Pentosidine and Increased Fracture Risk in Older Adults with Type 2 Diabetes

Context: Type 2 diabetes is associated with higher fracture risk at a given bone mineral density. Advanced glycation endproducts (AGEs) accumulate in bone collagen with age and diabetes and may weaken bone. Objective: The aim was to determine whether urine pentosidine, an AGE, was associated with fractures in older adults with and without diabetes. Design: We performed an observational cohort study. Setting: We used data from the Health, Aging and Body Composition prospective study of white and black, well-functioning men and women ages 70-79 yr. Participants: Participants with(n = 501) and with out(n = 427) diabetes were matched on gender, race, and study site. Predictor: Urine pentosidine was assayed from frozen stored baseline specimens. Main Outcome Measures: Incident clinical fractures and baseline vertebral fractures were measured. Results: Despite higher bone mineral density, clinical fracture incidence (14.8 vs. 12.6%) and vertebral fracture prevalence (2.3 vs. 2.9%) were not lower in those with diabetes (P > 0.05). In multivariable models, pentosidine was associated with increased clinical fracture incidence in those with diabetes [relative hazard, 1.42; 95% confidence interval (CI), 1.10, 1.83, for 1 SD increase in log pentosidine] but not in those without diabetes (relative hazard, 1.08; 95% CI, 0.79, 1.49; P value for interaction = 0.030). In those with diabetes, pentosidine was associated with increased vertebral fracture prevalence (adjusted odds ratio, 5.93; 95% CI, 2.08, 16.94, for 1 SD increase in log pentosidine) but not in those without diabetes (adjusted odds ratio, 0.74; 95% CI, 0.30, 1.83; P value for interaction = 0.005). Conclusions: Higher pentosidine levels are a risk factor for fracture in older adults with diabetes and may account in part for reduced bone strength in type 2 diabetes. (J Clin Endocrinol Metab 94: 2380-2386, 2009)