{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:08:25Z","timestamp":1782796105957,"version":"3.54.5"},"reference-count":175,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect associated with antiresorptive and antiangiogenic treatments commonly prescribed for patients with cancer or osteoporosis. The increasing prescription of these drugs, coupled with the introduction of new anti-cancer medications, has raised concerns regarding the increasing risk of MRONJ. While the precise mechanisms underlying MRONJ remain unclear and effective therapies are still lacking, two repurposed pharmacological protocols\u2014teriparatide (TPTD) and the combination of pentoxifylline (PTX) and \u03b1-tocopherol (TOC) [PENTO protocol]\u2014have demonstrated potential therapeutic benefits. However, large-scale clinical evidence remains insufficient. This review evaluates the therapeutic potential of these targeted drug repurposing protocols, exploring their mechanisms of action in MRONJ management and proposing a clinical application protocol for both prevention and treatment. This study also highlights the potential of drug repurposing as a rapid and cost-effective approach for MRONJ management, particularly for patients with cancer, and emphasises the need for further research on personalised and localised management strategies. Nevertheless, the current evidence base is limited by small sample sizes, heterogeneous patient populations, non-randomised study designs, and inconsistent outcome measures, precluding definitive conclusions regarding efficacy and optimal clinical use.<\/jats:p>","DOI":"10.3389\/fmed.2026.1750238","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:49:33Z","timestamp":1772520573000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted drug repurposing in medication-related osteonecrosis of the jaw: a review of teriparatide and pentoxifylline\/\u03b1-tocopherol protocols"],"prefix":"10.3389","volume":"13","author":[{"given":"Weijia","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]},{"name":"Division of Surgery and Interventional Science, Royal Free Hospital, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jishizhan","family":"Chen","sequence":"additional","affiliation":[{"name":"UCL Mechanical Engineering, Torrington Place, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azadeh","family":"Rezaei","sequence":"additional","affiliation":[{"name":"Division of Surgery and Interventional Science, Royal Free Hospital, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/s0278-2391(03)00720-1","article-title":"Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic","volume":"61","author":"Marx","year":"2003","journal-title":"J Oral Maxillofac Surg"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.joms.2022.02.008","article-title":"American Association of Oral and Maxillofacial Surgeons' position paper on medication-related osteonecrosis of the Jaws-2022 update","volume":"80","author":"Ruggiero","year":"2022","journal-title":"J Oral Maxillofac Surg"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"101931","DOI":"10.1016\/j.jormas.2024.101931","article-title":"Epidemiology, etiopathogenesis, and management of MRONJ: a European multicenter 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