Cheong, V.S., Roberts, B.C., Kadirkamanathan, V. et al. (1 more author) (2021) Positive interactions of mechanical loading and PTH treatments on spatio-temporal bone remodelling. Acta Biomater, 136. pp. 291-305. ISSN 1742-7061
Abstract
Osteoporosis is one of the most common skeletal diseases, but current therapies are limited to generalized antiresorptive or anabolic interventions, which do not target regions that would benefit from improvements to skeletal health. To improve the evaluation of treatment plans, we used a spatio-temporal multiscale approach that combines longitudinal in vivo micro-computed tomography (micro-CT) and in silico subject-specific finite element modeling to quantitatively map bone adaptation changes due to disease and treatment at high resolution. Our findings show time and region-dependent modifications in bone remodelling following one and two sets of mechanical loading and/or pharmacological interventions. The multiscale results highlighted that the distal section was unaffected by mechanical loading alone but the proximal tibia had the greatest gain from positive interactions of combined therapies. Mechanical loading abated the catabolic effect of PTH, but the main benefit of combined treatments occurred from the additive interactions of the two therapies in periosteal apposition. These results provide detailed insight into the efficacy of combined treatments, facilitating the optimisation of dosage and treatment duration in preclinical mouse studies, and the development of novel interventions for skeletal diseases.
Statement of Significance
Combined mechanical loading and pharmacotherapy have the potential to slow osteoporosis-induced bone loss but current therapies do not target the regions in need of strengthening. We show for the first time spatial region-dependant interactions between PTH and mechanical loading treatment in OVX mouse tibiae, highlighting local regions in the tibia that benefitted from separate and combined treatments. Combined experimental-computational analysis also detailed the lasting period of each treatment per location in the tibia, the extent of positive (or negative) interactions of the combined therapies, and the impact of each treatment on the regulation of bone adaptation spatio-temporally. This approach can be used to create hypothesis about the interactions of different treatments to optimise the design of biomaterials and medical interventions.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Author(s). Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
Keywords: | bone remodelling; in vivo loading; longitudinal imaging; micro-CT; osteoporosis; parathyroid hormone |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Automatic Control and Systems Engineering (Sheffield) |
Funding Information: | Funder Grant number NATIONAL CENTRE FOR THE REPLACEMENT, REFINEMENT AND REDUCTION OF ANIMALS IN RESEARCH NC/R001073/1 ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL EP/S032940/1 Engineering and Physical Sciences Research Council EP/K03877X/1 ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL nan ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL EP/K03877X/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 08 Oct 2021 14:05 |
Last Modified: | 11 Mar 2022 16:44 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.actbio.2021.09.035 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:178900 |