Cortical Thickness Adaptive Response to Mechanical Loading Depends on Periosteal Position and Varies Linearly With Loading Magnitude

Corey J Miller,Lee B Meakin,Silvia Trichilo,Peter Pivonka,Saulo Martelli,Peter Delisser,Edmund Pickering

doi:10.3389/fbioe.2021.671606

Abstract

The aim of the current study was to quantify the local effect of mechanical loading on cortical bone formation response at the periosteal surface using previously obtained μCT data from a mouse tibia mechanical loading study. A novel image analysis algorithm was developed to quantify local cortical thickness changes (ΔCt.Th) along the periosteal surface due to different peak loads (0N ≤ F ≤ 12N) applied to right-neurectomised mature female C57BL/6 mice. Furthermore, beam analysis was performed to analyse the local strain distribution including regions of tensile, compressive, and low strain magnitudes. Student’s paired t-test showed that ΔCt.Th in the proximal (25%), proximal/middle (37%), and middle (50%) cross-sections (along the z-axis of tibia) is strongly associated with the peak applied loads. These changes are significant in a majority of periosteal positions, in particular those experiencing high compressive or tensile strains. No association between F and ΔCt.Th was found in regions around the neutral axis. For the most distal cross-section (75%), the association of loading magnitude and ΔCt.Th was not as pronounced as the more proximal cross-sections. Also, bone formation responses along the periosteum did not occur in regions of highest compressive and tensile strains predicted by beam theory. This could be due to complex experimental loading conditions which were not explicitly accounted for in the mechanical analysis. Our results show that the bone formation response depends on the load magnitude and the periosteal position. Bone resorption due to the neurectomy of the loaded tibia occurs throughout the entire cross-sectional region for all investigated cortical sections 25, 37, 50, and 75%. For peak applied loads higher than 4 N, compressive and tensile regions show bone formation; however, regions around the neutral axis show constant resorption. The 50% cross-section showed the most regular ΔCt.Th response with increased loading when compared to 25 and 37% cross-sections. Relative thickness gains of approximately 70, 60, and 55% were observed for F = 12 N in the 25, 37, and 50% cross-sections. ΔCt.Th at selected points of the periosteum follow a linear response with increased peak load; no lazy zone was observed at these positions.

Highlights

Osteoporosis is a degenerative bone disease characterised by long-term bone loss and fragility (Black and Rosen, 2016)
This work is the first to demonstrate the link between magnitude of axial load and adaptive response around the periosteum of the tibia at a cross-section level
Our results clearly show that the cortical thickness change around the periosteal surface varies linearly with loading magnitude

Summary

Introduction

Osteoporosis is a degenerative bone disease characterised by long-term bone loss and fragility (Black and Rosen, 2016). Several animal loading models have been developed to investigate the relations between the applied mechanical load, the changes in bone mass, and the bone cells involved in mechano-transduction (Meakin et al, 2014; Javaheri et al, 2019). Among these models, the mouse tibia loading model is commonly used to assess both trabecular and cortical bone adaptation responses (De Souza et al, 2005; Sugiyama et al, 2010, 2012). A more detailed evaluation of bone’s adaptive response to local strain can be obtained by analysing the local cortical thickness change ( Ct.Th)

Objectives

Methods

Results

Conclusion