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.
METHODS
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.


BACKGROUND
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.
Martin
G J
GJ
Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Boden
S D
SD
Titus
L
L
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D016025:Bone Transplantation / Q000379:methods; D000075202:Contraindications; D004195:Disease Models, Animal; D020910:Ketorolac / Q000009:adverse effects*; D008159:Lumbar Vertebrae / Q000166:cytology / Q000187:drug effects* / Q000601:surgery*; D011817:Rabbits; D013123:Spinal Fusion / Q000379:methods*; D016212:Transforming Growth Factor beta
D000894:Anti-Inflammatory Agents, Non-Steroidal; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D020910:Ketorolac