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Bone Tissue Collagen Maturity and Mineral Content Increase With Sustained Hyperglycemia in the KK-Ay Murine Model of Type 2 Diabetes.

  • Hunt, Heather B1
  • Pearl, Jared C1
  • Diaz, David R1
  • King, Karen B2, 3
  • Donnelly, Eve1, 4
  • 1 Department of Materials Science and Engineering, Cornell University, Ithaca, NY, USA.
  • 2 Department of Orthopedics, University of Colorado School of Medicine, Aurora, CO, USA.
  • 3 Surgical Service/Orthopaedic Service, Veterans Affairs Eastern Colorado Health Care System, Denver, CO, USA.
  • 4 Research Division, Hospital for Special Surgery, New York, NY, USA.
Published Article
Journal of Bone and Mineral Research
Wiley (John Wiley & Sons)
Publication Date
Dec 27, 2017
DOI: 10.1002/jbmr.3365
PMID: 29281127


Type 2 diabetes mellitus (T2DM) increases fracture risk for a given bone mineral density (BMD), which suggests that T2DM changes bone tissue properties independently of bone mass. In this study, we assessed the effects of hyperglycemia on bone tissue compositional properties, enzymatic collagen crosslinks, and advanced glycation end-products (AGEs) in the KK-Ay murine model of T2DM using Fourier transform infrared (FTIR) imaging and high-performance liquid chromatography (HPLC). Compared to KK-aa littermate controls (n = 8), proximal femoral bone tissue of KK-Ay mice (n = 14) exhibited increased collagen maturity, increased mineral content, and less heterogeneous mineral properties. AGE accumulation assessed by the concentration of pentosidine, as well as the concentrations of the nonenzymatic crosslinks hydroxylysylpyridinoline (HP) and lysyl pyridinoline (LP), did not differ in the proximal femurs of KK-Ay mice compared to controls. The observed differences in tissue-level compositional properties in the KK-Ay mice are consistent with bone that is older and echo observations of reduced remodeling in T2DM. © 2017 American Society for Bone and Mineral Research.

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