The Journal of Bone and Joint Surgery (American). 2007;89:2241-2249.
doi:10.2106/JBJS.D.03054
© 2007 The Journal of Bone and Joint Surgery, Inc.
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 and
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{at}wfubmc.edu
Investigation performed at the Department of Orthopaedic Surgery, Wake
Forest University Health Sciences, Winston-Salem, North Carolina
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.
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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