Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 10, 2015; 6(5): 673-678
Published online Jun 10, 2015. doi: 10.4239/wjd.v6.i5.673
Update on type 2 diabetes-related osteoporosis
Kannikar Wongdee, Narattaphol Charoenphandhu
Kannikar Wongdee, Narattaphol Charoenphandhu, Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Kannikar Wongdee, Office of Academic Management, Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand
Narattaphol Charoenphandhu, Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Author contributions: Wongdee K and Charoenphandhu N contributed equally for literature review, data analysis and preparation of the manuscript.
Supported by Grants from the Cluster and Program Management Office (CPMO), National Science and Technology Development Agency (P-11-00639); the Thailand Research Fund (TRF)-Mahidol University through the TRF Senior Research Scholar Grant (RTA5780001 to NC); the Faculty of Allied Health Sciences, Burapha University and Thailand Research Fund through TRF Research Career Development Grant (RSA5780041 to KW); the Research and Development Fund Burapha University (05/2557 to KW); the Faculty of Allied Health Sciences, Burapha University Research Grant of Fiscal Year 2015 (AHS05/2558 to KW).
Conflict-of-interest: Kannikar Wongdee and Narattaphol Charoenphandhu declare no conflicts of interest.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Narattaphol Charoenphandhu, MD, PhD, Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. naratt@narattsys.com
Telephone: +66-2-3547154 Fax: +66-2-3547154
Received: January 11, 2015
Peer-review started: January 15, 2015
First decision: February 7, 2015
Revised: February 12, 2015
Accepted: March 5, 2015
Article in press: March 9, 2015
Published online: June 10, 2015
Processing time: 158 Days and 17.7 Hours
Abstract

It was previously understood that body weight gain and obesity observed in type 2 diabetes mellitus (T2DM) could be beneficial since body weight increase elevated bone mineral density and thus helped maintain the skeletal framework. However, a number of recent findings in humans and rodents have revealed that T2DM is not only associated with trabecular defects but also increases cortical porosity, and compromised bone cell function and bone mechanical properties. Hyperglycemia and insulin resistance in T2DM may further induce osteoblast apoptosis and uncoupling bone turnover. Prolonged accumulation of advanced glycation end products and diminished activity of lysyl oxidase, an essential enzyme for collagen cross-link, can lead to structural abnormalities of bone collagen fibrils, brittle matrix, and fragility fractures. Our studies in T2DM rats showed that dyslipidemia, which often occurs in T2DM, could obscure the T2DM-associated changes in bone microstructure and osteopenia. Longitudinal bone growth regulated by the growth plate chondrocytes is also impaired by T2DM since differentiation of growth plate chondrocytes is arrested and retained in the resting state while only a small number of cells undergo hypertrophic differentiation. Such a delayed chondrocyte differentiation may have also resulted from premature apoptosis of the growth plate chondrocytes. Nevertheless, the underlying cellular and molecular mechanisms of insulin resistance in osteoblasts, osteoclasts, osteocytes, and growth plate chondrocytes remain to be investigated.

Keywords: Advanced glycation end products; Chondrocyte apoptosis; Collagen; Dyslipidemia; Fracture; Growth plate; Type 2 diabetes mellitus; Osteoporosis

Core tip: Type 2 diabetes mellitus (T2DM) negatively affects bone density and strength by inducing cellular and extracellular matrix failures. Insulin resistance in T2DM deteriorates osteoblast proliferation and activity, but enhances osteoclast activity, leading to uncoupled bone remodeling. Hyperglycemia also aggravates osteoblast dysfunction, thus contributing to cellular failure. Extracellular matrix failure is caused by abnormal collagen synthesis and aberrant collagen structure and alignment, the latter of which results, in part, from advanced glycation end products (AGEs). With hyperglycemia and AGEs, impaired bone strength may occur despite high bone mineral density. It is, therefore, concluded that T2DM can be considered a cause of osteoporosis and/or poor bone mechanical properties.