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

这项翻译研究旨在建立慢性阻塞性肺疾病(COPD)特有的骨折 使用我们独特的基于计算机断层扫描(CT)的周围骨微结构评估的预测模型 建筑。骨质疏松症是慢性阻塞性肺疾病患者的常见共病，它会加速发病率和 死亡率。这种共病的基础尚不清楚，因此有必要确定两者之间的联系 慢性阻塞性肺疾病相关因素和骨骼微结构及其与骨折风险的关系。多种慢性阻塞性肺疾病相关疾病 这些因素与骨质疏松症有关。不同的COPD相关原因对骨丢失的影响可能不均匀 皮质和松质骨结构具有不同的力学后果，反映了发育性COPD- 具有相似骨密度(BMD)的个体的相关骨折风险。人们对这种联系知之甚少， 我们的目标是使用一种临床上适用的基于CT的新工具来描述特征，以填补这一知识空白 周围部位的骨微结构。具体地说，这项研究将-(1)建立我们的 骨微结构评价在不同型号低剂量/高分辨率CT扫描中的应用 供应商；(2)评估其与双能x射线吸收法(DXA)相比较的潜力，以解释流行 骨折和预测COPD患者中发生的骨折；(3)量化不同COPD- 影响骨结构的相关因素及其对骨折风险的影响；(4)快速鉴别慢性阻塞性肺疾病亚型 骨结构退行性变；以及(5)开发COPD特异性模型，用于评估骨折风险 患者特定的数据。我们将利用-(1)具有肺部特征的现有COPD患者队列 爱荷华大学(UI)和哥伦比亚大学(CU)代表广泛的人口统计范围；(2)访问 两个地点的新兴CT扫描仪；以及(3)独特的图像处理方法，用于量化三个- 多维骨骼结构度量。我们将从UI和CU队列中招募470名COPD患者和80名年龄- 性生活相似的不吸烟者对照。在基线和3年的跟踪访问中，我们将收集-(1)与风险相关的数据 因素；(2)脊柱侧位CT扫描以评估脊椎骨折；(3)脚踝高分辨率CT扫描 以及(4)全身、脊柱和髋部的DXA。西门子强制CT 除了从UI中随机选择的100名患者和对照组外，所有参与者都将使用扫描仪 他们将通过东芝Aquilion One 320扫描仪进行成像。这项研究将建立一个 新出现的基于CT的不依赖于扫描仪的通用工具来评估不同治疗方案的骨骼反应 旨在减缓或逆转骨丢失，并可能恢复骨结构的干预措施，可能导致 更多针对患者的干预措施。此外，这项研究还试图解释各种COPD之间的关系- 相关因素、骨骼结构变化及其对骨折风险的影响。最后，针对慢性阻塞性肺病的模型 对于骨折风险的评估，将开发将利用患者特定的人口统计学、临床和 放射学数据和脊柱的CT骨密度，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.