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. 

Original Text by Clifford R. Wheeless, III, MD.

Last updated by Data Trace Staff on Tuesday, June 28, 2016 8:12 am