title: 1995 Volvo Award in basic sciences. The use of an osteoinductive growth factor for lumbar spinal fusion. Part II: Study of dose, carrier, and species.
abstract: METHODS
  Efficacy of a bovine-derived osteoinductive growth factor was studied in a rabbit model and in a nonhuman primate model of posterolateral lumbar spinal fusion.
  
  
  OBJECTIVE
  To determine the minimum effective dose of growth factor and the influence of different carrier material on the outcome of intertransverse process lumbar fusion.
  
  
  BACKGROUND
  Bone morphogenetic proteins and related growth factors are becoming increasingly available in purified extract or genetically engineered forms and are capable of inducing new bone formation in vivo. Osteoinductive growth factors to enhance lumbar spinal infusion have not been well studied in models of posterolateral intertransverse process fusion. Because of the diminished potential of bone regeneration in primates (including humans) compared with phylogenetically lower animals, extrapolations regarding dose and efficacy cannot be made directly from results obtained in experiments performed on phylogenetically lower animals. Experiments on non-human primates are a critical step before attempting to use these growth factors on humans. METHODS. One hundred fifteen adult New Zealand white rabbits and 10 adult rhesus macaques underwent single level posterolateral intertransverse process lumbar spinal arthrodesis to evaluate different doses and carrier materials for a bovine-derived osteoinductive bone protein extract. Rabbit fusion masses were evaluated 5 weeks after arthrodesis by manual palpation, radiography, biomechanical testing, and light microscopy. Monkey fusion masses were evaluated 12 weeks after arthrodesis by radiography and light microscopy.
  
  
  RESULTS
  Successful posterolateral intertransverse process spinal fusions were achieved in the rabbit models using an osteoinductive growth factor with three different carriers (autogenous iliac bone, demineralized allogeneic bone matrix, and natural coral). There was a dose-dependent response to the osteoinductive growth factor in the rabbit model, indicating that a threshold must be overcome before bone formation is induced. The methodology for biologic enhancement of spinal fusion developed in the rabbit model transferred successfully to the rhesus monkey, where the use of the osteoinductive growth factor with a demineralized bone matrix carrier resulted in spinal fusion in 12 weeks.
  
  
  CONCLUSIONS
  These experiments provide an essential building block in the understanding of the biology of spinal fusion and the use of osteoinductive growth factors to enhance a posterolateral intertransverse process spinal fusion. The achievement of posterolateral spinal fusion in the rhesus monkey using an osteoinductive growth factor is a significant step toward the biologic enhancement of spinal fusion in humans.
authors: Department of Orthopaedics, Emory University School of Medicine, Decatur, Georgia, USA.
authors: S D
authors: SD
authors: Boden
authors: J H
authors: JH
authors: Schimandle
authors: W C
authors: WC
authors: Hutton
mesh_terms: D000818:Animals; D001363:Awards and Prizes; D001690:Biological Science Disciplines; D016025:Bone Transplantation; D001842:Bone and Bones / Q000737:chemistry; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006023:Glycoproteins; D006133:Growth Substances; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000601:surgery* / Q000637:transplantation; D008253:Macaca mulatta; D011506:Proteins / Q000494:pharmacology; D011817:Rabbits; D011859:Radiography; D013123:Spinal Fusion
chemical_list: D004337:Drug Carriers; D006023:Glycoproteins; D006133:Growth Substances; D011506:Proteins