Evaluation of recombinant human bone morphogenetic protein-2 in oral applications including the use of endosseous implants: 3-year results of a pilot study in humans.

BACKGROUND: This study evaluated patients who had been treated with recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded in an absorbable collagen sponge (ACS) in human extraction sites or in sites that required alveolar ridge augmentation. An earlier report on the same patients revealed that after 4 months, implantation of rhBMP-2/ACS was safe, as determined by clinical, radiographic, systemic, and immunological analyses. In this longer-term follow-up, eligible patients were restored with endosseous dental implants in the area treated with rhBMP-2/ACS and bone biopsy samples were taken for histological analysis of the treated human bone tissue. The primary objective was to monitor the long-term safety of patients treated with rhBMP-2/ACS. Another objective was to evaluate the dental implants placed in the sites treated with rhBMP-2.

METHODS: Patient safety was evaluated by clinical examinations, periapical radiographs, and occurrence of adverse experiences. Dental implants were evaluated by radiographic and clinical examination. All 12 patients have been followed for 3 years.

RESULTS: Two years following surgical implantation of rhBMP-2/ACS, no serious or unexpected adverse experiences occurred. The adverse experiences that did occur were mostly benign and compatible with the dental implant surgeries performed in these patients. No adverse experiences were deemed as related to the rhBMP-2/ACS. Furthermore, no safety concerns in the local area of rhBMP-2/ACS placement were noted, based on oral wound examinations. In the 10 patients (6 extraction socket patients and 4 augmentation patients) who received endosseous implants, all implants were clinically stable at all assessments and all 10 patients have been functionally restored. Histological evaluation of the human bone core biopsies revealed normal bone tissue formation identical to the surrounding native bone. Three-year follow-up clinical examinations revealed that all implants had stable marginal bone levels and healthy peri-implant tissues.

CONCLUSIONS: These 3-year results demonstrate that rhBMP-2/ACS can be used safely in human patients. Human bone biopsies reveal normal bone formation in areas treated with rhBMP-2/ACS. Endosseous implants placed in these areas were all stable with no radiographic or clinical complications. The results from this study suggest that rhBMP-2/ACS (0.43 mg/ml) can be safely used in tooth extraction sites and in local ridge augmentation procedures and that endosseous dental implants placed in bony areas treated with rhBMP-2/ACS are stable and can be functionally restored without complication.