BMP-7 versus BMP-2 for the treatment of long bone nonunion.

The authors compared the results of treating nonunion with either bone morphogenetic protein (BMP)-7 or BMP-2. Between 2001 and 2009, 214 limb segments were treated for nonunion with either BMP-7 or BMP-2 at the authors' institution. Sixty-three subjects received 76 units of BMP-7. Radiographic healing occurred in 70% of limb segments at an average of 30 weeks after surgery, and 75% of limb segments were weight bearing at an average of 23 weeks after surgery. In 15.8%, persistent nonunion necessitated additional surgery. Average follow-up was 32 months. One hundred twelve subjects received 138 units of BMP-2. Radiographic healing occurred in 93% of limb segments at an average of 19 weeks after surgery, and 88% were weight bearing at an average of 15 weeks after surgery. In 6.25%, persistent nonunion necessitated additional surgery. Average follow-up was 17 months. Several significant differences were observed. Patients in both BMP-7 and BMP-2 groups were able to fully weight bear at an average of 23 and 15 weeks, respectively (P<.001). Further, both BMP-7 and BMP-2 groups healed at an average of 30 and 19 weeks, respectively (P<.001). Additionally, healing occurred in more limb segments in the BMP-2 group (93%) than in the BMP-7 group (70%) (P<.001). No difference in the complication rate was seen between groups. Patients who received BMP-2 for the treatment of nonunion had a higher rate of radiographic healing, achieved radiographic healing more quickly, and were able to bear weight sooner than those who underwent treatment with BMP-7.

[1]  H. An,et al.  Complications with the use of bone morphogenetic protein 2 (BMP-2) in spine surgery. , 2014, The spine journal : official journal of the North American Spine Society.

[2]  M. Bhandari,et al.  Efficacy and safety of recombinant human bone morphogenetic protein-2/calcium phosphate matrix for closed tibial diaphyseal fracture: a double-blind, randomized, controlled phase-II/III trial. , 2013, The Journal of bone and joint surgery. American volume.

[3]  E. Hurwitz,et al.  Cancer risk after use of recombinant bone morphogenetic protein-2 for spinal arthrodesis. , 2013, The Journal of bone and joint surgery. American volume.

[4]  E. Woo.  Adverse Events After Recombinant Human BMP2 in Nonspinal Orthopaedic Procedures , 2013, Clinical orthopaedics and related research.

[5]  P. Kloen,et al.  Co-expression of BMPs and BMP-inhibitors in human fractures and non-unions. , 2012, Bone.

[6]  A. Nohe,et al.  Bone morphogenetic proteins: a critical review. , 2011, Cellular signalling.

[7]  P. Giannoudis,et al.  Autologous bone graft: when shall we add growth factors? , 2010, Foot and ankle clinics.

[8]  M. Suk,et al.  Treatment of recalcitrant, multiply operated tibial nonunions with the RIA graft and rh-BMP2 using intramedullary nails. , 2010, Injury.

[9]  Chuan-ju Liu,et al.  Matrix Metalloproteinases That Associate With and Cleave Bone Morphogenetic Protein-2 In Vitro Are Elevated in Hypertrophic Fracture Nonunion Tissue , 2010, Journal of orthopaedic trauma.

[10]  P. Giannoudis,et al.  The Effect of Bone Morphogenetic Protein-2, Bone Morphogenetic Protein-7, Parathyroid Hormone, and Platelet-Derived Growth Factor on the Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells Derived From Osteoporotic Bone , 2010, Journal of orthopaedic trauma.

[11]  Jeffrey C. Wang,et al.  Bone Morphogenetic Protein-2 and Bone Marrow Aspirate With Allograft as Alternatives to Autograft in Instrumented Revision Posterolateral Lumbar Spinal Fusion: A Minimum Two-Year Follow-up Study , 2010, Spine.

[12]  A. Rogozinski,et al.  Accelerating autograft maturation in instrumented posterolateral lumbar spinal fusions without donor site morbidity. , 2009, Orthopedics.

[13]  D. Patel,et al.  Recombinant Bone Morphogenetic Protein-2 (rhBMP-2) in High-Risk Ankle and Hindfoot Fusions , 2009, Foot & ankle international.

[14]  P. Giannoudis,et al.  The Synergistic Effect of Autograft and BMP-7 in the Treatment of Atrophic Nonunions , 2009, Clinical orthopaedics and related research.

[15]  M. Fehlings,et al.  The Safety and Efficacy of OP-1 (rhBMP-7) as a Replacement for Iliac Crest Autograft in Posterolateral Lumbar Arthrodesis: A Long-term (>4 Years) Pivotal Study , 2008, Spine.

[16]  C. Court-Brown,et al.  A comparison of RhBMP-7 (OP-1) and autogenous graft for metaphyseal defects after osteotomy of the distal radius. , 2008, Injury.

[17]  P. Giannoudis,et al.  Application of BMP-7 to tibial non-unions: a 3-year multicenter experience. , 2008, Injury.

[18]  R. Verdonk,et al.  The role of bone morphogenetic protein-7 (Osteogenic Protein-1) in the treatment of tibial fracture non-unions. An overview of the use in Belgium. , 2008, Acta orthopaedica Belgica.

[19]  D. P. O'connor,et al.  Metabolic and endocrine abnormalities in patients with nonunions , 2007, Journal of orthopaedic trauma.

[20]  Rozalia Dimitriou,et al.  Health economics: a cost analysis of treatment of persistent fracture non-unions using bone morphogenetic protein-7. , 2007, Injury.

[21]  A. F. Dinah,et al.  Smoking increases failure rate of operation for established non-union of the scaphoid bone , 2007, International Orthopaedics.

[22]  Frank A. Liporace,et al.  Diabetic fracture healing. , 2006, Foot and ankle clinics.

[23]  Paolo Cherubino,et al.  Recombinant human bone morphogenetic protein-7 for treatment of long bone non-union: an observational, retrospective, non-randomized study of 105 patients. , 2006, Injury.

[24]  A. Reddi,et al.  Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[25]  S. Mirza,et al.  Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. A randomized, controlled trial. , 2006, The Journal of bone and joint surgery. American volume.

[26]  M. Swiontkowski,et al.  Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies. , 2006, The Journal of bone and joint surgery. American volume.

[27]  J. Goulet,et al.  Delayed unions of the tibia. , 2006, Instructional course lectures.

[28]  R. Derner,et al.  The bone morphogenic protein. , 2005, Clinics in podiatric medicine and surgery.

[29]  E. Mackenzie,et al.  Impact of Smoking on Fracture Healing and Risk of Complications in Limb-Threatening Open Tibia Fractures , 2005, Journal of orthopaedic trauma.

[30]  C. Court-Brown,et al.  Estimating the risk of nonunion following nonoperative treatment of a clavicular fracture. , 2004, The Journal of bone and joint surgery. American volume.

[31]  G. Friedlaender.  Osteogenic protein-1 in treatment of tibial nonunions: current status. , 2004, Surgical technology international.

[32]  H. Kreder,et al.  The Effect of Smoking on Clinical Outcome and Complication Rates Following Ilizarov Reconstruction , 2003, Journal of orthopaedic trauma.

[33]  G. Guyatt,et al.  Predictors of reoperation following operative management of fractures of the tibial shaft , 2003, Journal of orthopaedic trauma.

[34]  J. Szatkowski,et al.  Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). , 2003, The Journal of bone and joint surgery. American volume.

[35]  G. Zych,et al.  Osteogenic Protein-1 (Bone Morphogenetic Protein-7) in the Treatment of Tibial Nonunions: A Prospective, Randomized Clinical Trial Comparing rhOP-1 with Fresh Bone Autograft* , 2001, The Journal of bone and joint surgery. American volume.

[36]  D. Macdonald,et al.  Nonunion of the femoral diaphysis. The influence of reaming and non-steroidal anti-inflammatory drugs. , 2000, The Journal of bone and joint surgery. British volume.

[37]  D. Macdonald,et al.  Nonunion of the femoral diaphysis , 2000 .

[38]  M. Finnegan,et al.  Effect of smoking on tibial shaft fracture healing. , 1999, Clinical orthopaedics and related research.

[39]  P. Hernigou,et al.  Abnormalities in the Bone Marrow of the Iliac Crest in Patients Who Have Osteonecrosis Secondary to Corticosteroid Therapy or Alcohol Abuse* , 1997, The Journal of bone and joint surgery. American volume.

[40]  P. Hernigou,et al.  Articular Penetration Is More Likely In Garden-I Fractures Of The Hip , 1997 .

[41]  K Banovac,et al.  Effect of Nonsteroidal Antiinflammatory Drugs on Fracture Healing: A Laboratory Study in Rats , 1995, Journal of orthopaedic trauma.

[42]  G. Paiement,et al.  The importance of the blood supply in the healing of tibial fractures. , 1995, Contemporary orthopaedics.

[43]  D. Paley,et al.  Variables affecting time to bone healing during limb lengthening. , 1994, Clinical orthopaedics and related research.

[44]  I. Kunnamo,et al.  Are smokers a risk group for delayed healing of tibial shaft fractures? , 1993, Annales chirurgiae et gynaecologiae.

[45]  Jones Re,et al.  Primary versus delayed soft tissue coverage for severe open tibial fractures. A comparison of results. , 1983 .

[46]  R. Jones,et al.  Primary versus delayed soft tissue coverage for severe open tibial fractures. A comparison of results. , 1983, Clinical orthopaedics and related research.

[47]  J. States,et al.  Factors influencing the rate of healing in tibial shaft fractures. , 1967, Surgery, gynecology & obstetrics.

[48]  Hoaglund Ft,et al.  Factors influencing the rate of healing in tibial shaft fractures. , 1967 .