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Bioprotection of Tendon Repair: Adjunctive Use of Botulinum Toxin A in Achilles Tendon Repair in the Rat
Jianjun Ma, MD, PhD1; Jian Shen, MD, PhD1; Beth Paterson Smith, PhD1; Andrew Ritting, MD1; Thomas L. Smith, PhD1; L. Andrew Koman, MD1
1 Department of Orthopaedic Surgery, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157. E-mail address for B.P. Smith: bpsmith@wfubmc.edu
View Disclosures and Other Information
Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the Musculoskeletal Research Department of Orthopaedic Surgery, Wake Forest University Health Sciences; the Orthopaedic Research and Education Foundation; and Allergan. In addition, one or more of the authors or a member of his or her immediate family received, in any one year, payments or other benefits of less than $10,000 or a commitment or agreement to provide such benefits from a commercial entity (Allergan). Also, a commercial entity (Allergan) paid or directed in any one year, or agreed to pay or direct, benefits in excess of $10,000 to a research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which one or more of the authors, or a member of his or her immediate family, is affiliated or associated.
Investigation performed at the Department of Orthopaedic Surgery, Wake Forest University Health Sciences, Winston-Salem, North Carolina

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2007 Oct 01;89(10):2241-2249. doi: 10.2106/JBJS.D.03054
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Abstract

Background: Tendon-repair techniques have evolved to increase the construct strength of the repair site in order to permit early active range of motion without tendon gap or rupture. The present study evaluated the hypothesis that the injection of botulinum neurotoxin type-A (BoNT-A) into the gastrocnemius muscle will reduce the active force production of that muscle below the force required to rupture the associated, repaired Achilles tendon.

Methods: Seventy-nine rat Achilles tendons were surgically bisected and were repaired with use of a two-strand core suture with a running epitenon repair. After the repair, the animals were treated with unilateral intramuscular (gastrocnemius) injections of either BoNT-A (6 U/kg body weight) (thirty-seven rats) or saline solution (forty-two rats). Operatively treated ankles were fixed in the neutral position with a percutaneous pin for the first two days after surgery. Unrestricted ankle motion and weight-bearing were allowed after the second postoperative day. An assessment of gap formation or rupture at the repair site, electrophysiologic measurements of force applied to the tendon, and an assessment of the strength of the repaired tendon were performed.

Results: Intramuscular BoNT-A injections produced a significant, reversible reduction in active muscle force (p < 0.007). Twitch and tetanus contractions decreased to approximately 25% of the values for the control side within one week, remained at <50% of the values for the control side at one month, and returned to normal levels by six months. The tetanic force capability of the muscles that had been injected with BoNT-A was fivefold to tenfold less than the force required to rupture the associated Achilles tendon for as long as four weeks after tendon repair. The spontaneous Achilles tendon rupture rate of repaired tendons in the BoNT-A group was three times lower than that in the saline solution group at one week, and the tendon rupture force was significantly higher in the BoNT-A group between one and three weeks after repair (p < 0.007). There was no significant difference in tendon rupture force between the two groups after three weeks.

Conclusions: Intramuscular gastrocnemius BoNT-A injections were associated with a significant reduction in force-generating potential, such that the muscle was incapable of actively producing enough force to rupture the repaired Achilles tendon in this rat model of tendon repair.

Clinical Relevance: The temporary decrease of active muscle-tendon forces produced by intramuscular BoNT-A injections has the potential to allow early active motion, to provide a pharmacologically mediated aid (bioprotection) to improve patient compliance with rehabilitation, and to enhance patient outcomes.

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    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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