Low bone toughness in the TallyHO model of juvenile type 2 diabetes does not worsen with age

Amy Creecy, Sasidhar Uppuganti, Mustafa Unal, R. Clay Bunn, Paul Voziyan, Jeffry S. Nyman

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Fracture risk increases as type 2 diabetes (T2D) progresses. With the rising incidence of T2D, in particular early-onset T2D, a representative pre-clinical model is needed to study mechanisms for treating or preventing diabetic bone disease. Towards that goal, we hypothesized that fracture resistance of bone from diabetic TallyHO mice decreases as the duration of diabetes increases. Femurs and lumbar vertebrae were harvested from male, TallyHO mice and male, non-diabetic SWR/J mice at 16 weeks (n ≥ 12 per strain) and 34 weeks (n ≥ 13 per strain) of age. As is characteristic of this model of juvenile T2D, the TallyHO mice were obese and hyperglycemic at an early age (5 weeks and 10 weeks of age, respectively). The femur mid-shaft of TallyHO mice had higher tissue mineral density and larger cortical area, as determined by micro-computed tomography, compared to the femur mid-shaft of SWR/J mice, irrespective of age. As such, the diabetic rodent bone was structurally stronger than the non-diabetic rodent bone, but the higher peak force endured by the diaphysis during three-point (3pt) bending was not independent of the difference in body weight. Upon accounting for the structure of the femur diaphysis, the estimated toughness at 16 weeks and 34 weeks was lower for the diabetic mice than for non-diabetic controls, but neither toughness nor estimated material strength and resistance to crack growth (3pt bending of contralateral notched femur) decreased as the duration of hyperglycemia increased. With respect to trabecular bone, there were no differences in the compressive strength of the L6 vertebral strength between diabetic and non-diabetic mice at both ages despite a lower trabecular bone volume for the TallyHO than for the SWR/J mice at 34 weeks. Amide I sub-peak ratios as determined by Raman Spectroscopy analysis of the femur diaphysis suggested a difference in collagen structure between diabetic and non-diabetic mice, although there was not a significant difference in matrix pentosidine between the groups. Overall, the fracture resistance of bone in the TallyHO model of T2D did not progressively decrease with increasing duration of hyperglycemia. However, given the variability in hyperglycemia in this model, there were correlations between blood glucose levels and certain structural properties including peak force.

Original languageEnglish
Pages (from-to)204-214
Number of pages11
JournalBone
Volume110
DOIs
StatePublished - May 2018

Bibliographical note

Funding Information:
This work was funded in part by a training grant from NIDDK ( DK101003 ) and by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases ( AR067871 ). The VUMC Hormone and Analytical Core is supported by NIH grants DK059637 and DK020593. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funding agencies. Appendix A

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • Bone quality
  • Fracture risk
  • Mechanical properties
  • Micro-computed tomography
  • Pentosidine
  • Raman spectroscopy
  • Type 2 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Fingerprint

Dive into the research topics of 'Low bone toughness in the TallyHO model of juvenile type 2 diabetes does not worsen with age'. Together they form a unique fingerprint.

Cite this