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Osteogenic Proteins

- Discussion:
    - see: homeobox genes database
    - history: discovered by Marshall Urist in the early 1960s;
    - currently sixteen different proteins (BMP-1 through BMP-16) have been identified;
    - these proteins can now be produced by recombinant DNA technology and are further purified by column chromatography;
    - proteins are a homodimer (2 subunits);
    - osteoinduction is mediated by BMP-2 through BMP-7 and BMP-9: these allow differentiation of mesenchymal stem cells into osteoblasts;
    - osteogenic proteins usually require type I collagen as a carrier protein;
    - ref: Bone morphogenic protein and its application in trauma cases: a current concept update. 

- Specific BMP Types:
    - BMP-2 (see: infuse rhBMP-2 (medtronics))
            - spine:
                   - Use of rhBMP-2 in combination with structural cortical allografts: clinical and radiographic outcomes in anterior lumbar spinal surgery.
                   - Cancer risk after use of recombinant bone morphogenetic protein-2 for spinal arthrodesis. 
            - basic science:

                   - The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats.
                   - Percutaneous injection of recombinant human bone morphogenetic protein-2 in a calcium phosphate paste accelerates healing of a canine tibial osteotomy.
                   - rhBMP-2/calcium phosphate matrix accelerates osteotomy-site healing in a nonhuman primate model at multiple treatment times and concentrations. 
                   - Improved healing of large segmental defects in the rat femur by reverse dynamization in the presence of bone morphogenetic protein-2.
           - fracture care:
                   - Recombinant human bone morphogenic protein-2 in fracture care.
                   - Recombinant human bone morphogenetic protein-2: a randomized trial in open tibial fractures treated with reamed nail fixation.
                   - Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies.
                   - Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. A randomized, controlled trial.
                   - BMP-7 Versus BMP-2 for the Treatment of Long Bone Nonunion
                   - Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies.
                   - The use of  (rhBMP-2) in children undergoing revision surgery for persistent non-union
                   - Treatment of recalcitrant, multiply operated tibial nonunions with the RIA graft and rh-BMP2 using intramedullary nails

    - BMP-3
                - inhibits bone formation (down regulates BMP 2)
                - Bone Morphogenic Protein 3 Signaling in the Regulation of Osteogenesis

    - sigma aldrich
    - OP-1 (BMP-7) from Stryker
         - references:  
              - The Effect of Recombinant Human Osteogenic Protein-1 on Healing of Large Segmental Bone Defects.
              - Effect of recombinant human osteogenic protein-1 on healing of segmental defects in non-human primates.
              - Application of recombinant BMP-7 on persistent upper and lower limb non-unions.
              - Recombinant human bone morphogenic protein-7: applications for clinical trauma.
              - Treatment of congenital pseudarthrosis of the tibia with rhBMP-7. A report of five cases.
              - RhBMP-7 accelerates the healing in distal tibial fractures treated by external fixation.
              - Application of BMP-7 to tibial non-unions: a 3-year multicenter experience
              - Application of bone morphogenetic proteins to femoral non-unions: a 4-year multicentre experience.
              - RhBMP-7 for the treatment of nonunion of fractures of long bones.
              - Clinical application of BMP 7 in non-unions.
              - OP-1 Compared with Iliac Crest Autograft in Instrumented Posterolateral Fusion A Randomized, Multicenter Non-Inferiority Trial

    - BMP's obtained from cadavera:
              - in the study by Cunningham, et al (1999), osteogenic proteins were equivalent to autogenous grafting for achieving interbody fusions;
              - note: these proteins are fragile and care must be taken with sterilization techniques;
                     - sterilization via irradiation will dramatically decrease the effectiveness of BMPs;
                     - defatting via chloroform/ethanol and freezing to minus 70 deg appear to have little effect on BMP effectiveness;
              - references:
                     - Osteogenic protein vs autologous arthrodesis in sheep thoracic spine. A comparative endoscopic study using fusion device.
                     - The use of demineralized bone matrix in the repair of segmental defects. Augmentation with extracted matrix proteins and a comparison with autologous grafts.
                     - Resistant nonunions and partial or complete segmental defects of long bones. Treatment with implants of a composite of human bone morphogenetic protein (BMP) and autolyzed, antigen-extracted, allogeneic (AAA) bone. 

Recombinant human bone morphogenetic protein induces bone formation.
Enhancement of bone ingrowth by transforming growth factor-beta.
Bone: formation by autoinduction
Osteogenic protein versus autologous interbody arthrodesis in the sheep thoracic spine. A comparative endoscopic study using the Bagby and Kuslich interbody fusion device.
The effect of osteogenin (a bone morphogenetic protein) on the formation of bone in orthotopic segmental defects in rats.