Time-dependent inhibitory effects of indomethacin on spinal fusion

The use of nonsteroidal anti-inflammatory drugs following spine arthrodesis is discouraged because of the negative effects on bone-healing. We are not aware of any data regarding when nonsteroidal anti-inflammatory drugs may be safely resumed postoperatively. We hypothesized that these drugs have a time-dependent deleterious effect on fusion, with the greatest inhibition during the early phases of fusion.

Seventy New Zealand White rabbits underwent posterior intertransverse process arthrodesis at L5-L6 with use of iliac autograft. Rabbits randomly received indomethacin (10 mg/kg orally) starting at two weeks after surgery (twenty-four animals), indomethacin starting at four weeks postoperatively (twenty-three), or saline starting at two weeks postoperatively (twenty-three) (the control group). The animals were killed at six weeks, and the spines were denuded of soft tissues and palpated for L5-L6 motion. Fusion was defined as the complete absence of motion.

Sixty-five percent (fifteen) of the twenty-three spines in the control group and 48% (eleven) of the twenty-three in the four-week group fused. However, only 21% (five) of the twenty-four spines in the two-week group fused. The difference between the two-week and control groups was significant (p < 0.002), as was the difference between the two and four-week groups (p = 0.05). The difference between the four-week and control groups was not significant (p = 0.2).

The earlier that indomethacin was resumed postoperatively, the greater was its negative effect on fusion. Indomethacin appears to play a significant inhibitory role in the early phase of healing. Initiating indomethacin treatment in the latter phase of healing does not appear to significantly affect fusion rates, although there was a nonsignificant trend toward inhibition. To our knowledge, this is the first investigation of the time-dependent nature of indomethacin's effect on bone-healing.