The evaluation of chronic zoledronate usage on jaw and long bones by TNF-a, IL-6, IL-8, RANKL and osteoprotegerin levels in an animal model.

The evaluation of chronic zoledronate usage on jaw and long bones by TNF- ? , IL-6, IL-8, RANKL and osteoprotegerin levels in an animal model.Introduction: Bisphosphonates are a group of medications that are effective in inhibiting bone resorption. Bisphosphonate-related osteonecrosis or osteomyelitis of the jaws (BRONJ) was first described by Marx and Stern in 2003. It is an important possible late adverse effect of bisphosphonates, and the pathogenesis of this new phenomen remains unclear.The aim of the study was to evaluate the TNF- ? , IL-6, IL-8, RANKL and OPG levels after chronic bisphosphonate application in rat.Material and Method: 30 female Spraque-Dawley rats were used in this study. They were randomly divided into three groups. Z1; zolendronate group was injected with zolendronate for 10 weeks, S1; control group was injected with saline solution for 10 weeks and K1; control group that was not given any injection. Z1 group received injection of zolendronate at a dose of 0.1 mg/kg, 3 times a week. After 10 weeks, without any dental intervention, the rats were sacrificed. The posterior region of the mandible including first and second molars and 1/3 upper side of tibia were disected subperiosteally. Homogenization of tissues were performed before ELISA tests. All of the concentrations of the selected parameters were determined using ELISA kits.Results: The increase on tibia osteoprotegerin levels were statistically significant.(p<0.05) While not reaching statistical significance the increase in osteoprotegerin levels of the mandible considered as inhibition of osteoclastogenesis. There was an elevation on RANKL tibia levels however mandible RANKL levels revealed a decrease.The TNF- ? and IL-6 ratios showed an increase on tibia levels both in Z1 and S1 groups which were considered as not to reletad with drug administration. There were no difference on mandible TNF- ? and IL-6 levels. IL-8 levels revealed no difference between the studied groups both in mandible and tibia.According to our data; the occurence of BRONJ only in jaws could be reletad with the lack of osteoclastic activation reletad with the decrease on RANKL levels. Long term investigations have to be made before clinical applications.