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Association between non-enzymatic glycation, resorption, and microdamage in human tibial cortices

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Abstract

Summary

To better understand the association between different components of bone quality, we investigated the relationship among in vivo generated non-enzymatic glycation, resorption, and microdamage. The results showed negative correlation between advanced glycation end-products (AGEs) and resorption independent of age highlighting the interaction between these parameters that may lead to bone fragility.

Introduction

Changes in the quality of bone material contribute significantly to bone fragility. In order to establish a better understanding of the interaction of the different components of bone quality and their influence on bone fragility, we investigated the relationship between non-enzymatic glycation, resorption, and microdamage generated in vivo in cortical bone using bone specimens from the same donors.

Methods

Total fluorescent advanced glycation end-products (AGEs) were measured in 96 human cortical bone samples from 83 donors. Resorption pit density, average resorption pit area, and percent resorption area were quantified in samples from 48 common donors with AGE measurements. Linear microcrack density and diffuse damage were measured in 21 common donors with AGE and resorption measurements. Correlation analyses were performed between all measured variables to establish the relationships among them and their variation with age.

Results

We found that average resorption pit area and percent resorption area decreased with increasing AGEs independently of age. Resorption pit density and percent resorption area demonstrated negative age-adjusted correlation with diffuse damage. Furthermore, average resorption pit area, resorption pit density, and percent resorption area were found to decrease significantly with age.

Conclusions

The current study demonstrated the in vivo interrelationship between the organic constituents, remodeling, and damage formation in cortical bone. In addition to the age-related reduction in resorption, there is a negative correlation between AGEs and resorption independent of age. This inverse relationship indicates that AGEs alter the resorption process and/or accumulate in the tissue as a result of reduced resorption and may lead to bone fragility by adversely affecting fracture resistance through altered bone matrix properties.

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Acknowledgments

Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and National Institute on Aging (NIA), part of the National Institutes of Health, under Award Numbers AR49635 and AG020618. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We acknowledge the use of core facilities at the Center for Biotechnology and Interdisciplinary Studies at Rensselaer Polytechnic Institute.

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Author notes

  1. L. Karim

    Present address: Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Department of Orthopedic Surgery, Harvard Medical School, 330 Brookline Avenue, RN-122, Boston, MA, 02215, USA

Authors and Affiliations

  1. Department of Mechanical Engineering, Villanova University, 800 Lancaster Avenue, Villanova, PA, 19085, USA

    A. Ural

  2. Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    C. Janeiro, L. Karim, T. Diab & D. Vashishth

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  1. A. Ural
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Correspondence to D. Vashishth.

Additional information

Ani Ural and Colleen Janeiro have contributed equally to the manuscript.

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Ural, A., Janeiro, C., Karim, L. et al. Association between non-enzymatic glycation, resorption, and microdamage in human tibial cortices. Osteoporos Int 26, 865–873 (2015). https://doi.org/10.1007/s00198-014-2938-4

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  • DOI: https://doi.org/10.1007/s00198-014-2938-4

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