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rhBMP-2 Complications
rhBMP-2 Complications
Jeffrey S. Ross, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        TERMINOLOGY

        • Abbreviations

          • Recombinant human bone morphogenetic protein 2 (rhBMP-2)

        • Definitions

          • rhBMP-2
            • Member of transforming growth factors-β super family of proteins
            • Used in surgery to decrease time of graft union and to reduce morbidity from nonunion
            • These types of proteins have roles in cell proliferation, differentiation, apoptosis, and embryologic development
            • BMP induces differentiation of undifferentiated mesenchymal cells into osteogenic cells and enhances function of osteoblasts
            • BMP-induced endochondral ossification → undifferentiated mesenchymal cells develop into chondrocytes
              • Chondrocytes lay down cartilage, which is later resorbed by chondroblasts
              • Allows osteoblasts to begin new bone formation
            • BMPs also have role in regulation of osteoclastogenesis
              • This regulation can lead to stimulation of bone resorption
            • rhBMP-2 commercially supplied in USA as INFUSE bone graft (Medtronic)
              • Delivered on absorbable collagen sponge
              • FDA approved for use with LT-CAGE (Medtronic) device for anterior lumbar interbody fusion
            • rhBMP-7 commercially available as OP-1 putty (Olympus Biotech)

        IMAGING

        • General Features

          DIFFERENTIAL DIAGNOSIS

            Selected References

            1. Liu S et al: Comparative clinical effectiveness and safety of bone morphogenetic protein versus autologous iliac crest bone graft in lumbar fusion: a meta-analysis and systematic review. Spine (Phila Pa 1976). 45(12):E729-E41, 2020
            2. Dettori JR et al: Longer follow-up continues to reveal no increased risk of cancer with the use of recombinant human bone morphogenetic protein in spine fusion. Spine J. 19(10):1640-7, 2019
            3. Fu R et al: Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis. Ann Intern Med. 158(12):890-902, 2013
            4. Simmonds MC et al: Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data. Ann Intern Med. 158(12):877-89, 2013
            5. Carragee EJ et al: A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J. 11(6):471-91, 2011
            6. Garrett MP et al: Formation of painful seroma and edema after the use of recombinant human bone morphogenetic protein-2 in posterolateral lumbar spine fusions. Neurosurgery. 66(6):1044-9; discussion 1049, 2010
            7. Mroz TE et al: Complications related to osteobiologics use in spine surgery: a systematic review. Spine (Phila Pa 1976). 35(9 Suppl):S86-104, 2010
            8. Agarwal R et al: Osteoinductive bone graft substitutes for lumbar fusion: a systematic review. J Neurosurg Spine. 11(6):729-40, 2009
            9. Carragee EJ et al: Pseudomorbidity in iliac crest bone graft harvesting: the rise of rhBMP-2 in short-segment posterior lumbar fusion. Spine J. 9(11):873-9, 2009
            10. Valdes MA et al: Recombinant bone morphogenic protein-2 in orthopaedic surgery: a review. Arch Orthop Trauma Surg. 129(12):1651-7, 2009
            11. Benglis D et al: A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery. Neurosurgery. 62(5 Suppl 2):ONS423-31; discussion ONS431, 2008
            12. McKay WF et al: A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft). Int Orthop. 31(6):729-34, 2007
            Related Anatomy
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            Related Differential Diagnoses
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            References
            Tables

            Tables

            KEY FACTS

            • Terminology

              • Imaging

                • Top Differential Diagnoses

                  TERMINOLOGY

                  • Abbreviations

                    • Recombinant human bone morphogenetic protein 2 (rhBMP-2)

                  • Definitions

                    • rhBMP-2
                      • Member of transforming growth factors-β super family of proteins
                      • Used in surgery to decrease time of graft union and to reduce morbidity from nonunion
                      • These types of proteins have roles in cell proliferation, differentiation, apoptosis, and embryologic development
                      • BMP induces differentiation of undifferentiated mesenchymal cells into osteogenic cells and enhances function of osteoblasts
                      • BMP-induced endochondral ossification → undifferentiated mesenchymal cells develop into chondrocytes
                        • Chondrocytes lay down cartilage, which is later resorbed by chondroblasts
                        • Allows osteoblasts to begin new bone formation
                      • BMPs also have role in regulation of osteoclastogenesis
                        • This regulation can lead to stimulation of bone resorption
                      • rhBMP-2 commercially supplied in USA as INFUSE bone graft (Medtronic)
                        • Delivered on absorbable collagen sponge
                        • FDA approved for use with LT-CAGE (Medtronic) device for anterior lumbar interbody fusion
                      • rhBMP-7 commercially available as OP-1 putty (Olympus Biotech)

                  IMAGING

                  • General Features

                    DIFFERENTIAL DIAGNOSIS

                      Selected References

                      1. Liu S et al: Comparative clinical effectiveness and safety of bone morphogenetic protein versus autologous iliac crest bone graft in lumbar fusion: a meta-analysis and systematic review. Spine (Phila Pa 1976). 45(12):E729-E41, 2020
                      2. Dettori JR et al: Longer follow-up continues to reveal no increased risk of cancer with the use of recombinant human bone morphogenetic protein in spine fusion. Spine J. 19(10):1640-7, 2019
                      3. Fu R et al: Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis. Ann Intern Med. 158(12):890-902, 2013
                      4. Simmonds MC et al: Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data. Ann Intern Med. 158(12):877-89, 2013
                      5. Carragee EJ et al: A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. Spine J. 11(6):471-91, 2011
                      6. Garrett MP et al: Formation of painful seroma and edema after the use of recombinant human bone morphogenetic protein-2 in posterolateral lumbar spine fusions. Neurosurgery. 66(6):1044-9; discussion 1049, 2010
                      7. Mroz TE et al: Complications related to osteobiologics use in spine surgery: a systematic review. Spine (Phila Pa 1976). 35(9 Suppl):S86-104, 2010
                      8. Agarwal R et al: Osteoinductive bone graft substitutes for lumbar fusion: a systematic review. J Neurosurg Spine. 11(6):729-40, 2009
                      9. Carragee EJ et al: Pseudomorbidity in iliac crest bone graft harvesting: the rise of rhBMP-2 in short-segment posterior lumbar fusion. Spine J. 9(11):873-9, 2009
                      10. Valdes MA et al: Recombinant bone morphogenic protein-2 in orthopaedic surgery: a review. Arch Orthop Trauma Surg. 129(12):1651-7, 2009
                      11. Benglis D et al: A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery. Neurosurgery. 62(5 Suppl 2):ONS423-31; discussion ONS431, 2008
                      12. McKay WF et al: A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE Bone Graft). Int Orthop. 31(6):729-34, 2007