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

This translational study seeks to establish a Chronic Obstructive Pulmonary Disease
(COPD)-specific fracture prediction model using the investigators 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 the study
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 the investigators 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.

The study 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. The study will
recruit 550 smokers with and without COPD from the UI and CU cohorts of the COPDGene and
SPIROMICS studies. Smokers without COPD will comprise the control group for the study. At
baseline and 3-year follow-up visits, the study team 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 hip and ankle for computation of bone structural metrics; (4) whole-body,
spine and hip DXA scans for evaluation of bone mineral density and body composition; and (5)
DXA vertebral fracture assessment.

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 hip and/or ankle.

Inclusion Criteria:

- Current or former smoker, defined as having at least 10-pack year lifetime history

- Age: 45-90

Subjects will be stratified into groups based on COPD disease status: smokers with COPD and
smokers without COPD.

Smokers with COPD will be further stratified into three groups: low emphysema (< 3%),
moderate emphysema (between 3 and 10%), and severe emphysema (> 10%).

Exclusion Criteria:

- Pregnant or breast-feeding

- Metastatic Malignancy

- Currently receiving dialysis

- Any lower extremity fracture within the last year

- Any lower extremity fracture with hardware implant(s)

- History of bilateral tibia fractures