Zernicke, Ronald F.LaMothe, Jeremy Michael2005-08-162005-08-1620040612978788http://hdl.handle.net/1880/41702Bibliography: p. 141-174Some pages are in colour.Mechanical stimuli can be a vital determinant of bone morphology. How bones perceive and respond to those stimuli remains equivocal, but intracortical bone fluid flow has been suggested to influence bone cell activities. The current studies were designed to determine indirectly relations between intracortical fluid flow and adaptive osteogenesis. A cantilever loading device was constructed to apply non-invasive loads to skeletally mature female C57BL/6 tibiae 5 d·wk-1 for 4 wk. Double calcein injections were administered to permit histomorphometrical indices of adaptation. Loading was conducted while under halothane anaesthesia. Halothane was found to be a good anaesthetic agent for chronic adaptation studies as it did not confound histomorphometrical indices of osteogenesis. Periosteal osteogenesis exhibited a dose­response relation with loading rate. Those adaptations were histomorphometrically and biomechanically relevant. When loading cycles were separated by brief rest periods (< 1 s), osteogenesis was significantly enhanced. Similarly, longer rest periods (10 s) were effectively used in combination with short bouts of high-frequency loading regimes. The current studies also showed substantial periosteal responses and slight endosteal responses. Periosteal osteogenesis was significantly negatively correlated with endosteal osteogenesis; the spatial distribution of osteogenesis showed that medial-lateral tibial cantilever bending accelerated an age-related modeling drift. Spatially, endosteal osteogenesis was significantly correlated with circumferential strain gradients in only two of the loading groups. Thus, no single mechanical parameter could explain adaptive osteogenesis in all of the loading groups supporting the complexity of bone adaptation. The data from the current studies emphasized the sensitivity of the adult skeleton to specific physical parameters. Those parameters the skeleton was most sensitive to related to enhanced intracortical fluid flow velocities and volumes. Optimization of osteogenesis in response to mechanical loading may underpin the development of nonpharmacological regiments designed to increase bone mass.xxiv, 181 leaves : ill. ; 30 cm.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.doctoral thesis10.11575/PRISM/20368AC1 .T484 2004 L365