Local application of platelet-rich plasma (PRP) after dental extraction in rats that show the main risk factors for osteonecrosis of the jaws associated with the use of bisphosphonates: evaluation of a preventive therapy

Abstract

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 pathogenesis of the disease is poorly understood, which hinders its prevention and treatment. Among 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. Among the few therapeutic approaches is preventive antibiotic therapy, which shows failure and adverse effects. The local application of platelet rich plasma (PRP) has biological properties that improve the repair process both soft tissue as hard tissue, antimicrobial effect and anti-inflammatory action, placing it as a potential therapeutic strategy for preventive BRONJ. The purpose of this study is to evaluate the effect of local application of PRP at the side of tooth extraction of rats that presenting the main risk factors for the development of BRONJ. Forty rats (female; 20-month-old) will be divided into four experimental groups: SAL, ZOL, SAL/PRP and ZOL/PRP. The duration of the treatment plan will be of seven weeks. Rats will receive intraperitonial injections of 0.45 ml solution of 0.9% sodium chloride (SAL and SAL/PRP groups) or 0.45 ml of same solution added with 100 mg/kg of zoledronate (ZOL and ZOL/PRP groups) with an interval of two days between the applications. After three weeks of treatment, all rats will be submitted to blood collection, via cardiac puncture, and extraction of right mandibular first molar. Blood collected in groups SAL/PRP and ZOL/PRP will be allocated to the preparation of PRP, which will be applied within the site of tooth extraction. After 28 postoperative days, all rats will be euthanized. Subsequently, the hemi-mandibles will undergo histological processing and staining by hematoxylin-eosin. At the extraction site and mucosa overlying will be carried out histopathological analysis of alveolar healing process and histometric analysis of epithelium, connective and bone tissue newly formed. Results will be analyzed under light microscopy and will be submitted to quantication and statistical analysis at 5% significance level.