Computed Tomography to Identify Structural Mechanisms of Hip Fragility in T1DM

项目摘要/摘要 1型糖尿病(T1D)患者在任何骨骼部位骨折的风险都会增加，而且令人担忧的是 与非糖尿病患者相比，髋部骨折的风险增加了7倍， 骨折。然而，T1D骨骼脆性的潜在机制却知之甚少，这使得很难 找出有风险的人，并为他们提供适当的干预措施，以防止骨折。T1D患者有 中度低的DXA-骨密度(BMD)，这只是部分解释了他们患高血压的风险显著增加 骨折。骨脆性不仅由骨量决定，还与骨的大小、形状和结构有关。 尽管髋部骨折的风险很高，但还没有研究评估骨密度和骨的3D分布 患有T1D的老年人髋部的结构是骨折风险最高的。我们的目标是使用以前的 从T1D和非糖尿病对照组≥60获得股骨近端的三维CT扫描 年龄，以确定导致T1D髋关节脆性的结构性和软组织缺陷，以及增益 深入了解T1D特征如何影响股骨结构和强度。在一项回顾研究中 患有T1D的老年人和有腹部或骨盆的年龄、种族和性别匹配的非糖尿病对照组 无对比的诊断CT扫描，我们将评估CT衍生的面骨密度(ABMD)和积分、皮质和 股骨近端的骨小梁体积骨密度和结构(目标1)。此外，我们将确定 患有T1D的老年人是否在近端有局灶性皮质骨缺损，使用一种新的技术 绘制股骨近端表面的皮质骨测量图，以确定髋部的局部区域 T1D和对照组在皮质骨测量上的不同之处。当载荷作用于髋部时，会发生髋部骨折 超过其强度，我们将比较T1D组和对照组髋部骨折的负荷强度比， 考虑到与跌倒相关的冲击载荷和股骨强度的特定受试者差异(目标2)。最后，我们 将确定导致髋关节脆性的潜在因素，如血糖控制、微血管疾病和T1D 持续时间(目标3)。这个项目将产生很大的影响，因为结果将提供关于 T1D中髋关节脆性的基础，临床医生需要选择最佳的干预措施来减少髋关节 在这一脆弱的患者群体中出现骨折。

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.