Individual and mixed effects of PFAS on osteoporosis: Insights from epidemiological and bioinformatic approaches

IF 2.9 3区医学 Q2 TOXICOLOGY

Toxicology letters Pub Date : 2025-09-27 DOI:10.1016/j.toxlet.2025.111731

Wei Wei , Hongjin Huo , Xinxi Song , Dongxuan Wang , Hongyu Huang , Fei Jiang

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引用次数: 0

Abstract

This cross-sectional study investigated the associations between individual and mixed exposure to per- and polyfluoroalkyl substances (PFAS) and osteoporosis, and explored potential biological mechanisms in 2764 U.S. adults. Multivariable logistic regression and weighted quantile sum (WQS) regression were applied to examine associations between individual and mixed PFAS exposure and osteoporosis. Restricted cubic spline (RCS) was used to assess dose-response relationships. Mediation analysis was used to evaluate the mediated effects of neutrophil-to-lymphocyte ratio (NLR). Five PFAS compounds (PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; PFHxS, perfluorohexane sulfonic acid; PFDeA, perfluorodecanoic acid; PFNA, perfluorononanoic acid) with > 80 % detection rates were selected for investigation in this study. Individual exposure to PFOA, PFOS, PFHxS and PFNA were associated with increased lumbar osteoporosis risk (OR _Ln-PFOA = 1.963, 95 %CI: 1.433, 2.687, OR _Ln-PFOS = 1.422, 95 %CI: 1.061, 1.907, OR _Ln-PFHxS = 1.530, 95 %CI: 1.141, 2.052, OR _Ln-PFNA = 1.597, 95 %CI: 1.218, 2.094). Dose-response relationships were observed for PFOA and PFHxS, particularly in women and young adults. WQS regression demonstrated that mixed PFAS exposure increased osteoporosis risk (OR = 1.198, 1.077–1.318) and decreased bone mineral density (BMD, β = −0.017, −0.026 to −0.008), with PFOA contributing most significantly (41–48 % weight). NLR partially mediated these associations. Bioinformatic analyses further identified osteoporosis-related targets and pathways, with inflammation emerging as a key mechanistic link in these associations. Our findings demonstrated a significant association between PFAS exposure and osteoporosis risk, underscoring the importance of reducing PFAS exposure in mitigating bone disease burden.

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PFAS对骨质疏松症的个体和混合作用：来自流行病学和生物信息学方法的见解。

这项横断面研究调查了个体和混合暴露于全氟烷基和多氟烷基物质（PFAS）与骨质疏松症之间的关系，并探讨了2764名美国成年人的潜在生物学机制。采用多变量logistic回归和加权分位数和（WQS）回归来检验单个和混合PFAS暴露与骨质疏松症之间的关系。限制三次样条（RCS）用于评估剂量-反应关系。采用中介分析评价中性粒细胞与淋巴细胞比值（NLR）的中介作用。本研究选取检出率为80%的5种PFAS化合物（PFOA、全氟辛酸、PFOS、全氟辛烷磺酸、PFHxS、全氟己烷磺酸、PFDeA、全氟癸酸、PFNA、全氟壬酸）进行研究。个体暴露于PFOA、PFOS、PFHxS和PFNA与腰椎骨质疏松风险增加相关（OR Ln-PFOA = 1.963, 95%CI: 1.433, 2.687, OR Ln-PFOS = 1.422, 95%CI: 1.061, 1.907, OR Ln-PFHxS = 1.530, 95%CI: 1.141, 2.052, OR Ln-PFNA = 1.597, 95%CI: 1.218, 2.094）。观察到PFOA和PFHxS的剂量-反应关系，特别是在女性和年轻人中。WQS回归显示，混合PFAS暴露增加骨质疏松风险（OR = 1.198, 1.077 ~ 1.318），降低骨密度（BMD, β = -0.017, -0.026 ~ -0.008），其中PFOA贡献最大（41 ~ 48%体重）。NLR部分介导了这些关联。生物信息学分析进一步确定了骨质疏松相关的靶点和途径，炎症是这些关联的关键机制环节。我们的研究结果证明了PFAS暴露与骨质疏松风险之间的显著关联，强调了减少PFAS暴露对减轻骨病负担的重要性。

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