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J Biomech. 2011 Feb 24;44(4):637-43. doi: 10.1016/j.jbiomech.2010.11.011. Epub 2010 Dec 24.

Vertical ground reaction forces diminish in mice after botulinum toxin injection.

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  • 1Faculty of Kinesiology, University of Calgary, Calgary, Canada.


We examined changes in weight-bearing ability in mice after injection with botulinum toxin type A (BTX) to determine whether BTX can be used to isolate the effects of muscle on bone. As ambulation patterns were previously shown to improve within two weeks post-injection, we hypothesized that BTX injection to the posterior hindlimb would not significantly affect the mouse's ability to bear weight in the affected limb one week post-injection. Female BALB/c mice (N=13, 16-17 week old) were injected with either 20 μL of BTX (1U/100 g) or saline (SAL) in the left posterior hindlimb. Vertical ground reaction forces (GRF), hindlimb muscle cross-sectional area (MCSA), and tibial bone micro-architecture were assessed for 42 d following injection. Peak and average vertical GRF were 11±1% and 23±3% lower, respectively, in the BTX-injected hindlimb within 4d post-injection and remained lower than the SAL-injected hindlimb 14-21 d post-injection (15±4% and 10±2%, respectively). Time between forelimb and hindlimb peaks was 30-40% greater in the BTX-injected hindlimb than SAL-injected hindlimb 4-14 d post-injection. Peak vertical GRF recovered earlier following BTX injection than MCSA or bone volume fraction. These results indicate that weight-bearing ability recovered despite persistent muscle atrophy, and that weight-bearing alone was insufficient to maintain bone in the absence of muscle activity. We suggest that the absence of high-frequency signals typically associated with fast-twitch muscle activity may be contributing to the ongoing degradation of bone after BTX injection.

Copyright © 2010 Elsevier Ltd. All rights reserved.

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