Jonathan A Mitchell, Alessandra Chesi, Shana E McCormack, Diana L Cousminer, Heidi J Kalkwarf, Joan M Lappe, Vicente Gilsanz, Sharon E Oberfield, John A Shepherd, Andrea Kelly, Struan F A Grant, Babette S Zemel

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). We analyzed data from the longitudinal Bone Mineral Density in Childhood Study (N=2,337 with up to 7 visits). The participants were aged 5-19 years at baseline, 51.2% were female and 80.6% were non-Black. Spine, total hip, and femoral neck areal BMD (aBMD) and total body less head (TBLH) BMC Z-scores were calculated. Hours per day (h/d) 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 aBMD lowering alleles carried) were tested. 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=2.0x10), whereas low impact PA was not associated with any of the bone Z-scores. In isotemporal substitution models, replacing 1 h/d of low-for-high impact PA was associated with higher bone Z-scores (e.g., TBLH-BMC Z-score: beta=0.06, P=2.9x10). Conversely, replacing 1 h/d of high-for-low impact PA was associated with lower bone Z-scores (e.g., TBLH-BMC Z-score: beta=-0.06, P=2.9x10). 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). 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.