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Studies were eligible if they involved adults (\u2265\u200918\u00a0years) with or at risk for ORN or MRONJ and reported AEs associated with PENTO or PENTOCLO for prevention or treatment. A proportion meta-analysis estimated the overall frequency of AEs. Subgroup analyses compared AE rates between prevention and treatment contexts and between the two regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 1,075 records screened, 9 studies met the inclusion criteria. No studies reported AEs in MRONJ patients; all focused on ORN. The pooled AE proportion was 15% (95% CI: 3.6%\u201311.5%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.1; I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200955.8%). Gastrointestinal symptoms were the most reported AEs (46.38%), followed by neurovegetative effects (18.84%). AEs were more frequent in treatment settings and more prevalent in patients using PENTOCLO (28%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The PENTO(CLO) protocols were associated with a 15% overall AE rate, predominantly gastrointestinal symptoms. AEs occurred more often during treatment and with the PENTOCLO regimen. These findings highlight the need for close monitoring and further studies to assess safety in MRONJ patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00520-026-10428-0","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T01:03:40Z","timestamp":1771549420000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adverse effects of the PENTO(CLO) protocol in the prevention and management of iatrogenic head and neck bone necrosis in cancer patients: A systematic review and meta-analysis"],"prefix":"10.1007","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7548-4618","authenticated-orcid":false,"given":"Marco Tulio Leandro","family":"Ribeiro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7504-7597","authenticated-orcid":false,"given":"Caique Mariano","family":"Pedroso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana Mayume Carvalho","family":"Kadooka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3265-2671","authenticated-orcid":false,"given":"Maria Eduarda","family":"P\u00e9rez-de-Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0317-8878","authenticated-orcid":false,"given":"Fabio Ramoa","family":"Pires","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6677-0065","authenticated-orcid":false,"given":"M\u00e1rcio Ajudarte","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-6617","authenticated-orcid":false,"given":"Alan Roger","family":"Santos-Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"issue":"5-6","key":"10428_CR1","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.currproblcancer.2016.06.001","volume":"40","author":"A Villa","year":"2016","unstructured":"Villa A, Sonis S (2016) Toxicities associated with head and neck cancer treatment and oncology-related clinical trials. 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