Cortical Porosity as Disease-Specific Bone Phenotype in Diabetic Patients with Fragility Fractures

Type 2 diabetes mellitus is a major public health problem. Although bone mineral density seems to be higher in patients with type 2 diabetes, they are not protected from fragility fractures. On the contrary, multiple studies have shown that diabetic bone disease is related to an increased risk of fragility fractures. This clinically relevant discrepancy leaves many patients with type 2 diabetes underdiagnosed. Considering the fact that efficient fracture risk reduction by antiresorptive or osteoanabolic therapies is now available, it would be extremely important to identify individuals at risk and to quantify their fracture risk. Using clinical parameters, dual-energy x-ray absorptiometry (DXA), quantitative computed tomography (QCT), high resolution peripheral quantitative computed tomography (HR-pQCT) as well as magnetic resonance (MR) spectroscopy, the aim of this cross-sectional study is to develop novel imaging approaches to identify the risk for fragility fractures in patients with type 2 diabetes mellitus by defining and validating new measures of bone quality that are more predictive than bone mineral density measurements. Postmenopausal women with type 2 diabetes mellitus and prevalent fragility fractures (n=20) will be compared with diabetic age-, ethnicity- and body-mass-index(BMI)-matched diabetic controls without prevalent fractures (n=20). Further non-diabetic women with (n=20) and without (n=20) fragility fractures will serve as additional reference groups. Based on preliminary data, we hypothesize that HR-pQCT-derived cortical porosity will be able to differentiate diabetic patients with fractures from those without fractures. Moreover, we believe that cortical porosity will be different in diabetic fracture patients than in non-diabetic post-menopausal controls with and without low energy fractures. We aim to demonstrate that parameters of trabecular microarchitecture will be able to differentate fragility fracture subjects with and without diabetes, with non-diabetic subjects demonstrating reduced trabecular number and increased trabecular separation, while diabetics will have maintained trabecular bone structure. Further we believe that diabetic subjects will display a generally higher bone marrow adiposity than control subjects.