Safety of recombinant human bone morphogenetic protein-2 after spinal laminectomy in the dog.
METHODS
This was a randomized, blinded trial of the safety of the application of recombinant human bone morphogenetic protein (rhBMP)-2 or autologous bone graft onto a laminectomy defect of the dog in the presence or absence of a dural membrane puncture.


OBJECTIVE
To test the safety of rhBMP-2 in an application in which direct contact of the material with neural tissue occurs.


BACKGROUND
Application of rhBMP-2 in laboratory animals stimulates local bone formation to effect spinal fusion and healing of segmental bone defects. The use of rhBMP-2 as a bone graft substitute in spinal fusion would eliminate donor site morbidity and may augment the rate of successful fusion. Because rhBMP-2 may unintentionally come in contact with neural 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 followed 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 received either autologous bone graft with the bone removed from the laminectomy site or an implant of the rhBMP-2 device. The animals was observed for 12 weeks with periodic clinical examinations and monthly computed tomographic scans.


RESULTS
There was no clinical, radiographic, or histologic evidence of neurologic abnormalities in these animals. The rhBMP-2 stimulated bone growth in the laminectomy defect and came into direct contact with the dural membrane. 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 laminectomy site. Neither autologous bone, rhBMP-2, nor the dural puncture had deleterious consequences for the animals.
Meyer
R A
RA
Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, North Carolina, USA. rmeyer@carolinas.org
Gruber
H E
HE
Howard
B A
BA
Tabor
O B
OB
Murakami
T
T
Kwiatkowski
T C
TC
Wozney
J M
JM
Hanley
E N
EN
D000287:Administration, Topical; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D002113:Calcification, Physiologic / Q000187:drug effects*; D004195:Disease Models, Animal; D004285:Dogs; D004388:Dura Mater; D005500:Follow-Up Studies; D007796:Laminectomy; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012449:Safety; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000627:therapeutic use
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta