The overall aim was to describe how muscle influences bone adaptation and maintenance of bone morphology. Botulinum toxin type A (BTX) was used to trigger muscle disuse in the posterior hindlimb of skeletally mature mice (14-18 weeks). Muscle cross-sectional area and bone morphology were monitored with in vivo micro-computed tomography, and muscle mass was assessed after sacrifice.

Muscle cross-sectional area and proximal tibia metaphyseal bone volume fraction both began to recover 4 weeks post- injection. Weight-bearing ability, assessed by vertical ground reaction forces, began to recover sooner than both muscle and bone outcomes after BTX injection. The absence of a lag between muscle and bone recovery indicated that muscle cross-sectional area was not the factor responsible for triggering bone recovery. The earlier recovery of soleus muscle mass, containing primarily slow- twitch muscle fibres, suggests that postural muscle activity may have contributed to the early recovery of weight-bearing and may have triggered the onset of bone recovery.

BTX resulted in more adverse muscle and bone effects than Achilles tenotomy, and effects were amplified when procedures were combined. However, muscle cross- sectional area could account for differences in bone morphometric parameters. Thus any independent effect of BTX on bone morphometry is likely small when compared with the effect of muscle. Peak and average vertical ground reaction forces were 10-23% lower in the BTX-injected hindlimb than saline-injected controls for 4-21 days post-injection, and recovered despite persistent muscle and bone loss. These combined results demonstrate that BTX can be used to examine the effects of muscle on bone, although there is also a short-term effect on weight-bearing.

High-magnitude, low-frequency vibration could not prevent BTX-induced bone loss. Previous hypotheses had suggested that vibration may enhance bone formation by mimicking postural muscle activity. The results of this study did not support that hypothesis, although the vibration intensity, particularly the duration of stimulation, may have been insufficient to mimic postural muscle activity.

In combination, the results of this thesis provide insight into the interaction between muscle and bone, and suggest that muscle is not the only factor that influences bone formation and maintenance.