title: Cortical bone mechanical properties are altered in an animal model of progressive chronic kidney disease.
abstract: Chronic kidney disease (CKD), which leads tocortical bone loss and increasedporosity,increases therisk of fracture. Animal models have confirmed that these changes compromise whole bone mechanical properties. Estimates from whole bone testing suggest that material properties are negatively affected, though tissue-level assessmentshavenot been conducted. Therefore, the goal of the present study was to examine changes in cortical bone at different length scales using a rat model with theprogressive development of CKD. At 30 weeks of age (∼75% reduction in kidney function), skeletally mature male Cy/+ rats were compared to their normal littermates. Cortical bone material propertieswere assessed with reference point indentation (RPI), atomic force microscopy (AFM), Raman spectroscopy,and high performance liquid chromatography (HPLC). Bones from animals with CKD had higher (+18%) indentation distance increase and first cycle energy dissipation (+8%) as measured by RPI.AFM indentation revealed a broader distribution of elastic modulus values in CKD animals witha greater proportion of both higher and lower modulus values compared to normal controls. Yet, tissue composition, collagen morphology, and collagen cross-linking fail to account for these differences. Though the specific skeletal tissue alterations responsible for these mechanical differences remain unclear, these results indicate that cortical bone material properties are altered in these animals and may contribute to the increased fracture risk associated with CKD.
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Newman
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Roudebush VA Medical Center, Indianapolis, Indiana, United States of America.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Neal X
authors.initials: NX
authors.lastname: Chen
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Max A
authors.initials: MA
authors.lastname: Hammond
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America; Department of Biomedical Engineering, Indiana University-Purdue University, Indianapolis, Indiana, United States of America.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Wallace
authors.affiliation: Department of Orthopaedic Surgery and Rehabilitation and Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, United States of America.
authors.forename: Jeffry S
authors.initials: JS
authors.lastname: Nyman
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Allen
mesh_terms: D000818:Animals; D018488:Bone Demineralization, Pathologic / Q000209:etiology* / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D055595:Mechanical Phenomena; D018625:Microscopy, Atomic Force; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D013059:Spectrum Analysis, Raman
chemical_list: D003094:Collagen