Abstract
Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation.
Highlights
Ageing of the skeleton is closely linked to osteoporotic fragility fractures and a failure to retain bone mass
Whilst we do not currently know how the local mechanical environment correlates with regions of bone formation, these observations lead to two questions: (a) does adaptation in aged mice fail because the mechanical stimulus is maintained below a certain threshold and, (b) can this threshold be exceeded to prime mechanoadaptive new bone formation in response to levels of strain to which aged mice would otherwise be insensitive?
Our analysis of the entire tibia finds that short-term priming in aged mice with loads high enough to generate maximum strains matching those capable of driving osteogenesis in younger mice, termed surplus high-load can partially restore cortical but not trabecular mechanoadaptive response in aged bone
Summary
Ageing of the skeleton is closely linked to osteoporotic fragility fractures and a failure to retain bone mass. Based on studies showing that load responses could be boosted by prior sciatic neurectomy (SN) in young mice[17], it was found that reduced capacity for load-induced osteogenesis in aged mice could be reversed by a short 4 day-long period of SN18 These authors speculated that short-term disuse eliminated any age-related differences in the sensitivity to external mechanical stimuli in both cortical and trabecular bone[18]. More recent study which reported that longer-term SN-related disuse more effectively eliminated differences in sensitivity to external mechanical stimuli in aged cortical bone, but instead abolished the beneficial effects of short-term SN in trabecular bone[19] The origins of such priming events that facilitate a restoration in bones’ mechanoadaptive response to loading in the aged skeleton are incompletely defined and, whether they might be instigated by alternative short-term modifications in the mechanical environment remains unexplored. Our data suggest that age-related failure of mechanoadaptation is due to insufficient mechanical stimulus to trigger adaptation and that aged bone’s response to loading can be reactivated by short bursts of high magnitude loading
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
