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This was a prospective study to determine the potential effects of indomethacin on spinal fusions in the rat.To determine if indomethacin exerts a deleterious effect on spinal fusions in the rat model.Nonsteroidal anti-inflammatory drugs are a class of compound that affect bone osteogenesis during fracture healing and heterotopic ossification. Spinal fusion is a process that occurs via osteogenesis and, therefore, may be similarly affected.Thirty-nine adult, Sprague-Dawley rats underwent a three-level posterior spinal fusion. Fusion was performed using morselized autogenous vertebral bone graft obtained via caudectomy and stabilized using a cerclage wiring technique. The 39 rats were divided into two groups consisting of 17 study animals and 22 control animals. The control group was injected with 1.5 cc of 0.9 normal saline subcutaneously for 12 weeks, whereas the test animals were injected on an identical schedule using 3 mg/kg of indomethacin sodium salt. Two control animals died, and three animals in the treatment group died of drug-related complications. Twelve weeks after surgery, all animals were killed, and the involved spinal segments were evaluated by direct manual examination. A fusion was probable if the spinal segments exhibited decreased scaled micromotion.Sixty segmental levels in 20 control animals were assessed. Overall, 27 of 60 levels (45%) achieved fusion. In the indomethacin-treated group, 42 levels in 14 animals were evaluated. Overall, four of 42 levels (10%) achieved a fusion. Chi-square analysis demonstrated a significant difference (P<0.001) between the control and indomethacin-treated groups.This study raises serious questions about the inhibitory effects of nonsteroidal anti-inflammatory drugs on spinal fusion. Clinically, the widespread use of nonsteroidal anti-inflammatory drugs in the postoperative period after spinal fusion may need to be avoided.