University of Utah mechanical engineering assistant professor Claire Acevedo has received the National Institutes of HealthExploratory/Developmental R21 award to research the mechanisms of increased fracture risk in diabetic bone at the collagen molecular level.
Diabetic adults have double the risk of fracture compared with non-diabetic adults with a similar bone mass. While it is becoming clear that high blood glucose affects bone quality and is involved in fragility fracture, the pathogenesis and mechanisms of increased fracture risk in type 2 diabetes (T2D) are not well understood. Acevedo’s recent findings in a diabetic rat model indicate that brittle behavior in type 2 diabetic bone was primarily due to a substantial reduction in collagen capacity of deformation rather than change in bone structure. This is thought to be associated with the increase of specific non-enzymatic cross-links known as Advanced Glycation End products (AGEs), preventing the collagen molecules from sliding onto each other. However, the independent influence of AGEs cross-links on the whole-bone resistance to fracture is unknown. The overall objective of this project is to characterize the collagen nanoscale behavior to establish the role of AGE collagen crosslinks on the whole-bone mechanical behavior and bone fragility in T2D. Acevedo proposes to identify these mechanisms by combining multiscale experiments with numerical modeling ranging from the collagen molecules to the microstructural level. This new multiscale model will establish a new quantitative understanding of the mechanisms by which changes at the collagen level of cortical bone increase bone fracture risk in the diabetic population, ultimately identifying a novel pathway to prevent and treat fracture in diabetic patients.