Causal effects of different exercise intensities on the risk of osteoarthritis

doi:10.12307/2025.317

Abstract

Abstract:
BACKGROUND: Increasing evidence supports the association between different exercise intensities and the risk of osteoarthritis, but this may be affected by confounding and reverse causality, and the conclusions have not been unified.
OBJECTIVE: To explore the causal association between different exercise intensities and osteoarthritis using Mendelian randomization method.
METHODS: Data from genome-wide association studies associated with different exercise intensities were selected, and instrumental variables were screened with a threshold of P < 5×10-8. Causal associations between exposure and risk of outcome were assessed using five analysis methods of Mendelian randomization with inverse variance weighting as the primary analysis method. Selected instrumental variables were used to assess causal associations between different exercise intensities and osteoarthritis, and sensitivity analyses with inverse Mendelian randomization were performed.
RESULTS AND CONCLUSION: In the analysis results of the inverse variance weighting method, low-intensity exercise showed a significant protective effect on knee osteoarthritis [odds ratio (OR)=0.14, 95% confidence interval (CI): 0.06-0.32, P < 0.001], while sedentary behavior without exercise intensity, such as watching TV, was confirmed to be a risk factor for knee osteoarthritis and hip osteoarthritis (OR=2.24, 95% CI: 1.74-2.88, P < 0.001; OR=1.34, 95% CI: 1.01-1.78, P=0.04). Through the reverse Mendelian randomization analysis of osteoarthritis to different exercise intensities, it was found that osteoarthritis was negatively correlated with low-intensity exercise and positively correlated with watching TV. The analysis results show that there is a two-way causal relationship between different exercise intensity and osteoarthritis risk.

Key words: exercise intensity, osteoarthritis, Mendelian randomization, causal association, knee osteoarthritis, hip osteoarthritis

CLC Number:

Ma Haoyu, Qiao Hongchao, Hao Qianqian, Shi Dongbo. Causal effects of different exercise intensities on the risk of osteoarthritis [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(6): 1305-1311.

Figures/Tables 8

2.1 工具变量经过初步筛选，选出了与运动强度相关的4个表型作为工具变量，分别提取出112，20，18和11个单核苷酸多态性，涉及到久坐行为(例如电视观看)、低强度运动(例如为娱乐而步行)、中强度运动(每周中的每天进行10 min以上运动)和高强度运动(每周中的每天进行10 min以上运动)。在匹配和去除离群值的基础上，最终确定了工具变量数量，并对其有效性进行了评估。结果显示，各工具变量的F统计量均超过10，表明不存在弱工具变量偏倚。此外，Q检验和PRESSO全局异质性检验的P > 0.05，暗示不存在异质性工具变量。MR-Egger截距项对应的P > 0.05，提示不存在方向多效性。 2.2 不同运动强度与膝骨关节炎的因果关系图2展示了不同强度运动与膝骨关节炎的分析结果，逆方差加权法结果表明，以散步为代表的低强度运动是膝骨关节炎的保护因素(OR=0.14，95%CI：0.06-0.32，P < 0.001)，而电视观看这种久坐行为是膝骨关节炎的危险因素(OR=2.24，95%CI：1.74-2.88，P < 0.001)。不同运动强度与膝骨关节炎的MR分析结果散点图，见图3，显示散点图回归线无明显偏移。 2.3 不同运动强度与髋骨关节炎的因果关系逆方差加权法分析结果显示，久坐行为是髋骨关节炎的危险因素(OR=1.34，95%CI：1.01-1.78，P=0.04)，5种方法因果效应方向一致(OR值均> 1)，见图4。不同强度运动与髋骨关节炎的MR分析结果散点图，见图5，显示回归线无明显偏移，故提示久坐行为与髋骨关节炎有正向因果关系，久坐行为时间增长是髋骨关节炎发生的风险因素。在低、中、高强度运动与髋骨关节炎的分析中所有结果P均> 0.05，无因果关联。 2.4 敏感性分析结果如表2所示，根据MR-Egger截距检验，所有P > "

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