中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (2): 322-330.doi: 10.12307/2025.206

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Oswestry功能障碍指数评分中久坐和体力活动水平与椎间盘退变的因果关系

黄仁俊1 ,杨敬言1,马  涉1,王超逸1,赵余炀1,于  栋2   

  1. 1北京中医药大学第三临床医学院,北京市  100029;2北京中医药大学第三附属医院脊柱科,北京市  100029
  • 收稿日期:2024-01-02 接受日期:2024-01-29 出版日期:2025-01-18 发布日期:2024-05-24
  • 通讯作者: 于栋,博士,主任医师,硕士生导师,北京中医药大学第三附属医院脊柱科,北京市 100029
  • 作者简介:黄仁俊,男,1999年生,江西省上饶市人,汉族,北京中医药大学在读硕士,主要从事中医骨伤科学方面的研究。
  • 基金资助:
    北京中医药大学第三附属医院2022年度院内培育项目(BZYSY-2022-PYMS-18),项目负责人:于栋

Causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration

Huang Renjun1, Yang Jingyan1, Ma She1, Wang Chaoyi1, Zhao Yuyang1, Yu Dong2   

  1. 1The Third Clinical School of Beijing University of Chinese Medicine, Beijing 100029, China; 2Department of Spine, The Third Clinical Hospital of Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2024-01-02 Accepted:2024-01-29 Online:2025-01-18 Published:2024-05-24
  • Contact: Yu Dong, MD, Chief physician, Master’s supervisor, Department of Spine, The Third Clinical Hospital of Beijing University of Chinese Medicine, Beijing 100029, China
  • About author:Huang Renjun, Master candidate, The Third Clinical School of Beijing University of Chinese Medicine, Beijing 100029, China
  • Supported by:
    2022 Cultivation Project of the Ministry of Education Engineering Research Center, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, No. BZYSY-2022-GCYJZXQX-08 (to YD)

摘要:

文题释义:
孟德尔随机化:是使用遗传变异作为工具变量来评估暴露因素与结局因果关系的方法,利用受孕时等位基因随机分配进行因果推断,克服观察性研究的混杂和反向因果关系限制,提供更可靠的因果推断证据。
椎间盘退变:是脊柱椎间盘退化和结构损伤的结果,随着年龄增长,椎间盘髓核细胞和组织结构发生变化,失去水分、弹性和耐久性,导致椎间盘高度降低、变性。

背景:观察性研究表明,椎间盘退变会影响久坐和体力活动水平,然而Oswestry功能障碍指数评分中久坐和体力活动水平与椎间盘退变之间的因果关系尚不明确。
目的:通过孟德尔随机化方法探讨Oswestry功能障碍指数评分中久坐和体力活动水平与椎间盘退变的因果关系。
方法:从大规模人群全基因组关联分析中选择5个与Oswestry功能障碍指数评分中行为学相关的特征:看电视的时间、用电脑的时间、轻度/中度/剧烈体力活动,分别提取这些行为学相关特征的工具变量。结合Finn Gen最新第9版数据库中提取椎间盘退变作为结局,进行孟德尔随机化分析。使用逆方差加权法、MR-Egger回归、简单中位数法、加权中位数法、加权中值法等回归模型OR值和95%CI评估Oswestry功能障碍指数评分中久坐和体力活动水平与椎间盘退变的因果关系。使用Cochran’s Q检验异质性、MR-Egger截距检验多效性、“留一法”检验单核苷酸多态性观察暴露因素和椎间盘退变因果关系的敏感性。 
结果与结论:孟德尔随机化逆方差加权法结果显示,看电视/用电脑的时间与椎间盘退变发病风险呈正向因果关联(OR=1.775,95%CI:1.418-2.221,P < 0.001)/(OR=1.384,95%CI:1.041-1.839,P < 0.001),轻度体力活动与椎间盘退变发病风险呈反向因果关联(OR=1.000,95%CI:0.999-1.000,P=0.020);MR-Egger截距分析轻度体力活动与椎间盘退变存在潜在的水平多效性(P=0.005),看电视的时间、用电脑的时间与椎间盘退变不存在水平多效性(P=0.521,P=0.851)。Cochran’s Q异质性分析看电视的时间、用电脑的时间与椎间盘退变存在异质性(P=3.33×10-11,P=0.001),轻度体力活动与椎间盘退变没有观察到显著的异质性(P=0.186)。以上结果表明:Oswestry功能障碍指数评分中久坐和体力活动水平与椎间盘退变存在双向因果关系,即不仅椎间盘退变会影响Oswestry功能障碍指数评分中久坐和体力活动水平,Oswestry功能障碍指数评分中久坐和体力活动水平也会影响椎间盘退变。补充了轻度体力活动对椎间盘退变积极影响的遗传证据,表明中度/剧烈体力活动与椎间盘退变没有显著的因果关系,并扩大了长时间看电视/用电脑的久坐行为是椎间盘退变危险因素的证据基础。
https://orcid.org/0009-0008-0930-9414(黄仁俊)
中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 椎间盘退变, Oswestry功能障碍指数评分, 孟德尔随机化, 因果关系, 单核苷酸多态性, 久坐行为, 体力活动水平

Abstract: BACKGROUND: Observational studies have shown that intervertebral disc degeneration affects sedentary and physical activity levels; however, the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration is unclear.
OBJECTIVE: To explore the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration using the Mendelian randomization method.
METHODS: Five features associated with behavioral correlations in the Oswestry disability index score, including time spent watching TV, time spent on the computer, and light/moderate/vigorous physical activity, were selected from large-scale population-based genome-wide association studies, and instrumental variables were extracted for each of these behaviorally related features. Mendelian randomization analyses were performed in conjunction with the extraction of intervertebral disc degeneration as an outcome from the Finn Gen latest version 9 database. The results were analyzed using the inverse variance weighted, MR-Egger regression, simple mode, weighted mode, weighted median estimator, and regression model odds ratios (OR) and 95% confidence interval (CI) to assess the causal relationship between sedentary and physical activity levels in the Oswestry disability index scoring and intervertebral disc degeneration. Cochran’s Q was used to test for heterogeneity, MR-Egger intercept to test for multiplicity, and leave-one-out to test the sensitivity of single nucleotide polymorphisms to the causal relationship between exposure factors and disc degeneration.
RESULTS AND CONCLUSION: The results of the Mendelian randomization analysis using inverse variance weighted method showed a positive causal association between time spent watching TV/on the computer and the risk of intervertebral disc degeneration (OR=1.775, 95% CI: 1.418-2.221, P < 0.001)/(OR=1.384, 95% CI: 1.041-1.839, P < 0.001), an inverse causal association between light physical activity and the risk of intervertebral disc degeneration (OR=1.000, 95% CI: 0.999-1.000, P=0.020). MR-Egger intercept analysis indicated there was potential horizontal polytropy between light physical activity and intervertebral disc degeneration (P=0.005), while there was no horizontal pleiotropy between time spent watching TV, time spent on the computer and intervertebral disc degeneration (P=0.521, P=0.851). Cochran’s Q analysis showed that heterogeneity was observed between time spent watching TV, time spent on the computer and intervertebral disc degeneration (P=3.33×10-11, P=0.001), and no significant heterogeneity was observed between light physical activity and intervertebral disc degeneration (P=0.186). Overall, there is a bidirectional causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration, i.e., not only does intervertebral disc degeneration affect sedentary and physical activity levels in the Oswestry disability index score, but sedentary and physical activity levels in the Oswestry disability index score also affect intervertebral disc degeneration. These findings add to the genetic evidence for a positive effect of light physical activity on intervertebral disc degeneration, indicate that moderate/vigorous physical activity shows no significant causal relationship with intervertebral disc degeneration, and expand the evidence base for sedentary behaviors such as prolonged time spent watching TV/on the computer as a risk factor for intervertebral disc degeneration.

Key words: intervertebral disc degeneration, Oswestry disability index score, Mendelian randomization, causality, single nucleotide polymorphism, sedentary behavior, physical activity level

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