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Intravenous bisphosphonate therapy influence in mandible rabbits grafted with Osteconductive biomaterials

Grant number: 14/23710-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2015
Effective date (End): February 28, 2019
Field of knowledge:Health Sciences - Dentistry
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Cassio Edvard Sverzut
Grantee:Felipe Perraro Sehn
Home Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

To make possible the reconstruction of atrophic jaws, throws up the hand of bone grafting material during the rehabilitation surgical procedures. An important aspect in the study of maxillary reconstruction is mandatory patient reports no use of medications such as bisphosphonates, drugs known to inhibit bone metabolism. These substances have the potential to adhere to bone structures, targeting the osteoclast cells, hampering their structural conformation, adhesion to bone and mechanisms for the maintenance of bone resorption by acting as potent inhibitors and inducers of apoptosis of the resorptive cells. A few years ago, its use has been linked to a new pathological condition, called osteonecrosis of the jaw, in which after surgical procedures at bone level as tooth extractions and periodontal surgery, there is lack of tissue repair for at least 8 weeks and local bone exposure. We will check if the use of biomaterials can transcend the limits of bone formation caused by suppression of bone turnover by bisphosphonates, when compared with control sites (blood and autologous bone) and determine if the access route (intra / extra oral) is decisive in the formation of bone necrotic process. Prior to the surgical stage, laboratory evaluations of blood collected for ELISA, centrifuged and frozen at -80 ° C for quantification of serum proteins formation and remodeling (osteocalcin, osteoprotegerin and phosphatase tartrate resistant acid - TRAP) and levels of proinflammatory cytokines interleukin be performed 1beta (IL-1²), tumor necrosis factor alpha (TNF-±) and interleukin 6 (IL-6), and for qPCR analysis of gene expression for alkaline phosphatase, osteocalcin, collagen type 1 alpha (COL1A1), TRAP, cathepsin K (CatK), the ligand receptor activator of nuclear factor case B (RANK-L), and CTX (C-terminal telopeptide) to evaluate serum levels and to compare in each stage of the study . Infusions of zoledronic acid (4 mg) are administered intravenously in 100 mL of 0.9% sodium chloride, endovenous infusion pump for a period not less than 15 minutes in groups under the action of the drug. In the control group, saline will be administered only. The animals of the test group are treated with intravenous infusion of zoledronic acid (0.1 mg / kg) twice a week for the rostral auricular vein four weeks before bone biopsy surgery until the end of the study. Animals also will receive doses of dexamethasone intramuscular (1 mg / kg per week). After euthanasia, the mandibular segments containing the grafts will be dissected, reduced block, stored in buffered formaldehyde solution for performing micro-computed tomography, embedded in paraffin and processed for histological preparation of slides for study. (AU)