2型糖尿病患者骨折风险升高的机制

Mechanisms of increased fracture risk in patients with type 2 diabetes mellitus

2型糖尿病患者的骨折发生风险较非糖尿病人群升高,但其骨密度与非糖尿病人群相比可升高或不变,因此2型糖尿病患者的高骨折发生风险主要由骨质量下降引起。引起2型糖尿病患者骨转换异常致骨折风险升高的机制包括血糖升高、晚期糖基化终末产物增加、胰岛素水平降低或作用缺陷、胰岛素样生长因子1水平降低、氧化应激和促炎细胞因子增加等,从而引起成骨细胞和破骨细胞功能异常、骨折发生风险增加。另外,某些降糖药物的应用也可导致骨折风险增加,如胰岛素、噻唑烷二酮类、钠-葡萄糖协同转运蛋白2抑制剂(sodium-dependent glucose transporters 2 inhibitors,SGLT-2i)。此外,2型糖尿病患者因低血糖发作、糖尿病慢性并发症或肌肉功能减退所引起的跌倒风险增加也可增加骨折的发生风险。

Fracture risk in the patients with type 2 diabetes mellitus(T2DM)is higher than the non-diabetic population,however,bone mineral density(BMD)in T2DM patients is higher or equal to that of non-diabetic population.Thus,the increased fracture risk in T2DM patients may induced by the impaired bone quality.Data have shown that the increased fracture risk in T2DM patients can be contributed by hyperglycemia,increased advanced glycation end products,decreased insulin concentration or defects of insulin function,decreased insulin-like growth factor-1 level,increased oxidative stress and improper secretion of proinflammatory cytokines.These pathophysiological factors in T2DM patients may induce the imbalance of osteoblast and osteoclast function leading to increase of fracture risk.Moreover,several types of antidiabetic drugs can also increase the fracture risk,such as insulin,thiazolidinediones(TZDs)and sodium-dependent glucose transporters 2 inhibitors(SGLT-2i).In addition,increased risk of fall induced by hypoglycemia,chronic diabetic complications and muscle dysfunction may also contribute to fractures in patients with type 2 diabetes.