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Summary We investigated bone structural adaptations to a 16-month school-based physical activity intervention in 202 young boys using a novel analytical method for peripheral quantitative computed tomography scans of the tibial mid-shaft. Our intervention effectively increased bone bending strength in the anterior-posterior plane as estimated with the maximum second moment of area (Imax). Introduction We previously reported positive effects of a physical activity intervention on peripheral quantitative computed tomography (pQCT)-derived bone strength at the tibial mid-shaft in young boys. The present study further explored structural adaptations to the intervention using a novel method for pQCT analysis. Methods Participants were 202 boys (aged 9-11 years) from 10 schools randomly assigned to control (CON, 63 boys) and intervention (INT, 139 boys) groups. INT boys participated in 60 min/week of classroom physical activity, including a bone-loading program. We used ImageJ to process pQCT images of the tibial mid-shaft and determine the second moments of area (Imax, Imin) and cortical area (CoA) and thickness (CTh) by quadrant (anterior, medial, lateral, posterior). We defined quadrants according to pixel coordinates about the centroid. We used mixed linear models to compare change in bone outcomes between groups. Results The INT boys had a 3% greater gain in Imax than the CON boys (p = 0.04) and tended to have a greater gain in Imin (~2%, NS). Associated with the greater gain in Imax was a slightly greater (NS) gain (1-1.4%) in CoA and CTh in the anterior, medial, and posterior (but not lateral) quadrants. Conclusion Our results suggest regional variation in bone adaptation consistent with patterns of bone formation induced by anterior-posterior bending loads.