Radiation-induced impairment of bone healing in the rat femur: effects of radiation dose, sequence and interval between surgery and irradiation.

Abstract

Impairment of osseous healing in treatment combining surgery and radiotherapy is a frequent complication. Its dependence on sequence and interval was studied in a defined experimental model. The effect of pre- and postoperative irradiation by single doses of X-rays on osseous closure of a 1.2 mm drill hole in the rat femur was measured 6 or 7 weeks after surgery in histological sections using morphometrical methods. Irradiation delivered between 1 day and 6 months before surgery resulted in a reduction of bone healing following very similar dose response relationships; there was no evidence of any slow repair of latent radiation damage. Radiosensitivity of bone healing during the first 3 days after surgery was not different from preoperative irradiation; however, irradiation 4 days or later after surgery failed to reduce osseous healing even after very high radiation doses. Tolerance increases enormously if radiotherapy is given later than 4 days after surgery. This has great implications for combined radiotherapy and surgery schedules involving bone reconstruction, but may be even more important for radiotherapy applied to prevent heterotopic ossification after total hip arthroplasty. Biologically, target cell regeneration alone is insufficient to account for the drastic rise in radiotolerance; it must be accompanied by an increase in cellular resistance due to differentiation.