The Effects of botulinum toxin A on muscle histology during distraction osteogenesis

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Abstract
Distraction osteogenesis is a highly successful method of bone formation, yet muscle fibrosis and contractures can result in significant morbidity. In the current study, we investigate the efficacy of botulinum toxin A in preventing fibrosis and potentially increasing muscle development in distracted muscles. Fifteen New Zealand White rabbits underwent tibial distraction at 1.5 mm/day until a 20% gain was achieved. Treatment groups were divided by drug (saline or botulinum toxin) and target muscle (gastrocnemius or tibialis anterior). Two additional control animals received no treatment. Bromeodeoxyuridine was delivered continuously throughout the 8‐week experiment, and following muscle harvest. Tissues were stained for BrdU, Pax‐7, vimentin, and haematoxylin and eosin staining. Mitotic activity increased in all distracted animals; however, in the animals receiving botulinum toxin A injections into the gastrocnemius, the antagonist tibialis anterior suffered up to 9% less fibrosis than distraction alone (p = 0.024). Use of botulinum A toxin did not appear to promote or improve neogenesis of muscle fibers, nor did it decrease fibrosis in the injected muscles. It appears from this study, and a previously published study on the effects of this toxin on muscle function, that botulinum A toxin maybe of some benefit in decreasing morbidity in the antagonist muscle but not the muscle injected with the toxin. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:310–317, 2009

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