Inhibition of Heterotopic Ossification With Radiation Therapy in an Animal Model

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Abstract
An animal model for the study of heterotopic ossification was developed and the effects of perioperative radiation were analyzed. In Phase I, New Zealand White rabbits (n = 18) underwent surgery either with or without muscle injury on each hip to establish the most reliable model in which to study heterotopic ossification. In Phase II, rabbits (n = 36) underwent either 400, 800, or 1200 cGy radiation to one hip 24 hours after bilateral hip surgery to establish a dose response relationship for postoperative radiation therapy. In Phase III, rabbits (n = 24) underwent preoperative radiation therapy (800 cGy) at 4, 16, or 24 hours preoperatively to investigate the mechanism of action and efficacy of preoperative radiation therapy. Monthly radiographs were graded by blinded observers for severity of heterotopic ossification. Mean grade, intraobserver and interobserver variability, and statistical significance were evaluated. In Phase II, 17 of 18 rabbits generated heterotopic ossification in both hips, and the mean grade of heterotopic ossification was always greater on the operative side with intentional muscle injury. Variability in the grading was considered excellent. Phase II revealed that 800 cGy was the minimal effective dose. Contrary to hypothesis, Phase III revealed an increasing grade of heterotopic ossification coinciding with a decreasing preoperative time interval, with the difference in heterotopic ossification grade with 24-hour versus 4-hour preoperative radiation being significant. The rabbit model is reliable and reproducible and closely resembles the human clinical situation after hip surgery. Preoperative and postoperative radiation effectively prevented heterotopic ossification formation. The results support the use of preoperative radiation and establish a need for additional investigation regarding the mechanism of action and timing of preoperative radiation therapy.

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