CT-Based Modeling of Bone Micro-Architecture and Fracture-Risk in COPD

这项转化研究旨在建立慢性阻塞性肺疾病（COPD）特异性骨折 预测模型使用我们独特的基于计算机断层扫描（CT）的外周骨微评估， 架构骨质疏松症是COPD患者的常见合并症， mortality.对这一共同现象的基础知之甚少，因此，需要确定 COPD相关因素和骨微结构及其与骨质疏松风险的关系多种COPD相关 因素与骨质疏松症有关。不同的COPD相关的骨质流失原因可能会不均匀地影响 具有不同机械后果的皮质骨和松质骨结构，反映了不同的COPD- 骨矿物质密度（BMD）相似的个体中的相关骨密度风险。人们对这种联系知之甚少， 我们的目标是使用临床上合适的新兴CT表征工具来填补这一知识空白 骨骼的微结构。具体而言，这项研究将-（1）建立我们的普遍性 骨微结构评估应用于新兴的低剂量/高分辨率CT扫描仪， 供应商;（2）评估其与双能X线吸收测定法（DXA）相比的潜力，以解释 骨折和预测COPD患者的骨折事件;（3）量化不同COPD- 骨结构的相关因素及其对患病风险的影响;（4）快速识别COPD亚型 骨结构退化;和（5）开发COPD特异性模型，用于使用 患者特定数据。我们将利用-（1）现有的COPD患者队列， 爱荷华州大学（UI）和哥伦比亚大学（CU）代表了广泛的人口范围;（2）获得 新兴的CT扫描仪在这两个网站;和（3）独特的图像处理方法，量化三个- 三维骨结构指标。我们将从UI和CU队列中招募470名COPD患者， 性别相似的从不吸烟者对照组。在基线和3年随访时，我们将收集-（1）与风险相关的数据 因素;（2）侧位脊柱CT定位扫描，以评估椎体骨折;（3）踝关节高分辨率CT扫描 和手腕，用于计算骨结构度量;以及（4）全身、脊柱和髋DXA。Siemens Force CT 除100名随机选择的患者和来自UI的对照组外，所有参与者都将使用扫描仪 相反，他们将通过东芝Aquarium ONE 320扫描仪进行成像。这项研究将建立一个 一种新兴的基于CT的扫描仪独立的可推广工具，用于评估对不同治疗方法的骨反应 旨在减缓或逆转骨丢失的干预措施，并可能恢复骨结构， 更多针对患者的干预措施。此外，本研究旨在解释各种COPD之间的关系- 相关因素，骨结构变化及其对骨风险的影响。最后，一个专门针对COPD的模型 将开发一种用于评估乳腺癌风险的方法，该方法将利用患者特定的人口统计学、临床和 X射线照相数据和脊柱的CT BMD，以及手腕和/或脚踝的骨结构测量。

This translational study seeks to establish a Chronic Obstructive Pulmonary Disease (COPD)-specific fracture prediction model using our unique computed tomography (CT)-based assessment of peripheral bone micro- architecture. Osteoporosis, a common comorbidity among patients with COPD, accelerates morbidity and mortality. The basis for this comorbidity is poorly understood, thus the need for characterizing the link between COPD-related factors and bone micro-architecture and their association to fracture-risk. Multiple COPD-related factors are associated with osteoporosis. Different COPD-related causes of bone loss may non-uniformly impact cortical and trabecular bone structures with varying mechanical consequences, reflective of divergent COPD- associated fracture-risk in individuals with similar bone mineral density (BMD). Little is known about this linkage, and our goal is to fill this knowledge gap using a clinically suitable emerging CT-based tool for characterization of bone micro-architecture at peripheral sites. Specifically, this study will—(1) establish the generalizability of our bone micro-architecture assessment applied to emerging low dose / high resolution CT scanners from different vendors; (2) assess its potential as compared to dual energy x-ray absorptiometry (DXA) to explain prevalent fractures and predict incident fractures among patients with COPD; (3) quantify the impact of different COPD- related factors on bone structures and their implications for fracture-risk; (4) identify COPD subtypes with rapid bone structural degeneration; and (5) develop a COPD-specific model for assessment of fracture-risk using patient-specific data. We will take advantage of—(1) existing COPD patient cohorts with lung characterization at the University of Iowa (UI) and Columbia University (CU) representing a wide demographic range; (2) access to emerging CT scanners at both sites; and (3) unique image processing methodologies for quantifying three- dimensional bone structural metrics. We will recruit 470 COPD patients from the UI and CU cohorts and 80 age- sex-similar never-smoker controls. At baseline and 3-year follow-up visits, we will collect—(1) data related to risk factors; (2) a lateral spine CT scout scan to assess vertebral fractures; (3) high resolution CT scans of the ankle and wrist for computation of bone structural metrics; and (4) whole-body, spine and hip DXA. Siemens Force CT scanners will be used for all participants except for 100 randomly-selected patients and controls from the UI cohort who, instead, will be imaged via a Toshiba Aquilion ONE 320 scanner. This study will establish an emerging CT-based scanner-independent generalizable tool to assess bone response to different therapeutic interventions aimed at slowing or reversing bone loss, and possibly restoring bone structure, potentially leading to more patient-specific interventions. Also, this study seeks to explain the relationships among various COPD- related factors, bone structural changes and their implications for fracture-risk. Finally, a COPD-specific model for assessment of fracture-risk will be developed that will utilize patient-specific demographic, clinical and radiographic data, and CT BMD at the spine, as well as bone structural measures at the wrist and/or ankle.