title: Bone regeneration by statin and low-intensity pulsed ultrasound (LIPUS) in rabbit nasal bone.
abstract: OBJECTIVE
  To compare bone regeneration between local implantation of statin and low-intensity pulsed ultrasound (LIPUS), and the combination of statin with LIPUS in rabbit nasal bone using histological and immunohistochemical methods.
  
  
  METHODS
  Thirty-two adult male Japanese white rabbits (age: 12-16 weeks, weight: 2.5-3.0 kg) were used in this study. Two bone circular defects (5 mm in diameter) per rabbit were created in the nasal bone while preserving the nasal membrane. The two defects in each rabbit were filled with 2.5 mg/ml simvastatin in 0.2 ml water with an atelocollagen sponge (ACS) and ACS alone respectively. Sixteen rabbits (32 sides) received the LIPUS application; the remaining 16 rabbits (32 sides) did not. Therefore, the subjects composed of 4 groups, namely, (1) LIPUS + ACS + simvastatin (the LAS group), (2) LIPUS + ACS (the LA group), (3) ACS + simvastatin (the AS group) and (4) ACS alone (the A group). Four animals were killed in each period, at 1, 2, 4 and 8 weeks postoperative. The parts that had been operated on were removed and prepared for histological assessment. The expression of BMP-2 and the bone area ratio were evaluated using histological and immunohistochemical methods.
  
  
  RESULTS
  Bone square in the LAS group was significantly larger than that in the AS group after 1 (P < 0.0001) and 2 week (P = 0.0113). The bone square in the LA group was significantly larger than that in the A group after 1 (P < 0.0001) and 2 weeks (P = 0.0090). However, there was no significant difference between the LAS and LA groups. In the number of cells that stained positive for BMP-2, the LAS group was significantly larger than that in the AS group after 1 (P < 0.0001) and 2 weeks (P = 0.0113).
  
  
  CONCLUSIONS
  This study suggests that bone regeneration can be promoted by LIPUS alone and statin alone, respectively. However the combination use of LIPUS with statin does not differ from LIPUS alone or statin alone.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ishihara
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan. Electronic address: kueki@yamanashi.ac.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ueki
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Sotobori
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Marukawa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Division of Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Moroi
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000473:pathology / Q000601:surgery; D055396:Bone Morphogenetic Protein 2 / Q000032:analysis; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D003094:Collagen; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D004337:Drug Carriers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D009295:Nasal Bone / Q000187:drug effects* / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D019821:Simvastatin / Q000627:therapeutic use*; D013997:Time Factors; D014465:Ultrasonics
chemical_list: D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C059821:atelocollagen; D003094:Collagen; D019821:Simvastatin
keywords: Bone regeneration; Low-intensity pulsed ultrasound (LIPUS); Rabbit; Statin