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,...