Pentosidine and increased fracture risk in older adults with type 2 diabetes

J Clin Endocrinol Metab. 2009 Jul;94(7):2380-6. doi: 10.1210/jc.2008-2498. Epub 2009 Apr 21.

Abstract

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.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arginine / analogs & derivatives*
  • Arginine / analysis
  • Arginine / urine
  • Bone Density
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / urine
  • Female
  • Fractures, Bone / blood
  • Fractures, Bone / epidemiology*
  • Fractures, Bone / etiology*
  • Fractures, Bone / urine
  • Humans
  • Incidence
  • Lysine / analogs & derivatives*
  • Lysine / analysis
  • Lysine / urine
  • Male
  • Prevalence
  • Risk Factors
  • Spinal Fractures / epidemiology
  • Spinal Fractures / etiology
  • Spinal Fractures / urine

Substances

  • Arginine
  • pentosidine
  • Lysine