Purified bovine BMP extract and collagen for spine arthrodesis: preclinical safety and efficacy.
METHODS
Rabbit and nonhuman primate posterolateral intertransverse process spinal fusions were performed.


OBJECTIVE
To determine the preclinical safety and efficacy of bBMPx product (a composite of collagen and bovine bone morphogenetic protein extract) mixed with demineralized bone matrix for posterolateral intertransverse process spinal fusions.


BACKGROUND
A dose response of bovine BMP extract with collagen in demineralized bone matrix has demonstrated spinal fusion to a rate of 100% in a rabbit spinal fusion model. This study furthers the research to demonstrate safety in the rabbit and efficacy of bovine BMP extract for spinal fusion applications in nonhuman primates. Additionally, preliminary human clinical data are presented.


METHODS
For the safety portion of the study, 45 New Zealand white rabbits underwent posterolateral intertransverse process spinal fusion after laminectomy. Nine additional rabbits served as nontreated control subjects. Graft material (autograft or bBMPx product) was placed in the gutters in 30 animals, and no material was used in 15 animals. The animals were observed for abnormal physical activity, then killed at 8, 29, or 57 days. Histologic evaluation was performed on explanted spines. In the nonhuman primate efficacy studies, 54 rhesus macaques also underwent bilateral posterolateral intertransverse process fusion. bBMPx product with varying bovine BMP extract doses was implanted bilaterally. The animals were killed at 4, 8, 12, 18, or 24 weeks. Plain radiograph, computed tomography scanning, and histology were performed.


RESULTS
The rabbit safety study demonstrated that any spinal cord compression or degeneration was caused by the inflammatory response after surgery and was equivalent in all groups. These issues resolved over time. Efficacy data demonstrated an autograft fusion rate of only 21% in the rhesus macaques. The bovine BMP extract demonstrated a dose response in which 3 mg per side gave twice the fusion rate as autograft.


CONCLUSIONS
bBMPx product is safe and effective as an autograft substitute for posterolateral intertransverse process spinal fusion. Clinical studies are underway.
Damien
Christopher J
CJ
Sulzer Biologics, Wheat Ridge, Colorado, USA.
Grob
Dieter
D
Boden
Scott D
SD
Benedict
James J
JJ
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D016025:Bone Transplantation / Q000379:methods; D002417:Cattle; D003094:Collagen / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000601:surgery*; D008253:Macaca mulatta; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects; D011817:Rabbits; D013123:Spinal Fusion / Q000379:methods*; D014020:Tissue Extracts / Q000737:chemistry; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D019485:Bone Morphogenetic Proteins; D014020:Tissue Extracts; D003094:Collagen