Reversing the Inhibitory Effect of Nicotine on Spinal Fusion Using an Osteoinductive Protein Extract

Abstract
The effect on spinal fusion of an osteoinductive bone protein extract in the presence of a known inhibitor of spinal fusion (systemic nicotine) was studied prospectively in an animal model of posterolateral lumbar fusion. To evaluate the ability of a bovine-derived osteoinductive bone protein extract to overcome the inhibitory effect of nicotine in a rabbit spine fusion model. Multiple studies have demonstrated the ability of a variety of osteoinductive growth factors to serve as a bone graft substitute for lumbar spinal fusion under "normal" healing conditions. Forty-eight adult female New Zealand white rabbits underwent spine arthrodesis at L5-L6 while receiving systemic nicotine through a subcutaneous miniosmotic pump. Arthrodesis was performed using one of the following three graft materials: 1) autogenous iliac crest, 2) osteoinductive bone protein delivered in an allogeneic demineralized bone matrix/collagen carrier, or 3) osteoinductive bone protein delivered with autogenous iliac crest. Fusions were assessed by blinded manual palpation, radiography, and biomechanical testing. Of the 44 rabbits manually tested by blinded observers, all 14 in the osteoinductive bone protein plus autogenous iliac crest bone group had solid fusions (14 of 14), whereas the fusion rate was less in the osteoinductive bone protein plus demineralized bone matrix group (nine of 14, 64%; P = 0.02), and there were no fusions in the autogenous iliac crest only group (0 of 16, 0%; P = 0.000001). The use of osteoinductive bone protein with autogenous bone produced stronger and stiffer fusions compared with those using autogenous bone alone or osteoinductive bone protein with allograft bone. Cigarette smoking and nicotine are inhibitory factors in the healing of fractures and spine fusions. This study shows that the inhibitory effect of nicotine can be overcome with an osteoinductive bone growth factor in an animal model.