Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (27): 4340-4345.doi: 10.12307/2024.555

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Relationship between statin drugs and bone density: a drug target-mediated Mendelian randomization study

Ma Weiwei1, Xiong Yong1, Chen Honggu2, Huang Wenzhuo1, Huang Xin1, Zhou Xiaohong1   

  1. 1Hubei University of Chinese Medicine, Wuhan 430061, Hubei Province, China; 2Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
  • Received:2023-10-07 Accepted:2023-11-10 Online:2024-09-28 Published:2024-01-27
  • Contact: Xiong Yong, MD, Associate professor, Associate chief physician, Master’s supervisor, Hubei University of Chinese Medicine, Wuhan 430061, Hubei Province, China Chen Honggu, Master, Affiliated Hospital of Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
  • About author:Ma Weiwei, Master candidate, Hubei University of Chinese Medicine, Wuhan 430061, Hubei Province, China
  • Supported by:
    Young and Middle-aged Talent Project of Hubei Provincial Department of Education, No. Q20212004 (to ZXH); Scientific Research Program Guiding Project of Hubei Provincial Department of Education, No. B2022107 (to XY)

Abstract: BACKGROUND: Observational studies have suggested that statin drugs may have a protective effect on bone density, making them a potential treatment option for osteoporosis.
OBJECTIVE: To evaluate the causal relationship between drug target-mediated lipid phenotypes and bone mineral density (BMD) using Mendelian randomization methods. 
METHODS: We obtained single nucleotide polymorphismsrelated to statin drugs and BMD data from the IEU Open GWAS database. The primary analysis method was the inverse variance weighted method, and we also used weighted median, simple median, weighted mode, and MR-Egger regression. We used β values and 95% confidence intervals (CI) to assess the causal relationship between statin drugs and BMD. Additionally, we conducted sensitivity analyses to validate the results, assessed heterogeneity using Cochran’s Q test, examined for horizontal pleiotropy using the MR-Egger intercept test, and performed leave-one-out analyses to determine if individual or multiplesingle nucleotide polymorphism influenced the results.
RESULTS AND CONCLUSION: There was a significant association between the statin target of action, 3-hydroxy-3-methyl glutaryl coenzyme A reductase-mediated low-density lipoprotein cholesterol, and heel bone BMD (β=-0.086, 95% CI: -0.117 to -0.055, P=5.42×10-8) and whole-body BMD (β=-0.193, 95% CI: -0.288 to -0.098, P=7.35×10-5). The findings of this study support the protective effect of statin drugs on BMD. These findings not only deepen our understanding of the relationship between cholesterol-related genes and bone health but also reveal potential therapeutic targets for improving BMD.

Key words: statin drugs, bone mineral density, Mendelian randomization, genome-wide association study, causal relationship

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