Radiation-induced impairment of osseous healing: quantitative studies using a standard drilling defect in rat femur.

The femora of adult Wistar rats were locally irradiated with single doses of X rays and 1 day later were wounded by a standardized drilling defect that extended through the diaphyseal cortex into the marrow cavity. Healing of the lesion was followed over 30 weeks to assess the time course of osseous closure. In unirradiated bones healing was complete by week 7. Irradiation with doses up to 15 Gy imparted a dose-dependent delay in the formation of primary callus and its subsequent replacement by more mature bone, while after higher doses healing remained permanently compromised or even suppressed. Using histomorphometry, osseous closure was also measured quantitatively for healing periods of 7, 10, 16 and 30 weeks and the data were expressed as the percentage of responders with < or = 40% fractional closure. The resulting dose-response curves were steep, displaying a large threshold dose and ED50 values between 16.8 to 17.5 Gy (7 to 16 weeks) and 19.4 Gy (30 weeks), respectively.