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The objective of this study was to evaluate cortical bone material behavior in T1D by examining specimens from cadaveric femora from older adults with long-duration T1D (\u226550\u00a0yr; n\u2009=\u200920) and age- and sex-matched nondiabetic controls (n\u2009=\u200914). Cortical bone was assessed by mechanical testing (4-point bending, cyclic reference point indentation, impact microindentation), AGE quantification [total fluorescent AGEs, pentosidine, carboxymethyl lysine (CML)], and matrix composition via Raman spectroscopy. Cortical bone from older adults with T1D had diminished postyield toughness to fracture (\u221230%, p\u2009=\u2009.036), elevated levels of AGEs (pentosidine, +17%, p\u2009=\u2009.039), lower mineral crystallinity (\u22121.4%, p\u2009=\u2009.010), greater proline hydroxylation (+1.9%, p\u2009=\u2009.009), and reduced glycosaminoglycan (GAG) content (\u22121.3%, p\u2009&amp;lt;\u2009.03) compared to nondiabetics. In multiple regression models to predict cortical bone toughness, cortical tissue mineral density, CML, and Raman spectroscopic measures of enzymatic collagen crosslinks and GAG content remained highly significant predictors of toughness, while diabetic status was no longer significant (adjusted R2\u2009&amp;gt;\u20090.60, p\u2009&amp;lt;\u2009.001). Thus, the impairment of cortical bone to absorb energy following long-duration T1D is well explained by AGE accumulation and modifications to the bone matrix. These results provide novel insight into the pathogenesis of skeletal fragility in individuals with T1D.<\/jats:p>","DOI":"10.1093\/jbmr\/zjae184","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T18:16:19Z","timestamp":1732040179000},"page":"87-99","source":"Crossref","is-referenced-by-count":17,"title":["Long-duration type 1 diabetes is associated with deficient cortical bone mechanical behavior and altered matrix composition in human femoral bone"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1085-4128","authenticated-orcid":false,"given":"Shannon R","family":"Emerzian","sequence":"first","affiliation":[{"name":"Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center , Boston, MA 02215 ,","place":["United States"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["United 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,","place":["United States"]},{"name":"Department of Bioengineering, Karamanoglu Mehmetbey University , Karaman 70100 ,","place":["T\u00fcrkiye"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Brooks","sequence":"additional","affiliation":[{"name":"Center for Advanced Orthopedic Studies, Department of Orthopedic Surgery, Beth Israel Deaconess Medical Center , Boston, MA 02215 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Hsien","family":"Wu","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center , Boston, MA 02215 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center , Boston, MA 02215 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surya Vishva Teja","family":"Jangolla","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center , Boston, MA 02215 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc Gregory","family":"Yu","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center , Boston, MA 02215 ,","place":["United States"]},{"name":"Department of Internal Medicine, Harvard Medical School , Boston, MA 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetal S","family":"Shah","sequence":"additional","affiliation":[{"name":"Research Division, Joslin Diabetes Center , Boston, MA 02215 ,","place":["United States"]},{"name":"Department of Internal Medicine, Harvard Medical School , Boston, MA 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George L","family":"King","sequence":"additional","affiliation":[{"name":"Research 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