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 without (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.