ABSTRACT
Fragility fractures are a substantial public health problem in older adults in the United States (US), with vertebral
fractures being the most prevalent fracture type. Cardiometabolic disorders (e.g., hypertension, type 2
diabetes mellitus, abdominal obesity, and hyperlipidemia) have been associated with lower bone strength, bone
mineral density (BMD), and higher fracture risk. Although several epidemiologic studies have evaluated the role
of cardiometabolic health on vertebral fractures, by not accounting for the clustering of cardiometabolic
conditions, many of the study findings are limited. Large studies with the ability to adjust for multiple
cardiometabolic conditions are needed to provide information on the full effect of cardiometabolic conditions on
vertebral health, including BMD and strength. Studies evaluating molecular mechanisms of cardiometabolic
conditions on vertebral health also have study design limitations, including the lack of adjustment for clustering
of other cardiometabolic conditions and/or biomarkers, and cross-sectional evaluations where either the
cardiometabolic exposures and/or bone health data are assessed at a single time point. The lack of longitudinal
data limits our ability to understand how cardiometabolic health is related to vertebral health. Lastly, advances
in computed tomography (CT) technology has allowed for bone mass and strength measurements.
Biomechanical CT (BCT) analysis has allowed researchers to obtain validated bone mass and strength on CT
images obtained for other clinical indications, opening the investigation of the role of cardiometabolic disorders
on vertebral health in individuals who do not routinely receive DXA imaging (i.e. women of color and men). The
Coronary Artery Risk Development in Young Adults (CARDIA) study has followed 5,115 Black and White male
and female adults aged 18-30 years at baseline for 35 years. The proposed study will build on CARDIA’s
previously collected cardiometabolic disease and biomarker data. It will also add vertebral strength data through
BCT analysis of Year 25 and 35 abdominal CT scans. Our aims are to: 1) Evaluate the association between
cardiometabolic disease patterns and vertebral health, 2) Determine the role of cardiometabolic
biomarkers on vertebral health, and 3) Identify cardiometabolic health factors that predict 10-year
changes in vertebral health. Our overall goal is to provide unbiased and longitudinal estimates of the
association between cardiometabolic health and vertebral health, and to explore the potential biologic
mechanisms of these associations. Determining how cardiometabolic disease patterns and biomarkers, at
clinical or subclinical levels, impact vertebral bone health is highly desirable and can lead to changes in fracture
screening protocols in this high risk population.
