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Muscle Changes Can Account for Bone Loss After Botulinum Toxin Injection

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Abstract

Studies to date have assumed that botulinum toxin type A (BTX) affects bone indirectly, through its action on muscle. We hypothesized that BTX has no discernable effect on bone morphometry, independent of its effect on muscle. Therefore, we investigated whether BTX had an additional effect on bone when combined with tenotomy compared to tenotomy in isolation. Female BALB/c mice (n = 73) underwent one of the following procedures in the left leg: BTX injection and Achilles tenotomy (BTX-TEN), BTX injection and sham surgery (BTX-sham), Achilles tenotomy (TEN), or sham surgery (sham). BTX groups were injected with 20 μL of BTX (1 U/100 g) in the posterior lower hindlimb. At 4 weeks, muscle cross-sectional area (MCSA) and tibial bone morphometry were assessed using micro-CT. Each treatment, other than sham, resulted in significant muscle and bone loss (P < 0.05). BTX-TEN experienced the greatest muscle loss (23–45% lower than other groups) and bone loss (20–30% lower bone volume fraction than other groups). BTX-sham had significantly lower MCSA and bone volume fraction than TEN and sham. After adjusting for differences in MCSA, there were no significant between-group differences in bone properties. We found that BTX injection resulted in more adverse muscle and bone effects than tenotomy and that effects were amplified when the procedures were combined. However, between-group differences in bone could be accounted for by MCSA. We conclude that any independent effect of BTX on bone morphometry is likely small or negligible compared with the effect on muscle.

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Acknowledgements

We thank Dr. Linda Andersen for performing the surgeries, Adam Wasylyshyn for assistance with data collection, as well as Helen Buie and Christopher Moore for designing the scanning fixture. We also thank Dr. Walter Herzog for feedback on the manuscript. S. L. M. was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC), Alberta Innovates – Health Solutions, and the Killam Trust.

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Authors and Affiliations

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

    Sarah L. Manske, Steven K. Boyd & Ronald F. Zernicke

  2. Schulich School of Engineering, University of Calgary, Calgary, Canada

    Sarah L. Manske & Steven K. Boyd

  3. School of Kinesiology, University of Michigan, 1402 Washington Heights, 4170 OBL, Ann Arbor, MI, 48109, USA

    Ronald F. Zernicke

  4. Departments of Orthopaedic Surgery and Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA

    Ronald F. Zernicke

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  1. Sarah L. Manske
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  2. Steven K. Boyd
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Correspondence to Ronald F. Zernicke.

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The authors have stated that they have no conflict of interest.

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Manske, S.L., Boyd, S.K. & Zernicke, R.F. Muscle Changes Can Account for Bone Loss After Botulinum Toxin Injection. Calcif Tissue Int 87, 541–549 (2010). https://doi.org/10.1007/s00223-010-9428-2

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