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The use of recombinant human bone morphogenetic protein 2 (rhBMP-2) to promote spinal fusion in a nonhuman primate anterior interbody fusion model. Spine (Phila Pa 1976) 1999 Apr 01;24(7):629-36

Date

04/21/1999

Pubmed ID

10209790

DOI

10.1097/00007632-199904010-00004

Scopus ID

2-s2.0-0033118704 (requires institutional sign-in at Scopus site)   149 Citations

Abstract

STUDY DESIGN: A study on the efficacy of recombinant human bone morphogenetic protein 2 (rhBMP-2) in a nonhuman primate anterior interbody fusion model.

OBJECTIVES: To investigate the efficacy of rhBMP-2 with an absorbable collagen sponge carrier to promote spinal fusion in a nonhuman primate anterior interbody fusion model.

SUMMARY OF BACKGROUND DATA: RhBMP-2 is an osteoinductive growth factor capable of inducing new bone formation in vivo. Although dosage studies using rhBMP-2 have been performed on species of lower phylogenetic level, they cannot be extrapolated to the primate. Dosage studies on nonhuman primates are essential before proceeding with human primate application.

METHODS: Six female adult Macaca mulatta (rhesus macaque) monkeys underwent an anterior L7-S1 interbody lumbar fusion. All six sites were assigned randomly to one of two fusion methods: 1) autogenous bone graft within a single freeze-dried smooth cortical dowel allograft cylinder (control) or 2) rhBMP-2-soaked absorbable collagen sponges within a single freeze-dried smooth cortical dowel allograft cylinder also soaked in rhBMP-2. The animals underwent a baseline computed tomography scan followed by 3- and 6-month postoperation scans. Anteroposterior and lateral radiographs of the lumbosacral spine were performed monthly. After the monkeys were killed, the lumbar spine fusion sites were evaluated. Histologic evaluation of all fusion sites was performed.

RESULTS: The three monkeys receiving rhBMP-2-soaked collagen sponges with a freeze-dried allograft demonstrated radiographic signs of fusion as early as 8 weeks. The control animals were slower to reveal new bone formation. The computed tomography scans revealed extensive fusion of the L7-S1 lumbar vertebrae in the group with rhBMP-2. A pseudarthrosis was present in two of the control animals.

CONCLUSIONS: This study was able to document the efficacy of rhBMP-2 with an absorbable collagen sponge carrier and a cortical dowel allograft to promote anterior interbody fusion in a nonhuman primate model at a dose of 0.4 mg per implant site (1.5 mg/mL concentration). The late of new bone formation and fusion with the use of rhBMP-2 and cortical dowel allograft appears to be far superior to that of autogenous cancellous iliac crest graft with cortical dowel allograft.

Author List

Hecht BP, Fischgrund JS, Herkowitz HN, Penman L, Toth JM, Shirkhoda A

Author

Jeffrey M. Toth PhD Associate Dean for Research in the School of Dentistry department at Marquette University




MESH terms used to index this publication - Major topics in bold

Animals
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Bone Transplantation
Collagen
Drug Carriers
Female
Follow-Up Studies
Lumbar Vertebrae
Macaca mulatta
Osseointegration
Random Allocation
Recombinant Proteins
Sacrum
Spinal Fusion
Tomography, X-Ray Computed
Transforming Growth Factor beta
Treatment Outcome