Diabetes and bone fragility: a dangerous liaison.

Patients with diabetes are at greater risk of fractures not only for bone mineral density (BMD) decrease, showed for type 1 diabetes mellitus (T1DM), but also for bone tissue alterations that reduce bone quality and strength; thus, BMD values do not reflect bone fragility in diabetics. Higher rates of fracture in diabetic patients can be related both to changes in bone quality and in long standing diabetes to microvascular complications that lead to a greater risk of falling. Diabetes leads to impaired bone formation through many mechanisms: insulin deficiency and hyperglycemia, prevalently by AGE/RAGE axis alteration, insulin growth factors reduction, and alterations in osteocalcin and/or Wnt signaling pathways. Therefore, an adequate glycemic control is mandatory in diabetes to preserve bone health. Metformin, incretins, and DPP-4 inhibitors have a potentially positive effect on bone status, while close attention should be paid to a long-term therapy with thiazolidinediones, because they are associated to an increased risk of fracture.