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Optimal Timing of Preoperative Radiation for Prophylaxis Against Heterotopic OssificationA Rabbit Hip Model
Mustasim N. Rumi, MD1; Gurvinder S. Deol, MD1; Jason A. Bergandi, MD1; Kishor P. Singapuri, MD2; Vincent D. PellegriniJr., MD3
1 Department of Orthopaedics and Rehabilitation and the Musculoskeletal Research Laboratory, the Milton S. Hershey Medical Center of the Pennsylvania State University College of Medicine, P.O. Box 850, MCH089, Hershey, PA 17033
2 Lancaster General Health Campus, 2102 Harrisburg Pike, Lancaster, PA 17603
3 Department of Orthopaedics, University of Maryland School of Medicine, 22 South Greene Street, Suite S11B, Baltimore, MD 21201. E-mail address: vpellegrini@umoa.umm.edu
View Disclosures and Other Information
In support of their research or preparation of this manuscript, one or more of the authors received Grant 95-027 from the Orthopaedic Research and Education Foundation. None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at the Department of Orthopaedics and Rehabilitation and the Musculoskeletal Research Laboratory, the Milton S. Hershey Medical Center of the Pennsylvania State University College of Medicine, Hershey, Pennsylvania

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2005 Feb 01;87(2):366-373. doi: 10.2106/JBJS.C.00974
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Background: In a previous study, we developed a rabbit model of heterotopic ossification and demonstrated that 800 or 1200 cGy of radiation before an operation on the hip significantly decreased postoperative ectopic bone formation compared with that seen after the operation on the non-irradiated, contralateral hip. The purpose of this study was to determine the optimal preoperative timing of radiation prophylaxis against heterotopic ossification following hip surgery in this same experimental model.

Methods: Seventy-two hips in thirty-six New Zealand White rabbits were divided into four treatment groups corresponding to four preoperative points in time (four hours, twenty-four hours, seventy-two hours, and three weeks). The hips were irradiated with 1200 cGy at the different preoperative time points (eighteen hips at each time) to investigate the efficacy of the four preoperative radiation protocols. The rabbits then underwent bilateral hip surgery. They were killed and radiographs were made four months postoperatively. Heterotopic ossification was graded according to a modification of the scale of Brooker et al. The mean grade, the interobserver and intraobserver reliability, and the significance (p < 0.05) of the differences between the groups were evaluated.

Results: Radiation delivered at twenty-four hours preoperatively was significantly more effective for prophylaxis against heterotopic ossification than was radiation delivered at four hours or seventy-two hours preoperatively (p < 0.05), and the difference between the twenty-four-hour and three-week groups approached significance (p = 0.088). Furthermore, the twenty-four-hour group had a significantly lower percentage of hips with high-grade heterotopic ossification than did the four-hour (p = 0.02), seventy-two-hour (p = 0.002), and three-week (p = 0.03) groups.

Conclusions: Preoperative irradiation to prevent heterotopic ossification optimally should be administered twenty-four hours before the operation. This latency period probably allows expression of radiation-induced sublethal mutations in the genetic code of pluripotential stem cells and precludes differentiation to osteoblastic cell lines.

Clinical Relevance: If the findings of this study are validated in human clinical trials, they may allow preoperative outpatient radiation prophylaxis for patients at risk for heterotopic ossification. This approach would minimize patient discomfort and eliminate the risk of prosthetic hip dislocation associated with transport and positioning of the patient for radiation therapy in the early postoperative period.

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    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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