Complications associated with the use of bone morphogenetic protein in pediatric patients.
BACKGROUND
Recombinant human bone morphogenetic protein (rhBMP) has been found to be a powerful adjunct to healing nonunions and obtaining fusions. Despite the apparent clinical efficacy and good safety profile reported with rhBMP use in adults, there is little data regarding the safety of this product in pediatric patients. We evaluated the use of rhBMP-2 in pediatric patients to determine if any complications were associated with its use.


METHODS
We performed a retrospective review of 81 patients, all less then 18 years old, in whom rhBMP-2 was used. Theoretical complications associated with rhBMP-2 use were compiled based on a review of the published literature on rhBMP-2. A review of each patient's chart and radiographs was performed to record the occurrences of complications, which may have been associated with the use of rhBMP-2.


RESULTS
A total of 16 complications were found, which may have been attributed to the use of rhBMP-2. There were no incidences of systemic toxicity associated with rhBMP-2 use. Nine patients were noted to have some local operative site problem, 3 deep infections were noted, 1 patient was found to have a postoperative compartment syndrome, 2 patients were found to have neurologic complications (1 with progressive myelopathy and 1 with weakness and dural fibrosis), and 1 patient with neurofibromatosis and previously diagnosed intracranial gliomas was found to have subsequent enlargement of these gliomas. In reviewing these complications, only the case of dural fibrosis and subsequent weakness was thought to possibly be directly related to the use of rhBMP-2.


CONCLUSIONS
We found few complications in pediatric patients, which were felt to be directly attributable to the use of rhBMP-2. As such, rhBMP-2 use seems to be relatively safe in this young patient population. Due to the current use of this product in pediatric patients in an "off-label" fashion, we recommend a thorough discussion of the possible risks and benefits of this product with the family before its use.


METHODS
Therapeutic studies-Level IV.
Oetgen
Matthew E
ME
Children's National Medical Center, Washington, DC 20010, USA. moetgen@cnmc.org
Richards
B Stephens
BS
D000293:Adolescent; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004388:Dura Mater / Q000473:pathology; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D017102:Fracture Healing / Q000187:drug effects; D005599:Fractures, Ununited / Q000188:drug therapy; D006801:Humans; D007223:Infant; D008297:Male; D011994:Recombinant Proteins / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D013123:Spinal Fusion / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000009:adverse effects* / Q000627:therapeutic use
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2