Investigating the causal relationship between thyroid dysfunction diseases and osteoporosis: a two-sample Mendelian randomization analysis

Abstract

Background Thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) have a high prevalence in the population. Previous studies have indicated a potential association between TDFDs and OP, yet the causal direction remains unclear. This study aims to investigate the potential causal relationship between TDFDs and the risk of developing OP and related fracture. Methods We obtained pooled data from genome-wide association studies (GWAS) conducted on TDFDs and OP in European populations, and identified single nucleotide polymorphisms (SNPs) with genome-wide significance levels associated with exposure to TDFDs as instrumental variables. Inverse variance weighting (IVW) was employed as the primary method for MR analysis, supplemented by MR-Egger, Weighted median, Simple mode and Weighted mode methods. Sensitivity analyses were conducted to evaluate the robustness of the findings. Results The IVW method demonstrated an increased risk of osteoporosis (OP) in patients with TDFDs, including hyperthyroidism and hypothyroidism (TDFDs: OR = 1.11; 95% CI 1.09, 1.13; hypothyroidism: OR = 1.14; 95% CI 1.10, 1.17; hyperthyroidism: OR = 1.09; 95% CI 1.06, 1.12). These findings were further supported by the supplementary analysis, which revealed a positive correlation between TDFDs and the risk of OP. Multiple sensitivity analyses confirmed the absence of horizontal pleiotropy and heterogeneity in the study, thus indicating the robustness of our results. Conclusion The observed causal association between TDFDs and OP, indicating an increased risk of OP in patients with TDFDs, implies the necessity of early BMD screening and implementation of proactive prevention and treatment strategies for individuals with TDFDs.