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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 15, 2025; 16(10): 111813
Published online Oct 15, 2025. doi: 10.4239/wjd.v16.i10.111813
Published online Oct 15, 2025. doi: 10.4239/wjd.v16.i10.111813
Diabetic bone fragility through advanced glycation end product-collagen axis: Mechanisms and therapy of sodium glucose cotransporter 2 inhibitors
Zhi-Peng Li, Peng Wang, Yao-Bin Wang, Chang-Jiang Zhang, Second Department of Orthopedics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Zhi-Peng Li, Tianjian Advanced Biomedical Laboratory, Zhengzhou University, Zhengzhou 450001, Henan Province, China
Cheng Luo, Cheng-Zheng Duan, Shi-Yu Xu, Zi-Yuan Peng, Department of Endocrinology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Xian-Mei Yu, Dong-Juan He, Department of Endocrinology, The Second People’s Hospital of Quzhou, Quzhou 324002, Zhejiang Province, China
Li-Ya Ye, Department of Gynecology, The Second People’s Hospital of Quzhou, Quzhou 324002, Zhejiang Province, China
Da Sun, Institute of Life Sciences and Biomedical Collaborative Innovation Center, Wenzhou University, Wenzhou 325000, Zhejiang Province, China
Mei-Qi Zeng, Department of Ophthalmology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Hui Xu, Department of Hospital Management, Quzhou Hospital of Traditional Chinese Medicine, Quzhou 324000, Zhejiang Province, China
Yao-Bin Wang, Henan Key Laboratory for Helicobacter pylori and Digestive Tract Mic
Wen-Jie Ruan, Postgraduate Training Base Alliance, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
Meng-En Xue, Spine and Spinal Cord Surgery Ward I, Zhengzhou University People’s Hospital, Zhengzhou 462000, Henan Province, China
Co-first authors: Zhi-Peng Li and Cheng Luo.
Co-corresponding authors: Chang-Jiang Zhang and Dong-Juan He.
Author contributions: Li ZP and Luo C conceptualized and designed the study, and contributed equally to the development and writing of this review as co-first authors; Yu XM, Ye LY, Sun D, Duan CZ, Xu SY, Zeng MQ, Peng ZY, Wang YB, and Wang P conducted the literature review, extracted and analyzed key references, and drafted the initial manuscript; Ruan WJ and Xue ME prepared the figures and graphical illustrations; Xu H and Zeng MQ critically revised the manuscript for intellectual content and contributed to methodological refinement; He DJ and Zhang CJ provided funding support, coordinated project administration and supervision, and made equal contributions as co-corresponding authors; all authors approved the final version to publish.
Supported by Clinical Medical Research Fund of the Zhejiang Medical Association, No. 2025ZYC-Z32; Henan Provincial Key Research and Development Program, No. 231111311000; Henan Provincial Science and Technology Research Project, No. 232102310411; and Clinical Medical Research Fund of the Zhejiang Medical Association, 2024ZYC-Z30.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dong-Juan He, MD, Chief Physician, Director, Professor, Department of Endocrinology, The Second People’s Hospital of Quzhou, No. 338 Xin’an Avenue, Qujiang District, Quzhou 324002, Zhejiang Province, China.
Received: July 10, 2025
Revised: July 30, 2025
Accepted: September 15, 2025
Published online: October 15, 2025
Processing time: 97 Days and 20.1 Hours
Revised: July 30, 2025
Accepted: September 15, 2025
Published online: October 15, 2025
Processing time: 97 Days and 20.1 Hours
Core Tip
Core Tip: This review highlights how advanced glycation end products (AGEs) exacerbate bone fragility in type 2 diabetes by cross-linking type I collagen and disrupting bone mineralization. These findings elucidate the AGE-type I collagen axis as a key pathogenic mechanism underlying the diabetic bone paradox. Emerging evidence suggests that sodium-glucose cotransporter 2 inhibitors may mitigate AGE-related bone damage beyond glycemic control. Targeting AGE formation, cross-linking, and receptor-mediated signaling offers novel therapeutic strategies to improve bone quality in diabetic pa