A drug holiday reduces the frequency and severity of Medication Related Osteonecrosis of the jaw in a minipig model.

Treatment of medication related osteonecrosis of the jaw (MRONJ) is challenging and no clear consensus has been achieved. This study investigated preventive measures recommended for tooth extractions under antiresorptive treatment and the role of discontinuation of antiresorptive therapy to avoid the onset of MRONJ in a minipig model. Thirty-six Gottingen minipigs were divided into four groups. Group 1 (negative control): tooth extractions but no zoledronate. Group 2 (positive control): weekly zoledronate infusions for 12 weeks followed by tooth extractions without wound management followed by eight weeks of zoledronate treatment. Group 3: weekly zoledronate infusions for 12 weeks followed by tooth extractions. Surgical wound management (resection of sharp bone edges, mucoperiosteal coverage). Continuation of zoledronate infusions for 8 weeks plus antibiotic treatment. . Group 4: 12 weeks of zoledronate infusions followed by a drug holiday for 6 weeks. Tooth extrations with preventive wound management followed by antibiotic treatment for 8 weeks but no zoledronate infusions. Jawbones were subjected to macroscopic, radiological (CT and μCT) 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. This article is protected by copyright. All rights reserved.