Dimorphic mechanisms of fragility in diabetes mellitus:​ the role of reduced collagen fibril deformation

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

Affiliations

¹Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

²Interdisciplinary Competence Center for Interface Research (ICCIR), University Medical Center Hamburg-Eppendorf, Hamburg, Germany

³Department of Macroscopic and Clinical Anatomy, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria

⁴Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

⁵Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM) School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands

⁶Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

⁷Mildred Scheel Cancer Career Center Hamburg, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

⁸School of Mechanical and Manufacturing Engineering, University of New South Wales (UNSW Sydney), Sydney, New South Wales, Australia

⁹Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

¹⁰Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany

¹¹Center for Healthy Aging, Technische Universität Dresden Medical Center, Dresden, Germany

¹²Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany

¹³Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, Quebec, Canada

Abstract and keywords

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.

Keywords: advanced glycation end-products; bone quality; collagen deformation; cortical bone; diabetes mellitus

Links

DOI: 10.1002/jbmr.4706

PubMed: 36112316

WoS: 000869906900001

History

Received: 2021-10-10

Revised: 2022-08-25

Accepted: 2022-09-10

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