title: Evaluation of complications associated with off-label use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in pediatric orthopaedics.
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.
authors: Department of Trauma-, Hand-, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Norbert
authors: N
authors: Stiel
authors: Department of Trauma-, Hand-, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Tim N
authors: TN
authors: Hissnauer
authors: Department of Pediatric Orthopaedic Surgery, Children's Hospital, Hamburg-Altona, Germany.|Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Martin
authors: M
authors: Rupprecht
authors: Department of Pediatric Orthopaedic Surgery, Children's Hospital, Hamburg-Altona, Germany.|Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Kornelia
authors: K
authors: Babin
authors: Department of Trauma-, Hand-, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Carsten W
authors: CW
authors: Schlickewei
authors: Department of Trauma-, Hand-, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Johannes M
authors: JM
authors: Rueger
authors: Department of Pediatric Orthopaedic Surgery, Children's Hospital, Hamburg-Altona, Germany.|Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Ralf
authors: R
authors: Stuecker
authors: Department of Trauma-, Hand-, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. aspiro@uke.uni-hamburg.de.|Department of Pediatric Orthopaedic Surgery, Children's Hospital, Hamburg-Altona, Germany. aspiro@uke.uni-hamburg.de.
authors: Alexander S
authors: AS
authors: Spiro
mesh_terms: D000293:Adolescent; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D003094:Collagen / Q000737:chemistry; D005260:Female; D006801:Humans; D007431:Intraoperative Complications; D008159:Lumbar Vertebrae / Q000601:surgery; D008297:Male; D009369:Neoplasms / Q000378:metabolism; D056687:Off-Label Use; D009985:Orthopedics / Q000379:methods*; D010372:Pediatrics / Q000379:methods; D011994:Recombinant Proteins / Q000627:therapeutic use; D012086:Reoperation; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen
keywords: Bone morphogenetic protein; Cancer; Complications; Pediatrics; Safety; rhBMP-2