School of Medicine, Shanghai University, Shanghai, China.
Department of Emergency, Changhai Hospital, Naval Military Medical University, Shanghai, China.
Front Endocrinol (Lausanne). 2023 Apr 20;14:1125427. doi: 10.3389/fendo.2023.1125427. eCollection 2023.
Osteoporosis (OP) is primarily diagnosed through bone mineral density (BMD) measurements, and it often leads to fracture. Observational studies suggest that several mental diseases (MDs) may be linked to OP, but the causal direction of these associations remain unclear. This study aims to explore the potential causal association between five MDs (Schizophrenia, Depression, Alzheimer's disease, Parkinson's disease, and Epilepsy) and the risk of OP.
First, single-nucleotide polymorphisms (SNPs) were filtered from summary-level genome-wide association studies using quality control measures. Subsequently, we employed two-sample Mendelian randomization (MR) analysis to indirectly analyze the causal effect of MDs on the risk of OP through bone mineral density (in total body, femoral neck, lumbar spine, forearm, and heel) and fractures (in leg, arm, heel, spine, and osteoporotic fractures). Lastly, the causal effect of the MDs on the risk of OP was evaluated directly through OP. MR analysis was performed using several methods, including inverse variance weighting (IVW)-random effects, IVW-fixed effects, maximum likelihood, weighted median, MR-Egger regression, and penalized weighted median.
The results did not show any evidence of a causal relationship between MDs and the risk of OP (with almost all P values > 0.05). The robustness of the above results was proved to be good.
In conclusion, this study did not find evidence supporting the claim that MDs have a definitive impact on the risk of OP, which contradicts many existing observational reports. Further studies are needed to determine the potential mechanisms of the associations observed in observational studies.
骨质疏松症（OP）主要通过骨密度（BMD）测量来诊断，并且常常导致骨折。观察性研究表明，几种精神疾病（MDs）可能与 OP 有关，但这些关联的因果关系尚不清楚。本研究旨在探讨五种 MDs（精神分裂症、抑郁症、阿尔茨海默病、帕金森病和癫痫）与 OP 风险之间的潜在因果关系。
首先，使用质量控制措施从汇总水平全基因组关联研究中筛选出单核苷酸多态性（SNPs）。随后，我们采用两样本 Mendelian 随机化（MR）分析，通过骨密度（全身、股骨颈、腰椎、前臂和脚跟）和骨折（腿部、手臂、脚跟、脊柱和骨质疏松性骨折）间接分析 MD 对 OP 风险的因果作用。最后，通过 OP 直接评估 MD 对 OP 风险的因果作用。使用几种方法（包括逆方差加权（IVW）-随机效应、IVW-固定效应、最大似然、加权中位数、MR-Egger 回归和惩罚加权中位数）进行 MR 分析。
结果没有显示 MDs 与 OP 风险之间存在因果关系的任何证据（几乎所有 P 值均>0.05）。上述结果的稳健性被证明很好。
总之，本研究没有发现证据支持 MDs 对 OP 风险有明确影响的说法，这与许多现有的观察性报告相矛盾。需要进一步的研究来确定观察性研究中观察到的关联的潜在机制。
