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ORIGINAL RESEARCH article
Front. Med.
Sec. Geriatric Medicine
Volume 11 - 2024 |
doi: 10.3389/fmed.2024.1453502
This article is part of the Research Topic Endocrinology, Lipids, and Disease: Unraveling the Links View all 3 articles
Hypothyroidism Correlates with Osteoporosis: Potential Involvement of Lipid Mediators
Provisionally accepted- 1 Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- 2 School of Nursing, Hangzhou Normal University, Hangzhou, Jiangsu Province, China
Background: Observational studies have demonstrated a correlation between thyroid dysfunction and osteoporosis (OP); however, the underlying causality has yet to be fully elucidated.The necessary dataset was sourced from public databases. Initially, instrumental variables (IVs) were selected based on three primary hypotheses.Subsequently, Cochran's Q test was employed to exclude IVs exhibiting heterogeneity.The MR-PRESSO test and the leave-one-out sensitivity test were further applied to detect potential pleiotropy. Inverse variance was utilized for the analysis. This study primarily utilized the inverse variance weighted (IVW) model for Mendelian analysis.Since Type 1 diabetes mellitus can also contribute to the development of osteoporosis, this study additionally employed multivariate Mendelian analysis. Furthermore, 249 circulating metabolites were selected for mediation analysis in the Mendelian randomization framework.Results: In this study, the two-sample Mendelian randomization (MR) analysis primarily employed the random-effects IVW model and demonstrated a causal relationship between hypothyroidism (OR=1.092, 95% CI: 1.049-1.137, P<0.001) and hyperthyroidism (OR=1.080, 95% CI: 1.026-1.137, P=0.003) with the risk of OP. No causal relationships were identified between FT3, FT4, TSH, and the risk of OP (P>0.05). The results of the multivariate Mendelian randomization (MVMR) analysis indicated that hyperthyroidism was no longer a risk factor for OP (OR=0.984, 95% CI: 0.918-1.055, P=0.657), whereas hypothyroidism persisted as a risk factor (OR=1.082, 95% CI: 1.021-1.147, P=0.008). The mediated Mendelian randomization analysis revealed that hypothyroidism may exert an indirect effect on OP via triglycerides in large VLDL, mediating approximately 2.47% of the effect.This study identifies a potential link between hypothyroidism and OP, possibly mediated indirectly via triglyceride levels in large VLDL. Further investigations are required to elucidate the direct or indirect causal mechanisms underlying this association.
Keywords: circulating metabolites, Mendelian randomization, Mediation analysis Thyroid dysfunction, Osteoporosis, Thyroid-related hormones
Received: 23 Jun 2024; Accepted: 15 Oct 2024.
Copyright: © 2024 Leng, Qiu, Liu, Wu, Zhou, Zhu, Zhou and Yin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
yuan P. Leng, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Ying Qiu, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Min Liu, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
li w. Wu, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
xue M. Zhou, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
ming M. Zhou, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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