title: Optimal timing of preoperative radiation for prophylaxis against heterotopic ossification. A rabbit hip model.
abstract: 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.
authors.affiliation: 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, USA.
authors.forename: Mustasim N
authors.initials: MN
authors.lastname: Rumi
authors.forename: Gurvinder S
authors.initials: GS
authors.lastname: Deol
authors.forename: Jason A
authors.initials: JA
authors.lastname: Bergandi
authors.forename: Kishor P
authors.initials: KP
authors.lastname: Singapuri
authors.forename: Vincent D
authors.initials: VD
authors.lastname: Pellegrini
mesh_terms: D000818:Animals; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D006621:Hip Joint / Q000000981:diagnostic imaging / Q000528:radiation effects / Q000601:surgery; D008297:Male; D023421:Models, Animal; D009999:Ossification, Heterotopic / Q000209:etiology / Q000517:prevention & control*; D011300:Preoperative Care / Q000379:methods*; D011817:Rabbits; D011859:Radiography; D011878:Radiotherapy / Q000379:methods*; D011879:Radiotherapy Dosage; D013997:Time Factors; D016896:Treatment Outcome