Department of Oral and Maxillofacial Surgery, College of Dentistry, Yonsei University, Seoul, Korea.
Department of Periodontology, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Korea.
J Dent Res. 2015 Sep;94(9 Suppl):158S-65S. doi: 10.1177/0022034515594573. Epub 2015 Jul 16.
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).
本随机、单盲、阳性药物对照的临床研究旨在评估小剂量大肠杆菌来源重组人骨形态发生蛋白 2(rhBMP-2)与羟基磷灰石颗粒(BMP-2/H)负载物较单纯无机牛骨移植物(ABX)在提升上颌窦底的早期疗效。共纳入 6 家中心的 127 例患者,将 rhBMP-2(每窦 0.5 至 2.0mg,浓度 1mg/ml)与 BMP-2/H(0.5 至 2.0g)或 ABX(0.5 至 2.0g)分别应用于上颌窦底提升术。术后 3 个月取窦内核心活检,行组织形态计量学分析。rhBMP-2/H 和 ABX 提升组的新骨形成率分别为 16.10%±10.52%和 8.25%±9.47%。rhBMP-2/H 组不劣于 ABX 组;2 组间差值的双侧 97.5%置信区间下限计算为 4.33%,大于预设的非劣效性界值-3.75%。双侧 5%显著性水平的 Wilcoxon 秩和检验进一步表明 2 组间的骨形成存在显著差异(P<0.0001)。2 组间的软组织和剩余移植物区域无显著差异。安全性方面,2 组间无显著差异;BMP-2/H 移植物后血清中 rhBMP-2 抗体量无显著增加。本研究提示小剂量大肠杆菌来源 rhBMP-2 与羟基磷灰石在上颌窦底提升早期成骨中有效,无有害不良事件(Clinicaltrials.gov NCT01634308)。