Is There a Causal Relationship between Physical Activity and Bone Microarchitecture? A Study of Adult Female Twin Pairs

The reasons for the association between physical activity (PA) and bonemicroarchitecture traits are unclear. We examined whether these associations were consistent with causation and/orwith shared familial factors using a cross-sectional study of 47 dizygotic and 93monozygotic female twin pairs aged 31-77 years. Images of the nondominant distal tibia were obtained using high-resolutionperipheral quantitative computed tomography. The bone microarchitecture was assessed using StrAx1.0 software. Based on a self-completed questionnaire, a PA index was calculated as a weighted sum of weekly hours of light (walking, light gardening), moderate (social tennis, golf, hiking), and vigorous activity (competitive active sports) = light + 2 * moderate + 3 * vigorous. We applied Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) to test whether cross-pair cross-trait associations changed after adjustment for within-individual associations. Within-individual distal tibia cortical cross-sectional area (CSA) and cortical thickness were positively associated with PA (regression coefficients [ss] = 0.20 and 0.22), while the porosity of the inner transitional zone was negatively associated with PA (ss = -0.17), all p < 0.05. Trabecular volumetric bonemineral density (vBMD) and trabecular thickness were positively associated with PA (ss = 0.13 and 0.14), and medullary CSA was negatively associated with PA (ss = -0.22), all p = 0.01. Cross-pair crosstrait associations of cortical thickness, cortical CSA, andmedullary CSA with PA attenuated after adjustment for thewithin-individual association (p = 0.048, p = 0.062, and p = 0.028 for changes). In conclusion, increasing PA was associated with thicker cortices, larger cortical area, lower porosity of the inner transitional zone, thicker trabeculae, and smaller medullary cavities. The attenuation of cross-pair crosstrait associations after accounting for the within-individual associations was consistent with PA having a causal effect on the improved cortical and trabecular microarchitecture of adult females, in addition to shared familial factors. (c) 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).