Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies

J Bone Joint Surg Am. 2006 Jun;88(6):1258-65. doi: 10.2106/JBJS.E.00499.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorbable Implants
  • Adult
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / administration & dosage
  • Bone Morphogenetic Proteins / therapeutic use*
  • Drug Implants
  • Female
  • Follow-Up Studies
  • Fracture Fixation, Intramedullary*
  • Fracture Healing / physiology
  • Fractures, Open / physiopathology
  • Fractures, Open / therapy*
  • Humans
  • Male
  • Prospective Studies
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use*
  • Tibial Fractures / physiopathology
  • Tibial Fractures / therapy*
  • Time Factors
  • Transforming Growth Factor beta / administration & dosage
  • Transforming Growth Factor beta / therapeutic use*
  • Treatment Outcome
  • Weight-Bearing / physiology

Substances

  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Drug Implants
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2