Influence of monoclonal anti-sclerostin antibody on alveolar sockets healing of ovariectomized rats

• Grant number: 21/10829-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2022
• End date: June 30, 2023
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Joni Augusto Cirelli
• Grantee: Gabriel Henrique Perles
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Osteoporosis is an osteometabolic disease, characterized by a reduction in bone mass in long bones and vertebrae, which occurs due to a decrease in estrogen levels, especially in postmenopausal women. Recently, a new drug based on an anti-sclerostin antibody (Scl-Ab) was approved for postmenopausal osteoporosis treatment. Its mechanism of action corresponds to an increase in the activity and number of osteoblasts, favoring bone formation. Therefore, this research project aims to evaluate the effect of Scl-Ab on alveolar sockets healing of ovarectomized rats. A total of 15 rats will be randomly distributed into 3 experimental groups (n=5/group): CTR (control - systemically healthy animals), OST (osteoporosis induction by ovarectomy surgery) and OST+Scl-Ab (osteoporosis induction and Scl-Ab administration). All animals will be submitted to OVX (OST and OST+Scl-Ab groups) or Sham surgery (C group) 30 days before the baseline (day 0) and, at this timepoint, Scl-Ab or vehicle administration will begin in the indicated groups. On day 7 all animals of all groups will be subjected to lower first molar extraction. On day 21 all animals will be euthanized by anesthetic overdose. The body weight will be recorded weekly. All animals will be evaluated for bone volume and density by in vivo computed microtomography (micro-CT) after surgery, at baseline and day 21. After euthanasia, the mandibular jaws will be collected and separated into two hemimandible to Micro-CT analysis. After that, the hemimandible will be used for histologic, stereometric and immunohistochemistry analysis for the following antibodies: Tartrate-resistant acid phosphatase (TRAP), Osteocalcin (OCN), Sclerostin (SCL), Osteopontin (SPP1), Procollagen Type 1 N-Terminal Propeptide (P1NP) and Alkaline Phosphatase (ALP). All data will be obtained and submitted to a statistical test of normality. From that, appropriate statistical tests will be used to compare the groups. In all procedures, a 5% significant level will be used.(AU)