Zeng Xin, Luo Fei, Wang Xiao-Dong, Cao Wan-Jun, Chen Yong-Jie, Su Qiang
Nanchong Key Laboratory of Individualized Drug Therapy, Beijing Anzhen Hospital Affiliated to Capital Medical University Nanchong Hospita, Nanchong Central Hospital, Nanchong, China.
Department of Nuclear Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, People's Republic of China.
Inflammopharmacology. 2025 Jul 25. doi: 10.1007/s10787-025-01864-1.
Observational studies suggest that statins may be protective against osteoporosis and osteoarthritis. However, the association between statins and the risk of osteoporosis and osteoarthritis has not been fully clarified.
The association between statins and the risk of osteoporosis and osteoarthritis was explored by Mendelian randomization analyses using pooled data from a large population-based genome-wide association study (GWAS).
Data on statin-associated single-nucleotide polymorphisms were obtained from version 10 of the FinnGen database, while information regarding osteoporosis and osteoarthritis was sourced from IEU Open GWAS and UK Biobank, database. The primary analytical method employed was inverse variance weighting to assess causal effects. Additional methods including weighted median, simple median, weighted mode, and MR-Egger regression were utilized for further clarification. Odds ratios along with 95% confidence intervals were calculated to evaluate the causal relationship between statins and the risks associated with osteoarthritis and osteoporosis. Subsequently, sensitivity analyses were conducted to verify result reliability by employing Cochran's Q test for heterogeneity assessment, MR-Egger intercept for detecting horizontal pleiotropy presence, as well as leave-one-out analysis to identify potentially influential single nucleotide polymorphisms.
(1) The results of the inverse variance weighting method showed a negative causal relationship between genetically predicted statins and osteoporosis (OR = 0.998, 95% CI 0.996-0.999, P = 0.01) risk; and a negative causal relationship between statins and osteoarthritis (OR = 0.974, 95% CI 0.951-0.998, P = 0.037) risk; (2) MR-Egger-intercept analysis did not detect potential horizontal pleiotropy (osteoporosis: P = 0.848; osteoarthritis: P = 0.483); and (3) the findings provide favorable evidence that statins reduce the risk of osteoporosis and osteoarthritis as described in the observational study, but further research is needed on the specific mechanisms of statins for osteoporosis and osteoarthritis.
Statins reduce the risk of osteoporosis and osteoarthritis, which is consistent with the results of observational studies. Further studies are essential to validate these results and explore the underlying mechanisms in detail.
观察性研究表明，他汀类药物可能对骨质疏松症和骨关节炎具有保护作用。然而，他汀类药物与骨质疏松症和骨关节炎风险之间的关联尚未完全阐明。
利用来自一项基于人群的大型全基因组关联研究（GWAS）的汇总数据，通过孟德尔随机化分析探讨他汀类药物与骨质疏松症和骨关节炎风险之间的关联。
他汀类药物相关单核苷酸多态性的数据来自芬兰基因数据库第10版，而关于骨质疏松症和骨关节炎的信息则来自IEU开放GWAS和英国生物银行数据库。采用的主要分析方法是逆方差加权法来评估因果效应。还使用了加权中位数、简单中位数、加权众数和MR-Egger回归等其他方法进行进一步阐明。计算比值比及95%置信区间，以评估他汀类药物与骨关节炎和骨质疏松症相关风险之间的因果关系。随后，进行敏感性分析，通过采用Cochran's Q检验评估异质性、MR-Egger截距检测水平多效性的存在以及逐一剔除分析来识别潜在有影响的单核苷酸多态性，以验证结果的可靠性。
（1）逆方差加权法的结果显示，基因预测的他汀类药物与骨质疏松症风险之间存在负向因果关系（OR = 0.998，95% CI 0.996 - 0.999，P = 0.01）；他汀类药物与骨关节炎风险之间存在负向因果关系（OR = 0.974，95% CI 0.951 - 0.998，P = 0.037）；（2）MR-Egger截距分析未检测到潜在的水平多效性（骨质疏松症：P = 0.848；骨关节炎：P = 0.483）；（3）研究结果提供了有利证据，表明他汀类药物可降低骨质疏松症和骨关节炎的风险，正如观察性研究所描述的那样，但需要进一步研究他汀类药物对骨质疏松症和骨关节炎的具体作用机制。
他汀类药物可降低骨质疏松症和骨关节炎的风险，这与观察性研究的结果一致。进一步的研究对于验证这些结果并详细探索潜在机制至关重要。
