Evaluation of antimicrobial photodynamic therapy employing curcumin and light emitting diode in the prevention of medication-related osteonecrosis of the jaw

Abstract

Bisphosphonates (BPs) are antiresorptive drugs used in the treatment of lytic bone diseases. Among its adverse effects is the medication-related osteonecrosis of the jaw (MRONJ). Studies show that among the risk factors for MRONJ are: advanced age, female gender, use of oncologic doses of potent BPs and invasive dental procedures. The etiopathogenesis of MRONJ is poorly understood, making prevention and treatment extremely difficult. Among the preventive proposals for MRONJ is prolonged antibiotic therapy, which may be failing. The search for effective preventive therapies is something that is necessary, especially in the function of the increasingly frequent use of this type of drug. Studies show that curcumin (CUR) has anti-inflammatory action, antimicrobial effect and high capacity to stimulate tissue repair, in addition, it can be used as a photosensitizer. Antimicrobial photodynamic therapy (aPDT) consists of the local deposition of a photosensitizer, in the case of the present study the CUR, followed by its irradiation with a light of adequate wavelength, in the case of the present study a light-emitting diode (LED). This therapy has been widely used in the treatment of inflammatory/infectious diseases due to its potent antimicrobial, biostimulatory action and absence of an adverse effects. The objective of the present study is to evaluate the effect of aPDT, using CUR and LED, on the dental extraction site of rats that present high risk for MRONJ. Eighty senile rats will be distributed in eight experimental groups: VEI; VEI-LED; VEI-CUR; VEI-aPDT; ZOL; ZOL-LED; ZOL-CUR; ZOL-aPDT. The drug treatment plan will last 7 weeks. The rats of the VEI groups; VEI-LED; VEI-CUR; VEI-aPDT will receive 0.45 ml of carrier (0.9% sodium chloride). The rats of the ZOL groups; ZOL-LED; ZOL-CUR; ZOL-aPDT will receive the vehicle plus 100 ¼g/kg zoledronate. The vehicle and zoledronate will be administered by the intraperitoneal route every three days. After 3 weeks of treatment, all rats will be submitted to the extraction of the lower left first molar. In the VEI-LED and ZOL-LED groups, four sessions of LED irradiation will be performed. In the VEI-CUR and ZOL-CUR groups, four sessions of CUR deposition will be performed. In the VEI-aPDT and ZOL-aPDT groups, four sessions of aPDT will be performed using CUR and LED. Local treatments will be performed at 0, 2, 4 and 6 postoperative days. Euthanasia will be performed after 28 postoperative days. The hemimandibula will be properly processed so that it can be done at the dental extraction site: 1) clinical analysis; 2) histological analysis of tissue repair; 3) histometric analysis of Percentage of Neoformed Bone Tissue (nfBTP) and, histometric analysis of Percentage of Non-Vital Bone Tissue (nvBTP). The data will be submitted to qualitative, quantitative and statistical analysis with a significance level of 5%.