title: Sclerostin antibody treatment causes greater alveolar crest height and bone mass in an ovariectomized rat model of localized periodontitis.
abstract: BACKGROUND
  Periodontitis and osteoporosis are bone destructive diseases with a high prevalence in the adult population. The concomitant presence of osteoporosis may be a risk factor of progression of periodontal destruction. We studied the effect of sclerostin-neutralizing monoclonal antibody (Scl-Ab) on alveolar bone endpoints in an ovariectomized (OVX) rat model of induced experimental periodontitis.
  
  
  METHODS
  Sixty female, 4-month-old Sprague-Dawley rats underwent sham operation or bilateral OVX and were left untreated for 2 months. Experimental periodontitis (ligature) was established by placing silk sutures subgingival to the right maxillary first and second molar teeth for 4 weeks, and feeding the rats food and high-sugar drinking water during this period. Thereafter, ligatures were removed and 25mg/kg vehicle or Scl-Ab was administered subcutaneously twice weekly for 6 weeks. Rats were randomized into four groups: (1) Control (Sham+Vehicle), (2) Sham+Ligature+Vehicle, (3) OVX+Ligature+Vehicle, and (4) OVX + Ligature + Scl-Ab. Terminal blood and right maxilla specimens were collected for analyses.
  
  
  RESULTS
  Group 3 rats showed lower bone volume fraction (BVF) of alveolar bone with higher bone resorption and lower bone formation than Group 2 rats. Group 4 rats had higher alveolar crest height, as assessed by linear distance of cementoenamel junction to the alveolar bone crest and greater alveolar bone mass using Micro CT, than Group 3 rats. Significantly higher values of mineral apposition rate (MAR) and mineralizing surface/bone surface (MS/BS) were also observed in Group 4 rats by analyzing polychrome sequential labeling data. Increased serum osteocalcin and osteoprotegerin, and deceased serum tartrate-resistant acid phosphatase and CTx-1 illustrate the ability of Scl-Ab to increase alveolar bone mass by enhancing bone formation and decreasing bone resorption in an animal model of estrogen deficiency osteopenia plus periodontitis.
  
  
  CONCLUSIONS
  Scl-Ab could be a potential bone anabolic agent for improving alveolar crest height and higher alveolar bone mass in conditions where alveolar bone loss in periodontitis is compounded by estrogen deficiency osteopenia.
authors: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China.
authors: Hui
authors: H
authors: Chen
authors: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China.
authors: Xinchen
authors: X
authors: Xu
authors: Department of Metabolic Disorders, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA 91320, United States.
authors: Min
authors: M
authors: Liu
authors: Soochow University Orthopaedic Institute, 708 Renming Road, Soochow 215006, China.
authors: Wen
authors: W
authors: Zhang
authors: Department of Metabolic Disorders, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA 91320, United States.
authors: Hua-zhu
authors: HZ
authors: Ke
authors: Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China. Electronic address: dr.qinan@gmail.com.
authors: An
authors: A
authors: Qin
authors: Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China. Electronic address: tingtingtang@hotmail.com.
authors: Tingting
authors: T
authors: Tang
authors: Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai 200011, China. Electronic address: lueryi222@126.com.
authors: Eryi
authors: E
authors: Lu
mesh_terms: D000539:Alveolar Process / Q000000981:diagnostic imaging / Q000473:pathology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005819:Genetic Markers / Q000276:immunology*; D015675:Osteocalcin / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood; D010052:Ovariectomy; D010518:Periodontitis / Q000000981:diagnostic imaging / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography
chemical_list: D057134:Antibodies, Neutralizing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D053244:Osteoprotegerin; C486031:Sost protein, rat; D015675:Osteocalcin
keywords: Bone anabolic agent; Estrogen deficiency osteopenia; Periodontitis; Sclerostin antibody