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Meta-Analysis
. 2025 Mar;43(2):96-107.
doi: 10.1007/s00774-024-01559-7. Epub 2024 Dec 6.

Multiple thyroid disorders and risk of osteoporosis: a two-sample Mendelian randomization study

Guang Shi #  1 , Zhao Lin #  2   3 , Qixiao Shen #  4 , Wei Jin #  1 , Zhuowen Hao  1 , Junwu Wang  1 , Tianhong Chen  1 , Jiayao Chen  1 , Xin Wang  5 , Jingfeng Li  6
Affiliations
Meta-Analysis

Multiple thyroid disorders and risk of osteoporosis: a two-sample Mendelian randomization study

Guang Shi et al. J Bone Miner Metab. 2025 Mar.

Abstract

Introduction: Previous research has demonstrated that even minor changes in thyroid function are associated with an increased risk of osteoporosis (OP). However, the causal relationship between thyroid disorders and the development of OP remains unclear. To address this, we aim to investigate the connection between genetic predispositions to various thyroid disorders and OP using a two-sample Mendelian randomization (MR) approach.

Materials and methods: Instrumental variables (IVs) for multiple thyroid disorders were sourced from a large genome-wide association study (GWAS) meta-analysis dataset. Summary-level data for OP were obtained from the FinnGen consortium. Inverse variance weighting (IVW) methods served as the primary approach for MR analysis. Sensitivity analyses included MR-Egger regression, heterogeneity testing, multiple validity tests, and leaFve-one-out sensitivity tests.

Results: IVW analysis revealed a direct causal effect of hypothyroidism (OR = 1.105, 95% CI 1.023-1.194, P 0.011) and Hashimoto's thyroiditis (OR = 1.142, 95% CI 1.026-1.271, P 0.015) on OP. However, no direct causal association was found between hyperthyroidism (OR = 1.030, 95% CI 0.944-1.123, P 0.508) or thyroid cancer (OR = 0.971, 95% CI 0.898-1.051, P 0.469) and OP.

Conclusion: Our MR analysis revealed a causal association between hypothyroidism, Hashimoto's thyroiditis, and OP. This highlights the significant impact of thyroid function on bone health. However, further longitudinal studies are needed to confirm these findings conclusively.

Keywords: Genome-wide association study; Mendelian randomization; Osteoporosis; Thyroid disorders.

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Conflict of interest statement

Declarations. Conflict of interest: Guang Shi, Zhao Lin, Qixiao Shen, Wei Jin, Zhuowen Hao, Junwu Wang, Tianhong Chen, Jiayao Chen, Xin Wang, and Jingfeng Li declare that they have no conflict of interest. This work described is original research that has not been published previously and is not under consideration for publication elsewhere, in whole or in part. Ethical approval Ethical review and approval for research with human participants was not needed in accordance with local legislation and institutional requirements. Written informed consent was not needed for this study in accordance with national legislation and institutional requirements.

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