Among its medical complications, type 2 diabetes mellitus in older adults is associated with a two-fold increase in the risk of hip and other low-trauma bone fractures. Paradoxically, this increased risk occurs despite a higher average bone mineral density. This increased fracture risk is likely multifactorial, stemming from metabolic dysfunction that results in both increased falls risk and decreased bone strength. However, fracture risk stratification currently is limited largely to bone density testing and clinical risk tools that do not perform adequately for adults with diabetes. Because bone is both a metabolic and structural tissue, metabolomics and biomechanical analyses would be particularly useful for developing and assessing new measures of fracture risk. The objective of this application is to develop and evaluate radiographic and laboratory biomarkers of fracture risk among older adults with diabetes, utilizing biomechanical and translational measures. The proposed research has the following aims: 1) Determine the association between metabolomic profiles and incident clinical fracture among older adults with diabetes; 2) Compare geometric and biomechanical measures at the femoral neck and intertrochanteric region among older adults with diabetes, with and without hip fracture. This application builds upon the prior published work and clinical expertise of the Principle Investigator, Dr. Richard Lee, and provides him additional research skills to assist with his career development goal of understanding the interaction of chronic medical conditions on the bone health of older adults, focusing on diabetes. Dr. Lee is a dual-trained Geriatrician and Endocrinologist with expertise in metabolic bone disease. The primary training goals of this proposal include the following: 1) Develop laboratory and analytical skills in translational science that will be used in the development and evaluation of clinical biomarkers, including ?omics technologies; 2) Acquire principles and skills in biomechanical engineering and materials science to integrate with clinical and epidemiological analyses. By integrating biomechanical engineering and metabolomics approaches with epidemiologic research to identify new markers of fracture risk, this application addresses a significant source of morbidity and mortality among an increasing proportion of older adults.

Public Health Relevance

Diabetes mellitus affects 1 in 5 older adults in the US and is associated with significant medical comorbidities, including increased fracture risk. However, the factors associated with this fracture risk are not fully understood, and current clinical tests do not provide a sufficient assessment. In focusing on the NIH goals of fostering innovative research strategies to improve health and developing resources to prevent disease. The proposed research is relevant to public health because identifying radiographic and metabolic markers of fracture risk among older adults with diabetes will lead to increased understanding of bone strength in this increasingly prevalent population and therefore to improved clinical assessment tools.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Mentored Patient-Oriented Research Career Development Award (K23)
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Neuroscience of Aging Review Committee (NIA)
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Joseph, Lyndon
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Duke University
Internal Medicine/Medicine
Schools of Medicine
United States
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