Shi Guang, Lin Zhao, Shen Qixiao, Jin Wei, Hao Zhuowen, Wang Junwu, Chen Tianhong, Chen Jiayao, Li Jingfeng
Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, 430000, Hubei Province, China.
Department of Orthopedics, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, 350000, China.
J Bone Miner Metab. 2025 Mar;43(2):96-107. doi: 10.1007/s00774-024-01559-7. Epub 2024 Dec 6.
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.
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.
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.
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.
先前的研究表明，即使甲状腺功能的微小变化也与骨质疏松症（OP）风险增加有关。然而，甲状腺疾病与OP发生之间的因果关系仍不清楚。为解决这一问题，我们旨在使用两样本孟德尔随机化（MR）方法研究各种甲状腺疾病的遗传易感性与OP之间的联系。
多种甲状腺疾病的工具变量（IVs）来自一个大型全基因组关联研究（GWAS）荟萃分析数据集。OP的汇总水平数据来自芬兰基因组联盟。逆方差加权（IVW）方法作为MR分析的主要方法。敏感性分析包括MR-Egger回归、异质性检验、多重有效性检验和留一法敏感性检验。
IVW分析显示甲状腺功能减退（OR = 1.105，95% CI 1.023 - 1.194，P = 0.011）和桥本甲状腺炎（OR = 1.142，95% CI 1.026 - 1.271，P = 0.015）对OP有直接因果效应。然而，未发现甲状腺功能亢进（OR = 1.030，95% CI 0.944 - 1.123，P = 0.508）或甲状腺癌（OR = 0.971，95% CI 0.898 - 1.051，P = 0.469）与OP之间存在直接因果关联。
我们的MR分析揭示了甲状腺功能减退、桥本甲状腺炎与OP之间的因果关联。这突出了甲状腺功能对骨骼健康的重大影响。然而，需要进一步的纵向研究来最终证实这些发现。
