The effects of zoledronic acid on the progression of experimental periodontitis in rats: histological and microtomographic analyses
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Purpose: Periodontitis is considered a local risk factor for medication-related osteonecrosis of the jaws (MRONJ). However, little is known about the progression of periodontitis in the presence of zoledronic acid (ZOL). The aim of this study was to evaluate the effects of the systemic use of ZOL on the progression of experimental periodontitis (EP) in rats, as ZOL could modulate the progression of periodontitis and concomitantly cause MRONJ in individuals with periodontitis. Methods: Forty-eight male Wistar rats were randomly distributed in 6 groups (n=8 each). To induce EP, ligatures were placed around the right first mandibular molars. Three groups were treated with ZOL (0.15 mg/kg/week, intraperitoneal), and 3 with 0.9% saline solution (controls). In the ZOL/Lig30 and ZOL/Lig 15 groups, after 4 weeks of treatment with ZOL, EP was induced and euthanasia was performed after 30 and 15 days of EP induction, respectively. In both groups, the animals continued to receive ZOL after EP until the end of the experiment. In the Lig/ZOL group, EP was induced first, and 15 days later, ZOL was administered for 8 weeks, with euthanasia 1 week after the last dose. After euthanasia, the mandibles were evaluated using micro-computed microtomography (micro-CT) and histomorphometry. Bone loss was measured, and the presence of osteonecrosis was evaluated histologically. The data were evaluated using the Student t-test and the Mann-Whitney test, with a significance level of 5%. Results: In the Lig/ZOL group, micro-CT revealed less alveolar bone resorption in the distal root (P<0.01) than in the control group (Lig/Con). Histomorphometric analysis confirmed less alveolar bone resorption in the Lig/ZOL group (P=0.001). Histologically, osteonecrosis was more common in the ZOL groups. Conclusion: ZOL decreased alveolar bone resorption in rats with EP. However, it presented a higher risk for MRONJ.
Abstract
Purpose: Periodontitis is considered a local risk factor for medication-related osteonecrosis of the jaws (MRONJ). However, little is known about the progression of periodontitis in the presence of zoledronic acid (ZOL). The aim of this study was to evaluate the effects of the systemic use of ZOL on the progression of experimental periodontitis (EP) in rats, as ZOL could modulate the progression of periodontitis and concomitantly cause MRONJ in individuals with periodontitis. Methods: Forty-eight male Wistar rats were randomly distributed in 6 groups (n=8 each). To induce EP, ligatures were placed around the right first mandibular molars. Three groups were treated with ZOL (0.15 mg/kg/week, intraperitoneal), and 3 with 0.9% saline solution (controls). In the ZOL/Lig30 and ZOL/Lig 15 groups, after 4 weeks of treatment with ZOL, EP was induced and euthanasia was performed after 30 and 15 days of EP induction, respectively. In both groups, the animals continued to receive ZOL after EP until the end of the experiment. In the Lig/ZOL group, EP was induced first, and 15 days later, ZOL was administered for 8 weeks, with euthanasia 1 week after the last dose. After euthanasia, the mandibles were evaluated using micro-computed microtomography (micro-CT) and histomorphometry. Bone loss was measured, and the presence of osteonecrosis was evaluated histologically. The data were evaluated using the Student t-test and the Mann-Whitney test, with a significance level of 5%. Results: In the Lig/ZOL group, micro-CT revealed less alveolar bone resorption in the distal root (P<0.01) than in the control group (Lig/Con). Histomorphometric analysis confirmed less alveolar bone resorption in the Lig/ZOL group (P=0.001). Histologically, osteonecrosis was more common in the ZOL groups. Conclusion: ZOL decreased alveolar bone resorption in rats with EP. However, it presented a higher risk for MRONJ.
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