Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation
Abstract
ABSTRACT Diabetes mellitus (DM) is an emerging metabolic disease, and the management of diabetic bone disease poses a serious challenge worldwide. Understanding the underlying mechanisms leading to high fracture risk in DM is hence of particular interest and urgently needed to allow for diagnosis and treatment optimization. In a case–control postmortem study, the whole 12th thoracic vertebra and cortical bone from the mid‐diaphysis of the femur from male individuals with type 1 diabetes mellitus (T1DM) ( n = 6; 61.3 ± 14.6 years), type 2 diabetes mellitus (T2DM) ( n = 11; 74.3 ± 7.9 years), and nondiabetic controls ( n = 18; 69.3 ± 11.5) were analyzed with clinical and ex situ imaging techniques to explore various bone quality indices. Cortical collagen fibril deformation was measured in a synchrotron setup to assess changes at the nanoscale during tensile testing until failure. In addition, matrix composition was analyzed including determination of cross‐linking and non‐crosslinking advanced glycation end‐products like pentosidine and carboxymethyl‐lysine. In T1DM, lower fibril deformation was accompanied by lower mineralization and more mature crystalline apatite. In T2DM, lower fibril deformation concurred with a lower elastic modulus and tendency to higher accumulation of non‐crosslinking advanced glycation end‐products. The observed lower collagen fibril deformation in diabetic bone may be linked to alteredmore »
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1893950
- Alternate Identifier(s):
- OSTI ID: 1987416; OSTI ID: 1992468
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Published Article
- Journal Name:
- Journal of Bone and Mineral Research
- Additional Journal Information:
- Journal Name: Journal of Bone and Mineral Research Journal Volume: 37 Journal Issue: 11; Journal ID: ISSN 0884-0431
- Publisher:
- Oxford University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; advanced glycation end-products; bone quality; collagen deformation; cortical bone; diabetes mellitus
Citation Formats
Wölfel, Eva M., Schmidt, Felix N., vom Scheidt, Annika, Siebels, Anna K., Wulff, Birgit, Mushumba, Herbert, Ondruschka, Benjamin, Püschel, Klaus, Scheijen, Jean, Schalkwijk, Casper G., Vettorazzi, Eik, Jähn-Rickert, Katharina, Gludovatz, Bernd, Schaible, Eric, Amling, Michael, Rauner, Martina, Hofbauer, Lorenz C., Zimmermann, Elizabeth A., and Busse, Björn. Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation. United States: N. p., 2022.
Web. doi:10.1002/jbmr.4706.
Wölfel, Eva M., Schmidt, Felix N., vom Scheidt, Annika, Siebels, Anna K., Wulff, Birgit, Mushumba, Herbert, Ondruschka, Benjamin, Püschel, Klaus, Scheijen, Jean, Schalkwijk, Casper G., Vettorazzi, Eik, Jähn-Rickert, Katharina, Gludovatz, Bernd, Schaible, Eric, Amling, Michael, Rauner, Martina, Hofbauer, Lorenz C., Zimmermann, Elizabeth A., & Busse, Björn. Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation. United States. https://doi.org/10.1002/jbmr.4706
Wölfel, Eva M., Schmidt, Felix N., vom Scheidt, Annika, Siebels, Anna K., Wulff, Birgit, Mushumba, Herbert, Ondruschka, Benjamin, Püschel, Klaus, Scheijen, Jean, Schalkwijk, Casper G., Vettorazzi, Eik, Jähn-Rickert, Katharina, Gludovatz, Bernd, Schaible, Eric, Amling, Michael, Rauner, Martina, Hofbauer, Lorenz C., Zimmermann, Elizabeth A., and Busse, Björn. Fri .
"Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation". United States. https://doi.org/10.1002/jbmr.4706.
@article{osti_1893950,
title = {Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation},
author = {Wölfel, Eva M. and Schmidt, Felix N. and vom Scheidt, Annika and Siebels, Anna K. and Wulff, Birgit and Mushumba, Herbert and Ondruschka, Benjamin and Püschel, Klaus and Scheijen, Jean and Schalkwijk, Casper G. and Vettorazzi, Eik and Jähn-Rickert, Katharina and Gludovatz, Bernd and Schaible, Eric and Amling, Michael and Rauner, Martina and Hofbauer, Lorenz C. and Zimmermann, Elizabeth A. and Busse, Björn},
abstractNote = {ABSTRACT Diabetes mellitus (DM) is an emerging metabolic disease, and the management of diabetic bone disease poses a serious challenge worldwide. Understanding the underlying mechanisms leading to high fracture risk in DM is hence of particular interest and urgently needed to allow for diagnosis and treatment optimization. In a case–control postmortem study, the whole 12th thoracic vertebra and cortical bone from the mid‐diaphysis of the femur from male individuals with type 1 diabetes mellitus (T1DM) ( n = 6; 61.3 ± 14.6 years), type 2 diabetes mellitus (T2DM) ( n = 11; 74.3 ± 7.9 years), and nondiabetic controls ( n = 18; 69.3 ± 11.5) were analyzed with clinical and ex situ imaging techniques to explore various bone quality indices. Cortical collagen fibril deformation was measured in a synchrotron setup to assess changes at the nanoscale during tensile testing until failure. In addition, matrix composition was analyzed including determination of cross‐linking and non‐crosslinking advanced glycation end‐products like pentosidine and carboxymethyl‐lysine. In T1DM, lower fibril deformation was accompanied by lower mineralization and more mature crystalline apatite. In T2DM, lower fibril deformation concurred with a lower elastic modulus and tendency to higher accumulation of non‐crosslinking advanced glycation end‐products. The observed lower collagen fibril deformation in diabetic bone may be linked to altered patterns mineral characteristics in T1DM and higher advanced glycation end‐product accumulation in T2DM. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).},
doi = {10.1002/jbmr.4706},
journal = {Journal of Bone and Mineral Research},
number = 11,
volume = 37,
place = {United States},
year = {Fri Sep 16 00:00:00 EDT 2022},
month = {Fri Sep 16 00:00:00 EDT 2022}
}
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