Pathophysiology of Bone Fragility in Type 2 Diabetes Mellitus

Individuals with type 2 diabetes mellitus (T2DM) are at greater risk of fragility fractures compared to those without diabetes despite comparable or higher bone mineral density (BMD). T2DM may increase skeletal fragility by altering aspects of bone quality including bone geometry, microstructure, tissue properties and remodeling independently of BMD, a parameter of bone quantity. The objective of this review is to synthesize recent work involving aspects of bone quantity and quality that may contribute to fragility in T2DM.

Compared to those without diabetes, women with T2DM have less structurally robust hip geometries despite greater BMD after covariate adjustment. A growing body of evidence indicates that cancellous microarchitecture may be maintained in T2DM; however, cortical bone microarchitecture may be impacted by dysglycemia. Bone material properties - inclusive of tissue and/or compositional properties - and mechanical properties are influenced by T2DM. These include greater concentrations of advanced glycation end-products (AGEs) and increased tissue mineral content, changes associated with greater modulus and hardness, as well as reduced ductility and ability to mitigate damage accumulation. T2DM bone and serum markers indicate reduced bone remodeling compared to controls. Recent work bolsters prior observations reporting greater AGE and tissue mineral content in T2DM bone and reinforces findings of reduced remodeling. While some evidence indicates that these differences may adversely affect mechanical properties and result in stiffer, stronger - but more brittle - bone, this finding is not universal. Future studies require consideration of the multifactorial underpinnings of bone fragility in T2DM to guide screening, prevention strategies and fracture treatment in this at-risk population.