title: Time-dependent inhibitory effects of indomethacin on spinal fusion.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Barnes-Jewish Hospital at Washington University, St. Louis, Missouri 63110, USA. riewd@msnotes.wustl.edu
authors.forename: K Daniel
authors.initials: KD
authors.lastname: Riew
authors.forename: John
authors.initials: J
authors.lastname: Long
authors.forename: John
authors.initials: J
authors.lastname: Rhee
authors.forename: Stephen
authors.initials: S
authors.lastname: Lewis
authors.forename: Timothy
authors.initials: T
authors.lastname: Kuklo
authors.forename: Yong Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Yukawa
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D007213:Indomethacin / Q000009:adverse effects / Q000494:pharmacology*; D011817:Rabbits; D013123:Spinal Fusion; D013131:Spine / Q000187:drug effects*; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin