Computed Tomography to Identify Structural Mechanisms of Hip Fragility in T1DM

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PROJECT SUMMARY / ABSTRACT Individuals with type 1 diabetes (T1D) have an increased risk of fracture at any skeletal site, and an alarming 7-fold increased risk of hip fracture compared to non-diabetics, along with worse clinical outcomes after a fracture. However, the mechanisms underlying T1D skeletal fragility are poorly understood, making it difficult to identify those at risk and offer them appropriate interventions to prevent fractures. T1D patients have moderately low DXA-bone mineral density (BMD), which only partially explains their markedly increased risk of fracture. Bone fragility is not only determined by bone mass but also bone size, shape and architecture. Despite the high risk of hip fracture, no studies have assessed 3D distribution of bone density and bone structure at the hip in older adults with T1D, who have the highest risk of fracture. Our goal is to use previously acquired 3D computed tomography (CT) scans of the proximal femur from T1D and non-diabetic controls ≥60 years of age to identify structural and soft tissue deficits that contribute to hip fragility in T1D, as well as gain insight into how T1D characteristics contribute to femoral bone structure and strength. In a retrospective study of older adults with T1D and age-, race- and sex-matched non-diabetic controls who had abdominal or pelvis diagnostic CT scans without contrast, we will assess CT-derived areal BMD (aBMD) and integral, cortical and trabecular volumetric bone density and structure in the proximal femur (Aim 1). Furthermore, we will determine whether older adults with T1D have focal cortical bone defects at the proximal, using a novel technique that maps cortical bone measurements over the surface of the proximal femur to identify localized regions of the hip where T1D and controls differ in cortical bone measures. As hip fracture occurs when loads applied to the hip exceed its strength, we will compare the load-to-strength ratio for hip fracture in T1D versus controls, accounting for subject-specific variation in fall-related impact loads and femoral strength (Aim 2). Finally, we will determine potential contributors to hip fragility, such as glycemic control, microvascular disease and T1D duration (Aim 3). This project will have high impact, as the results will provide novel insights about the underpinnings of hip fragility in T1D that is needed for clinicians to select optimal interventions to reduce hip fractures in this vulnerable patient group.