Mediation analysis of metabolic and inflammatory markers in the association between physical activity and musculoskeletal disease: Findings from NHANES 2013-2018.

Background: Musculoskeletal disease (MSD), including osteoarthritis, rheumatoid arthritis, osteoporosis, and sarcopenia, poses a serious social burden. While physical activity (PA) benefits musculoskeletal health, the optimal PA level for MSD prevention remains unclear. Clarifying risk factors and biological mechanisms is essential.

Methods: This study included 9,113 adults aged 20-60 years from NHANES 2013-2018. Blood and urine specimens were used to analyze metabolic and inflammatory markers. PA was assessed using the Global Physical Activity Questionnaire. Multivariate logistic regression, generalized additive models and mediation analysis were used to evaluate the relationships among PA, biomarkers and MSD.

Results: Among 9113 participants, 2685 (29.5%) had MSD. PA levels of 600-1200 MET-min/week were associated with the greatest MSD risk reduction (24%; 95% CI 0.62-0.93) compared with inactivity after full adjustment. Participants with MSD showed higher levels of metabolic and inflammatory markers and lower PA levels (P < 0.05). Mediation analysis revealed that atherogenic index of plasma (AIP), triglycerides (TG), neutrophils (NEU), total cholesterol (TC), and triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) acted as complementary mediators at the highly active PA level only, with mediation proportions of 12.4%, 7.6%, 6.1%, 6.0%, and 5.7%. While, lymphocytes (LYM) served as an indirect-only mediator across both active and highly active PA levels, accounting for 21.8% of the total effect.

Conclusion: In individuals aged 20-60 years, 600-1200 MET-min/week most effectively reduces MSD risk, with these associations likely mediated by metabolic and inflammatory markers. This study elucidates underlying biological mechanisms linking PA and MSD, highlighting potential metabolic and inflammatory pathways for prevention strategies.