Inhibition of fracture healing by indomethacin in rats

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Abstract
The effect of indomethacin (2 mg/kg per 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 3 different experiments were done. In a long-term experiment, the rats were treated with indomethacin or placebo for 29 days and fracture healing followed for a maximum of 91 days. In 2 short-term experiments, the rats were treated with indomethacin or placebo for a week and followed for a maximum of 122 days. The effect of age was studied in 1 experiment. Indomethacin plasma levels were .apprx. 1 .mu.g/ml in the indomethacin-treated animals. In the long-term experiment, indomethacin inhibited fracture healing (P < 0.006) and increased the angulation between the femur fragments. In the short-term experiments indomethacin inhibited fracture healing (P < 0.033) and increased the interfragmentary angle and fracture instability. All untreated fractures healed within 10 wk in younger rats (210 g), but only 44% healed in older rats (295 g).