Bone damage in type 2 diabetes mellitus

• Patients with T2DM overall have increased fracture risk despite higher BMD values.
• Altered turnover and microarchitecture, accumulation of AGEs, affect bone quality.
• Bone fragility is poorly captured by both BMD and algorithms based on risk factors.
• Extraskeletal factors (frailty, complications, some therapies) increase fall rate.

This review focuses on the mechanisms determining bone fragility in patients with type 2 diabetes mellitus (T2DM). Despite bone mineral density (BMD) is usually normal or more often increased in these patients, fracture incidence is high, probably because of altered bone ”quality”. The latter seems to depend on several, only partly elucidated, mechanisms, such as the increased skeletal content of advanced glycation end-products causing collagen deterioration, the altered differentiation of bone osteogenic cells, the altered bone turnover and micro-architecture. Disease duration, its severity and metabolic control, the type of therapy, the presence or absence of complications, as like as the other known predictors for falls, are all relevant contributing factors affecting fracture risk in T2DM. In these patients the estimate of fracture risk in the everyday clinical practice may be challenging, due to the lower predictive capacity of both BMD and risk factors-based algorithms (e.g. FRAX).