title: Advanced Glycation Endproducts and Bone Material Properties in Type 1 Diabetic Mice.
abstract: Fractures, particularly at the lower extremities and hip, are a complication of diabetes. In both type 1 (T1D) and type 2 diabetes (T2D), fracture risk is disproportionately worse than that predicted from the measurement of bone mineral density. Although an explanation for this discrepancy is the presence of organic matrix abnormalities, it has not been fully elucidated how advanced glycation endproducts (AGEs) relate to bone deterioration at both the macroscopic and microscopic levels. We hypothesized that there would be a relationship between skeletal AGE levels (determined by Raman microspectroscopy at specific anatomical locations) and bone macroscopic and microscopic properties, as demonstrated by the biomechanical measures of crack growth and microindentation respectively. We found that in OVE26 mice, a transgenic model of severe early onset T1D, AGEs were increased by Raman (carboxymethyl-lysine [CML] wildtype (WT): 0.0143 ±0.0005 vs T1D: 0.0175 ±0.0002, p = 0.003) at the periosteal surface. These differences were associated with less tough bone in T1D by fracture mechanics (propagation toughness WT: 4.73 ± 0.32 vs T1D: 3.39 ± 0.24 NM/m1/2, p = 0.010) and by reference point indentation (indentation distance increase WT: 6.85 ± 0.44 vs T1D: 9.04 ± 0.77 μm; p = 0.043). Within T1D, higher AGEs by Raman correlated inversely with macroscopic bone toughness. These data add to the existing body of knowledge regarding AGEs and the relationship between skeletal AGEs with biomechanical indices.
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, College of Physicians & Surgeons Columbia University, New York, NY, United States of America.
authors.forename: Mishaela R
authors.initials: MR
authors.lastname: Rubin
authors.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK, and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Paschalis
authors.affiliation: Center for Biotechnology & Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, United States of America.
authors.forename: Atharva
authors.initials: A
authors.lastname: Poundarik
authors.affiliation: Center for Biotechnology & Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, United States of America.
authors.forename: Gyna E
authors.initials: GE
authors.lastname: Sroga
authors.affiliation: Department of Medicine, Metabolic Bone Diseases Unit, College of Physicians & Surgeons Columbia University, New York, NY, United States of America.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: McMahon
authors.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK, and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Gamsjaeger
authors.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK, and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Klaushofer
authors.affiliation: Center for Biotechnology & Interdisciplinary Studies, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, United States of America.
authors.forename: Deepak
authors.initials: D
authors.lastname: Vashishth
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001842:Bone and Bones / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D050723:Fractures, Bone / Q000150:complications; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D055595:Mechanical Phenomena; D051379:Mice
chemical_list: D017127:Glycation End Products, Advanced