Abstract
SummaryWe aimed to determine whether aged bone’s diminished response to mechanical loading could be rescued by modulating habitual activity. By reducing background loading, aged bone’s response to loading increased to a level no different to young mice. This suggests, given the right stimulus, that ageing bone can respond to mechanical loading.IntroductionAge-related decline in bone mass has been suggested to represent an impaired ability of bone to adapt to its mechanical environment. In young mice, the tibia’s response to external mechanical loading has been shown to increase when habitual activity is reduced by sciatic neurectomy. Here we investigate if neurectomy can rescue bone’s response to loading in old mice.MethodsThe effect of tibial disuse, induced by unilateral sciatic neurectomy (SN), on the adaptive response to a single peak magnitude of dynamic load-engendered mechanical strain was assessed in 19-month-old (aged) mice. In a second experiment, a range of peak loads was used to assess the load magnitude-related effects of loading on a background of disuse in young adult and aged mice. Bone architecture was analysed using micro-computed tomography (μCT) and dynamic histomorphometry.ResultsIn the first experiment, SN in aged mice was associated with a significant periosteal osteogenic response to loading not observed in sham-operated mice (7.98 ± 1.7 vs 1.02 ± 2.2 % increase in periosteally enclosed area, p < 0.05). In the second experiment, SN abrogated the expected age-related difference in the bones’ osteogenic response to peak strain magnitude (p > 0.05).ConclusionsThese data suggest that bones’ age-related decline in osteogenic responsiveness to loading does not originate in bone cells to either assess, or appropriately respond to strain, but rather is likely to be due to inhibitory “averaging” effects derived from the habitual strains to which the bone is already adapted. If such “strain averaging” is applicable to humans, it suggests that gentle exercise may degrade the beneficially osteogenic effects of short periods of more vigorous activity.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-015-3142-x) contains supplementary material, which is available to authorized users.
Highlights
Bones ensure that their structural strength is sufficient to withstand normal loading without fracture through a process of functional adaptation
sciatic neurectomy (SN) abrogated the expected age-related difference in the bones’ osteogenic response to peak strain magnitude (p>0.05). These data suggest that bones’ age-related decline in osteogenic responsiveness to loading does not originate in bone cells to either assess, or appropriately respond to strain, but rather is likely to be due to inhibitory Baveraging^ effects derived from the habitual strains to which the bone is already adapted
In the study reported here, we aimed to investigate whether sciatic neurectomy would increase the osteogenic response to artificial loading in aged animals and perhaps restore it to that seen in young adults
Summary
Bones ensure that their structural strength is sufficient to withstand normal loading without fracture through a process of functional adaptation. This adaptation is thought to be controlled by a local negative feedback mechanism with Btarget^ loading-engendered strain as its objective and Boff target^ strains as its controlling stimulus. This homeostatic mechanism is known as the mechanostat. The function of the mechanostat appears to be impaired since despite continued functional activity, sufficient bone tissue is lost that the incidence of fragility fracture increases [1]. In regions of cortical bone at least, the mechanism of the failure
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
