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

Study Design. An animal model of posterolateral intertransverse process spi ne fusion healing. Objective. To evaluate the effect of systemic ketorolac, alone and in combi nation with locally applied recombinant human bone morphogenetic protein-2, on spine fusion healing. Summary of Background Data. The effect of nonsteroidal anti-inflammatory dr ugs on bone graft healing in animals remains controversial. However, most s tudies point to the inhibition of fracture repair, especially during the ea rly 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 asa control or ketorolac. Rabbits were divided into three groups: 1) control (saline in pump); 2) non steroidal 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 p rotein-2. All rabbits were killed after 6 weeks. Results. In the central 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 ketoralacachieved fusion (P = 0.037). Of the animals that received ketorolac and recombinant bone morphogenetic prot ein-2, 100% (9 in 9) fused. Conclusions. The results of this study confirm the detrimental effect of a commonly used nonsteroidal antiinflammatory drug on spinal fusion during th e immediate postoperation period in a established rabbit mode(lf posterolat eral lumbar spine fusion. The addition of recombinant bone morphogenetic pr otein-2 to the autograft bane was able to compensate for the inhibitory eff ect of ketorolac on bone formation, On the basis of these data, caution is urged in the routine use of nonsteroidal anti-inflammatory drugs for postop eration analgesia in patients undergoing spine arthrodesis.