Department of Medicine, Division of Endocrinology, Diabetes & Metabolism, Johns Hopkins University, Baltimore, Maryland.
Department of Materials Science and Engineering, Cornell University, Ithaca.
Curr Opin Endocrinol Diabetes Obes. 2021 Aug 1;28(4):360-370. doi: 10.1097/MED.0000000000000641.
Individuals with type 2 diabetes (T2D) are at increased risk of fracture, often despite normal bone density. This observation suggests deficits in bone quality in the setting of abnormal glucose homeostasis. The goal of this article is to review recent developments in our understanding of how advanced glycation end products (AGEs) are incorporated into the skeleton with resultant deleterious effects on bone health and structural integrity in patients with T2D.
The adverse effects of skeletal AGE accumulation on bone remodeling and the ability of the bone to deform and absorb energy prior to fracture have been demonstrated both at the bench as well as in small human studies; however, questions remain as to how these findings might be better explored in large, population-based investigations.
Hyperglycemia drives systemic, circulating AGE formation with subsequent accumulation in the bone tissue. In those with T2D, studies suggest that AGEs diminish fracture resistance, though larger clinical studies are needed to better define the direct role of longstanding AGE accumulation on bone strength in humans as well as to motivate potential interventions to reverse or disrupt skeletal AGE deposition with the goal of fracture prevention.
2 型糖尿病（T2D）患者骨折风险增加，尽管其骨密度通常正常。这一观察结果表明，在葡萄糖稳态异常的情况下，骨质量存在缺陷。本文的目的是综述最近在理解晚期糖基化终产物（AGEs）如何在骨骼中积累以及在 T2D 患者中对骨骼健康和结构完整性产生有害影响方面的最新进展。
在实验室和小型人体研究中都已经证明了骨骼 AGE 积累对骨重塑的不利影响，以及骨骼在骨折前变形和吸收能量的能力；然而，如何在大型基于人群的研究中更好地探讨这些发现仍存在疑问。
高血糖会导致全身性、循环性 AGE 的形成，随后在骨组织中积累。在 T2D 患者中，研究表明 AGEs 降低了骨折抵抗力，尽管需要更大的临床研究来更好地确定长期 AGE 积累对人类骨骼强度的直接作用，并激发潜在的干预措施来逆转或破坏骨骼 AGE 沉积，以预防骨折。
