Low Serum Level of the Endogenous Secretory Receptor for Advanced Glycation End Products (esRAGE) Is a Risk Factor for Prevalent Vertebral Fractures Independent of Bone Mineral Density in Patients With Type 2 Diabetes

OBJECTIVE: Patients with type 2 diabetes are known to have an increased risk for fracture compared with non–type 2 diabetic control subjects, despite having higher bone mineral density (BMD). We previously showed that serum pentosidine, one of the advanced glycation end products (AGEs), was associated with prevalent vertebral fractures (VFs) in those with type 2 diabetes. The involvement of the endogenous secretory receptor for AGEs (esRAGE) in VFs in those with type 2 diabetes, however, is still unknown. RESEARCH DESIGN AND METHODS: We compared parameters including esRAGE, pentosidine, and BMD in Japanese type 2 diabetic patients (137 men >50 years old and 140 postmenopausal women) with and without VFs. RESULTS: The esRAGE-to-pentosidine ratio in type 2 diabetic patients with VFs was significantly lower than in those without VFs (men: 7.1 ± 2.8 vs. 9.4 ± 6.2, P = 0.013, respectively; women: 4.7 ± 2.7 vs. 8.2 ± 5.4, P < 0.001, respectively). Multivariate logistic regression analysis adjusted for age, BMI, A1C, serum creatinine, duration of diabetes, therapeutic agents, diabetes complications, osteoporotic risk factors, and lumbar BMD identified the serum esRAGE level and esRAGE-to-pentosidine ratio as factors associated with the presence of VFs, independent of BMD in men (odds ratio [OR] 0.46 [95% CI 0.25–0.84], P = 0.012; and OR 0.34 [0.15–0.76], P = 0.009, respectively) and in women (OR 0.32 [0.16–0.67], P = 0.002; and OR 0.14 [0.04–0.43], P = 0.001, respectively). CONCLUSIONS: These results show that serum esRAGE level and esRAGE-to-pentosidine ratio are more useful than BMD for assessing the risk of VFs in type 2 diabetic patients.