How does recombinant human bone morphogenetic protein-4 enhance posterior spinal fusion?
METHODS
A rabbit posterolateral intertransverse process fusion model was used to evaluate the effect that different doses of recombinant human bone morphogenetic protein-4 delivered in a porous hydroxyapatite-tricalcium phosphate ceramic had on osteogenesis and spinal fusion.


OBJECTIVE
To study the biologic effect and threshold dose of recombinant human bone morphogenetic protein-4 in enhancing spinal fusion.


BACKGROUND
Biologic manipulation for spinal fusion is an area undergoing active research. The enhancing effects of recombinant human bone morphogenetic proteins 2 and 7 on spinal fusion have been proved, and clinical trials of their application are in progress. Recombinant human bone morphogenetic protein-4 is another osteoinductive protein that has the ability to induce heterotopic bone formation, and its potential for enhancing spinal fusion has not yet been studied.


METHODS
For this study, 24 adult New Zealand white rabbits underwent single-level unilateral posterior intertransverse process spinal fusion at L5-L6. The animals were divided into four groups using different graft materials: allograft as well as hydroxyapatite-tricalcium phosphate augmented with 0, 1.25, and 5 microgram of recombinant human bone morphogenetic protein-4, respectively. The local changes were evaluated by sequential radiograph, manual palpation, histomorphology, and microradiography.


RESULTS
At week 7, ossification in the intertransverse process area ceased in groups without recombinant human bone morphogenetic protein-4, whereas active multicentric endochondral bone formation was demonstrated in groups with this growth factor. The success rate of contiguous bony bridging was found to correlate positively with the dose of recombinant human bone morphogenetic protein-4.


CONCLUSIONS
Recombinant human bone morphogenetic protein-4 effectively enhances new bone formation and accelerates fusion in the rabbit posterolateral posterior spinal fusion model. The effective dose of recombinant human bone morphogenetic protein-4 is 10 times lower than the reported dosage of recombinant human bone morphogenetic proteins 2 and 7.
Cheng
Jack C Y
JC
Department of Orthopaedics, The Chinese University of Hong Kong, the Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong. jackcheng@cuhk.edu.hk
Guo
Xia
X
Law
Lai Pang
LP
Lee
Kwong Man
KM
Chow
Daniel H K
DH
Rosier
Randy
R
D000818:Animals; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000235:genetics; D018786:Bone Substitutes / Q000008:administration & dosage; D002130:Calcium Phosphates / Q000008:administration & dosage; D002516:Ceramics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage; D006801:Humans; D006882:Hydroxyapatites / Q000008:administration & dosage; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000601:surgery; D010012:Osteogenesis / Q000187:drug effects*; D019736:Prostheses and Implants; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics; D013123:Spinal Fusion / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002130:Calcium Phosphates; D004337:Drug Carriers; D006882:Hydroxyapatites; D011994:Recombinant Proteins; C094280:hydroxyapatite-tricalciumphosphate composite