ABSTRACT
The discovery of the receptor activator of nuclear factor kappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) system (RANK/RANKL/OPG system) has been one of the most important advances in bone biology in the last decade. We investigated how the chronic application of bisphosphonate affects the RANKL and OPG levels in an animal model and whether this effect may be related to bisphosphonate-related osteonecrosis of the jaws (BRONJ). Thirty female Sprague-Dawley rats were used in this study. The rats were randomly divided into three groups (10 in each): Z, the zolendronate group, injected with zolendronate for 10 weeks; S, a control group, injected with saline solution for 10 weeks; and C, a control group, in which no injection was given. RANKL values in the tibia were increased in the Z group when compared with the two controls; however, the RANKL values in the mandible were decreased when compared with the controls. Although the differences did not reach statistical significance, the mandibular OPG values were increased in the Z group when compared with the C and S groups. The mechanism of RANKL negation and absence in osteoclastic activation could be a predisposing factor for the development of BRONJ.
Subject(s)
Bone Density Conservation Agents/pharmacology , Diphosphonates/pharmacology , Imidazoles/pharmacology , Mandible/drug effects , Tibia/drug effects , Animals , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bone Density Conservation Agents/administration & dosage , Diphosphonates/administration & dosage , Female , Imidazoles/administration & dosage , Injections, Intraperitoneal , Models, Animal , Osteoclasts/drug effects , Osteoprotegerin/analysis , Osteoprotegerin/drug effects , RANK Ligand/analysis , RANK Ligand/drug effects , Random Allocation , Rats , Rats, Sprague-Dawley , Sodium Chloride/administration & dosage , Time Factors , Zoledronic AcidABSTRACT
OBJECTIVES: Simvastatin, pravastatin and atorvastatin have been evaluated whether to have analgesic effects in mice in hot plate test. MATERIALS AND METHODS: Simvastatin (5, 10, 30 mg/kg), pravastatin (5, 10, 30 mg/kg) and atorvastatin (5, 10, 30 mg/kg) were administered acute and chronically by oral gavage in mice. Control (pretreatment value) and posttreatment (after drugs application) values in 60th and 120th minutes were measured in hot-plate test. RESULTS: All three drugs at 10, 30 mg/kg doses produced analgesic effects compared with their control values in 60th and 120th minutes on acute and chronic application in mice. The analgesic effects of drugs were evaluated after the application of L-nitro arginine methyl ester (L-NAME) (10 mg/kg) or naloxone (0.5 mg/kg). L-NAME (10 mg/kg) has no effect compared to the control value on both minutes. The analgesic effects of both atorvastatin (30 mg/kg) and simvastatin (30 mg/kg) in the presence of L-NAME (10 mg/kg) were not inhibited. However, the analgesic effect of pravastatin (30 mg/kg) in the presence of L-NAME (10 mg/kg) was inhibited significantly on both minutes (p < 0.05). Naloxone (0.5 mg/kg) has no effect compared to the control value on both minutes. The analgesic effect of atorvastatin (30 mg/kg) in the presence of naloxone (0.5 mg/kg) was partially (43%) but significantly inhibited only on 60th minute (p < 0.05). The analgesic effect of pravastatin (30 mg/kg) in the presence of naloxone (0.5 mg/kg) was partially (48-40%) but significantly inhibited on both minutes (p < 0.05). However, the analgesic effect of simvastatin (30 mg/kg) in the presence of naloxone (0.5 mg/kg) was inhibited significantly on both minutes (p < 0.05). CONCLUSIONS: These finding indicated that the analgesic effect of pravastatin was related to nitrergic systems and partially opioidergic system; analgesic effect of simvastatin was related to opiodergic system in hot plate test. However, the analgesic effect of atorvastatin was not directly related to both system.
