Efficacy of rhBMP-2/Hydroxyapatite on Sinus Floor Augmentation

Abstract

The aim of this randomized single-blinded active-controlled clinical study was to evaluate the early efficacy of low-dose Escherichia coli-derived recombinant human bone morphogenetic protein 2 (rhBMP-2) soaked with hydroxyapatite granules (BMP-2/H) as compared with an inorganic bovine bone xenograft (ABX) in maxillary sinus floor augmentation. In a total of 127 subjects who were enrolled at 6 centers, maxillary sinus floors were augmented with 1 mg/mL of rhBMP-2 (0.5 to 2.0 mg per sinus) and BMP-2/H (0.5 to 2.0 g; n = 65) or with ABX alone (0.5 to 2.0 g; n = 62). Core biopsies were obtained 3 mo after the augmentation surgery and were analyzed histomorphometrically. The mean new bone formation with BMP-2/H and ABX augmentation was 16.10% ± 10.52% and 8.25% ± 9.47%, respectively. The BMP-2/H group was noninferior to the ABX group; the lower limit of the 1-sided 97.5% confidence interval for the difference between the 2 groups was calculated as 4.33%, which was greater than the prespecified noninferiority margin of -3.75%. An additional test with the Wilcoxon rank-sum test with a 2-sided 5% significance level showed that bone formation between the 2 groups was significantly different (P < 0.0001). The soft tissue and residual graft areas showed no significant differences between the groups. With regard to safety, no significant difference between the 2 groups was observed; there was no significant increase in the amount of rhBMP-2 antibody in the serum after BMP-2/H grafting. Our study suggested that low-dose Escherichia coli-derived rhBMP-2 with hydroxyapatite was effective in early stages for enhanced bone formation after maxillary sinus floor augmentation without harmful adverse events (Clinicaltrials.gov NCT01634308).

Bioactive treatments in bone grafts for implant‐based rehabilitation: Systematic review and meta‐analysis

“…The studies reported more extensive and longer-lasting edema after using rhBMP-2, 7,18,25,35 prolonged facial swelling, 24,35 and erythema. 24 However, some studies with autogenous bone graft reported that this type of bone graft showed long-term paresthesia 27 ; pain from the donor site 27,35 ; temporary discomfort, 35 or gait disturbance related to the bone graft harvest. 27 One important drawback of using heterologous sources of bioactive proteins is the costs associated with biomaterials.…”

“…Of the 17 included clinical trials, 13 were randomized clinical trials; 3 were controlled clinical trials, and one was a retrospective trial. Five studies reported adverse events with bioactive treatment, such as more extensive and longer-lasting edema after using rhBMP-2, 7,18,25,35 prolonged facial swelling, 24,35 and erythema. 35 Among the adverse events reported for control groups with bone grafts, one study 7 reported that there was a higher proportion of subjects in the autogenous bone group with edema and pain than in the rhBMP-2 group.…”

“…The controls mainly used were: autogenous bone grafts in four studies, 7,26-28 and inorganic bovine bone xenografts in another four clinical trials. 19,[22][23][24] The other two clinical trials 9,20 with sinus floor augmentation used a mineralized cancellous bone allograft. For alveolar ridge augmentation (Supporting Information Table S3), the doses of rhBMP-2 used were: 0.5, 4,21 0.75, 10,35 and 1.50 mg/ ml.…”

A randomized controlled clinical trial evaluating efficacy and adverse events of different types of recombinant human bone morphogenetic protein‐2 delivery systems for alveolar ridge preservation

“…Notably, the potential for healing of the tooth extraction socket did not affect the outcome. Another randomized clinical trial comparing rhBMP-2-treated hydroxyapatite with inorganic bovine bone xenograft in maxillary sinus floor augmentation revealed that histomorphometric analysis showed non-inferiority of rhBMP-2-treated hydroxyapatite to the control (Kim et al, 2015).…”

Bone Regeneration Using N-Methyl-2-pyrrolidone as an Enhancer for Recombinant Human Bone Morphogenetic Protein-2 in a Rabbit Sinus Augmentation Model

“…When rhBMP-2 is used for bone augmentation, the quantity of rhBMP-2 applied increases in proportion to the carrier material used to fill the defect area [14]. Considering that sinus augmentation requires a large amount of bone substitute material, overdosing of rhBMP-2 and high treatment costs are likely.…”