Lu, Y., Boudiffa, M., Dall'Ara, E. orcid.org/0000-0003-1471-5077 et al. (3 more authors) (2017) Longitudinal effects of Parathyroid Hormone treatment on morphological, densitometric and mechanical properties of mouse tibia. Journal of the Mechanical Behavior of Biomedical Materials, 75. pp. 244-251. ISSN 1751-6161
Abstract
The use of Parathyroid Hormone (PTH) as bone anabolic is limited due to cost-benefit assessments. Preclinical studies evaluating the effects of PTH on bone have reported variable and often contradictory results. Here, we have applied a new approach using a combination of in-vivo longitudinal µCT, image processing techniques and finite element models to monitor early local changes in the whole tibia (divided in 40 compartments) and mechanical properties of female C57BL/6 J mice treated with PTH 1–34, compared to controls. Compared with standard 3D bone morphometric analysis, our new approach allowed detection of much smaller and localised changes in bone mineral content (BMC) at very early time points (1 week vs 3 weeks with standard methods) and showed that changes do not occur uniformly over time and across the anatomical space. Indeed, in the PTH treated mice, significant changes in BMC were observed in the medial and posterior sectors of the proximal tibia, a week after treatment, and in the medial sector of the tibia midshaft region a week later (p<0.05). By the third week, two thirds of the regions showed significantly higher values of BMC (p<0.05). The effect of PTH on bone regional volume is similar to that on BMC, but there is almost no effect of PTH on bone tissue mineral density. The differences in estimated mechanical properties became significant after three weeks of treatment (p<0.05). These results provide the first evidence of an early and localised PTH effect on murine bone, and show that our novel partitioning approach, compared to the standard evaluation protocol, allows a more precise quantification of bone changes following treatment, which would facilitate preclinical testing of novel mono- and/or combination therapies throughout the bone.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Elsevier. This is an author produced version of a paper subsequently published in Journal of the Mechanical Behavior of Biomedical Materials. Uploaded in accordance with the publisher's self-archiving policy. Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | PTH; bone remodeling; animal models; micro-CT; bone quantification |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Funding Information: | Funder Grant number ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL (EPSRC) EP/K03877X/1 NATIONAL CENTRE FOR THE REPLACEMENT, REFINEMENT AND REDUCTION OF ANIMALS IN RESEARCH NC/K000780/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 27 Jul 2017 10:33 |
Last Modified: | 03 Nov 2023 16:49 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.jmbbm.2017.07.034 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:119571 |