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.