Mechanisms of skeletal fragility in diabetes mellitus

Abstract Diabetes mellitus is well-recognized as a risk factor for osteoporotic fractures. Patients with type 1 diabetes (T1D) have lower bone mineral density (BMD) with associated increases in fracture risk. Patients with type 2 diabetes (T2D) also have a higher risk of fracture despite paradoxically elevated BMD suggesting differing mechanisms of skeletal fragility. In this chapter, we explore skeletal imaging methods as well as more invasive methods for evaluation of bone architecture and bone quality used in both clinical and research settings. We also discuss bone mineralization matrix alterations, disruptions in skeletal cellular function, and hormonal and metabolic influences that lead to skeletal fragility in diabetes mellitus. Finally, due to declines in muscle mass and strength in the setting of impaired balance, the fall risk is much higher in diabetes mellitus. Both skeletal fragility and higher fall risk contribute to osteoporotic fractures and clinicians should be aware of the higher risk of fracture in their diabetes mellitus patients.