Contributors to impaired bone health in type 2 diabetes

Type 2 diabetes (T2D) is associated with numerous complications, including increased risk of fragility fractures, despite seemingly protective factors [e.g., normal bone mineral density and increased body mass index(BMI)]. However, fracture risk in T2D is underestimated by current fracture risk calculators. Importantly, post-fracture mortality is worse in T2D following any fracture, highlighting the importance of identifying high-risk patients that may benefit from targeted management. Several diabetes-related factors are associated with increased fracture risk, including exogenous insulin therapy, vascular complications, and poor glycaemic control, although detailed comprehensive studies to identify the independent contributions of these factors are lacking. The underlying pathophysiological mechanisms are complex and multifactorial, with different factors contributing during the course of T2D disease. These include obesity, hyperinsulinaemia, hyperglycaemia, accumulation of advanced glycation end products, and vascular supply affecting bone-cell function and survival and bone-matrix composition. This review summarises the current understanding of the contributors to impaired bone health in T2D, and proposes an updated approach to managing these patients. Type 2 diabetes (T2D) is associated with increased risk of fragility fractures, especially at the hip and distal limbs, despite normal/elevated bone mineral density (BMD).T2D-related characteristics that may increase fracture risk include exogenous insulin therapy, vascular complications, longer duration of T2D, and worse glycaemic control.Post-fracture mortality is elevated after all types of fractures, including nonhip nonvertebral fractures, the most common sites for fracture in T2D.The pathophysiology of T2D skeletal fragility is complex. Obesity and insulin resistance may contribute to higher BMD, but visceral adiposity and chronic inflammation may impair bone strength. Chronic hyperglycaemia, accumulation of advanced glycation end products, and vascular complications impair bone angiogenesis and turnover, and collagen matrix properties.