Hu Hai, Huang Rui, Li Xue, Liu Pengfei, Ren Shujun, Shen Yiwei
Department of Orthopaedics,The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
Department of Orthopaedics, Li Huili Hospital, Ningbo Medical Center, Ningbo, Zhejiang Province, China.
Medicine (Baltimore). 2025 May 30;104(22):e42487. doi: 10.1097/MD.0000000000042487.
Osteonecrosis of the femoral head (ONFH) is a debilitating condition with unclear pathophysiology. Micronutrients are implicated in bone health, but their causal relationship with ONFH remains uncertain. This study aims to investigate the potential causal relationship between circulating levels of 15 micronutrients and the risk of ONFH using a 2-sample Mendelian randomization (MR) approach. The objective was to determine whether circulating levels of specific micronutrients (copper, calcium, carotene, folate, iron, magnesium, potassium, selenium, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D, vitamin E, and zinc) have a causal impact on the risk of ONFH. This study employed a 2-sample MR approach using summary-level data from 15 genome-wide association studies (GWAS) focused on micronutrient exposures and 1 GWAS for ONFH. The study adhered to 3 fundamental MR assumptions and used the inverse variance weighting method as the primary analysis method, supplemented by MR-Egger regression and MR-PRESSO to assess heterogeneity and pleiotropy. To minimize population stratification bias, the study included only individuals of European descent. The primary finding was a significant association between genetically predicted higher levels of potassium and a reduced risk of ONFH (OR = 0.440, 95% confidence interval (CI) 0.2012-0.959, P = .039 per 1 standard deviation). No other micronutrients showed significant associations with ONFH risk. Sensitivity analyses, including MR-Egger regression and leave-one-out analysis, confirmed the robustness of these findings. Our findings indicate a significant association between genetically predicted higher potassium levels and a reduced risk of ONFH in individuals of European descent, while no other micronutrients demonstrated significant associations. Sensitivity analyses confirmed these results, suggesting a potential protective role of potassium in ONFH.
股骨头坏死（ONFH）是一种病理生理学尚不明确的使人衰弱的病症。微量营养素与骨骼健康有关，但其与ONFH之间的因果关系仍不确定。本研究旨在采用两样本孟德尔随机化（MR）方法，调查15种微量营养素的循环水平与ONFH风险之间的潜在因果关系。目的是确定特定微量营养素（铜、钙、胡萝卜素、叶酸、铁、镁、钾、硒、维生素A、维生素B12、维生素B6、维生素C、维生素D、维生素E和锌）的循环水平是否对ONFH风险有因果影响。本研究采用两样本MR方法，使用来自15项关注微量营养素暴露的全基因组关联研究（GWAS）和1项ONFH的GWAS的汇总水平数据。该研究遵循3个基本的MR假设，并使用逆方差加权法作为主要分析方法，辅以MR-Egger回归和MR-PRESSO来评估异质性和多效性。为了尽量减少群体分层偏差，该研究仅纳入欧洲血统的个体。主要发现是，基因预测的较高钾水平与ONFH风险降低之间存在显著关联（每1个标准差的比值比（OR）=0.440，95%置信区间（CI）0.2012 - 0.959，P = 0.039）。没有其他微量营养素与ONFH风险显示出显著关联。敏感性分析，包括MR-Egger回归和留一法分析，证实了这些发现的稳健性。我们的研究结果表明，在欧洲血统个体中，基因预测的较高钾水平与ONFH风险降低之间存在显著关联，而没有其他微量营养素显示出显著关联。敏感性分析证实了这些结果，表明钾在ONFH中可能具有保护作用。
