Ratio of Endogenous Secretory Receptor for Advanced Glycation End Products to Pentosidine Predicts Fractures in Men

Context: Although the endogenous secretory receptor for advanced glycation end products (esRAGE) has been associated with reduced activity of pentosidine (PEN), the association between PEN, esRAGE, and fracture is poorly understood. Objectives: To evaluate the ability of serum PEN and esRAGE levels to predict fragility fractures. Methods: A cohort of 1285 Japanese men aged >= 65 years old participated in a 2007 to 2008 Fujiwara-kyo Osteoporosis Risk in Men study baseline survey, as part of the Fujiwara-kyo prospective cohort study. Those participants provided information regarding any fractures they experienced during 5 years. The baseline bone mineral density (BMD) was measured. Hazard ratios (HRs) per one standard deviation increase of log-transformed serum levels of PEN, esRAGE, and esRAGE-to-PEN ratio were estimated at baseline. Results: Twenty-five participating men suffered incident clinical fragility fractures. The crude HRs (95% confidence interval) for PEN, esRAGE, and esRAGE-to-PEN ratio were 1.56 (1.05 to 2.31), 0.79 (0.54 to 1.15), and 0.65 (0.44 to 0.95), respectively. HRs for PEN adjusted for age, esRAGE, and T score of BMD at femoral neck (FN) and lumbar spine (LS) were 1.48 (1.00 to 2.18) and 1.51 (1.03 to 2.21), respectively. The marginal significance adjusted for BMD at FN and the statistical significance adjusted for BMD at LS were attenuated after additional adjustment for glycated hemoglobin A1c level (P = 0.111 and 0.072, respectively). The HRs for esRAGE-to-PEN ratio adjusted for age, glycated hemoglobin A1c, and T-score of BMD at FN and LS were 0.67 (0.45 to 0.98) and 0.64 (0.43 to 0.95). Conclusions: Higher esRAGE-to-PEN ratios were associated with decreased risk of fragility fractures independent of BMD among elderly Japanese men.