The studies herein document the efforts to describe the behavior of the soft tissue in response to distraction osteogenesis, and investigate the usefulness of botulinum toxin (type A) treatment during the procedure. Both theoretical and experimental tools were utilized towards this goal. Distraction osteogenesis is a surgical procedure used to lengthen a bone, and the process often induces complications in the surrounding soft tissues. One of the more debilitating complications encountered during tibial elongation is contracture about the ankle. Botulinum toxin administration has been used to help ankle contractures caused by other pathologies, and experiments were conducted to explore its efficacy in treating distraction induced contracture.

The tibias of New Zealand White rabbits were lengthened with a distraction rate and final elongation selected to generate the complications reported during limb lengthening. The animals undergoing distraction were divided into three treatment groups. The first group received saline injections;​ the second group received botulinum toxin injections into the tibialis anterior muscle;​ and the third group received botulinum injections into the gastrocnemius muscle. All animals were implanted with osmotic pumps to deliver bromodeoxyuridine, a thymidine analog used for labeling dividing cells. Animals were evaluated for range of motion and muscle strength at the start and conclusion of the experiments. Each experiment lasted eight weeks after which the animals were sacrificed. Their muscles and tendons were harvested and analyzed using various biomechanical, histological and immunohistochemical tools.

The tendons of the harvested muscles were subjected to stress relaxation tests in order to determine any differences to contralateral control. These data were fit to a power law formulation and compared to controls. The initial stresses were fit to a model incorporating structural and microstructural parameters. The parameters influenced by distraction gave insights into the types of alterations occurring within the tendon.

Distraction impaired muscle function of the tibialis anterior, but had no effect on the gastrocnemius. Specifically, torque production in the tibialis anterior of distracted limbs was reduced by 80%. Toxin injection worsened the loss when injected into the tibialis anterior muscle and provided a slight improvement when injected into the gastrocnemius. All distracted limbs evidenced contracture and loss of joint excursion. Distraction alone caused a loss in range of motion from 150° to 57°. The greatest loss was in dorsiflexion with the animals no longer able to reach 90°, with 0° measured from the tibia. Injection of botulinum toxin improved this range:​ when injected into the gastrocnemius muscle, dorsiflexion was increased by 15° to a total range of 75°;​ when injected into the tibialis anterior, plantarflexion was increased by 22°, resulting in a total range of 85°.

In addition to altering limb function, distraction caused morphological changes to the muscle. Atrophy, increased intramuscular connective tissue, increased mitotic activity and rounded muscle fibers were pronounced following distraction. Injection of botulinum toxin resulted in reduced mitotic activity in the opposing un-injected muscle. Conversely, in the injected muscle it caused additional fibrosis and atrophy, but the toxin did counter the “rounding” effect observed. In muscle not undergoing distraction, the toxin caused increased angularity of the muscle fibers, as is common with denervation atrophy. Thus, the decrease in roundness it provided muscles into which it was injected was likely an artifact of this phenomenon. Conversely, toxin injection also reduced the number and extent of round muscle fibers when injected into the opposing muscle, so this protection against rounding appears genuine.

Compounded with alterations induced in the muscle, the biomechanical properties of the tendons were also affected. Though the procedure did not affect the Achilles tendon, the tibialis anterior tendon showed altered elastic and viscoelastic properties. Distraction caused increased stress relaxation rates;​ at low strains, these rates were at times over twice as fast, indicating a greater capacity for energy dissipation. Injection of the toxin into the gastrocnemius had little effect, but injection into the tibialis anterior returned the stress relaxation properties almost to normal. The load-deformation curves of the tibialis anterior tendons were shallower following distraction, indicating a reduction in stiffness. Botulinum toxin injection into the gastrocnemius further reduced the tendon’s stiffness, but injection into the tibialis anterior increased the stiffness.

Botulinum toxin injection impairs the muscle into which it is injected, while improving the outcome of the corresponding tendon. Conversely, there are protective effects for the tibialis anterior when the antagonist gastrocnemius is injected, but this harms the tibialis anterior tendon. Injection of the toxin induced fibrosis and caused muscle weakness and atrophy;​ however, it improved the range of motion in a joint with contracture. These studies demonstrate that there is a trade off between the benefit and harm provided by botulinum toxin in treating muscles undergoing distraction osteogenesis.