Relationship between subclinical thyroid dysfunction and the risk of fracture: a meta-analysis of prospective cohort studies

Abstract

Summary: To identify the relationship between subclinical thyroid dysfunction and the risk of fracture, we conducted a meta-analysis of prospective cohort studies. Results showed that subclinical hyperthyroidism is associated with an increased risk of fracture, especially in elder. Introduction: There are conflicting data on the association between subclinical thyroid dysfunction and the risk of fracture. This study is aimed at providing a summary of prospective evidence of the relationship between subclinical thyroid dysfunction and the risk of fracture. Methods: We systematically searched the MEDLINE, EMBASE, and the Chinese Biomedical literature database (CBM) from 1974 to August 2014 to identify prospective cohort studies which have studied the risk of fracture in patients with subclinical thyroid dysfunction. Various fractures were reported as the sole outcome. Results: Five population-based cohort studies including 314,146 participants with relationship of endogenous or exogenous subclinical thyroid dysfunction or euthyroidism and fractures were identified as eligible for the meta-analysis. In an unadjusted model, the relative risk (RR) of subclinical hypothyroidism for fracture was 1.30 (CI 1.08–1.56). Risk estimates were lower in a multivariable-adjusted model (RR = 1.20, CI 0.70–2.04) and when higher quality studies (RR = 0.95, CI 0.58–1.57) were analyzed. For subclinical hyperthyroidism, the RR was 1.52 (CI 1.33–1.73) in unadjusted model and 1.25 (CI 1.11–1.41) in a multivariable-adjusted model. An analysis of higher quality studies revealed a RR 1.18 (CI 1.07–1.29). Subgroup analysis indicated that the RR for risk of fracture was higher in the endogenous group than the exogenous group, taking thyroid-altering medicine in subclinical hyperthyroidism. Similar finding was also demonstrated in subclinical hypothyroidism. Conclusions: Despite heterogeneity across the studies, data suggest that subclinical hyperthyroidism is associated with an increased risk of fracture in the population older than 60 years. No evidence could prove a definite association between subclinical hypothyroidism and the risk of fracture yet.