Preoperative versus postoperative irradiation in the prophylaxis of heterotopic bone formation in rats

Irradiation treatment, commenced within 1-5 days post-surgery, reliably prophylaxes heterotopic bone formation but is painful and impairs desirable postop immobilization. To compare pre- versus post-op radiation, we bilaterally implanted bone matrix pellets into the thighs of 111 30-day-old Long Evans rats. Rats were randomized to time of radiation initiation (2 days pre-op, 1 hr pre-op, or 2 days post-op) and dose (300, 800, 1800, 2400, or 3000 cGy in 1 fraction). Pellets were removed on post-op day 16 or 48 and evaluated histologically and radiologically. Histologic analysis showed dose-related suppression in bone formation, that is, 40%, 27%, 6.8%, 2.5%, 6.4%, and 0.0% bone formed among sites receiving 0, 300, 800, 1800, 2400, and 3000 cGy, respectively. The difference in bone formation between control and irradiated implant sites was significant at every dose level in all treatment groups (p less than or equal to .03). There was no statistically significant difference in overall bone formation between post-op (7.1%) and 1 hr pre-op (5.3%) groups, whereas 2 day pre-op rats formed significantly more bone (12.6%). Stratified by dose, however, there were no significant differences between treatment groups except at 800 cGy. At this dose, 2 day pre-op rats formed more bone (10.6%) than 1 hr pre-op (6.6%) or post-op (3.3%) groups. Results suggest that a) radiation given shortly prior to a stimulus inducing proliferation among multipotential cells may inhibit subsequent proliferation and/or differentiation, and b) clinical formation of heterotopic bone may be preventable via modest doses of irradiation delivered shortly prior to surgery.