Age-related bone loss is associated with a failure in bone (re)modelling (modelling and remodelling) processes. Bone (re)modelling occurs at spatially and temporally discrete sites to remove damaged or older bone, replacing it with new bone. However, the evaluation of bone (re)modelling has mainly been retrospective. The aim of this study was to identify the time kinetics of (re)modelling in response to loading at different ages. The left tibiae of female C57Bl/6J mice (10 wks: n=6, 26 wks: n=13, 78 wks: n=10) underwent two weeks of in vivo cyclic compressive loading . The right tibia served as control. In vivo microCT at an isotropic voxel resolution of 10.5 μm was performed at the tibial mid-shaft (5% tibias length; day 0, 5, 10, 15). Images were registered, binarised, and segmented. Two consecutive images in a common coordinate system were compared (day kday k+1) to identify formation (F), resorption (R) and quiescence (Q) sites on the cortical endocortical and periosteal bone surfaces . Comparing the three time intervals (d0d5, d5d10, d10d15), 27 (re)modelling sequences (FFR, RRF, QQF, etc) were identified. Using this dynamic micro-tomography based technique we could show that during two weeks of skeletal loading, bone adaptation occurs predominantly by modelling-bases formation and resorption processes, which last less than 10 days. In young and adult bones adaptive formation processes can be extended to a longer time-interval, whereas the elderly mice lost this ability. Ageing reduced adaptive modelling (spatially unlinked formation and resoprtion) and increased remodelling (resorption followed by formation). This in vivo approach of tracking local movements of the endosteal and periosteal bone surface allows not only to detect how strong the local response to mechanical loading is, but when it sets in and how long it lasts. This should be of great help to find an adequate stimulation not only mechanical, but also pharmaceutical that results in a sustained response of bone formation on the cortical surfaces.
Disclosure: The authors declared no competing interests. This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft; WI 3761/1-1, WI 3761/4-1).
1. Willie et al. Bone 2013.
2. Birkhold et al. Biomaterials 2014.