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

Jingkai Di,1,2,* Yujia Xi,3,* Yaru Liu,4 Likun Qi,3 Shuai Chen,1,2 Yingda Qin,3 Chuan Xiang1,2 1Department of Orthopedics, Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Provincial Key Laboratory of Bone and Soft Tissue Injury Repair, Taiyuan, People’s Republic of China; 3The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4The Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuan Xiang, Department of Orthopedics, Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 15903410351, Email [email protected]: 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.Keywords: bone, brain, Mendelian randomization, osteoarthritis