Abstract
BACKGROUND: Subclinical thyroid dysfunction (STD) is associated with an elevated risk of non-vertebral fractures. However, whether STD is associated with the risk of vertebral fracture remains controversial. This study aimed to determine the relationship between STD and the risk of vertebral fracture using a meta-analysis approach. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library databases were searched for eligible studies published until March 01, 2025. Only prospective cohort studies that reported effect estimates with 95% confidence intervals (CIs) of vertebral fractures in participants with subclinical hyperthyroidism (SCH) and subclinical hypothyroidism (SH) compared to those with euthyroidism were included. A random-effects model was used to pool risk ratios (RRs), and analyses accounted for key covariates, including demographic factors, lifestyle variables, and disease history where reported. RESULTS: Ten prospective cohort studies involving 61,219 individuals were included in this meta-analysis. SCH was associated with an increased risk of vertebral fracture (RR: 2.20; 95% CI: 1.60-3.02; p < 0.001). Moreover, the risk of vertebral fracture in individuals with SH was higher than that in those with euthyroidism (RR, 1.22; 95% CI: 1.01-1.49; p = 0.044). The pooled conclusions for the association between SCH and vertebral fracture risk were robust, whereas the significant association between SH and vertebral fracture was variable. The relationship between SH and vertebral fracture risk was affected by the median age of individuals (p = 0.047). CONCLUSION: Our study found that SCH was an independent risk factor for vertebral fracture, and that SH may increase the risk of vertebral fracture. Clinically, these findings support the need for regular monitoring of thyroid function, particularly in older adults, to identify individuals with STD who may benefit from targeted interventions to reduce vertebral fracture risk.