Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2019; 10(8): 421-445
Published online Aug 15, 2019. doi: 10.4239/wjd.v10.i8.421
Bone health in diabetes and prediabetes
Silvia Costantini, Caterina Conte
Silvia Costantini, Caterina Conte, Department of Immunology, Transplantation and Infectious Diseases, Vita-Salute San Raffaele University, Milan 20123, Italy
Silvia Costantini, Epatocentro Ticino, Lugano 6900, Switzerland
Caterina Conte, IRCCS Ospedale San Raffaele, Internal Medicine and Transplantation, Milan 20123, Italy
Author contributions: Both authors equally contributed to this paper with conception and design of the article, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: No potential conflicts of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
Corresponding author: Caterina Conte, MD, PhD, Assistant Professor, Department of Immunology, Transplantation and Infectious Diseases, Vita-Salute San Raffaele University, via Olgettina 60, Milan 20123, Italy.
Telephone: +39-2-36432575
Received: April 6, 2019
Peer-review started: April 8, 2019
First decision: May 9, 2019
Revised: June 3, 2019
Accepted: July 20, 2019
Article in press: July 20, 2019
Published online: August 15, 2019

Bone fragility has been recognized as a complication of diabetes, both type 1 diabetes (T1D) and type 2 diabetes (T2D), whereas the relationship between prediabetes and fracture risk is less clear. Fractures can deeply impact a diabetic patient’s quality of life. However, the mechanisms underlying bone fragility in diabetes are complex and have not been fully elucidated. Patients with T1D generally exhibit low bone mineral density (BMD), although the relatively small reduction in BMD does not entirely explain the increase in fracture risk. On the contrary, patients with T2D or prediabetes have normal or even higher BMD as compared with healthy subjects. These observations suggest that factors other than bone mass may influence fracture risk. Some of these factors have been identified, including disease duration, poor glycemic control, presence of diabetes complications, and certain antidiabetic drugs. Nevertheless, currently available tools for the prediction of risk inadequately capture diabetic patients at increased risk of fracture. Aim of this review is to provide a comprehensive overview of bone health and the mechanisms responsible for increased susceptibility to fracture across the spectrum of glycemic status, spanning from insulin resistance to overt forms of diabetes. The management of bone fragility in diabetic patient is also discussed.

Keywords: Bone, Fractures, Type 1 diabetes, Type 2 diabetes, Prediabetes, Diabetes complications, Bone density, Hypoglycemic agents

Core tip: Diabetes mellitus, either type 1 or type 2, is associated with increased fracture risk. Diabetic hyperglycemia and insulin resistance underlie functional alterations of bone cells and bone marrow fat that affect several determinants of bone strength, including bone matrix proteins and bone mass, geometry and microarchitecture. Diabetes-related microvascular complications and certain antidiabetic drugs appear to further increase fracture risk, both directly and indirectly. The prevention and management of bone fragility in diabetes includes identification of patients at risk, correction of modifiable risk factors including appropriate choice of antidiabetic drugs and use of antifracture drugs with proven efficacy.