Volumetric bone density, geometry, strength and bone tissue material properties in type 1 diabetes

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Abstract Postmenopausal women with type 1 diabetes (T1D) have a six- to eight-fold higher risk for hip fractures compared to women without diabetes. Hip fractures are associated with significant morbidity, mortality, loss of independence, and financial burden. Moreover, hip fracture mortality is higher in patients with diabetes compared to subjects without diabetes. Dual x-ray absorptiometry (DXA), the most common test to assess bone health, measures only areal bone mineral density (BMD), and fails to provide information on bone quality; hence, it underestimates fracture risk in patients with T1D. Therefore, we hypothesize that hip structural and bone tissue material quality will be compromised in postmenopausal women with T1D compared to controls. Consistent with overarching hypothesis, we propose to determine hip bone structural quality (vBMD, bone geometry, and bone strength) using quantitative computed tomography (QCT) and a novel computerized image-based technique (finite element analysis) [Aim 1], and evaluate differences in bone tissue composition and tissue material properties from transiliac bone biopsy using Raman spectroscopy, nanoindentation, and backscattered electron microscopy [Aim 2] in postmenopausal women with T1D compared to age- and BMI- matched postmenopausal women without diabetes. With improved care, people with T1D are living longer and there is no specific approach for prevention and treatment of osteoporosis for older adults with T1D. Therefore, this study will elucidate possible mechanisms of bone fragility in postmenopausal women with T1D with the long-term goal to prevent hip fractures and related morbidity in this high-risk population. The proposed K23 award will facilitate my transition to independence by providing support necessary to; 1) acquire and consolidate clinical science knowledge and translational research skills; 2) develop professional research skills, and 3) develop a path to independent research. To achieve my professional goals, I have assembled a team of mentors comprised of 1) Dr. Janet Snell-Bergeon, PhD, an expert in the field of T1D complications and epidemiology, funded by the NIH for more than a decade; and 2) Dr. Wendy Kohrt, PhD, a senior scientist in the field of bone metabolism and aging, with over three decades of constant NIH funding. In addition, the expertise of Mentoring team (Dr. Chonchol, clinical researcher in the field of bone metabolism, Drs. Carpenter and Ferguson, biomechanical engineers and Dr. Pyle, biostatistician) will help advance my career in this field. The findings of the proposed study will generate essential data to propose an R01 focused on therapeutic strategies to reduce osteoporosis risk in T1D.