Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 52 10 2023 09 30 2099 2108 Yanpeng Wang Department of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China Yinzhen Zhang Department of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China Changwei Zhao Department of Orthopedics, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China Wenjun Cai Department of Orthopedics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130399, China ZhengYan Wang Department of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China Wenhai Zhao Department of Orthopedics, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130021, China 2023 03 31 2023 06 02 Background: Sedentary behavior and physical activity are still ambiguous in their effects on osteoarthritis. We aimed to evaluate the effects of physical activity and sedentary behavior on osteoarthritis to provide a reference for the prevention of osteoarthritis. Methods: This study was conducted in Changchun, China in 2022. We used two-sample Mendelian randomization with the SNP as an instrumental variable to investigate the effect of physical activity and sedentary behavior on osteoarthritis. In addition, a two-step Mendelian randomization method was used to test whether mediating factors (BMI, smoking, Apolipoprotein B) were involved in mediating the effects of exposure factors on osteoarthritis. Results: TV watching was causally related to knee osteoarthritis and spine osteoarthritis, and they were positively correlated (knee osteoarthritis: OR=1.162,95 %CI: 1.027-1.315, P=0.017; spine osteoarthritis: OR=1.208,95 %CI: 1.033-1.413, P=0.018). BMI played a mediating role in the process of TV watching with knee osteoarthritis and spine osteoarthritis. ((The proportion of BMI mediating effect: knee osteoarthritis: 47.1% (95% CI: 36.7%~63.2%); spine osteoarthritis: 29.5% (95% CI: 19.3%~40.8%)). The proportion of Smoking mediating effect in the process of TV watching with spine osteoarthritis was 16.1% (95% CI: 3.7% ~ 31.6%). Conclusion: TV watching is a potential risk factor for osteoarthritis and plays a role through modifiable factors such as BMI and smoking, therefore, interventions on these factors have the potential to reduce the burden of osteoarthritis caused by longer TV watching times. https://ijph.tums.ac.ir/index.php/ijph/article/view/31595 https://ijph.tums.ac.ir/index.php/ijph/article/download/31595/8057