Mechano-regulation of bone adaptation is controlled by the localin vivoenvironment and logarithmically dependent on loading frequency

Abstract

15It is well established that cyclic, but not static, mechanical loading has anabolic effects on bone. 16 However, the function describing the relationship between the loading frequency and the 17 amount of bone adaptation remains unclear. Using a combined experimental and computational 18 approach, this study aimed to investigate whether bone mechano-regulation is controlled by 19 mechanical signals in the local in vivo environment and dependent on loading frequency. 20Specifically, by combining in vivo micro-computed tomography (micro-CT) imaging with 21 micro-finite element (micro-FE) analysis, we monitored the changes in microstructural as well 22 of the mechanical signals influencing bone formation and resorption in the local in vivo 39 environment. 40 Keywords: 41Bone adaptation, mechanical loading, in vivo micro-CT imaging, frequency dependency 42

Application of subject-specific adaptive mechanical loading for bone healing in a mouse tail vertebral defect

“…The conditional probabilities of formation, quiescence and resorption (Fig. 4 ) in this defect study correlate with prior studies of intact vertebra, where (re)modelling events have a relationship to the strain percentile, and that loading may slightly shift the strain percentile in which formation events occur 15 , 25 . Considering the above studies, this rtFE study also supports these mechanoregulation theories and further validates the principle in mouse vertebral bone defect healing as well.…”

“…This can provide short time interval snapshots of the healing progression and create high-resolution datasets for FE simulations. This time-lapsed imaging method is currently most feasible in smaller animals, and has been previously demonstrated in vertebrae 22 , and recently within both mouse femoral defect models 29 , and to assess longer-term morphological changes of intact mouse vertebrae 25 , 30 . This method is highly relevant here to provide weekly insights into the subject-specific healing progression, and when used in combination with the rtFE methods, it enables in vivo assessment and proportional changes to the loading conditions simultaneously.…”

“…A previously described method enabled the loading of mouse vertebrae [22][23][24] , and importantly, allowed high-resolution scanning of the vertebrae. This was recently advanced on to investigate the loading frequency effect on mouse vertebral bone parameters 25 . To investigate specifically bone defect healing in this current study, a caudal vertebral bone defect model was developed, which could be incorporated into the previously successfully used workflows.…”

Application of subject-specific adaptive mechanical loading for bone healing in a mouse tail vertebral defect

“…The conditional probabilities of formation, quiescence and resorption (Fig. 4) in this defect study correlate with prior studies of intact vertebra, where (re)modelling events have a relationship to the strain percentile, and that loading may slightly shift the strain percentile in which formation events occur 15,25 . Considering the above studies, this rtFE study also supports these mechanoregulation theories and further validates the principle in mouse vertebral bone defect healing as well.…”

“…This can provide short time interval snapshots of the healing progression and create high-resolution datasets for FE simulations. This time-lapsed imaging method is currently most feasible in smaller animals, and has been previously demonstrated in vertebrae 22 , and recently within both mouse femoral defect models 29 , and to assess longer-term morphological changes of intact mouse vertebrae 25,30 . This method is highly relevant here to provide weekly insights into the subject-specific healing progression, and when used in combination with the rtFE methods, it enables in vivo assessment and proportional changes to the loading conditions simultaneously.…”