Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of bone fracture despite having normal to high bone mineral density, even after adjusting for covariates such as BMI and falls. Because fracture risk in T2DM individuals cannot be completely explained by bone quantity, this indicates that aspects of bone quality, such as microarchitecture, microdamage accumulation, and chemical composition, may play a role. Thus, the main objective of this research was to elucidate factors that contribute to increased fracture risk in individuals with T2DM by relating microdamage accumulation to trabecular microarchitecture and characterizing the collagen crosslinking profiles.

In this thesis, mechanical and material properties of two clinical populations were characterized. First, the confluence of micro-architecture and microdamage accumulation was observed in specimens from the femoral neck of men with and without T2DM. Specimens were compressed to 3% strain and stained with a heavy metal stain to illuminate microdamage. MicroCT scans of the damaged specimens were analyzed with Individual Trabeculae Segmentation (ITS) Technique software to correlate trabecular morphology with damage accumulation. Rod-like trabeculae were disproportionally damaged in controls, indicating that cancellous bone from men with T2DM may have an attenuated ability to mitigate microdamage accumulation through sacrificial rods. Second, enzymatic and non-enzymatic collagen crosslinks were quantified in specimens from the iliac crest of post-menopausal women with varying levels of glycemic control using high performance liquid chromatography (HPLC). T2DM specimens had higher quantities of the harmful crosslink pentosidine, indicating potential embrittlement of collagen fibers.

Taken together, both of these studies illuminate potential mechanisms behind increased fragility in bone from individuals with T2DM. The clinical relevance of this work is that understanding of the mechanisms behind higher fracture risk in individuals with T2DM can lead to improvements in pharmacologic treatments and fracture prevention methods