Progression and etiology of cortical porosity in diabetic bone disease

High resolution bone images comparing control and type 2 diabetes groups, showing differences in cortical and trabecular bone structure, with red circles highlighting regions of altered bone quality.
Comparison of (A)HR-pQCT, (B)fat-sensitive MR, (C)pre-contrast MR, and  (D)post-contrast MR for a healthy control subject displaying exclusively vessel-filled pores (LEFT) and a T2D subject with both marrow- and vessel-filled pores (RIGHT). Prominent vessels in the post-contrast scans are highlighted in red.
High resolution bone image showing cortical porosity with overlaid graph illustrating differences in signal intensity over time between blood vessels and marrow within cortical pores.
Contrast enhancement curves for regions of hyperintense signal on the post-contrast MR (vessel) and fat-sensitive MR (marrow).

Patients with type 2 diabetes (T2D) have an increased risk for fragility fractures despite normal or even elevated bone mineral density (BMD) Recent findings suggest that diabetic bone exhibits abnormalities in bone quality, including elevated cortical porosity. Cortical porosity has deleterious effects on bone strength, and is critical in fracture initiation and propagation, but the origins and temporal evolution of pathological cortical porosity in T2D are unknown. To develop treatments specifically targeted to the prevention or reversal of pathological cortical porosity and associated bone fragility in T2D, we must understand the mechanisms driving development of these cortical pores. The goal of this study is to investigate the underlying biological processes that drive increased cortical porosity in the setting of T2D and to understand the longitudinal evolution of human diabetic bone disease with a special focus on cortical porosity. We are currently conducting a longitudinal study of pore progression in T2D patients, using a novel combined high-resolution peripheral quantitative computed tomography (HR-pQCT) and dynamic contrast enhanced magnetic resonance imaging (DCE MRI) approach. We are developing novel image analysis approaches to characterize pore content and spatial distribution of porosity within the cortex, and are using micro finite element (μFE) analysis to quantify the biomechanical impact of porosity.

Funded by NIH/NIAMS R01 AR069670