title: Efficacy of rhBMP-2/Hydroxyapatite on Sinus Floor Augmentation: A Multicenter, Randomized Controlled Clinical Trial.
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).
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Yonsei University, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Periodontology, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Chung
authors.affiliation: Department of Periodontology, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Department of Periodontology, Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: S I
authors.initials: SI
authors.lastname: Shin
authors.affiliation: Department of Periodontology, Samsung Seoul Hospital, School of Medicine, Sungkyunkwan University, Seoul, Korea.
authors.forename: S B
authors.initials: SB
authors.lastname: Kye
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Yonsei University, Seoul, Korea.
authors.forename: N K
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: T G
authors.initials: TG
authors.lastname: Kwon
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Paeng
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyungpook National University, Daegu, Korea.
authors.forename: J W
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju, Korea.
authors.forename: O H
authors.initials: OH
authors.lastname: Oh
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju, Korea.
authors.forename: M S
authors.initials: MS
authors.lastname: Kook
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Dental Research Institute, BK 21 2nd Program, Seoul National University, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Dental Research Institute, BK 21 2nd Program, Seoul National University, Seoul, Korea sjhwang@snu.ac.kr.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001706:Biopsy / Q000379:methods; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use*; D018786:Bone Substitutes / Q000627:therapeutic use*; D016025:Bone Transplantation / Q000379:methods; D002417:Cattle; D005260:Female; D064593:Heterografts / Q000473:pathology / Q000637:transplantation; D006801:Humans; D006882:Hydroxyapatites / Q000627:therapeutic use*; D008297:Male; D008443:Maxillary Sinus / Q000473:pathology; D008875:Middle Aged; D010012:Osteogenesis / Q000502:physiology; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012449:Safety; D016037:Single-Blind Method; D059546:Sinus Floor Augmentation / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D006882:Hydroxyapatites; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2
keywords: Escherichia coli; biopsy; bone morphogenetic protein 2; clinical efficacy; comparative study; osteogenesis