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2024, Vol. 28 ›› Issue (33): 5326-5332

Causal effects of serum trace elements and nutrients on osteonecrosis: a Mendelian randomization analysis

Liu Yi1, Liu Yuan1, Liu Jinbao1, 2, Li Nianhu2, Zhu Weiming3, Xu Bo1, 2   

  1. 1Shandong University of Traditional Chinese Medicine, Jinan 250300, Shandong Province, China; 2Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China; 3Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China

  • Received:2023-09-11 Accepted:2023-10-20 Online:2024-11-28 Published:2024-01-30

  • Contact: Xu Bo, MD, Associate professor, Associate chief physician, Master’s supervisor, Shandong University of Traditional Chinese Medicine, Jinan 250300, Shandong Province, China; Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China

  • About author:Liu Yi, Master, Shandong University of Traditional Chinese Medicine, Jinan 250300, Shandong Province, China

  • Supported by:

    National Famous Traditional Chinese Medicine Expert Inheritance Studio Construction Project, No. [2022]75 (to LNH); Shandong Province Traditional Chinese Medicine Classic Formula Collaborative Innovation and Opening Project, No. 2019KFY17 (to XB); Shandong Province Traditional Chinese Medicine Technology Development Plan, No. 2019-0087 (to LJB)


Abstract: BACKGROUND: Multiple clinical observational studies have suggested a close relationship of serum trace elements and nutrients with osteonecrosis, but it remains unclear whether there is a genetic causal effect between serum trace elements and nutrients on osteonecrosis.
OBJECTIVE: To investigate the causal effects of serum trace elements and nutrients on osteonecrosis using the Mendelian randomization approach.
METHODS: The exposure factors of serum trace elements and vitamins with mononucleotide polymorphisms were obtained from the published UK Biobank database and publicly available databases of genome-wide association studies. The outcome event of osteonecrosis was derived from the FinnGen Biobank database. Mendelian randomization methods were employed to explore the causal relationship between seven trace elements and three nutrients with osteonecrosis. Causal inference was conducted using inverse variance weighting, MR-Egger, and weighted median methods. F-statistic was calculated to ensure the robustness of instrumental variables. Cochran's Q test and leave-one-out method were used for heterogeneity testing. MR-Egger regression and MR-PRESSO were employed for horizontal pleiotropy testing. PhenoScanner database was utilized to remove mononucleotide polymorphisms with horizontal pleiotropy to ensure the reliability of the results.
RESULTS AND CONCLUSION: Causal relationships were found between serum selenium, phosphate, vitamin C, vitamin E, and osteonecrosis through Mendelian randomization analysis. Serum selenium, vitamin C, and vitamin E were found to have a protective effect on osteonecrosis, while excessive intake of phosphate increased the risk of osteonecrosis. No heterogeneity or horizontal pleiotropy was observed during the study, and Mendelian randomization statistical power (Power value > 80%) indicated the reliability of the aforementioned four results. These findings have important clinical implications for the development of targeted preventive and therapeutic measures for osteonecrosis.

Key words: Mendelian randomization, trace element, nutrient, osteonecrosis, single nucleotide polymorphism, inverse variance weighted method


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