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Male Wistar rats were allocated to different treatments: (i) na\u00efve, (ii) MRONJ (zoledronic acid, 0.2\u00a0mg\/kg, i.v. on days 0, 7, 14, and 49), or (iii) MRONJ + metformin (250\u00a0mg\/kg, by gavage, daily for 70 days). All rats had the inferior first molar extracted on day 42. Mandibular arches were harvested for analyzing their gums on day 70. Additionally, RAW 264.7 cells were incubated with zoledronic acid or metformin for cell viability tests and analysis of interleukin\u20101\u03b2 (IL\u20101\u03b2) production. MRONJ was characterized by increased numbers of empty osteocyte lacunae, osteoclasts, and apoptotic osteoclasts, and by high expression of tartrate\u2010resistant acid phosphatase (TRAP) and F4\/80 (a macrophage marker). Zoledronic acid\u2010incubated RAW 264.7 macrophages showed increased IL\u20101\u03b2 expression. Metformin reduced the number of empty bone lacunae, apoptotic osteoclasts, leukocyte infiltrate, and F4\/80 positive cells in the alveolar bone. It increased TRAP expression levels without altering the number of osteoclasts. Metformin also reduced the myeloperoxidase activity and decreased IL\u20101\u03b2 levels in vitro. In conclusion, metformin reduced the severity of MRONJ by mitigating the inflammatory response.<\/jats:p>","DOI":"10.1111\/eos.70056","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T07:45:25Z","timestamp":1764920725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of metformin on inflammation and bone damage in a rat model of medication\u2010related osteonecrosis of the jaw"],"prefix":"10.1111","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5779-839X","authenticated-orcid":false,"given":"Liviane Maria Alves","family":"Rabelo","sequence":"first","affiliation":[{"name":"Drug Research and Development Center Department of Physiology and Pharmacology Faculty of Medicine Federal University of Ceara  Fortaleza 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