Shirley Ann Jackson Ph.D. Center of Biotechnology and Interdisciplinary Studies, Troy, NY 12180, USA; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
Shirley Ann Jackson Ph.D. Center of Biotechnology and Interdisciplinary Studies, Troy, NY 12180, USA; Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180, USA; Rensselaer - Icahn School of Medicine at Mount Sinai Center for Engineering and Precision Medicine, New York, NY 10019, USA.
Bone. 2023 Nov;176:116880. doi: 10.1016/j.bone.2023.116880. Epub 2023 Aug 12.
Hyperglycemia and oxidative stress, enhanced in diabetes and aging, result in excessive accumulation of advanced glycation and glycoxidation end products (AGEs/AGOEs) in bone. AGEs/AGOES are considered to be "the missing link" in explaining increased skeletal fragility with diabetes, aging, and osteoporosis where increased fracture risk cannot be solely explained by bone mass and/or fall incidences. AGEs/AGOEs disrupt bone turnover and deteriorate bone quality through alterations of organic matrix (collagen and non-collagenous proteins), mineral, and water content. AGEs and AGOEs are also associated with bone fragility in other conditions such as Alzheimer's disease, circadian rhythm disruption, and cancer. This review explains how AGEs and AGOEs accumulate in bone and impact bone quality and bone fracture, and how AGES/AGOEs are being targeted in preclinical and clinical investigations for inhibition or removal, and for prediction and management of diabetic, osteoporotic and insufficiency fractures.
高血糖和氧化应激在糖尿病和衰老中加剧，导致骨中晚期糖基化和糖基化终产物（AGEs/AGOEs）的过度积累。AGEs/AGOEs 被认为是解释糖尿病、衰老和骨质疏松症中骨骼脆性增加的“缺失环节”，在这些疾病中，骨折风险的增加不能仅用骨量和/或跌倒发生率来解释。AGEs/AGOEs 通过改变有机基质（胶原和非胶原蛋白）、矿物质和含水量来破坏骨转换并降低骨质量。AGEs 和 AGOEs 也与其他疾病中的骨脆性有关，如阿尔茨海默病、昼夜节律紊乱和癌症。本文综述了 AGEs 和 AGOEs 在骨中的积累如何影响骨质量和骨折，以及 AGEs/AGOEs 如何在临床前和临床研究中被靶向以进行抑制或清除，以及预测和管理糖尿病、骨质疏松症和非创伤性骨折。
