Recombinant human bone morphogenetic protein-2 overcomes the inhibitory effect of ketorolac, a nonsteroidal anti-inflammatory drug (NSAID), on posterolateral lumbar intertransverse process spine fusion

Spine (Phila Pa 1976). 1999 Nov 1;24(21):2188-93; discussion 2193-4. doi: 10.1097/00007632-199911010-00003.


Study design: An animal model of posterolateral intertransverse process spine fusion healing.

Objective: To evaluate the effect of systemic ketorolac, alone and in combination with locally applied recombinant human bone morphogenetic protein-2, on spine fusion healing.

Summary of background data: The effect of nonsteroidal anti-inflammatory drugs on bone graft healing in animals remains controversial. However, most studies point to the inhibition of fracture repair, especially during the early healing period.

Methods: Forty-nine adult New Zealand white rabbits underwent single-level lumbar fusion with autologous iliac bone graft. Two mini-osmotic pumps were implanted subcutaneously and filled with saline as a control or ketorolac. Rabbits were divided into three groups: 1) control (saline in pump); 2) nonsteroidal anti-inflammatory drug (ketorolac in pump); 3) nonsteroidal anti-inflammatory drug (ketorolac in pump) and bone morphogenetic protein (bone graft soaked in a 3.0 mg solution of recombinant human bone morphogenetic protein-2. All rabbits were killed after 6 weeks.

Results: In the control group, 75% (12 in 16) of the surviving rabbits were judged to have solidly fused lumbar spines as compared with only 35% (6 in 17) of the animals that received ketorolacachieved fusion (P = 0.037). Of the animals that received ketorolac and recombinant bone morphogenetic protein-2, 100% (9 in 9) fused.

Conclusions: The results of this study confirm the detrimental effect of a commonly used nonsteroidal anti-inflammatory drug on spinal fusion during the immediate postoperation period in a established rabbit model of posterolateral lumbar spine fusion. The addition of recombinant bone morphogenetic protein-2 to the autograft bone was able to compensate for the inhibitory effect of ketorolac on bone formation. On the basis of these data, caution is urged in the routine use of nonsteroidal anti-inflammatory drugs for postoperation analgesia in patients undergoing spine arthrodesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / therapeutic use*
  • Bone Transplantation / methods
  • Contraindications
  • Disease Models, Animal
  • Ketorolac / adverse effects*
  • Lumbar Vertebrae / cytology
  • Lumbar Vertebrae / drug effects*
  • Lumbar Vertebrae / surgery*
  • Rabbits
  • Spinal Fusion / methods*
  • Transforming Growth Factor beta*


  • Anti-Inflammatory Agents, Non-Steroidal
  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Transforming Growth Factor beta
  • Ketorolac