Individuals with type 2 diabetes mellitus show dimorphic and heterogeneous patterns of loss in femoral bone quality

Type 2 diabetes mellitus (T2DM), a metabolic disease on the rise, is associated with substantial increase in bone fracture risk. Because individuals with T2DM have normal or high bone mineral density (BMD), osteodensitometric measurements of BMD do not predict fracture risk with T2DM. Here, we aim to identify the underlying mechanism of the diabetes-induced fracture risk using a high-resolution multi-scale analysis of human cortical bone with special emphasis on osseous cellular activity. Specifically, we show increased cortical porosity in a subgroup of T2DM individuals accompanied by changed mineralization patterns and glycoxidative damage to bone protein, caused by non-enzymatic glycation of bone by reducing sugar. Furthermore, the high porosity T2DM subgroup presents with higher regional mineralization heterogeneity and lower mineral maturity, whereas in the T2DM subgroup regional higher mineral-to-matrix ratio was observed. Both T2DM groups show significantly higher carboxymethyl-lysine accumulation. Our results show a dimorphic pattern of cortical bone reorganization in individuals afflicted with T2DM and hence provide new insight into the diabetic bone disease leading to increased fracture risk.