Background 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. Objective 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). Methods 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. Results (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. Conclusion 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.

The use of statins can reduce the risk of osteoarthritis and osteoporosis

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发表日期：

2025年7月25日

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Xin Zeng,
Fei Luo,
Xiao-dong Wang,
Wan-jun Cao,
Yong-jie Chen,
Qiang Su

摘要

Background

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.

Objective

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).

Methods

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.

Results

(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.

Conclusion

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.