The Association Between Type 2 Diabetes and Bone Microarchitecture Assessed by HR-pQCT

Type 2 diabetic patients generally have higher BMD but greater fracture risk. Exploring their bone microarchitecture might help to explain their bone fragility. We conducted a cross-sectional matched analysis within three prospective cohorts including 477 men and women. Each patient with T2DM was matched for age, sex and BMI with two controls, yielding 159 cases and 318 controls. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to characterize cortical and trabecular bone microarchitecture. In predefined subgroup analyses within T2DM, we compared bone parameters according to glucose-lowering treatment, including metformin-containing regimens versus non-metformin oral regimens and metformin versus insulin-treated patients. In men, femoral neck aBMD was higher in T2DM (0.83 ± 0.13 vs. 0.79 ± 0.14 g/cm²; p < 0.05). Bone size was ~ 5% lower in T2DM-at the tibia in women (623.94 ± 92.42 vs. 656.65 ± 107.09 mm²; p < 0.05) and at the radius in men (386.66 ± 66.71 vs. 407.25 ± 62.53 mm²; p < 0.05). Among women, radial cortical area (44.38 ± 9.55 vs. 41.25 ± 9.94 mm²; p < 0.05) and cortical thickness (0.67 ± 0.16 vs. 0.62 ± 0.17 mm; p < 0.05) were higher in T2DM. Metformin use was associated with higher femoral neck/hip T-scores, and improved cortical microarchitecture-lower cortical porosity at the radius and tibia (p < 0.001 and p = 0.012) and greater tibial cortical thickness/area (p = 0.025/0.009)-compared with other oral therapies. T2DM was associated with lower tibial total and trabecular area in women, and lower radial total and trabecular area in men. Differences in bone microarchitecture between T2DM participants and controls were modest, heterogeneous, and site- and sex-specific. Exploratory subgroup analyses suggested that metformin use was associated with a more favorable cortical profile, but these findings require cautious interpretation.