Effects of Loading Duration and Short Rest Insertion on Cancellous and Cortical Bone Adaptation in the Mouse Tibia.

Haisheng Yang,Rachel E Embry,Russell P Main,Ryan K Roeder

doi:10.1371/journal.pone.0169519

Abstract

The skeleton’s osteogenic response to mechanical loading can be affected by loading duration and rest insertion during a series of loading events. Prior animal loading studies have shown that the cortical bone response saturates quickly and short rest insertions between load cycles can enhance cortical bone formation. However, it remains unknown how loading duration and short rest insertion affect load-induced osteogenesis in the mouse tibial compressive loading model, and particularly in cancellous bone. To address this issue, we applied cyclic loading (-9 N peak load; 4 Hz) to the tibiae of three groups of 16 week-old female C57BL/6 mice for two weeks, with a different number of continuous load cycles applied daily to each group (36, 216 and 1200). A fourth group was loaded under 216 daily load cycles with a 10 s rest insertion after every fourth cycle. We found that as few as 36 load cycles per day were able to induce osteogenic responses in both cancellous and cortical bone. Furthermore, while cortical bone area and thickness continued to increase through 1200 cycles, the incremental increase in the osteogenic response decreased as load number increased, indicating a reduced benefit of the increasing number of load cycles. In the proximal metaphyseal cancellous bone, trabecular thickness increased with load up to 216 cycles. We also found that insertion of a 10 s rest between load cycles did not improve the osteogenic response of the cortical or cancellous tissues compared to continuous loading in this model given the age and sex of the mice and the loading parameters used here. These results suggest that relatively few load cycles (e.g. 36) are sufficient to induce osteogenic responses in both cortical and cancellous bone in the mouse tibial loading model. Mechanistic studies using the mouse tibial loading model to examine bone formation and skeletal mechanobiology could be accomplished with relatively few load cycles.

Highlights

The skeleton is an adaptive structure that responds to mechanical loading by increasing bone mass under increased loads
Using a loading regimen based upon an interrupted triangle waveform with peak loads of -9 N and loading 5 days per week for 2 weeks, we found that, as few as 36 load cycles per day were able to induce osteogenic responses in both cancellous and cortical bone tissues in the mouse tibia
We found that insertion of a 10 s rest after every fourth load cycle did not improve the osteogenic response of the cortical or cancellous tissues compared to continuous loading with the same number of load cycles

Summary

Introduction

The skeleton is an adaptive structure that responds to mechanical loading by increasing bone mass under increased loads. Short rests inserted between load cycles can be important in enhancing mechanically induced bone formation in cortical bone [3, 8, 9]. Both the avian ulna axial-compression model and mouse tibia cantilever-bending model, have been used to demonstrate that insertion of 10 s rest periods following single load cycles transformed a low-magnitude, non-osteogenic loading regime into an osteogenic stimulus [3]. A related study using the mouse tibia cantilever-bending model found that cortical bone formation was amplified by rest-insertion compared to continuous loading [10]. In the rat tibia four-point bending model, load cycles interspersed with 14 s rest periods resulted in greater cortical bone formation rates compared to continuous load cycles, while rest periods less than 7 s did not enhance cortical osteogenesis [1]

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