Causal Associations of the Alterations in Peripheral Blood Immune Cell Characteristics on the Incidence of Osteoporosis: A Bidirectional Mendelian Randomization Study.

IF 2.8 3区医学 Q1 Pharmacology, Toxicology and Pharmaceutics

Therapeutics and Clinical Risk Management Pub Date : 2025-08-14 eCollection Date: 2025-01-01 DOI:10.2147/TCRM.S518164

Qunhui Yin, Kai Li, Rong Chen, Xin Li, Wai Leung Ambrose Lo, Qiuhua Yu, Minghui Ding, Siyun Zhang, Chuhuai Wang

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Abstract

Purpose: Osteoporosis is closely related to specific immune cell, yet the causal mechanism has not been clarified. Previous studies mostly adopted traditional unidirectional Mendelian randomization (MR) for analysis, failing to fully clarify their relationship. This study is the first to analyze the bidirectional causal relationship between the characteristics of peripheral immune cells and the risk of osteoporosis.

Methods: A bilateral two-sample MR was performed, with immune cells serving as instrumental variables and the incidence of osteoporosis as the outcome. We used five algorithms to evaluate the causal relationship between immune cells and the incidence of osteoporosis (inverse-variance weighted [IVW], MR-Egger, simple mode, weight median, and weight mode). The Cochran Q and leave-one-out tests were used to evaluate heterogeneity and stability, and the MR-Egger intercept test was used to evaluate horizontal pleiotropy.

Results: The eosinophil percentage of granulocytes (odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.08-1.44, P = 0.002), eosinophil percentage of white cells (OR = 1.17, 95% CI = 1.02-1.35, P = 0.027), and sum eosinophil basophil counts (OR = 1.16, 95% CI = 1.02-1.32, P = 0.027) had positive causal associations with the incidence of osteoporosis. The lymphocyte counts (OR = 0.83, 95% CI = 0.71-0.97, P = 0.016), neutrophil percentage of granulocytes (OR = 0.78, 95% CI = 0.67-0.90, P < 0.001) played negative effect on osteoporosis. The reverse direction showed that osteoporosis had no causal effect on the characteristics of the immune cells. Non-significant heterogeneity and horizontal pleiotropy indicated the results were robust.

Conclusion: This study identified a unidirectional causal link between five immune cell traits and osteoporosis, providing new insights into osteoporosis pathogenesis and potential targeted immunotherapy.

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外周血免疫细胞特性改变与骨质疏松发病率的因果关系：一项双向孟德尔随机研究

目的：骨质疏松症与特异性免疫细胞密切相关，但病因机制尚不清楚。以往的研究多采用传统的单向孟德尔随机化（MR）进行分析，未能充分阐明二者的关系。本研究首次分析了外周免疫细胞特征与骨质疏松风险之间的双向因果关系。方法：双侧双样本mri，以免疫细胞为工具变量，骨质疏松症发生率为结果。我们使用五种算法来评估免疫细胞与骨质疏松发病率之间的因果关系（反方差加权[IVW]、MR-Egger、简单模式、权重中位数和权重模式）。采用Cochran Q检验和留一检验评价异质性和稳定性，采用MR-Egger截距检验评价水平多效性。结果：粒细胞嗜酸性粒细胞百分比（比值比[OR] = 1.25, 95%可信区间[CI] = 1.08 ~ 1.44, P = 0.002）、白细胞嗜酸性粒细胞百分比（OR = 1.17, 95% CI = 1.02 ~ 1.35, P = 0.027）、嗜酸性碱性粒细胞总数（OR = 1.16, 95% CI = 1.02 ~ 1.32, P = 0.027）与骨质疏松的发生率呈正相关。淋巴细胞计数（OR = 0.83, 95% CI = 0.71 ~ 0.97, P = 0.016）、粒细胞中性粒细胞百分比（OR = 0.78, 95% CI = 0.67 ~ 0.90, P < 0.001）与骨质疏松呈负相关。相反的方向表明，骨质疏松症对免疫细胞的特性没有因果影响。非显著异质性和水平多效性表明结果是稳健的。结论：本研究确定了五种免疫细胞特性与骨质疏松之间的单向因果关系，为骨质疏松的发病机制和潜在的靶向免疫治疗提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Therapeutics and Clinical Risk Management HEALTH CARE SCIENCES & SERVICES-

CiteScore

5.30

自引率

3.60%

发文量

139

审稿时长

16 weeks

期刊介绍： Therapeutics and Clinical Risk Management is an international, peer-reviewed journal of clinical therapeutics and risk management, focusing on concise rapid reporting of clinical studies in all therapeutic areas, outcomes, safety, and programs for the effective, safe, and sustained use of medicines, therapeutic and surgical interventions in all clinical areas. The journal welcomes submissions covering original research, clinical and epidemiological studies, reviews, guidelines, expert opinion and commentary. The journal will consider case reports but only if they make a valuable and original contribution to the literature. As of 18th March 2019, Therapeutics and Clinical Risk Management will no longer consider meta-analyses for publication. The journal does not accept study protocols, animal-based or cell line-based studies.