Long-duration type 1 diabetes is associated with deficient cortical bone mechanical behavior and altered matrix composition in human femoral bone

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dc.contributor.authorEmerzian, Shannon R.
dc.contributor.authorUnal, Mustafa
dc.contributor.authorBrooks, Daniel J.
dc.contributor.authorWu, I-Hsien
dc.contributor.authorGauthier, John
dc.date.accessioned2025-01-12T17:19:54Z
dc.date.available2025-01-12T17:19:54Z
dc.date.issued2024
dc.departmentKMÜ, Mühendislik Fakültesi, Biyomühendislik Bölümü
dc.description.abstractType 1 diabetes (T1D) is associated with an increased risk of hip fracture beyond what can be explained by reduced bone mineral density, possibly due to changes in bone material from accumulation of advanced glycation end-products (AGEs) and altered matrix composition, though data from human cortical bone in T1D are limited. 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 (>= 50 yr; n = 20) and age- and sex-matched nondiabetic controls (n = 14). 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 (-30%, p = .036), elevated levels of AGEs (pentosidine, +17%, p = .039), lower mineral crystallinity (-1.4%, p = .010), greater proline hydroxylation (+1.9%, p = .009), and reduced glycosaminoglycan (GAG) content (-1.3%, p < .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 R-2 > 0.60, p < .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.
dc.description.sponsorshipNational Institutes of Health [ECCS-2025158]; National Science Foundation under NSF
dc.description.sponsorshipThis work was performed in part at the Harvard University Center for Nanoscale Systems (CNS); a member of the National Nanotechnology Coordinated Infrastructure Network (NNCI), which is supported by the National Science Foundation under NSF award no. ECCS-2025158.
dc.identifier.citationEmerzian, S. R., Chow, J., Behzad, R., Unal, M., Brooks, D. J., Wu, I.-H., Gauthier, J., Jangolla, S. V. T., Yu, M. G., Shah, H. S., King, G. L., Johannesdottir, F., Karim, L., Yu, E. W., & Bouxsein, M. L. (2024). Long-duration type 1 diabetes is associated with deficient cortical bone mechanical behavior and altered matrix composition in human femoral bone. Journal of Bone and Mineral Research : The Official Journal of the American Society for Bone and Mineral Research, 40(1), 87–99. https://doi.org/10.1093/jbmr/zjae184
dc.identifier.doi10.1093/jbmr/zjae184
dc.identifier.endpage99
dc.identifier.issn0884-0431
dc.identifier.issn1523-4681
dc.identifier.issue1
dc.identifier.pmid39561104
dc.identifier.scopus2-s2.0-85214855944
dc.identifier.startpage87
dc.identifier.urihttps://doi.org/10.1093/jbmr/zjae184
dc.identifier.urihttps://hdl.handle.net/11492/10256
dc.identifier.volume40
dc.identifier.wosWOS:001380333800001
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Sceince
dc.indekslendigikaynakPubMed
dc.indekslendigikaynakScopus
dc.institutionauthorUnal,Mustafa
dc.institutionauthoridUnal,Mustafa/0000-0002-9518-8952
dc.language.isoen
dc.publisherOxford Univ Press
dc.relation.ispartofJournal of Bone and Mineral Research
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjecttype 1 diabetes
dc.subjectcortical bone
dc.subjectbiomechanics
dc.subjectRaman spectroscopy
dc.subjectfracture
dc.subjectbone composition
dc.subjecttoughness
dc.titleLong-duration type 1 diabetes is associated with deficient cortical bone mechanical behavior and altered matrix composition in human femoral bone
dc.typeArticle

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