Comparative study of the effects of radiation, indomethacin, prednisolone, and ethane-1-hydroxy-1,1-diphosphonate (EHDP) in the prevention of ectopic bone formation

Abstract

Forty male New Zealand white rabbits were treated with immobilization and forcible manipulation of the right knee known to cause ectopic bone formation in the quadriceps muscle. The animals were also treated with either: A) A total radiation dose of 1840 rad (18.4 Gy); B) A 0.5 mg/kg/day oral dose of prednisolone; C) 10 mg/kg/day of indomethacin, given in two oral doses; D) Ethane-1-hydroxy-1,1-diphosphonate (EHDP) given in a 20-mg/kg/day oral dose; or E) with the vehicle given alone as a control. The experimental period was four weeks, and the amount of ectopic bone was determined by planimetry of serial transverse sections of the femur. The degree of knee stiffness was recorded during the experiment. The amount (mean +/- SEM) of ectopic bone was 1.412 +/- 0.264 cm3 in controls; it was insignificantly higher in the EHDP-treated group, but significantly lower (p less than 0.01) in rabbits treated with radiation (0.390 +/- 0.094 cm3), prednisolone (0.181 +/- 0.076 cm3), and indomethacin (0.314 +/- 0.112 cm3). In control animals and those given EHDP, the treatment invariably led to almost complete stiffness of the right knee. The rabbits treated with prednisolone and indomethacin offered the least resistance to the manipulations, and the group treated with radiation showed intermediate stiffness. Semiquantitative histologic evaluation demonstrated less inflammation in the group treated with prednisolone than in the control group.