Inhibition of fracture healing by indomethacin in rats

The effect of indomethacin (2 mg/kg/day) on the healing of closed unimmobilized femoral fractures was examined in rats. A standard femoral fracture was produced in 205 male adolescent rats, and three different experiments were done. In a long-term experiment, the rats were treated with either indomethacin or placebo for 29 days and fracture healing followed for a maximum of 91 days. In two short-term experiments, the rats were treated with either indomethacin or placebo for a week and followed for a maximum of 122 days. The effect of age was studied in one experiment. Indomethacin plasma levels were about 1 microgram/ml in the indomethacin-treated animals. In the long-term experiment, indomethacin inhibited fracture healing (P less than 0.006) and increased the angulation between the femur fragments. In the short-term experiments indomethacin inhibited fracture healding (P less than 0.033) and increased the interfragmentary angle as well as fracture instability. All untreated fractures healed within 10 weeks in younger rats (210 g), whereas only 44% healed in older rats (295 g).