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This study investigated preventive measures recommended for tooth extractions under antiresorptive (AR) treatment and the role of discontinuation of AR therapy to avoid the onset of MRONJ in a minipig model. Thirty-six G\u00f6ttingen minipigs were divided into four groups. Group 1 (negative control): tooth extractions but no zoledronate (ZOL). Group 2 (positive control): weekly ZOL infusions for 12\u2009weeks followed by tooth extractions without wound management followed by 8\u2009weeks of ZOL treatment. Group 3: weekly ZOL infusions for 12\u2009weeks followed by tooth extractions; surgical wound management (resection of sharp bone edges, mucoperiosteal coverage); and continuation of ZOL infusions for 8\u2009weeks plus antibiotic treatment. Group 4: 12\u2009weeks of ZOL infusions followed by a drug holiday for 6\u2009weeks. Tooth extractions with preventive wound management followed by antibiotic treatment for 8\u2009weeks but no ZOL infusions. Jawbones were subjected to macroscopic, radiological (CT and micro-CT) and histopathological investigations. No clinical cases of MRONJ were observed in the negative group, in the positive control all animals developed MRONJ. Group 3 developed MRONJ in 83% of cases. With a drug holiday, 40% developed MRONJ in areas of tooth extraction. This is the first large animal model that reduces the occurrence of MRONJ following tooth extraction by the implementation of a drug holiday combined with antibiotic prophylaxis and smoothening of sharp bony edges. \u00a9 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..<\/jats:p>","DOI":"10.1002\/jbmr.4119","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T12:44:47Z","timestamp":1592829887000},"page":"2179-2192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["A Drug Holiday Reduces the Frequency and Severity of Medication-Related Osteonecrosis of the Jaw in a Minipig Model"],"prefix":"10.1093","volume":"35","author":[{"given":"Sven","family":"Otto","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Ludwig Maximilians University Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2857-3524","authenticated-orcid":false,"given":"Christoph","family":"Pautke","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Ludwig 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