The effect of zoledronate during the alveolar healing process: study of the major risk factors for osteonecrosis of the jaw and evaluation with low-level laser therapy and antimicrobial photodynamic therapy proposed as a preventative

Author(s)

Cristian Statkievicz

• Document type: Master's Dissertation
• Press: Araçatuba. 2016-10-20.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araçatuba
• Defense date: 2016-08-30
• Advisor: Edilson Ervolino; Roberta Okamoto

Abstract

OBJECTIVES: The aim of this study was to evaluate the effects of Low Level Laser Therapy (LLLT) and antimicrobial photodynamic therapy (aPDT) in the alveolar bone repair in rats with the high risk factors for Medication-Related Osteonecrosis of the Jaw (MRONJ). MATERIALS AND METHODS: Senile rats (n = 29) were distributed into four groups: SAL, ZOL, ZOL/LLLT and ZOL/aPDT. For seven weeks, every two days, 0,45ml 0.9% NaCl (SAL) or 0,45ml of this same solution plus 100μg/kg zoledronate (ZOL, ZOL/LLLT and ZOL/aPDT) were administered intraperitoneally. After three weeks, the first lower left molar was extracted. In ZOL/LLLT and ZOL/aPDT groups, the rats were submitted to LLLT or aPDT therapy at 0, 2 and 4 days after tooth extraction. Euthanasia was performed 28 days after tooth extraction. In dental extraction site was performed the histopathology analysis of the tissue repair, histometric analysis of newly formed bone area (NFB) and immunohistochemistry related to the following biomarkers: PCNA, BAX, C3C, TNFα, IL-1β, IL-6, HIF-1α, VEGF, CD31, BMP2/4, RUNX-2, OCN, OPG, RANKL and TRAP. RESULTS: The groups treated with zoledronate showed higher immunolabeling for OPG and lower immunolabeling for RANKL and TRAP. In ZOL group was observed areas of osteonecrosis, impairment of wound healing, lower ATO, lower immunolabeling for PCNA, HIF-1α, VEGF, CD31, BMP2/4 and OCN, and higher immunolabeling for BAX, C3C, TNFα, IL-1β, IL-6 and RUNX-2 when compared to the SAL group. ZOL/LLLT showed improvement in some parameters regarding to ZOL (ATO, PCNA, TNFα, HIF-1α, VEGF, CD31 and RUNX-2), however, few parameters were similar to the SAL (PCNA, HIF-1α, VEGF, CD31 and RUNX-2). ZOL/aPDT did not present areas of osteonecrosis and the tissue repair did not differ significantly from the SAL groups, as well as the following parameters: PCNA, BAX, C3C, IL-1β, HIF-1α, VEGF, CD31, RUNX-2 and OCN. CONCLUSIONS: The zoledronate compromises the tissue repair of dental extraction site in rats with the high risk factors for MRONJ. LLLT and aPDT were able to improved the events related to wound's healing. The aPDT showed to be the most effective preventive therapy to MRONJ. CLINICAL RELEVANCE: The aPDT can be in a preventive therapy to prevent the triggering of MRONJ after dental extraction. (AU)

• FAPESP's process: 14/02199-1 - Evaluation of the effect of Antimicrobial Photodynamic Therapy (aPDT) during the alveolar healing process in rats that presents the major risk factors for developing osteonecrosis of the jaws associated with the use of bisphosphonates
• Grantee: Cristian Statkievicz
• Support Opportunities: Scholarships in Brazil - Master