Disuse rescues the age-impaired adaptive response to external loading in mice.
We 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.


BACKGROUND
Age-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.


METHODS
The 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.


RESULTS
In 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).


CONCLUSIONS
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 "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.
School of Veterinary Science, University of Bristol, Langford, Bristol, BS40 5DU, UK. lee.meakin@bristol.ac.uk.
L B
LB
Meakin
School of Veterinary Science, University of Bristol, Langford, Bristol, BS40 5DU, UK.
P J
PJ
Delisser
School of Veterinary Science, University of Bristol, Langford, Bristol, BS40 5DU, UK.
G L
GL
Galea
School of Veterinary Science, University of Bristol, Langford, Bristol, BS40 5DU, UK.
L E
LE
Lanyon
School of Veterinary Science, University of Bristol, Langford, Bristol, BS40 5DU, UK.
J S
JS
Price
D000222:Adaptation, Physiological / Q000502:physiology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D003714:Denervation / Q000379:methods; D005260:Female; D007103:Immobilization / Q000502:physiology; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000502:physiology*; D010521:Periosteum / Q000502:physiology; D012584:Sciatic Nerve / Q000601:surgery; D013977:Tibia / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology*; D055114:X-Ray Microtomography / Q000379:methods
Bone; Habitual activity; Mechanical loading; Neurectomy