Evaluating the Association between Cardiometabolic Health Over the Lifespan and Vertebral Strength

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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.