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Updated: Mar 26, 2026
Author Spotlight: An Economic and Efficient Method for Quantitative Evaluation of Bone Microarchitecture in a Murine Osteoporosis Model
Published on: September 8, 2023
Moderate chronic kidney disease impairs bone quality in C57Bl/6J mice
Chelsea M Heveran1, Alicia M Ortega1, Andrew Cureton1
1Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, USA.
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.
Insights
Chronic kidney disease (CKD) impairs bone material quality, not structure, leading to increased fracture risk. Newer bone tissue shows reduced quality in CKD mice, suggesting altered maturation impacts bone strength.
Area of Science:
- Bone Biology
- Nephrology
- Biomaterials Science
Background:
- Chronic kidney disease (CKD) is linked to increased bone fracture risk.
- The underlying causes of bone fragility in CKD, particularly changes in bone material quality, remain unclear.
- Disrupted mineral homeostasis in CKD may affect bone tissue's intrinsic material properties.
Purpose of the Study:
- To investigate the effects of moderate CKD on bone material quality, microarchitecture, and whole bone strength in mice.
- To determine if CKD-induced changes in bone material quality are associated with altered tissue maturation.
- To assess the impact of CKD on the heterogeneity of bone material properties.
Main Methods:
- Surgically induced moderate chronic kidney disease (5/6 nephrectomy) in mice.
- Assessment of bone material properties using nanoindentation and quantitative backscattered scanning electron microscopy.
- Evaluation of bone microarchitecture and whole bone mechanical strength.
Main Results:
- Moderate CKD did not significantly alter bone microarchitecture or whole bone strength.
- CKD led to decreased bone material quality, characterized by lower indentation modulus and mineral volume fraction in newly formed cortical bone.
- CKD altered the variance of modulus and mineral volume fraction, indicating increased tissue-scale heterogeneity.
Conclusions:
- Moderate CKD negatively impacts bone material quality, particularly in newly formed bone tissue, potentially through altered maturation processes.
- These CKD-induced changes in bone material quality, rather than structural deficits, may contribute to the increased fracture risk observed in patients with kidney disease.
- CKD may negatively affect the heterogeneity of bone material properties at the tissue level.
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