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

doi:10.1002/jbmr.4706

Title: Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation

Journal Article · 15 September 2022 · Journal of Bone and Mineral Research

DOI: https://doi.org/10.1002/jbmr.4706 · OSTI ID:1893950

Wölfel, Eva M.; Schmidt, Felix N.;

; Siebels, Anna K.; Wulff, Birgit; Mushumba, Herbert; Ondruschka, Benjamin; Püschel, Klaus; Scheijen, Jean; Schalkwijk, Casper G.; Vettorazzi, Eik;

; Gludovatz, Bernd; Schaible, Eric;

;

; Zimmermann, Elizabeth A.;

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).

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1893950

Journal Information:: Journal of Bone and Mineral Research, Journal Name: Journal of Bone and Mineral Research Journal Issue: 11 Vol. 37; ISSN 0884-0431

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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diabetes mellitus

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