John G Damrath1, Amy Creecy2, Joseph M Wallace2, Sharon M Moe3. 1. Purdue University Weldon School of Biomedical Engineering, West Lafayette. 2. Indiana University - Purdue University at Indianapolis Department of Biomedical Engineering. 3. Indiana University School of Medicine, Division of Nephrology, Indianapolis, Indiana, USA.
Abstract
PURPOSE OF REVIEW: Chronic kidney disease (CKD) affects over 15% of Americans and results in an increased risk of skeletal fractures and fracture-related mortality. However, there remain great challenges in estimating fracture risk in CKD patients, as conventional metrics such as bone density assess bone quantity without accounting for the material quality of the bone tissue. The purpose of this review is to highlight the detrimental effects of advanced glycation end products (AGEs) on the structural and mechanical properties of bone, and to demonstrate the importance of including bone quality when assessing fracture risk in CKD patients. RECENT FINDINGS: Increased oxidative stress and inflammation drive the production of AGEs in CKD patients that form nonenzymatic crosslinks between type I collagen fibrils in the bone matrix. Nonenzymatic crosslinks stiffen and embrittle the bone, reducing its ability to absorb energy and resist fracture. Clinical measurement of AGEs is typically indirect and fails to distinguish the identity and properties of the various AGEs. SUMMARY: Accounting for the impact of AGEs on the skeleton in CKD patients may improve our estimation of overall bone quality, fracture risk, and treatments to improve both bone quantity and quality by reducing AGEs in patients with CKD merit investigation in order to improve our understanding of the etiology of increased fracture risk.
PURPOSE OF REVIEW: Chronic kidney disease (CKD) affects over 15% of Americans and results in an increased risk of skeletal fractures and fracture-related mortality. However, there remain great challenges in estimating fracture risk in CKD patients, as conventional metrics such as bone density assess bone quantity without accounting for the material quality of the bone tissue. The purpose of this review is to highlight the detrimental effects of advanced glycation end products (AGEs) on the structural and mechanical properties of bone, and to demonstrate the importance of including bone quality when assessing fracture risk in CKD patients. RECENT FINDINGS: Increased oxidative stress and inflammation drive the production of AGEs in CKD patients that form nonenzymatic crosslinks between type I collagen fibrils in the bone matrix. Nonenzymatic crosslinks stiffen and embrittle the bone, reducing its ability to absorb energy and resist fracture. Clinical measurement of AGEs is typically indirect and fails to distinguish the identity and properties of the various AGEs. SUMMARY: Accounting for the impact of AGEs on the skeleton in CKD patients may improve our estimation of overall bone quality, fracture risk, and treatments to improve both bone quantity and quality by reducing AGEs in patients with CKD merit investigation in order to improve our understanding of the etiology of increased fracture risk.
Authors: R Meerwaldt; R Graaff; P H N Oomen; T P Links; J J Jager; N L Alderson; S R Thorpe; J W Baynes; R O B Gans; A J Smit Journal: Diabetologia Date: 2004-07-09 Impact factor: 10.122
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Authors: John G Damrath; Neal X Chen; Corinne E Metzger; Shruthi Srinivasan; Kalisha O'Neill; Annabel Biruete; Keith G Avin; Joseph M Wallace; Matthew R Allen; Sharon M Moe Journal: JBMR Plus Date: 2022-02-11