Physical Activity and Bone Accretion: Isotemporal Modeling and Genetic Interactions

Purpose This study aimed to determine if replacing time spent in high- and low-impact physical activity (PA) predicts changes in pediatric bone mineral density (BMD) and content (BMC). Methods We analyzed data from the longitudinal Bone Mineral Density in Childhood Study (N = 2337 with up to seven visits). The participants were age 5-19 yr at baseline, 51.2% were female, and 80.6% were nonblack. Spine, total hip, and femoral neck areal BMD and total body less head (TBLH) BMC Z-scores were calculated. Hours per day spent in high- and low-impact PA were self-reported. Standard covariate-adjusted (partition model) and time allocation-sensitive isotemporal substitution modeling frameworks were applied to linear mixed models. Statistical interactions with sex, self-reported ancestry, age, and bone fragility genetic scores (percentage of areal BMD-lowering alleles carried) were tested. Results In standard models, high-impact PA was positively associated with bone Z-score at all four skeletal sites (e.g., TBLH-BMC Z-score: beta = 0.05, P = 2.0 × 10^-22), whereas low-impact PA was not associated with any of the bone Z-scores. In isotemporal substitution models, replacing 1 h·d^-1 of low- for high-impact PA was associated with higher bone Z-scores (e.g., TBLH-BMC Z-score: beta = 0.06, P = 2.9 × 10^-15). Conversely, replacing 1 h·d^-1 of high- for low-impact PA was associated with lower bone Z-scores (e.g., TBLH-BMC Z-score: beta = -0.06, P = 2.9 × 10^-15). The substitution associations were similar for each sex and ancestry group, and for those with higher and lower genetic scores for bone fragility (P-interactions > 0.05), but increased in strength among the older adolescents (P-age interactions < 0.05). Conclusions Time-sensitive models suggest that replacing low-impact PA for high-impact PA would be beneficial for the growing skeleton in the majority of children.