title: Binding to COMP Reduces the BMP2 Dose for Spinal Fusion in a Rat Model.
abstract: METHODS
  The aim of this study is to test the effect of cartilage oligomeric matrix protein (COMP) on enhancing rhBMP-2 induced spinal fusion in a prospective 8-week interventional trial of spinal fusion in rats.
  
  
  OBJECTIVE
  To determine whether the amount of bone morphogenetic protein-2 (BMP-2) required to achieve spinal fusion in a pre-clinical model can be reduced by the addition of COMP.
  
  
  BACKGROUND
  BMPs are applied clinically at supraphysiological doses to promote spinal fusion by inducing osseous growth, but dose-related limitations include ectopic bone formation and local inflammatory reactions. COMP is a matricellular BMP-binding protein expressed during endochondral ossification and fracture healing. In vitro studies demonstrate enhanced activity of BMP bound to COMP. We hypothesized that BMP bound to COMP could achieve equivalent spinal fusion rates at lower doses and with fewer complications.
  
  
  METHODS
  Posterolateral intertransverse process spinal fusion at L4 to L5 was performed in 36 Lewis rats. COMP (10 μg) was tested with or without "low-dose" rhBMP-2 (2 μg), and the results were compared with the "low-dose" (2 μg rhBMP-2) and "high-dose" (10 μg rhBMP-2) groups. All groups utilized insoluble collagen bone matrix carrier (ICBM). Fusion was evaluated by radiology, histology, and manual palpation. BMP release kinetics were evaluated in vitro.
  
  
  RESULTS
  Fusion grading of microCT images demonstrated that the fusion rate with the COMP+LoBMP was statistically equivalent to HiBMP, and significantly better than LoBMP without COMP. These results were confirmed with radiographs and manual palpation. BMP release kinetics suggest that COMP increased local concentrations of BMP due to decreased growth factor retention on the scaffold.
  
  
  CONCLUSIONS
  COMP enhances BMP-induced bone formation, enabling lower doses of BMP to achieve the same level of spinal fusion. COMP may function by affecting the availability and biological presentation of BMP-2. A decrease of BMP-2 required for fusion may reduce dose-related adverse effects, surgical costs, and improve clinical outcomes.
  
  
  METHODS
  N/A.
authors.affiliation: Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis, Davis, CA.
authors.forename: Motasem
authors.initials: M
authors.lastname: Refaat
authors.affiliation: Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis, Davis, CA.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Klineberg
authors.affiliation: Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis, Davis, CA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fong
authors.affiliation: J.D. Wheat Veterinary Orthopaedic Laboratory, School of Veterinary Medicine, University of California Davis, One Shields Avenue, Davis, CA.
authors.forename: Tanya C
authors.initials: TC
authors.lastname: Garcia
authors.affiliation: Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis, Davis, CA.|Department of Biomedical Engineering, University of California Davis, Davis, CA.
authors.forename: J Kent
authors.initials: JK
authors.lastname: Leach
authors.affiliation: Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis, Davis, CA.
authors.forename: Dominik R
authors.initials: DR
authors.lastname: Haudenschild
mesh_terms: D000818:Animals; D001857:Bone Matrix / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000494:pharmacology*; D064236:Cartilage Oligomeric Matrix Protein / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D008159:Lumbar Vertebrae / Q000601:surgery*; D008297:Male; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013123:Spinal Fusion / Q000379:methods
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D064236:Cartilage Oligomeric Matrix Protein; D011994:Recombinant Proteins