Characterization of bone structural, geometric, and material properties in the TallyHO mouse model of type 2 diabetes mellitus
Patients with type 2 diabetes (T2DM) have higher fracture risk compared to patients without T2DM despite having comparable to higher bone mineral density (BMD). Thus, T2DM might alter other aspects of resistance to fracture beyond BMD such as bone geometry, microarchitecture, and tissue material properties. In this study, we characterized the skeletal phenotype of the TallyHO mouse model of T2DM. The minimum moment of inertia was smaller (-26%) and cortical porosity was greater (+490%) in TallyHo femurs compared to controls. Whole-bone mechanical properties were examined in three-point bending tests to failure of the femurs. Post-yield displacement was lower (-35%) in the TallyHO mice relative to that in C57Bl/6 age-matched controls after adjusting for body mass. The tissue level mechanical properties were determined by nanoindentation. The cortical bone of TallyHO mice was stiffer and harder, as indicated by greater mean tissue indentation modulus (+20%) and hardness (+15%) compared to controls. Raman mineral:matrix ratio and crystallinity were greater in TallyHO mice than in C57Bl/6 mice (mineral:matrix +10%, crystallinity +1%, both p < 0.05). Tissue level hardness and crystallinity increased with worsening hyperglycemia. The smaller femoral minimum moment of inertia and higher cortical porosity, which is related to lower structural resistance of bone in bending is compensated by increased tissue modulus and hardness to maintain whole-bone stiffness and strength in TallyHO mice. Furthermore, increased tissue mineralization and crystallinity could explain lower ductility in TallyHO mice.
hardness; modulus; nanoindentation; Raman spectroscopy; TallyHO mouse; Type 2 diabetes
Donnelly, Eve Lorraine
Hernandez, Christopher J.
Materials Science and Engineering
M.S., Materials Science and Engineering
Master of Science
dissertation or thesis