title: Moderate chronic kidney disease impairs bone quality in C57Bl/6J mice.
abstract: Chronic kidney disease (CKD) increases bone fracture risk. While the causes of bone fragility in CKD are not clear, the disrupted mineral homeostasis inherent to CKD may cause material quality changes to bone tissue. In this study, 11-week-old male C57Bl/6J mice underwent either 5/6th nephrectomy (5/6 Nx) or sham surgeries. Mice were fed a normal chow diet and euthanized 11weeks post-surgery. Moderate CKD with high bone turnover was established in the 5/6 Nx group as determined through serum chemistry and bone gene expression assays. We compared nanoindentation modulus and mineral volume fraction (assessed through quantitative backscattered scanning electron microscopy) at matched sites in arrays placed on the cortical bone of the tibia mid-diaphysis. Trabecular and cortical bone microarchitecture and whole bone strength were also evaluated. We found that moderate CKD minimally affected bone microarchitecture and did not influence whole bone strength. Meanwhile, bone material quality decreased with CKD; a pattern of altered tissue maturation was observed with 5/6 Nx whereby the newest 60μm of bone tissue adjacent to the periosteal surface had lower indentation modulus and mineral volume fraction than more interior, older bone. The variance of modulus and mineral volume fraction was also altered following 5/6 Nx, implying that tissue-scale heterogeneity may be negatively affected by CKD. The observed lower bone material quality may play a role in the decreased fracture resistance that is clinically associated with human CKD.
authors: Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USA.
authors: Chelsea M
authors: CM
authors: Heveran
authors: Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USA.
authors: Alicia M
authors: AM
authors: Ortega
authors: Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USA.
authors: Andrew
authors: A
authors: Cureton
authors: Department of Orthopaedics, University of Colorado School of Medicine, Aurora, CO, USA.
authors: Ryan
authors: R
authors: Clark
authors: Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA.
authors: Eric W
authors: EW
authors: Livingston
authors: Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA.
authors: Ted A
authors: TA
authors: Bateman
authors: Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA; Veterans Affairs, Eastern Colorado Health Care System, Denver, CO, USA.
authors: Moshe
authors: M
authors: Levi
authors: Department of Orthopaedics, University of Colorado School of Medicine, Aurora, CO, USA; Veterans Affairs, Eastern Colorado Health Care System, Denver, CO, USA.
authors: Karen B
authors: KB
authors: King
authors: Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USA; Department of Orthopaedics, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: virginia.ferguson@colorado.edu.
authors: Virginia L
authors: VL
authors: Ferguson
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001857:Bone Matrix / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology* / Q000503:physiopathology; D002113:Calcification, Physiologic / Q000235:genetics; D000071556:Cancellous Bone / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D000071538:Cortical Bone / Q000000981:diagnostic imaging / Q000473:pathology; D005265:Femoral Neck Fractures / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008810:Mice, Inbred C57BL; D051436:Renal Insufficiency, Chronic / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D013977:Tibia / Q000473:pathology / Q000503:physiopathology
keywords: Bone quality; CKD; CKD-MBD; Kidney disease; Nanoindentation; qBSE