Safety of recombinant human bone morphogenetic protein-2 after spinal laminectomy in the dog

Study Design. This was a randomized, blinded trial of the safety of the app lication of recombinant human bone morphogenetic protein (rhBMP)-2 or autol ogous bone graft onto a laminectomy defect of the dog in the presence or ab sence of a dural membrane puncture. Objective. To lest the safety of rhBMP-2 in an application in which direct contact of the material with neural tissue occurs. Summary of Background Data. Application of rhBMP-2 in laboratory animals st imulates local bone formation to effect spinal fusion and healing of segmen tal bone defects. The use of rhBMP-2 as a bone graft substitute in spinal f usion would eliminate donor site morbidity and may augment the rate of succ essful fusion. Because rhBMP-2 may unintentionally come in contact with neu ral tissue, the consequences of such a safety issue must be addressed in an animal model before human trials. Methods. Twenty skeletally mature beagles underwent spinal exposure followe d by bilateral laminectomy at L5. In half of the dogs, a puncture wound was made to;the dura with the expression of cerebrospinal fluid at the,Site of the puncture. In randomly selected animals, the exposed dural elements rec eived either autologous bone graft with the bone removed from the laminecto my site or an implant of the rhBMP-2 device. The animals were observed for 12 weeks with periodic clinical examinations, and monthly computed tomograp hic scans. Results, There was no clinical, radiographic, or histologic evidence of neu rologic abnormalities in these animals. The rhBMP-2 stimulated bone growth in the laminectomy defect and came into direct contact with the dural membr ane. There was no evidence of abnormal mineralization within the thecal sac or in the spinal cord itself. Conclusions. The rhBMP-2 implant stimulated bone formation in the laminecto my site. Neither autologous,bone, rhBMP-2, nor the dural puncture had delet erious consequences for the animals.