Adaptive responses of bone to mechanical loading
Creators: name: MacKay, Christopher James
Publisher: name: University of Calgary
Year: 2011

description: Bibliography: p. 90-99
description: Some pages are in colour.
description: Includes copy of animal protocol approval. Original copy with original Partial Copyright Licence.
description: Numerous experimental models[l,2,3,4] provide insights into the molecular signalling pathways by which bone senses and adapts to changes in functional demand but ambiguity persists about the mechanical components contributing to the principal determinants of skeletal morphology. Nevertheless, it has become increasingly evident that interstitial fluid flow within the lacunocanalicular network may play a primary role in functional bone adaptation to mechanical loading. This theory is linked to the concept that intracortical fluid flow through the lacunocanalicular network could change as a result of relatively small changes in loading parameters and that the osteocytes within the network are uniquely placed to sense and respond to increases or decreases in whole bone strain environment. The purpose of the current study was to develop an experimental loading model that utilized a well-defined loading environment and to identify the role that induced flow of bone interstitial fluid plays in the mechanotransductive responses of bone. To accomplish this, an experimental tibial cantilever loading apparatus was used to induce a non-physiological loading stimulus along the diaphysis of the right tibia of skeletally mature female Sprague-Dawley rats. In this model, the unloaded left tibia served as both a contralateral non-treated control and as a sham-loaded condition. The bone-targeted flourochrome calcein AM was administered to produce a double-label within the mineralized matrix to delineate and assess bone tissue response to the applied exogenous loading. Confocal microscopy was used to visualize the labeling fronts in mounted tibial cross sections and served to estimate relative bone formation rates as well as to localize osteogenic mineralization in response to exogenous loading. As a result of the experimental loading loaded limbs showed a statistically significant increase in mineral apposition rate of 2:0.02µm2 · dai' within 6 of the 12 regions of interest examined. The induced loading environment was quantified using three triple rosette strain gauges cemented along a transverse section of the experimental tibia within the specified region of interest. A maximum strain of approximately ±200µc: was induced in regions furthest from the neutral axis of bending during loading. The sectors that displayed increases in mineral apposition rate were contiguous with the calculated neutral axis of bending and were not associated with the maximum induced strains. The collected strain measurements were subsequently used in tandem with theoretical modelling software to develop a finite difference, finite element model (FD/FEM) of a tibial cross-section during the loading event. This model was used to calculate areas of maximal compression and tension, to estimate induced pressure gradients and to calculate related fluid flow vectors and magnitudes. Areas that displayed maximal induced fluid flow were localized to regions containing areas of maximal induced strain. The comparison of the resultant osteogenic responses within the tibiae collected with the calculated finite element-finite difference model results, provided insight into the specific mechanical signals and induced changes in fluid behavior that may influence dynamic skeletal morphology.