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).

Low-magnitude high-frequency (LMHF) vibrations have the ability to stimulate bone formation and reduce bone loss. However, the anabolic mechanisms that are mediated by vibration in human bone cells at the cellular level remain unclear. We hypothesized that human mesenchymal stromal cells (hMSCs) display direct osteoblastic responses to LMHF vibration signals. Daily exposure to vibrations increased the proliferation of hMSCs, with the highest efficiency occurring at a peak acceleration of 0.3 g and vibrations at 30 to 40 Hz. Specifically, these conditions promoted osteoblast differentiation through an increase in alkaline phosphatase activity and in vitro matrix mineralization. The effect of vibration on the expression of osteogenesis-related factors differed depending on culture method. hMSCs that underwent vibration in a monolayer culture did not exhibit any changes in the expressions of these genes, while cells in three-dimensional culture showed increased expression of type I collagen, osteoprotegerin, or VEGF, and VEGF induction appeared in 2 different hMSC lines. These results are among the first to demonstrate a dose-response effect upon LMHF stimulation, thereby demonstrating that hMSCs are mechanosensitive to LMHF vibration signals such that they could facilitate the osteogenic process.