Cortical thickness adaptation to combined mechanical loading and parathyroid hormone treatments is site specific and synergistic in the mouse tibia model.

Autor: Miller CJ; Queensland University of Technology, Brisbane, Queensland, Australia., Trichilo S; University of Melbourne, Melbourne, Victoria, Australia., Pickering E; Queensland University of Technology, Brisbane, Queensland, Australia., Martelli S; Queensland University of Technology, Brisbane, Queensland, Australia., Dall'Ara E; University of Sheffield, Sheffield, United Kingdom., Delisser P; Veterinary Specialist Services, Brisbane, Queensland, Australia., Meakin LB; University of Bristol, Bristol, United Kingdom., Pivonka P; Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address: peter.pivonka@qut.edu.au.
Jazyk: angličtina
Zdroj: Bone [Bone] 2024 Mar; Vol. 180, pp. 116994. Date of Electronic Publication: 2023 Dec 20.
DOI: 10.1016/j.bone.2023.116994
Abstrakt: In this study, we aimed to quantify the localised effects of mechanical loading (ML), low (20 μg/kg/day), moderate (40 μg/kg/day) or high (80 μg/kg/day) dosages of parathyroid hormone (PTH), and combined (PTHML) treatments on cortical bone adaptation in healthy 19-week old female C57BL/6 mice. To this end, we utilise a previously reported image analysis algorithm on μCT data of the mouse tibia published by Sugiyama et al. (2008) to measure changes in cortical area, marrow cavity area and local cortical thickness measures (ΔCt.Ar, ΔMa.Ar, ΔCt.Th respectively), evaluated at two cross-sections within the mouse tibia (proximal-middle (37 %) and middle (50 %)), and are compared to a superposed summation (P + M) of individual treatments to determine the effectiveness of combining treatments in vivo. ΔCt.Ar analysis revealed a non-linear, synergistic interactions between PTH and ML in the 37 % cross-section that saturates at higher PTH dosages, whereas the 50 % cross-section experiences an approximately linear, additive adaptation response. This coincided with an increase in ΔMa.Ar (indicating resorption of the endosteal surface), which was only counteracted by combined high dose PTH with ML in the middle cross-section. Regional analysis of ΔCt.Th changes reveal localised cortical thinning in response to low dose PTH treatment in the posteromedial region of the middle cross-section, signifying that PTH does not provide a homogeneous adaptation response around the cortical perimeter. We observe a synergistic response in the proximal-middle cross-section, with regions of compressive strain experiencing the greatest adaptation response to PTHML treatments, (peak ΔCt.Th of 189.32, 213.78 and 239.30 μm for low, moderate and high PTHML groups respectively). In contrast, PTHML treatments in the middle cross-section show a similar response to the superposed P + M group, with the exception of the combined high dose PTHML treatment which shows a synergistic interaction. These analyses suggest that, in mice, adding mechanical loading to PTH treatments leads to region specific bone responses; synergism of PTHML is only achieved in some regions experiencing high loading, while other regions respond additively to this combined treatment.
Competing Interests: Declaration of competing interest The authors hereby declare that they have no conflict of interest in the submitted manuscript.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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