Using HR-pQCT, three studies investigated bone architecture in patients with and without diabetes [9, 10, 19]. Shu et al. [19] analyzed a cohort of 14 T2DM postmenopausal women and 14 control postmenopausal women. Standard trabecular and cortical bone parameters were calculated from the HR-pQCT images, which included cortical thickness and density but not cortical porosity. None of the investigated parameters showed significant differences. It should be noted that information on fragility fractures in this cohort was not available.

Burghardt et al. [9] applied HR-pQCT to characterize cortical and trabecular microarchitecture and biomechanics in the peripheral skeleton of female patients with T2DM using a cross-sectional study design. Elderly female patients (age, 62.9 ± 7.7 years) with a history of T2DM (n = 19) and age- and height-matched controls (n = 19) were recruited and imaged using HR-pQCT at the distal radius and tibia. The T2DM cohort included patients with and without fragility fractures. Quantitative measures of volumetric (BMD), cross-sectional geometry, trabecular and cortical microarchitecture were calculated. Additionally, compressive mechanical properties were determined by microfinite element analysis. These investigators found that compared to the controls, the T2DM cohort had 10 % higher trabecular volumetric BMD (P < 0.05) adjacent to the cortex and higher trabecular thickness in the tibia (13.8 %; P < 0.05). Cortical porosity differences, however, were consistent with impaired bone strength in T2DM patients and were significant in the radius (> +50 %; P < 0.05), whereas pore volume approached significance in the tibia (+118 %; P = 0.1). They concluded that, in T2DM patients, the impaired resistance to bending loads may be due to inefficient redistribution of bone mass, characterized by loss of intracortical bone offset by an elevation in trabecular bone density. These results may provide a potential explanation for the inability of standard BMD measures to explain the elevated fracture incidence in patients with T2DM.

In a more recent study comparing T2DM postmenopausal women and age-matched control women differences were found in cortical porosity at the distal radius and tibia between T2DM patients with and without fragility fractures [10]. This study provided evidence for the key importance of cortical abnormalities in the increased prevalence of fragility fractures in T2DM patients and the potential role of HR-pQCT as a novel diagnostic imaging test measuring cortical porosity. For this study 80 women (mean age 61.3 ± 5.7 years) were recruited into four groups (n = 20 per group) with and without diabetes and with and without fragility fractures. Participants underwent DXA and HR-pQCT of the ultradistal and distal radius and tibia. In the HR-pQCT images volumetric bone mineral density, cortical and trabecular structure measures, including cortical porosity, were calculated. Bone strength was estimated using microfinite element analysis (microFEA). At the ultradistal and distal tibia, women with diabetic fractures had substantially greater intracortical pore volume (+52.6 %, p = 0.009; +95.4 %, p = 0.020), relative porosity (+58.1 %; p = 0.005; +87.9 %, p = 0.011) and endocortical bone surface (+10.9 %, p = 0.031; +11.5 %, 0.019) compared to diabetic women without fracture. At the distal radius T2DM women with fractures had a 4.7-fold greater relative porosity (p < 0.01) than women without fractures. At the ultradistal radius, intracortical pore volume was significantly higher in T2DM women with fractures compared to those without fractures (+67.8 %, p = 0.018). T2DM women with fractures also displayed larger trabecular heterogeneity (ultradistal radius; +36.8 %, p = 0.035), and lower total and cortical BMD (ultradistal tibia: −12.6 %, p = 0.031; −6.8 %, p = 0.011) than women without fractures. T2DM women with fractures also exhibited significantly higher pore-related deficits in stiffness, failure load and cortical load fraction at the ultradistal and distal tibia, and the distal radius than women with diabetes and no fractures. Figure 11.2 illustrates the findings of increased cortical porosity in a woman with type 2 diabetes and fragility fracture in relation to a diabetic woman without fracture. Interestingly, comparing nondiabetic fracture and control women, only a nonsignificant trend was found with increase in pore volume (+38.9 %, p = 0.060) at the ultradistal radius. Overall, similar to the previous study, the results of this study suggested that severe deficits in cortical bone quality may be responsible for fragility fractures in postmenopausal diabetic women.