探寻大脑在骨关节炎中的作用：预防的新证据

Mapping the Brain's Role in Osteoarthritis: New Evidence for Prevention.

作者信息

Di Jingkai, Xi Yujia, Liu Yaru, Qi Likun, Chen Shuai, Qin Yingda, Xiang Chuan

机构信息

Department of Orthopedics, Second Hospital of Shanxi Medical University, Taiyuan, People's Republic of China.

Shanxi Provincial Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, People's Republic of China.

出版信息

J Multidiscip Healthc. 2025 Jun 24;18:3605-3617. doi: 10.2147/JMDH.S522952. eCollection 2025.

DOI:10.2147/JMDH.S522952

PMID:40584645

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12205704/

Abstract

PURPOSE

This study explores the causal link between brain structural parameters and Osteoarthritis (OA), aiming to prevent OA progression.

PATIENTS AND METHODS

We used two-sample Mendelian randomization. In addition to European OA data with a sample size of 484,598, Firth correction OA data from the same source, and SPA correction OA data were included as outcome data. 3913 brain imaging-derived phenotypes (IDPs) from the UK Biobank were used as exposure data. Weighted median, MR Egger, and IVW validated causal correlations. Analyses of sensitivity and heterogeneity validated the robustness of the findings.

RESULTS

Thirteen brain regions significantly linked to OA. Increased fractional anisotropy (FA) in the cingulate hippocampal gyrus (OR: 0.99, 95% CI: 0.98-1.00, P = 0.003), orientation diffusion(OD) in the fornix and Stria terminalis (OR: 0.99, 95% CI: 0.98-1.00, P = 0.004) and isotropic volume fraction (ISOVF) (OR: 0.99, 95% CI: 0.99-1.00, P = 0.039) in the fornix, as well as an increase in OD in the posterior thalamic radiation (R) (OR: 0.99, 95% CI: 0.98-1.00, P = 0.047) reduce OA risk as protective factors. Increased subparietal lobule area (OR: 0.99, 95% CI: 0.98-1.00, P = 0.045) and middle temporal gyrus volume (OR: 0.98, 95% CI: 0.97-1.00, P = 0.029) also demonstrated a protective effect against OA. Conversely, OA risk was increased by increases in the medial thalamic tract's OD (OR: 1.01, 95% CI: 1.00-1.02, P = 0.034), the cerebral peduncle's intracellular volume fraction (ICVF) (OR: 1.01, 95% CI: 1.00-1.01, P = 0.010), the anterior limb of the internal capsule's ISOVF (OR: 1.01, 95% CI: 1.00-1.01, P = 0.033), and the posterior thalamic radiation(L) 's MO (OR: 1.02, 95% CI: 1.00-1.03, P = 0.024). Interestingly, lateral orbitofrontal volume decreased (R: OR: 0.99, 95% CI: 0.98-1.00, P = 0.013; L: OR: 0.99, 95% CI: 0.98-1.00, P = 0.038), while medial orbitofrontal increased risk (OR: 1.02, 95% CI: 1.00-1.04, P = 0.024).

CONCLUSION

Our findings provide genetic evidence for the prevention of OA based on the bone-brain axis and suggest a clinical strategy for integrated pain-psychomotor intervention through neural nociceptive modulation, limbic circuit stabilization, and motor pathway enhancement.

摘要

目的

本研究探讨脑结构参数与骨关节炎（OA）之间的因果关系，旨在预防OA进展。

患者与方法

我们采用了两样本孟德尔随机化方法。除了样本量为484,598的欧洲OA数据外，还纳入了来自同一来源的Firth校正OA数据和SPA校正OA数据作为结局数据。来自英国生物银行的3913个脑成像衍生表型（IDP）用作暴露数据。加权中位数、MR-Egger和IVW验证了因果相关性。敏感性和异质性分析验证了研究结果的稳健性。

结果

13个脑区与OA显著相关。扣带回海马回的分数各向异性（FA）增加（比值比：0.99，95%置信区间：0.98-1.00，P = 0.003），穹窿和终纹的方向扩散（OD）增加（比值比：0.99，95%置信区间：0.98-1.00，P = 0.004），穹窿的各向同性体积分数（ISOVF）增加（比值比：0.99，95%置信区间：0.99-1.00，P = 0.039），以及丘脑后辐射（R）的OD增加（比值比：0.99，95%置信区间：0.98-1.00，P = 0.047）作为保护因素可降低OA风险。顶下小叶面积增加（比值比：0.99，95%置信区间：0.98-1.00，P = 0.045）和颞中回体积增加（比值比：0.98，95%置信区间：0.97-1.00，P = 0.029）也显示出对OA的保护作用。相反，内侧丘脑束的OD增加（比值比：1.01，95%置信区间：1.00-1.02，P = 0.034）、大脑脚的细胞内体积分数（ICVF）增加（比值比：1.01，95%置信区间：1.00-1.01，P = 0.010）、内囊前肢的ISOVF增加（比值比：1.01，95%置信区间：1.00-1.01，P = 0.033）以及丘脑后辐射（L）的MO增加（比值比：1.02，95%置信区间：1.00-1.03，P = 0.024）会增加OA风险。有趣的是，外侧眶额体积减小（R：比值比：0.99，95%置信区间：