The causal relationship between hyperthyroidism, hypothyroidism, and osteoporosis: a Mendelian randomization study

Abstract To investigate the association between hyperthyroidism、hypothyroidism and osteoporosis by bidirectional two-sample Mendelian randomization (MR) to clarify the casual relationship. Independent genetic variants for hyperthyroidism、hypothyroidism and osteoporosis were selected as instruments from published genome-wide association studies (GWAS), mainly in European ancestry. Instrumental variables (IVs) associated with hyperthyroidism、hypothyroidism and osteoporosis were extracted separately from the largest GWAS meta-analysis. MR analyses included inverse variance weighting, weighted median estimator, MR Egger regression, and sensitivity analyses with Steiger fltering and MR PRESSO. In the data samples for hyperthyroidism、hypothyroidism and osteoporosis, there was a negative causal relationship between hyperthyroidism and osteoporosis [IVW, OR = 1.001%, 95% CI: 0.999–1.002, ]; while hypothyroidism and osteoporosis [IVW, OR = 2.648%, 95% CI: 2.582–2.715, p < 0.001]. The results of the bidirectional MR Study suggest that hyperthyroidism and hypothyroidism have negative causal effect on Osteoporosis, which provides implications for clinical treatment decisions in patients with Osteoporosis.