Thyroid dysfunction and osteoporosis: A two-sample bidirectional Mendelian randomization study

Previous observational studies have suggested a potential link between hyperthyroidism and osteoporosis (OP) risk. However, the relationship between hypothyroidism and osteoporosis risk remains uncertain due to the inherent limitations of observational studies, such as reverse causality and confounders, which complicate the determination of causality. To address these issues, we conducted a 2-way, 2-sample Mendelian randomized study using instrumental variables selected from a large genome-wide association study meta-analysis dataset of European origin. This approach allowed us to assess the causal effects of hyperthyroidism and hypothyroidism on OP. Additionally, inverse Mendelian randomization (MR) analysis was employed to estimate the causal effect of OP on hyperthyroidism and hypothyroidism. The primary analytical method used was inverse variance weighting, supplemented by MR-Egger and weighted median methods. Heterogeneity tests, sensitivity analyses, and assessments for horizontal pleiotropy complemented the primary analysis. The MR analysis revealed a causal relationship between hyperthyroidism (odds ratio [OR] = 1.17, 95% confidence interval [CI] 1.00-1.36; P = 3.61E-07) and hypothyroidism (OR = 1.01, 95% CI 1.00-1.03; P = .013) and the risk of OP. Conversely, no causal relationship was found between OP and hyperthyroidism (OR = 1.00, 95% CI 0.98-1.09; P = .208) or hypothyroidism (OR = 1.11, 95% CI 0.92-1.33; P = .297) in reverse MR analysis. Therefore, our study confirms a causal link between hyperthyroidism and hypothyroidism with OP, suggesting that individuals with these conditions may have an increased risk of developing osteoporosis. Further research is needed to elucidate the underlying biological mechanisms and provide robust evidence for clinical guidelines aimed at preventing OP.