Abstract
Matrix maturation within cortical bone is an important but oft-neglected component of bone remodeling because of the lack of a suitable small animal model. Intra-cortical remodeling can be induced in rodents by feeding virgin or lactating animals a low-calcium diet. The current study aimed to determine which of these two models is most suitable for studying intra-cortical matrix maturation. We compared intra-cortical remodeling in female rats fed a normal calcium diet (virgin/normal Ca), a low-calcium diet (virgin/low Ca), or a low-calcium diet during lactation (lactation/low Ca). The low-calcium diet was administered for 23 days (induction phase) followed by return to normal calcium for 30 days (recovery phase). At the end of induction, the virgin/normal Ca and virgin/low-Ca animals had no difference in cortical porosity, but the lactation/low-Ca animals had elevated cortical porosity at various diaphyseal sites in the femur and tibia. The distal femoral site had the greatest amount of induced porosity in the size range of rat secondary osteons. Neither global mineralization nor tissue age-specific mineral-to-matrix ratio in the bone formed during recovery were affected in the lactation/low-Ca rats. Serum calcium levels did not differ from controls, but phosphate levels were slightly elevated, consistent with the rapid recovery of lost bone mass. We conclude that the lactation/low-Ca model represents a means to increase intra-cortical remodeling in adult rats with no apparent detrimental effect on matrix maturation. This model will provide researchers with a new tool to study matrix maturation throughout the cortex.
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Acknowledgements
The authors would like to thank Maleeha Mashiatulla, Meghan Moran, and Diana Goldstein for their help with the animal husbandry. The authors would like to thank Dr. Mitch Schaffler for pointing out the early publications by Ellinger et al. and Ruth. Micro-Computed Tomography data were collected at the Rush University microCT/Histology Core. Scanning electron imaging was performed at the Rush University Internal Medicine Research and Drug Discovery Imaging Core. Synchrotron Fourier Transform Infrared Microspectroscopy was collected at the Advanced Light Source at the Lawrence Berkeley National Laboratory. The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R21AR065604. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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RDR contributed substantially to the research design, data acquisition, analysis and interpretation of the data, drafting and revising manuscript, and approving the final version to be published. DRS contributed substantially to the research design, interpretation of the data, drafting and revising manuscript, and approving the final version to be published. DRS is responsible for the content of the manuscript.
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Ryan D. Ross and D. Rick Sumner declare that they have no conflict of interest.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.
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The original version of this article was revised: The captions for Figs. 5 and 6 were interchanged. This has been corrected in this version.
An erratum to this article is available at http://dx.doi.org/10.1007/s00223-017-0281-4.
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Ross, R.D., Sumner, D.R. Bone Matrix Maturation in a Rat Model of Intra-Cortical Bone Remodeling. Calcif Tissue Int 101, 193–203 (2017). https://doi.org/10.1007/s00223-017-0270-7
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DOI: https://doi.org/10.1007/s00223-017-0270-7