Since reduced BMD alone does not fully explain bone fragility, particularly not in type 2 diabetes, alteration in “bone quality” is being investigated using various techniques. With magnetic resonance imaging (MRI), Pritchard et al. measured larger holes in trabecular network of type 2 diabetes compared to controls at baseline [
54]. Using HR-pQCT (Xtreme CT) at the distal radius and/or tibia, studies in postmenopausal women with or without diabetes suggest that there is a trend towards greater cortical porosity in type 2 diabetes compared to controls [
55‐
57]. In 99 elderly women with type 2 diabetes and 954 age-matched controls from the Gothenburg Study, Nilsson et al. reported higher cortical porosity at the distal radius but not at the distal tibia in subjects with type 2 diabetes (+ 16%,
p < 0.001) [
58]. However, they did not find any other alteration in the trabecular or cortical microarchitecture nor decreased estimated bone strength among diabetics in this cohort [
58]. Trabecular bone volume is more heterogeneous and is preserved or (apparently) increased [
55], though the latter may arise from the trabecularization of the cortex [
59]. Furthermore, the increased cortical porosity and larger trabecular heterogeneity is more evident in type 2 diabetes with fractures compared to type 2 diabetes without prevalent fractures [
56]. In African-American women with diabetes, cortical porosity was reported to be 26% greater while cortical volumetric BMD (vBMD) was lower compared to controls [
60]. A recent study of 52 subjects with type 2 diabetes, of whom 25 had microvascular disease demonstrated, such cortical deficits noted on HR-pQCT were only present in patients with the microvascular complications [
25]. Higher cortical porosity in mid-cortical and periosteal layers in type 2 diabetes patients with prior fracture compared to type 2 diabetes without fractures suggests that these cortical sub-compartments might be sensitive to type 2 diabetes-induced toxicity and may reflect microvascular disease [
61].
Bone strength estimated by microfinite element analysis (micro-FEA) was shown to be lower in type 2 diabetes compared to controls in association with increased cortical porosity at the distal radius [
55,
58]. Furthermore, in type 2 diabetes with fractures, stiffness, failure load, and cortical load fraction were significantly decreased at the ultradistal and distal tibia compared to type 2 diabetes without fractures and this deficit is related to the higher cortical porosity [
56]. However, it is unlikely that HR-pQCT will become sufficiently widely available for routine clinical purposes. DXA-derived surrogates for cortical bone volume and strength may provide additional information regarding cortical alterations in diabetes, as well as having potentially widespread accessibility.
Finally, few studies using microindentation of the tibia outer cortex have suggested that the estimated bone material strength index (BMSI) is decreased in type 2 diabetes compared to controls [
58,
62], which could reflect alterations in collagen crosslinks by advanced glycation end products (AGEs) and in mineralization (also see below) [
63]. These findings are consistent with the concept of “diabetoporosis” as previously suggested to characterize the bone fragility in this particular population [
64].