Abstract
In order to validate whether bones' functional adaptation to mechanical loading is a local phenomenon, we randomly assigned 21 female C57BL/6 mice at 19 weeks of age to one of three equal numbered groups. All groups were treated with isoflurane anesthesia three times a week for 2 weeks (approximately 7 min/day). During each anaesthetic period, the right tibiae/fibulae in the DYNAMIC+STATIC group were subjected to a peak dynamic load of 11.5 N (40 cycles with 10-s intervals between cycles) superimposed upon a static “pre-load” of 2.0 N. This total load of 13.5 N engendered peak longitudinal strains of approximately 1400 microstrain on the medial surface of the tibia at a middle/proximal site. The right tibiae/fibulae in the STATIC group received the static “pre-load” alone while the NOLOAD group received no artificial loading. After 2 weeks, the animals were sacrificed and both tibiae, fibulae, femora, ulnae and radii analyzed by three-dimensional high-resolution (5 μm) micro-computed tomography (μCT). In the DYNAMIC+STATIC group, the proximal trabecular percent bone volume and cortical bone volume at the proximal and middle levels of the right tibiae as well as the cortical bone volume at the middle level of the right fibulae were markedly greater than the left. In contrast, the left bones in the DYNAMIC+STATIC group showed no differences compared to the left or right bones in the NOLOAD or STATIC group. These μCT data were confirmed by two-dimensional examination of fluorochrome labels in bone sections which showed the predominantly woven nature of the new bone formed in the loaded bones. We conclude that the adaptive response in both cortical and trabecular regions of bones subjected to short periods of dynamic loading, even when this response is sufficiently vigorous to stimulate woven bone formation, is confined to the loaded bones and does not involve changes in other bones that are adjacent, contra-lateral or remote to them.
Highlights
Since Frost's introduction of the concept of the “mechanostat” [1], it has been accepted that bone mass and architecture are regulated in response to the local strains engendered in their tissue by functional loading
This mechanism has been the subject of a number of in vivo studies in animals in which artificial loads have been applied to the bones on one side and the modelling and remodelling responses in the loaded bones compared with those in the non-loaded contra-lateral pair [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. For this approach to be valid, it is necessary to be sure that the adaptive response of the loaded bones is confined to those bones and does not influence their contra-lateral controls. This assumption has been challenged by the work of Sample et al [30] who recently reported that in rapidly growing male rats a single period of dynamic high-magnitude axial loading of the ulna on one side was associated with significant levels of new cortical bone formation at the periosteal surface of the contra-lateral non-loaded ulna and in the cortical
C57BL/6 mice are extensively used as the background of genetically modified animals in the field of bone research, and we used the C57BL/6 mouse unilateral tibia/fibula axial loading model [12,27,29]
Summary
Since Frost's introduction of the concept of the “mechanostat” [1], it has been accepted that bone mass and architecture are regulated in response to the local strains engendered in their tissue by functional loading This mechanism has been the subject of a number of in vivo studies in animals in which artificial loads have been applied to the bones on one side and the modelling and remodelling responses in the loaded bones compared with those in the non-loaded contra-lateral pair [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. This model has the advantage over the ulna loading model [2,8,30] of enabling the study of trabecular as well as cortical bone compartments
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