Sclerostin antibody treatment causes greater alveolar crest height and bone mass in an ovariectomized rat model of localized periodontitis |
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| Institution: | 1. 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;2. Department of Metabolic Disorders, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA 91320, United States;3. Soochow University Orthopaedic Institute, 708 Renming Road, Soochow 215006, China;4. 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;1. The Key Laboratory of Aerospace Medicine, Ministry of Education, The Fourth Military Medical University, 710032 Xi''an, Shaanxi, China;2. Center of Cardiology, Navy General Hospital, 100048 Beijing, China;1. Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, 1795 Zonal Ave, Los Angeles, CA 90033, USA;2. Department of Medicine, Keck School of Medicine, University of Southern California, 1795 Zonal Ave, Los Angeles, CA 90033, USA;3. Department of Orthopaedic Surgery, Keck School of Medicine, University of Southern California, 1795 Zonal Ave, Los Angeles, CA 90033, USA;4. Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, 1795 Zonal Ave, Los Angeles, CA 90033, USA;5. Metabolic Disorders Research, Amgen Inc., 1 Amgen Center Dr, Thousand Oaks, CA 91320, USA;6. UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, David Geffen School of Medicine, UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095, USA;7. Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, P.O. Box 39040, Tel Aviv 69978, Israel;1. Seattle Children''s Research Institute, Center for Developmental Biology and Regenerative Medicine, Seattle, WA, USA;2. University of Washington, Center for Ecogenetics and Environmental Health, Seattle, WA, USA;3. Washington University, Department of Neurosurgery and St. Louis Children''s Hospital, St. Louis, MO, USA;4. School of Pharmacy, Pacific University, Hillsboro, OR, USA;5. Trialomics, Seattle, WA, USA;6. Seattle Children''s Craniofacial Center, Seattle, WA, USA;1. Gerontology Section, Department of Medical Science, University of Torino, Italy;2. Unit of Cancer Epidemiology, Department of Medical Science, University of Torino, Italy |
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| Abstract: | IntroductionPeriodontitis 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.MethodsSixty 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 25 mg/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.ResultsGroup 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.ConclusionScl-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. |
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