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Recombinant Human Bone Morphogenetic Protein-2 in Open Tibial FracturesA Subgroup Analysis of Data Combined from Two Prospective Randomized Studies
Marc F. Swiontkowski, MD1; Hannu T. Aro, MD, PhD2; Simon Donell, MD3; John L. Esterhai, MD4; James Goulet, MD5; Alan Jones, MD6; Philip J. Kregor, MD7; Lars Nordsletten, MD, PhD8; Guy Paiement, MD9; Amratlal Patel, MD3
1 Department of Orthopaedic Surgery, University of Minnesota, 2450 Riverside Avenue South, Suite R200, Minneapolis, MN 55454. E-mail address: swion001@umn.edu
2 University of Turku and University Central Hospital of Turku, FIN-20520 Turku, Finland
3 Institute of Orthopaedics, Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, United Kingdom
4 Department of Orthopaedic Surgery, University of Pennsylvania Hospital, 3400 Spruce Street, Philadelphia, PA 19104-4271
5 Department of Orthopaedics, University of Michigan Hospital, 1500 East Medical Center Drive, TC2914, Ann Arbor, MI 48109-0328
6 University of Texas Southwestern, 5323 Harry Hines Boulevard, Room G8.238B, Dallas, TX 75390-8883
7 Vanderbilt University, 131 Medical Center South, 2100 Pierce Avenue, Nashville, TN 37212
8 Orthopaedic Centre, Ullevål University Hospital, N-0407 Oslo, Norway
9 Mission Orthopaedics, 27800 Medical Center Road, Suite 126, Mission Viejo, CA 92861
The Journal of Bone & Joint Surgery.  2006; 88:1258-1265  doi:10.2106/JBJS.E.00499
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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.

Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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