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Effect of zoledronic acid during healing process of soft tissue overlying the site of tooth extraction: a study involving the main risk factors for developing osteonecrosis of the jaws

Grant number: 13/25367-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2014
Effective date (End): November 30, 2015
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Edilson Ervolino
Grantee:Thamires Priscila Cavazana
Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil


Bisphosphonates (BPs) are a class of drugs used in the treatment of some bone diseases or osteotropic malignancies. BPs exert potent inhibitory effect on bone resorption. Among the adverse effects is the occurrence of bisphosphonate-related osteonecrosis of the jaws (BRONJ). The risk factors for the onset of BRONJ are: chronic use of nitrogen-containing- BPs, especially zoledronate, intravenous route of administration, female gender, older age and oral surgeries, especially exodontia. The pathogenesis of the disease is poorly understood, which hinders its prevention and treatment. Some in vitro studies point to an action of BPs in the soft tissues, especially those overlying the site of tooth extraction. The action of BPs on these cells needs further investigation because it could help to elucidate the pathogenesis of ONJ. The purpose of this study is to evaluate in vivo the effect of chronic therapy with zoledronate during healing process of soft tissue overlying the site of tooth extraction in rats that show the main risk factors for the development of ONJ. Forty-two rats (females; 20-month-old) will be divided into two experimental groups, SAL and ZOL, which will be submitted to a by intraperitoneal injection. The interval between applications of zoledronate or vehicle will be two days. After three weeks of treatment, all rats will be submitted to the exodontitreatment plan for seven weeks. SAL group will receive 0.45 ml of 0.9% sodium chloride by intraperitoneal injection. ZOL group will receive 0.45 ml of 0.9% sodium chloride added 100 mg/kg zoledronate a of right mandibular first molar. Then each of these groups will be divided into three subgroups, each consisting of 7 animals : SAL-7d and ZOL-7d, SAL-14d and ZOL-14d, SAL-28d and ZOL-28d, whose animals will be euthanized 7, 14 and 28 postoperative days, respectively. Subsequently, the hemi-mandibles will undergo histological processing and staining by hematoxylin-eosin or picro-sirius red. At the mucosa overlying the site of tooth extraction will be carried out: histopathological analysis, histometric analysis of the area occupied by epithelial tissue and connective tissue and histochemical analysis of collagen maturation level. Results will be analyzed under light microscopy and will be submitted to quantication and statistical analysis at 5% significance level. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ERVOLINO, EDILSON; STATKIEVICZ, CRISTIAN; TORO, LUAN FELIPE; DE MELLO-NETO, JOAO MARTINS; CAVAZANA, THAMIRES PRISCILA; MARDEGAN ISSA, JOAO PAULO; MENEGATI DORNELLES, RITA CASSIA; DE ALMEIDA, JULIANO MILANEZI; HITOMI NAGATA, MARIA JOSE; OKAMOTO, ROBERTA; et al. Antimicrobial photodynamic therapy improves the alveolar repair process and prevents the occurrence of osteonecrosis of the jaws after tooth extraction in senile rats treated with zoledronate. BONE, v. 120, p. 101-113, . (13/25367-4, 12/03067-6, 13/26779-4, 14/02199-1, 15/22395-2)

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