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Evaluation of complications associated with off-label use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in pediatric orthopaedics

  • Clinical Applications of Biomaterials
  • Original Research
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Abstract

The off-label use of recombinant human bone morphogenetic protein-2 to promote bone healing in adults has significantly increased in recent years, while reports of recombinant human bone morphogenetic protein-2 application in children and adolescents are very rare. The aim of this study was to evaluate the safety of single and repetitive recombinant human bone morphogenetic protein-2 use in pediatric orthoapedics. Therefore we reviewed the medical records of 39 patients who had been treated with recombinant human bone morphogenetic protein-2 at our institution. Their mean age was 10.9 years. Recombinant human bone morphogenetic protein-2 was used in 17 patients for spine fusion, in 11 patients for the treatment of congenital pseudarthrosis of the tibia or tibial nonunion, in 5 patients for the management of femoral nonunion, in 5 patients for nonunions at other locations, and in 1 case for tibial shortening. Special attention was paid to identify all adverse events that may be attributed to recombinant human bone morphogenetic protein-2 use, including local inflammatory reactions, allergic reactions, systemic toxicity, excessive wound swelling, hematoma, compartment syndrome, infection, heterotopic ossification, excessive bone growth, carcinogenicity, and the consequences of repeated applications of recombinant human bone morphogenetic protein-2. Follow-up was a mean of 39 months. Forty-six operations with application of rhBMP-2 were performed. Complications that may be due to application of recombinant human bone morphogenetic protein-2 were seen after 18 operations including swelling, increase in temperature, wound secretion, redness and hyperthermia. We consider the three cases of necessary revisions, one due to hematoma, one due to development of a compartment syndrome, and one due to deep infection, to be the only complications related to the use of recombinant human bone morphogenetic protein-2. In conclusion, we found few complications attributable to application of recombinant human bone morphogenetic protein-2 in pediatric patients.

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Acknowledgments

The authors received no financial support for this study.

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    Authors and Affiliations

    1. Department of Trauma-, Hand-, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

      Norbert Stiel, Tim N. Hissnauer, Carsten W. Schlickewei, Johannes M. Rueger & Alexander S. Spiro

    2. Department of Pediatric Orthopaedic Surgery, Children’s Hospital, Hamburg-Altona, Germany

      Martin Rupprecht, Kornelia Babin, Ralf Stuecker & Alexander S. Spiro

    3. Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

      Martin Rupprecht, Kornelia Babin & Ralf Stuecker

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    1. Norbert Stiel
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    2. Tim N. Hissnauer
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    5. Carsten W. Schlickewei
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    Correspondence to Alexander S. Spiro.

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    The authors declare that they have no competing interests.

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    Norbert Stiel and Tim N. Hissnauer contributed equally to this work and therefore share first authorship.

    Study conducted at the Pediatric Orthopaedic Department of Children’s Hospital Hamburg- Altona.

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    Stiel, N., Hissnauer, T.N., Rupprecht, M. et al. Evaluation of complications associated with off-label use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in pediatric orthopaedics. J Mater Sci: Mater Med 27, 184 (2016). https://doi.org/10.1007/s10856-016-5800-8

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