Characterization of Material Properties, Microarchitecture, and Mechanics of Bone from Subjects with Type 2 Diabetes Mellitus
Hunt, Heather Brittany
People with type 2 diabetes mellitus (T2DM) have normal to high bone mineral densities, but counterintuitively have greater fracture risks than people without T2DM, even after accounting for potential confounders like BMI and falls. Therefore, T2DM may alter aspects of the quality of bone, independently of bone mass, through metabolic or biochemical mechanisms as a result of a T2DM disease state. The main objective of this research was to elucidate the material factors that increase fragility in T2DM by characterizing the material properties, microarchitecture, and mechanics of bone from subjects with and without T2DM. The tissue material properties of bone from two clinical populations and from a rodent model of T2DM were evaluated, and the microarchitecture and and mechanics were evaluated for one of the clinical populations. In the rodent model of T2DM, mice with T2DM had more mineralized tissue, more mature collagen, and less heterogenous mineral properties compared to non-DM littermate controls, all of which are consistent with an older tissue that has undergone less remodeling. Tissue properties of the iliac crest from post-menopausal women varied with different stages of glycemic control, from normal glucose tolerance, impaired glucose tolerance, and overt T2DM. Glycemic derangement was associated with increased mineralization, decreased collagen maturity, and atypical mineral maturation, all of which can alter the mechanics of bone. Finally, femoral neck cancellous bone from men with T2DM had increased mineralization, a less mature mineral, more numerous trabeculae, and greater accumulation of non-enzymatically-formed collagen crosslinks compared to men without T2DM. The mechanical properties of the T2DM specimens reflected these alterations: stiffness and strength were greater in the T2DM specimens because of the greater mineral content and improved microarchitecture. Regression modeling of post-yield toughness demonstrated a significant deleterious impact of mineral maturity and non-enzymatic crosslinks once the improvement in microarchitecture was mathematically accounted for. Together, these results indicate a beneficial effect of T2DM on cancellous microarchitecture, but a deleterious effect of T2DM on the collagen matrix and mineral maturation. In conclusion, this work aids in the understanding of how bone becomes more fragile with T2DM, and this work is clinically relevant because it demonstrates that different populations of T2DM patients may have distinctly different bone fragilities as a result of varying tissue composition and microarchitecture.
advanced glycation endproducts; translational; type 2 diabetes mellitus; Materials Science; bone; Biomechanics; Biochemistry; Collagen
Donnelly, Eve Lorraine
Hernandez, Christopher J.; Estroff, Lara A.
Materials Science and Engineering
Ph. D., Materials Science and Engineering
Doctor of Philosophy
dissertation or thesis