This animal study enrolled 54 adult male Sprague–Dawley rats, each weighing 250 g and aged 7 weeks (Janvier Labs, Le Genest-Saint-Isle, France). Two experimental groups and one control group, each with 18 animals, were randomly assigned to the following treatments: zoledronic acid (Group 1), alendronic acid (Group 2), and no medicine (Group 3). Systemic antiresorptive medicine was started 4 weeks prior to implantation and continued for 4 months. Before administration, the medicines were diluted in physiologic phosphate-buffered saline. Once a week, rats in Group 1 were given 0.04 mg/kg of body weight of zoledronic acid (Mylan dura GmbH, Darmstadt, Germany) intravenously in the tail vein [19 (link)]. The rats in Group 2 were given 0.2 mg/kg of body weight of alendronic acid (alendronate sodium trihydrate, Sigma Aldrich GmbH, Munich, Germany) subcutaneously five times a week [20 (link)].
One examiner performed the surgery, and another examiner assessed the histopathological samples using blinded data evaluation. This study was carried out in accordance with the guidelines of the European Parliament and of the Council on the protection of animals used for scientific purposes, Animal Research: Reporting of In Vivo Experiments (ARRIVE) and Directive 2010/63/EU. The study protocol received ethical approved from the appropriate local authority (Landesamt für Natur und Verbraucherschutz, Recklinghausen, Germany; Ref. 2018A314). The rats were given free access to food and water, with only soft moistened food provided following implantation until the end of the study.
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