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 Basic Science Test 2: Bone Growth, Healing, Regeneration
Spine Test 2: Perioperative Care
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The Journal of Bone and Joint Surgery (American) 85:632-634 (2003)
© 2003 The Journal of Bone and Joint Surgery, Inc.

Scientific Article

Time-Dependent Inhibitory Effects of Indomethacin on Spinal Fusion

K. Daniel Riew, MD, John Long, DVM, John Rhee, MD, Stephen Lewis, MD, Timothy Kuklo, MD, Yong Jung Kim, MD, Yasutsugu Yukawa, MD and Yong Zhu, MD

Investigation performed at the Department of Orthopaedic Surgery, Barnes-Jewish Hospital at Washington University, St. Louis, Missouri

K. Daniel Riew, MD
John Long, DVM
John Rhee, MD
Stephen Lewis, MD
Timothy Kuklo, MD
YongJung Kim, MD
Yasutsugu Yukawa, MD
Yong Zhu, MD
Department of Orthopaedic Surgery, Barnes-Jewish Hospital at Washington University, One Barnes-Jewish Hospital Plaza, West Pavilion, Suite 11300, St. Louis, MO 63110. E-mail address for K.D. Riew: riewd{at}msnotes.wustl.edu

The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Clinical Relevance: Our data suggest that caution be used when initiating nonsteroidal anti-inflammatory drugs after spinal arthrodesis, particularly in the early phase of healing.



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