Systematic review and meta-analysis links Type 2 Diabetes to higher fracture risk across multiple anatomical sites

OBJECTIVE: This review aimed to quantify the association between Type 2 Diabetes (T2D) and the risk of fracture at various anatomical sites by synthesising data from cohort studies. METHODS: A systematic search was conducted across Medline, Embase, CINAHL and Web of Science databases, from inception to 10 June 2025. We estimated pooled hazard ratios (HRs) with corresponding 95% confidence intervals using random-effects models. This study is registered with PROSPERO (CRD42024548795). RESULTS: This meta-analysis of 22 studies, selected from 6534 screened studies, assessed a total of 13,074,868 individuals (2,644,443 people with T2D and 10,430,425 without T2D). People with T2D have a 25% increased risk of fractures (all anatomical sites) compared to individuals without T2D (HR: 1.25; 95% CI: 1.20 to 1.31). T2D was significantly associated with an increased risk of appendicular lower limb fractures (HR: 1.43; 95% CI: 1.30 to 1.57), upper limb fractures (HR: 1.29; 95% CI: 1.16 to 1.45), osteoporotic/fragility fractures (HR: 1.14; 95% CI: 1.02 to 1.28) and appendicular unspecified fractures (HR: 1.25; 95% CI: 1.05 to 1.48). Subgroup analyses indicated stronger associations in prospective studies. Women with T2D had a significantly higher fracture risk than men. Meta-regression analyses showed that a higher percentage of women participants and a longer duration of T2D were associated with stronger associations between T2D and fracture risk, particularly for lower limb fractures. CONCLUSION: T2D is associated with an increased risk of fractures, especially in lower limbs (hip, ankle and foot). These findings highlight the importance of targeted fracture prevention strategies and site-specific risk assessment for individuals with T2D. However, due to the heterogeneity among studies, caution is required in the interpretation of these findings.