Exploring the genetic link between hypothyroidism and osteoporosis in patients without cancer: a two-sample Mendelian randomization analysis

Background: Osteoporosis (OP) is a global health issue. Essential for the metabolism of bone, thyroid function plays a crucial role. The connection between hypothyroidism and OP in individuals without cancer remains ambiguous. The aim of this study was to investigate the impact of hypothyroidism on the onset of OP in patients who did not have cancer. Methods: The exposures of individuals with non-cancer hypothyroidism were obtained from the publicly accessible MRC-IEU consortium of the UK Biobank, while the outcomes were derived from the GWAS of patients with OP included in the European Bioinformatics Institute (EBI) biobank. Furthermore, a two-sample Mendelian randomization (MR) method was employed to investigate the causal relationship between hypothyroidism and OP among non-cancer patients. This analysis identified single nucleotide polymorphisms (SNPs) that were closely associated with hypothyroidism in this population, which were then used as instrumental variables. Statistical analyses were conducted using four distinct approaches: inverse variance weighted (IVW), weighted median, MR Egger regression, and the weighted mode method. Results: We identified a total of 119 SNPs that exhibited strong associations with hypothyroidism in non-cancer patients (P < 5 × 10 ⁻⁸ ; LDr ² < 0.001). The consistent association between hypothyroidism and OP in non-cancer patients was demonstrated through various analyses: IVW yielded an odds ratio (OR) of 1.017 with a 95% confidence interval (CI) of 1.003-1.031; MR-Egger regression produced an OR of 1.018 with a 95% CI of 0.989-1.049; the weighted median estimate indicated an OR of 1.021 with a 95% CI of 1.001-1.041; and the weighted mode analysis showed an OR of 1.039 with a 95% CI of 1.003-1.076. These findings suggest that hypothyroidism is associated with the development of OP in this population. Additionally, there was no evidence of horizontal pleiotropy affecting the relationship between hypothyroidism and OP among non-cancer patients, as indicated by an MR-Egger intercept of −5.9 × 10 ⁻⁶ (P = 0.932). Conclusion: The findings from the MR analysis indicate a potential causal relationship between hypothyroidism and the occurrence of OP in non-cancer patients.