不同阶段2型糖尿病诱发骨质疏松症的致病机制研究进展

Research progress on the pathogenesis type 2 diabetes-induced osteoporosis of different stages

大量临床研究表明,2型糖尿病(type 2 diabetes mellitus,T2DM)患者的骨折风险明显增加。因此,T2DM诱发的骨质疏松症(osteoporosis,OP)被认为是最严重的糖尿病并发症之一。骨脆性增加是糖尿病性骨质疏松症(diabetic osteoporosis,DOP)的典型特征,其发病机制是多因素引起的,包括肥胖、高胰岛素血症、高血糖(hyperglycemia,HG)、晚期糖基化终产物(advanced glycation end products,AGEs)积聚和氧化产物积累以及微血管病变的存在等。这些因素在T2DM不同时期是相互平衡或相互促进的,而肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、白细胞介素-1(interleukin 1,IL-1)、白细胞介素-6(interleukin 6,IL-6)等炎症因子的异常活化打破了骨形成和骨吸收的代谢平衡,导致骨脆性增加。骨强度和骨折风险的变化取决于疾病进展的阶段。因此,糖尿病骨病的病理生理变化可以通过分别考虑糖尿病早期和晚期骨骼相关因素来广泛讨论,其中早期阶段以胰岛素抵抗和高胰岛素血症为特征,这些因素会导致糖尿病发病和初始阶段的骨密度(bone mineral density,BMD)增加。而晚期阶段的特征是β细胞衰竭,AGEs和氧化产物的堆积,加速衰老和血管并发症的发展。为此,本文希望对T2DM的不同阶段与骨代谢的关系进行综述,以便更好的认识T2DM的进展加速骨脆性风险的病理过程和致病机制,为治疗T2DM和T2DM诱发的OP、降低T2DM患者骨折发生的风险发挥积极的作用。

A large number of clinical studies have reported that patients with type 2 diabetes(T2DM)have a significantly increased risk of fracture.Therefore,T2DM-induced osteoporosis is considered to be one of the most serious complications of diabetes.Increased bone fragility is a typical feature of diabetic osteoporosis,and its pathogenesis is caused by multiple factors including obesity,hyperinsulinemia,hyperglycemia,accumulation of AGEs and oxidation products,and the presence of microangiopathy.These factors offset or promote each other during different stages of T2DM.If the balance of bone formation and bone resorption is disrupted by the abnormal activation of some inflammatory factors such as TNF-α,IL-1,and IL-6,it will lead to an increase in bone fragility.The changes in bone strength and fracture risk depend on the stage of disease progression.Therefore,the pathophysiological changes of diabetic bone disease can be widely discussed by considering the early and late skeletal related factors of diabetes,in which the early stage is characterized by insulin resistance and hyperinsulinemia,which lead to the onset of diabetes and an increase in BMD in the initial stage.The late stage is characterized by the failure of beta cell,accumulation of AGEs and oxidation products,and the accelerated development of aging and vascular complications.In order to clarify the pathogenesis of T2DM increasing the risk of bone fragility,we reviewed the relationship between different stages of T2DM and bone metabolism in this paper.The result would play a positive role in the treatment of T2DM-induced osteoporosis and the reduction of fracture risk in T2DM patients.