between low and high activity levels. Influence of activity was greater in older women: older women with low activity had lower Cort‐vBMD than older men, but older women with high activity had higher Cort‐vBMD than older men (age‐by‐sex‐by‐activity interaction, p = 0.04). Conclusions: High heritability estimates for DXA and pQCT measures varied across bone sites. Percent time spent in moderate to vigorous activity had the most notable effect on bone, and in some cases, this effect was age or sex specific.