title: Intermittent hypoxia induces disturbances in craniofacial growth and defects in craniofacial morphology.
abstract: OBJECTIVE
  To investigate intermittent hypoxia (IH) induced changes in craniofacial morphology and bone mineral density (BMD) in the mandible of growing rats.
  
  
  METHODS
  Seven-week-old male Sprague-Dawley rats were exposed to IH for 4 days or 3 weeks. Sham-operated rats simultaneously breathed room air. Lateral and transverse cephalometric radiographs of the craniofacial region were obtained, and the linear distances between cephalometric landmarks were statistically analyzed. BMD and bone microstructure of the mandible were evaluated using micro-computed tomography (micro-CT).
  
  
  RESULTS
  Cephalometric analyses demonstrated that exposure to IH only in the two groups for 3 weeks decreased the size of the mandibular and viscerocranial bones, but not that of the neurocranial bones, in early adolescent rats. These findings are consistent with upper airway narrowing and obstructive sleep apnea (OSA). Micro-CT showed that IH increased the BMD in the cancellous bone of the mandibular condyle and the inter-radicular alveolar bone in the mandibular first molar (M1) region.
  
  
  CONCLUSIONS
  This study is the first to identify growth retardation of the craniofacial bones in an animal model of sleep apnea. Notably, 3 weeks of IH can induce multiple changes in the bones around the upper airway in pubertal rats, which can enhance upper airway narrowing and the development of OSA. The reproducibility of these results supports the validity and usefulness of this model. These findings also emphasize the critical importance of morphometric evaluation of patients with OSA.
authors.affiliation: Orthodontic Science, Department of Orofacial Development and Function, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Oishi
authors.affiliation: Orthodontic Science, Department of Orofacial Development and Function, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Orthodontic Science, Department of Orofacial Development and Function, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. Electronic address: hosomichi.orts@tmd.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Hosomichi
authors.affiliation: Orthodontic Science, Department of Orofacial Development and Function, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kuma
authors.affiliation: Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nagai
authors.affiliation: Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Forensic Medicine, Graduate School of Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Orthodontic Science, Department of Orofacial Development and Function, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Usumi-Fujita
authors.affiliation: Orthodontic Science, Department of Orofacial Development and Function, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Sawa
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Orthodontic Science, Department of Orofacial Development and Function, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Chisa
authors.initials: C
authors.lastname: Shitano
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Suzuki
authors.affiliation: Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Forensic Medicine, Graduate School of Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Orthodontic Science, Department of Orofacial Development and Function, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ono
mesh_terms: D000818:Animals; D015519:Bone Density; D002508:Cephalometry; D019465:Craniofacial Abnormalities / Q000000981:diagnostic imaging / Q000209:etiology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D021621:Imaging, Three-Dimensional; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000503:physiopathology; D055114:X-Ray Microtomography
keywords: Bone mineral density; Craniofacial growth; Growth retardation; Intermittent hypoxia; Micro-CT analysis; Obstructive sleep apnea