Primary reconstruction of alveolar clefts using recombinant human bone morphogenic protein-2: clinical and radiographic outcomes.

There are a number of growth factors; growth/differentiation factor 5, fibroblast growth factor 2, transforming growth factor b, platelet-derived growth factor, and parathyroid hormone along with bone morphogenetic proteins (BMP-2, BMP-7) all influence local bone production to various degrees. I remember being on a panel with Marshall Urist in the 1970s when he was working on identifying and defining Ba protein[ found in bone that was osteoinductive. Many naysayers thought Bhe was crazy. [ He, of course, went on to identify and purify BMP. Today, we have 2 commercially available sources of recombinant human bone morphogenic protein-2 (rhBMP-2), one of which is from Medtronic Sofamor Danek, Memphis, TN, with whom the senior author has a financial relationship. Recombinant human bone morphogenic protein-2 is the most extensively studied of the bonestimulating growth factors. In 1990, I first used demineralized bone (DMB) (Pacific Bone Bank, Los Angeles, CA) for craniofacial reconstruction and found this osteoinductive processed and sterilized Bpoor man’s BMP[ to be very useful in craniofacial reconstruction in the cranial vault and maxillofacial skeleton. I have successfully used more than 1500 implants from 1990 to 2006. This osteoinductive implant proved invaluable for skull replacement in children where there was frequently inadequate material available. I did not use it for alveolar grafting. When BMP-2 became available, we began to evaluate it experimentally and then used it for the first time in total skull replacement in 2004 as off-label institutional review boardYapproved study using rhBMP-2 impregnated on an absorbable collagen sponge in combination with DMB and a resorbable lattice work composed of Lactosorb (Walter Lorenz Surgical, Inc, Jacksonville, FL). This combination was the most successful arm experimentally in our research before using it clinically. This was used in craniopagus Egyptian twins who were separated by our Dallas team in 2003 and had total skull reconstruction using this for the first time to reconstruct absent skulls in children in 2004. That experience prompted us to evaluate it in selected skull reconstructive cases. It was also used in older patients with alveolar cleft defects or secondary failed or late cases. It was found to be highly successful as found by the University of California, Los Angeles, team. We did find in some patients more postoperative swelling and inflammation with overlying soft tissue reaction to the rhBMP-2. In 1 case, there was a prolonged period of tissue reaction below the forehead skin, which acted like a low-grade infection, but it was not. Below the forehead skin, it was soft to palpation and it lasted for months but ultimately healed. Dr Carstens and his team have extensive experience using BMP-2 and have reported extensively in the literature successful use of it for cleft and cranial vault reconstruction. Their application of it as reported in this article is very controversial, and there is no proof that early primary grafting using BMP-2 will be any more successful than all the previous techniques that used early primary bone grafting that have been shown after growth to be detrimental to occlusion and facial aesthetics. I believe that BMP-2 is more powerful than gingivoperiosteoplasty, but it will lock in the segments in the infant, producing similar effects to gingivoperiosteoplasty. It would be very desirable and wonderful if Carstens’ hypothesis proves to be correct, and it is as simple as replacing the final anatomic design by placing the absent Lego piece, which magically solves the complex puzzle of cleft deformity. I am afraid it is not that simple. Further information is needed. What we have learned experimentally and clinically to date would not support the authors’ thesis.