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.

Public Health Relevance

The goal of this translational study is to establish a newly emerging CT-based tool for the characterization of changes in bone micro-architecture and assessment of their implications for fracture-risk in a population of COPD patients at risk for osteoporosis. The tool will be suitable and generalizable across emerging CT scanners from different vendors, and it will provide a more structurally-based assessment of osteoporosis and bone loss than is provided by simple bone density measures. The study will characterize the impact of different COPD-related factors on bone structure, and their implications for fracture-risk, leading to the development of a COPD-specific model for assessment of fracture-risk 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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Punturieri, Antonello
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Schools of Medicine
Iowa City
United States
Zip Code