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Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2022; 13(11): 900-911
Published online Nov 15, 2022. doi: 10.4239/wjd.v13.i11.900
Type 2 diabetes and bone fragility in children and adults
Maria Felicia Faienza, Paola Pontrelli, Giacomina Brunetti
Maria Felicia Faienza, Department of Biomedical Sciences and Human Oncology, Pediatric Unit, University of Bari Aldo Moro, Bari 70124, Italy
Paola Pontrelli, Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari 70124, Italy
Giacomina Brunetti, Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Bari 70125, Italy
Author contributions: Faienza MF wrote the clinical implications; Pontrelli P explored the bone-kidney axis; Brunetti G performed the majority of the writing and coordinated the writing of the paper.
Conflict-of-interest statement: All the authors report having 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: Giacomina Brunetti, PhD, Associate Professor, Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona, 4, Bari 70125, Italy. giacomina.brunetti@uniba.it
Received: May 30, 2022
Peer-review started: May 30, 2022
First decision: August 7, 2022
Revised: August 17, 2022
Accepted: October 11, 2022
Article in press: October 11, 2022
Published online: November 15, 2022
Processing time: 164 Days and 14.5 Hours
Abstract

Type 2 diabetes (T2D) is a global epidemic disease. The prevalence of T2D in adolescents and young adults is increasing alarmingly. The mechanisms leading to T2D in young people are similar to those in older patients. However, the severity of onset, reduced insulin sensitivity and defective insulin secretion can be different in subjects who develop the disease at a younger age. T2D is associated with different complications, including bone fragility with consequent susceptibility to fractures. The purpose of this systematic review was to describe T2D bone fragility together with all the possible involved pathways. Numerous studies have reported that patients with T2D show preserved, or even increased, bone mineral density compared with controls. This apparent paradox can be explained by the altered bone quality with increased cortical bone porosity and compr-omised mechanical properties. Furthermore, reduced bone turnover has been described in T2D with reduced markers of bone formation and resorption. These findings prompted different researchers to highlight the mechanisms leading to bone fragility, and numerous critical altered pathways have been identified and studied. In detail, we focused our attention on the role of microvascular disease, advanced glycation end products, the senescence pathway, the Wnt/β-catenin pathway, the osteoprotegerin/receptor-activator of nuclear factor kappa B ligand, osteonectin and fibroblast growth factor 23. The understanding of type 2 myeloid bone fragility is an important issue as it could suggest possible interventions for the prevention of poor bone quality in T2D and/or how to target these pathways when bone disease is clearly evident.

Keywords: Type 2 diabetes; Bone remodeling; Cytokines; Bone fragility; Bone mineral density; Chronic kidney disease

Core Tip: Type 2 diabetes (T2D) patients show increased susceptibility to bone fractures, despite their bone mineral density being normal or increased, leading to difficult identification for clinicians. The prevalence of T2D in adolescents and young adults is increasing alarmingly. Different researchers highlighted the mechanisms leading to bone fragility, and different critical altered pathways have been identified and studied. In this review, we described the different metabolic pathways responsible for bone fragility in patients with T2D. They can be useful for its management, although further studies are needed to deepen our understanding of the mechanisms underlying bone fragility in T2D.