Evaluation of the effectiveness and safety of scaling and root planing for the treatment of experimental periodontitis in rats under therapy with oncologic dose of zoledronate

Abstract

Bisphosphonates (BPs) consist of a range of drugs used in the treatment of certain bone diseases or osteotropics malignant neoplasms. Bisphosphonates exert potent inhibitory effect on bone resorption process. One of their adverse effects is the occurrence of the so-called medication-related osteonecrosis of the jaws (MRONJ). The etiology of the disease is still poorly understood, which makes its prevention and treatment difficult. Nowadays, the periodontal disease has been identified as an important local risk factor for MRONJ (BPs). However, little is known about the interrelation between the pathogenesis of the periodontal disease and the MRONJ (BPs). In addition, the effectiveness and safety of the conventional mechanical treatment for periodontal disease during the therapy with potent BPs were not still explored. The aim of this study is to evaluate the progression of experimental periodontitis and the periodontal tissue response due to scaling and root planing (SRP) during the treatment with oncologic dose of zoledronate. Sixty-four rats (6 months) will be divided into four experimental groups: SAL-EP, ZOL-EP, SAL-EP/SRP and ZOL-EP/SRP. 0.45ml solution of 0.9% NaCl (SAL-EP and SAL-EP/SRP) or 0.45ml of this solution plus 100 ¼g/kg of zoledronate (ZOL-EP and ZOL-EP/SRP) will be administered during 8 weeks, every 3 days, by intraperitoneal injection. After two weeks of drug treatment, a cotton ligature will be installed around the first lower left molar. In SAL-EP and ZOL-EP groups, this ligature will be maintained until the end of the experiment. In SAL-EP/SRP and ZOL-EP/SRP groups, the ligature will be removed after two weeks, and the RAR will be done. The euthanasia will be performed at 3 or 6 weeks after installation of the ligature, which for SAL-EP/SRP and ZOL-EP/SPR groups will correspond to 7 or 28 days post-treatment with SRP. Histological processing of hemi-mandibles will be done and histological sections will be stained with hematoxylin-eosin. Histopathology analysis, histometric analysis of the percentage of bone tissue (PBF) and the percentage of necrotic bone (PNB) will be performed focusing furcation region of the first lower left molar. The results will be analyzed under light microscopy, and will be submitted to quantitative and statistical analysis considering significance level of 5%. (AU)