Fracture risk is increased in patients with type 2 diabetes mellitus (T2DM). In addition, these patients sustain fractures despite having higher levels of areal bone mineral density, as measured by dual-energy X-ray absorptiometry, than individuals without T2DM. Thus, additional factors such as alterations in bone quality could have important roles in mediating skeletal fragility in patients with T2DM. Although the pathogenesis of increased fracture risk in T2DM is multifactorial, impairments in bone material properties and increases in cortical porosity have emerged as two key skeletal abnormalities that contribute to skeletal fragility in patients with T2DM. In addition, indices of bone formation are uniformly reduced in patients with T2DM, with evidence from mouse studies published over the past few years linking this abnormality to accelerated skeletal ageing, specifically cellular senescence. In this Review, we highlight the latest advances in our understanding of the mechanisms of skeletal fragility in patients with T2DM and suggest potential novel therapeutic approaches to address this problem.

2 型糖尿病 (T2DM) 患者的骨折风险增加。此外，尽管通过双能 X 射线骨密度测定法测量，这些患者的面骨矿物质密度水平高于非 T2DM 患者，但仍会发生骨折。因此，骨质量改变等其他因素可能在调节 T2DM 患者骨骼脆性方面发挥重要作用。尽管 T2DM 骨折风险增加的发病机制是多因素的，但骨材料特性受损和皮质孔隙度增加已成为导致 T2DM 患者骨骼脆性的两个关键骨骼异常。此外，T2DM 患者的骨形成指数普遍降低，过去几年发表的小鼠研究证据表明，这种异常与骨骼加速衰老（特别是细胞衰老）有关。在这篇综述中，我们重点介绍了我们对 T2DM 患者骨骼脆弱机制理解的最新进展，并提出了解决这一问题的潜在新治疗方法。