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

Swiontkowski, Marc F.; Aro, Hannu T.; Donell, Simon; Esterhai, John L.; Goulet, James; Jones, Alan; Kregor, Philip J.; Nordsletten, Lars; Paiement, Guy; Patel, Amratlal

Affiliations

¹Department of Orthopaedic Surgery, University of Minnesota, 2450 Riverside Avenue South, Suite R200, Minneapolis, MN 55454

²University of Turku and University Central Hospital of Turku, FIN-20520 Turku, Finland

³Institute of Orthopaedics, Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, United Kingdom

⁴Department of Orthopaedic Surgery, University of Pennsylvania Hospital, 3400 Spruce Street, Philadelphia, PA 19104-4271

⁵Department of Orthopaedics, University of Michigan Hospital, 1500 East Medical Center Drive, TC2914, Ann Arbor, MI 48109-0328

⁶University of Texas Southwestern, 5323 Harry Hines Boulevard, Room G8.238B, Dallas, TX 75390-8883

⁷Vanderbilt University, 131 Medical Center South, 2100 Pierce Avenue, Nashville, TN 37212

⁸Orthopaedic Centre, Ullevål University Hospital, N-0407 Oslo, Norway

⁹Mission Orthopaedics, 27800 Medical Center Road, Suite 126, Mission Viejo, CA 92861

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.

Links

DOI: 10.2106/JBJS.E.00499

PubMed: 16757759

WoS: 000238035400013

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Cited By (9)

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2011	Kolambkar YM, Dupont KM, Boerckel JD, Huebsch N, Mooney DJ, Hutmacher DW, Guldberg RE. An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. Biomaterials. January 2011;32(1):65-74.
2011	Boerckel JD, Kolambkar YM, Dupont KM, Uhrig BA, Phelps EA, Stevens HY, García AJ, Guldberg RE. Effects of protein dose and delivery system on BMP-mediated bone regeneration. Biomaterials. November 2011;32(22):5241-5251.
2011	Kolambkar YM, Boerckel JD, Dupont KM, Bajin M, Huebsch N, Mooney DJ, Hutmacher DW, Guldberg RE. Spatiotemporal delivery of bone morphogenetic protein enhances functional repair of segmental bone defects. Bone. September 2011;49(4):485-492.
2023	Priddy LB, Krishnan L, Hettiaratchi MH, Karthikeyakannan S, Gupte N, Guldberg RE. Amniotic membrane attenuates heterotopic ossification following high-dose bone morphogenetic protein-2 treatment of segmental bone defects. J Orthop Res. January 2023;41(1):130-140.
2007	Oest ME. Dual Osteogenic and Angiogenic Growth Factor Delivery as a Treatment for Segmental Bone Defects [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2007.
2009	Kolambkar YM. Electrospun Nanofiber Meshes for the Functional Repair of Bone Defects [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; December 2009.
2010	Johnson MR. Delivery of BMP-2 for Bone Tissue Engineering Applications [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; May 2010.
2011	Boerckel JD. Mechanical Regulation of Bone Regeneration and Vascular Growth in Vivo [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2011.
2015	Priddy LB. Biomaterial Strategies for Improved Bone Healing With Bone Morphogenetic Protein-2 Delivery [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2015.