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

University of California, San Francisco (A.V.S., D.E.S., K.R.F., D.M.B., D.C.B.), San Francisco, California 94107; Hopital E. Herriot and Center for Clinical and Basic Research-Synarc (P.G.), 69003 Lyon, France; Kaiser Permanente Center for Health Research (T.A.H.), Portland, Oregon 97227; University of Pittsburgh (E.S.S.), Pittsburgh, Pennsylvania 15260; American Association of Homes and Services for the Aging (H.E.R.), Washington, D.C. 20008; University of Tennessee Health Science Center (F.A.T.), Memphis, Tennessee 38163; California Pacific Medical Center (S.R.C.), San Francisco, California 94115; and National Institute on Aging (T.B.H.), Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Ann V. Schwartz, Ph.D., Department of Epidemiology and Biostatistics, University of California San Francisco, 185 Berry Street, Suite 5700, San Francisco, California 94107-1762. E-mail: Aschwartz{at}psg.ucsf.edu.

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.