Exploring the mediating role of telomere length in the association between physical activity and bone mineral density.

Background: Physical activity may mitigate osteoporosis progression by modulating telomere shortening processes.

Aims: To explore the mediating role of telomere length (TL) in the relationship between physical activity and bone mineral density (BMD).

Methods: This study enrolled 2,394 participants aged 50 years and older from the U.S. National Health and Nutrition examination Surveys. TL was measured by quantitative polymerase chain reaction (qPCR) method (TeloMean) and DNA methylation data (HorvathTelo), and accelerated telomere attrition was assessed through residual-based indices of TeloMeanAccel and HorvathTeloAccel. Physical activity was assessed via questionnaire and BMD was measured at multiple body sites. Multiple linear regression models were utilized to evaluate associations between TL metrics, physical activity, and BMD. Mediation analysis, restrict cubic spline (RCS) modeling, subgroup analyses and sensitivity analyses were further conducted.

Results: After adjusting for covariates, TL metrics of TeloMean and HorvathTelo were found significantly positive correlations with BMD. HorvathTeloAccel, reflecting accelerated telomere shortening, also exhibited significant association with BMD. Physical activity demonstrated a significant positive association with total BMD (β = 0.046, 95%CI: 0.004-0.088). Mediation analysis revealed that TeloMean and HorvathTelo accounted for 4.78% and 20.86% of the total effect of physical activity on BMD, respectively, while HorvathTeloAccel explained 5.24% of the observed association.

Conclusion: Reduced physical activity and accelerated telomere attrition were related with BMD decline, and TL partially mediated the association. These findings suggest that enhancing physical activity could mitigate telomere shortening and promote bone health.