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.

Congenital pseudarthrosis of the tibia: Biological and biomechanical considerations to achieve union and prevent refracture

“…Specifically, parents should be advised of the theoretical risk (no reported cases to date) of tumorigenesis because BMP stimulates the RAS pathway, which is also a tumour pathway. 69 Patients with NF or fibrous dysplasia already have a propensity for both benign and malignant tumours.…”

Functionalized Scaffold and Barrier Membrane with Anti‐BMP‐2 Monoclonal Antibodies for Alveolar Ridge Preservation in a Canine Model

“…One of the most investigated biologics is rhBMP-2, which was approved by the U.S. Food and Drug Administration (FDA) for clinical use to repair bone defects [ 66 – 68 ]. The growing clinical use of rhBMP-2 has been associated with numerous complications such as graft migration [ 69 ], formation of neutralizing antibodies against BMP-2 [ 69 ], and extreme edema that may obstruct the airway or affect critical structures [ 46 ]. Additional disadvantages of exogenous growth factors (e.g., rhBMP-2) include a short biological half-life and lower biologic activity compared to the autogenous analog [ 70 ] that necessitates the use of high doses of rhBMP-2 to achieve the therapeutic effect.…”

Is Reconstruction of Large Mandibular Defects Using Bioengineering Materials Effective?

“…More study is required regarding the safety of BMP in the pediatric patient population. 29 The known and theoretical complications associated with the use of BMP in pediatric patients include hematoma or seroma formation, excessive wound swelling, acute compartment syndrome, systemic toxicities (ie, organ failure), excessive bone growth, wound breakdown, erythema, enlargement or formation of tumors, deep infections, and neurologic compromise. 30 For our purpose, all the patients in the present study had been informed of the off-label use of rhBMP-2 and provided written informed consent before surgery.…”