A longitudinal imaging study of the effects of type 2 diabetes and microvascular disease on diabetic bone disease

Skeletal fragility is a major complication of type 2 diabetes (T2D), occurring despite normal or elevated bone mineral density. However, pathophysiological mechanisms underlying diabetic bone disease remain poorly understood, partly due to the lack of longitudinal studies evaluating bone microarchitecture and function in T2D. Therefore, the current study employed an imaging-centered approach, applying high-resolution peripheral quantitative computed tomography and dynamic contrast-enhanced magnetic resonance imaging to assess changes in bone microarchitecture, biomechanics, and intracortical vessel microstructure and perfusion in 55 participants with or without T2D over 2 years. Both longitudinal and cross-sectional comparisons were conducted within and between groups. Interactions between T2D and microvascular disease (MVD), a common T2D comorbidity increasingly implicated in diabetic bone deterioration, were also examined for key cortical microarchitecture and intracortical vessel metrics. The findings suggested a trend toward greater longitudinal cortical deterioration in participants with T2D compared with controls, including a 3-fold greater loss in cortical bone mineral density and 6-fold greater increase in cortical porosity at the tibia. Significant longitudinal declines in intracortical vessel volume and perfusion were also observed in participants with T2D. No (T2D × MVD) interaction was observed for cortical microarchitecture or intracortical vessel metrics. Interestingly, significant decline in intracortical perfusion was associated with peripheral neuropathy, a common T2D sequela. In conclusion, this is the first longitudinal study capturing bone quality alterations with T2D in both men and women, highlighting adverse changes in cortical microarchitecture and intracortical vasculature. Peripheral neuropathy may represent a clinically relevant factor for managing diabetic skeletal fragility.