title: Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies.
abstract: BACKGROUND
  The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) to improve the healing of open tibial shaft fractures has been the focus of two prospective clinical studies. The objective of the current study was to perform a subgroup analysis of the combined data from these studies.
  
  
  METHODS
  Two prospective, randomized clinical studies were conducted. A total of 510 patients with open tibial fractures were randomized to receive the control treatment (intramedullary nail fixation and routine soft-tissue management) or the control treatment and an absorbable collagen sponge impregnated with one of two concentrations of rhBMP-2. The rhBMP-2 implant was placed over the fracture at the time of definitive wound closure. For the purpose of this analysis, only the control treatment and the Food and Drug Administration-approved concentration of rhBMP-2 (1.50 mg/mL) were compared. Patients who anticipated receiving planned bone-grafting as part of a staged treatment were excluded from enrollment.
  
  
  RESULTS
  Fifty-nine trauma centers in twelve countries participated, and patients were followed for twelve months postoperatively. Two subgroups were analyzed: (1) the 131 patients with a Gustilo-Anderson type-IIIA or IIIB open tibial fracture and (2) the 113 patients treated with reamed intramedullary nailing. The first subgroup demonstrated significant improvements in the rhBMP-2 group, with fewer bone-grafting procedures (p = 0.0005), fewer patients requiring invasive secondary interventions (p = 0.0065), and a lower rate of infection (p = 0.0234), compared with the control group. The second subgroup analysis of fractures treated with reamed intramedullary nailing demonstrated no significant difference between the control and the rhBMP-2 groups.
  
  
  CONCLUSIONS
  The addition of rhBMP-2 to the treatment of type-III open tibial fractures can significantly reduce the frequency of bone-grafting procedures and other secondary interventions. This analysis establishes the clinical efficacy of rhBMP-2 combined with an absorbable collagen sponge implant for the treatment of these severe fractures.
authors.affiliation: Department of Orthopaedic Surgery, University of Minnesota, 2450 Riverside Avenue South, Suite R200, Minneapolis, MN 55454, USA. swion001@umn.edu
authors.forename: Marc F
authors.initials: MF
authors.lastname: Swiontkowski
authors.forename: Hannu T
authors.initials: HT
authors.lastname: Aro
authors.forename: Simon
authors.initials: S
authors.lastname: Donell
authors.forename: John L
authors.initials: JL
authors.lastname: Esterhai
authors.forename: James
authors.initials: J
authors.lastname: Goulet
authors.forename: Alan
authors.initials: A
authors.lastname: Jones
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kregor
authors.forename: Lars
authors.initials: L
authors.lastname: Nordsletten
authors.forename: Guy
authors.initials: G
authors.lastname: Paiement
authors.forename: Amratlal
authors.initials: A
authors.lastname: Patel
mesh_terms: D020341:Absorbable Implants; D000328:Adult; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D004343:Drug Implants; D005260:Female; D005500:Follow-Up Studies; D005594:Fracture Fixation, Intramedullary; D017102:Fracture Healing / Q000502:physiology; D005597:Fractures, Open / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D013978:Tibial Fractures / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D004343:Drug Implants; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2