Bisphosphonates (BPs) are drugs used in the treatment of bone disease and osteotropics malignant neoplasms. BPs exert inhibitory effect on bone resorption. One of their adverse effects is the bisphosphonate related osteonecrosis of the jaws (BRONJ). The aetiology of the disease is still poorly understood, which makes its prevention and treatment difficult. There are few preventive therapies nowadays. Antimicrobial Photodynamic Therapy (aPDT) presents biological properties that turn it into a promising preventive proposed to avoid the onset and development BRONJ. These study evaluated the action of the aPDT on the osteogenic potential during alveolar repair in rats treated with oncologic dose of zoledronate. Twenty rats were divided in groups: SAL, ZOL, SAL/aPDT and ZOL/aPDT. 0.45mL of solution of 0.9% NaCl (SAL and SAL/aPDT) or 0.45mL of this solution plus 100 μg/kg of zoledronate (ZOL and ZOL/aPDT) was administered during 7 weeks, every 2 days, by intraperitoneal injection. After three weeks of treatment, extraction of the lower first molar was performed. At 0, 2 and 4 days post extraction, the aPDT sessions were performed (methylene blue - 100 μg/ml; InGaAIP; 660 nm; 35mW; 74,2J/cm2; 60s). Twenty 8 days after the surgeries the animals were euthanised. Histological sections of the mandibles were stained with hematoxylin and eosin or prepared for immunohistochemistry for transcription fator Runt-related-2 (RUNX2) and osteocalcin (OCN). The immunostained cells were quantified in the site of tooth extraction. In ZOL group, a small area of newly formed bone was observed in the site of tooth extraction and lot of bone necrosis areas surrounding the dental socket. It presented the highest number of RUNX2-positive cells and the lowest of OCN-positive cells. In SAL, SAL/aPDT and ZOL/aPDT groups, the newly formed bone filled almost all the sites of tooth extractions and they were not found bone necrosis areas, the number of RUNX2-positive cells and OCN-positive cells was similar among these groups. aPDT is presented as an effective preventive therapy in order to improve tissue repair in dental sockets, which is highly compromised by the treatment with oncologic doses of zoledronate.
Disclosure: The authors declared no competing interests. This work was supported by the FAPESP (grant number 2013/26779-4) and PROPE UNESP (grant number 0168/0008/13-PROPE/CDC).