FGF21 is a novel biomarker to predict fragility fractures in patients with type 2 diabetes mellitus

Fibroblast growth factor 21 (FGF21) levels are elevated with type 2 diabetes mellitus (T2D). This study aimed to elucidate whether FGF21 is a predictor for fragility fractures and to construct a predictive model using FGF21 as a risk factor to predict fractures in T2D. This prospective cohort study enrolled 371 individuals with high atherosclerotic risk, of whom 60.4% had T2D. FGF21 was measured at enrollment. The first incident fragility fractures were recorded. Individuals with T2D had a higher risk of major fractures (SHR 3.64, 95% CI 1.24-10.71) and tended toward a higher risk of any fractures (SHR 2.50, 95% CI 0.99-6.33). FGF21 was an independent risk factor for fractures in individuals with T2D. A predictive model comprising age, gender, 10-year probability of major osteoporotic fractures (FRAX-M) based on body mass index (BMI), FGF21, and aspartate transaminase (AST) demonstrated an AuROC of 0.84 and sensitivity and specificity of 84.2% and 74.5%, respectively, to predict fractures in T2D. The predictive risk score with the threshold of 103, which had an AuROC of 0.79, a sensitivity of 84.2%, and a specificity of 75.5%, was proposed for clinical application. In conclusion, FGF21 was a novel risk factor for fragility fractures in T2D. A predictive model and predictive risk score using age, gender, BMI-based FRAX-M, AST, and FGF21 showed high performance for predicting fractures in T2D. This predictive model may benefit clinical practice after further external validation.