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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\u2013control 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\u00a0=\u20096; 61.3\u2009\u00b1\u200914.6\u2009years), type 2 diabetes mellitus (T2DM) (n\u00a0=\u200911; 74.3\u2009\u00b1\u20097.9\u2009years), and nondiabetic controls (n\u00a0=\u200918; 69.3\u2009\u00b1\u200911.5) 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. \u00a9 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).<\/jats:p>","DOI":"10.1002\/jbmr.4706","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T15:10:06Z","timestamp":1663341006000},"page":"2259-2276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation"],"prefix":"10.1093","volume":"37","author":[{"given":"Eva M.","family":"W\u00f6lfel","sequence":"first","affiliation":[{"name":"Interdisciplinary Competence Center for Interface Research (ICCIR) University Medical Center Hamburg-Eppendorf Hamburg Germany"},{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix N.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3756-8770","authenticated-orcid":false,"given":"Annika","family":"vom Scheidt","sequence":"additional","affiliation":[{"name":"Department of Macroscopic and Clinical Anatomy, Gottfried Schatz Research Center Medical University of Graz Graz Austria"},{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Siebels","sequence":"additional","affiliation":[{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf Hamburg 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