In January 2015, the US Food and Drug Administration (FDA) issued a drug safety communication warning related to the use of bone graft substitutes containing recombinant proteins or synthetic peptides in patients under 18 years of age. The safety communication cited reports of serious injuries such as excess bone growth, fluid accumulation, inhibited bone healing, swelling, and pressure on the adjacent vital organs following the use of bone graft substitutes containing proteins or synthetic peptides. These complications are common among all age groups; they are of more importance in patients under 18 years of age owing to their overall smaller size and the fact that their bones are still growing.
The FDA safety communication was issued with reference to specific specialties namely paediatrics, plastic surgery, dentistry, orthopaedics, and neurosurgery. The purpose of the warning was to inform healthcare providers that bone graft substitutes containing recombinant proteins or synthetic peptides should not be the first-line treatment choice in skeletally immature patients.
Any product that affects bone growth could have the potential to negatively impact skeletal development by altering normal bone formation and growth. The FDA considers bone graft substitutes containing recombinant proteins or synthetic peptides as high-risk (class III) medical devices and it has not evaluated their safety and efficacy in skeletally immature patients.
Most of the adverse events after maxillofacial procedures involving recombinant proteins have been related to off-label uses. The risk appears to be imminent with the increasing reports related to the use of recombinant proteins in combination with other substitutes in alveolar cleft repair in the paediatric population.
Our concern is regarding the use of bone morphogenetic proteins (BMPs) in various bone grafting techniques in children, such as alveolar bone grafting and the restoration of mandibular continuity defects. The usage of BMPs in paediatric alveolar clefts and other off-label uses have been supported by many authors previously, but the safety profile has to be taken into consideration. There is a need to arrive at a consensus regarding the use of recombinant protein-containing bone grafts for use in the paediatric population for maxillofacial surgery applications. However until then, these products should be used with great caution, with a detailed explanation of the possible adverse effects conveyed to the patient’s caregivers.