{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T22:16:47Z","timestamp":1770675407820,"version":"3.49.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Breast cancer is the most diagnosed cancer in women worldwide. Radiotherapy is a cornerstone of treatment for both early-stage ductal carcinoma\n                      <jats:italic>in situ<\/jats:italic>\n                      (DCIS) and metastatic disease, but concerns about side effects remain. Bisphosphonates (BPs), particularly zoledronic acid (ZOL), have shown anti-tumor effects in preclinical models and reduce skeletal complications in patients with bone metastases. This study aimed to evaluate the radiosensitizing potential of BPs and their relationship with skeletal complications in breast cancer patients undergoing radiotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study at the American University of Beirut Medical Center, including female patients aged 40\u201365 years with primary DCIS who received radiotherapy between November 2018 and September 2023. Data on patient demographics, tumor characteristics, treatment modalities, and outcomes were extracted from electronic medical records. Associations between BP use and pathologic fractures, musculoskeletal (MSK) complications, and treatment response were analyzed using logistic regression adjusted for relevant confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 397 patients with breast cancer in our cohort, only 122 (30.7%) received ZOL. BP use was independently associated with increased odds of MSK complications (OR = 4.34; 95% CI: 2.42\u20137.77; p &amp;lt; 0.001) and pathologic fractures (OR = 2.93; 95% CI: 1.37\u20136.24; p = 0.005). No significant association was observed between BP use and tumor response, skin complications, fatigue, or other adverse effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings likely reflect baseline skeletal fragility rather than a direct harmful effect of BPs. BPs remain an important indicator of bone vulnerability rather than a therapeutic modifier.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1725699","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T05:22:06Z","timestamp":1770614526000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bisphosphonates in breast cancer radiotherapy: associations with skeletal complications and treatment outcomes - a retrospective cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Khanom","family":"Baalbaki","sequence":"first","affiliation":[{"name":"Department of Orthopedics Surgery, American University of Beirut Medical Center","place":["Beirut, Lebanon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Hemdanieh","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, American University of Beirut Medical Center","place":["Beirut, Lebanon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Yammine","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, American University of Beirut Medical Center","place":["Beirut, Lebanon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bshara","family":"Sleem","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, American University of Beirut","place":["Beirut, Lebanon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Souad","family":"Sawaf","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, American University of Beirut","place":["Beirut, Lebanon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rawad","family":"Lakkis","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, American University of Beirut Medical Center","place":["Beirut, Lebanon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamad","family":"Nassereddine","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Surgery, American University of Beirut Medical Center","place":["Beirut, Lebanon"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry","family":"Bodgi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, American University of Beirut Medical Center","place":["Beirut, Lebanon"]},{"name":"Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut","place":["Beirut, Lebanon"]},{"name":"Unit\u00e9 INSERM UMR 1296 \u201cRadiations: D\u00e9fense, Sant\u00e9, Environnement\u201d","place":["Lyon, France"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.breast.2022.08.010","article-title":"Current and future burden of breast cancer: Global statistics for 2020 and 2040","volume":"66","author":"Arnold","year":"2022","journal-title":"Breast"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30675-6","article-title":"Global demand for cancer surgery and an estimate of the optimal surgical and anesthesia workforce between 2018 and 2040: a population-based modelling study","volume":"22","author":"Perera","year":"2021","journal-title":"Lancet Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/his.14786","article-title":"An update on the pathological classification of breast cancer","volume":"82","author":"Rakha","year":"2023","journal-title":"Histopathology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-018-6580-9","article-title":"American society of breast surgeons\u2019 Practice patterns after publication of the SSO-ASTRO-ASCO DCIS consensus guideline on margins for breast-conserving surgery with whole-breast irradiation","volume":"25","author":"DeSnyder","year":"2018","journal-title":"Ann Surg Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/jncimonographs\/lgq039","article-title":"Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast","volume":"2010","author":"Correa","year":"2010","journal-title":"J Natl Cancer Inst Monogr"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/jcm2030151","article-title":"Prevention and treatment of bone metastases in breast cancer","volume":"2","author":"Ripamonti","year":"2013","journal-title":"J Clin Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14823","article-title":"The role of radiation therapy in bone metastases management","volume":"8","author":"De Felice","year":"2017","journal-title":"Oncotarget"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2021.10.030","article-title":"Advances and controversies in management of breast ductal carcinoma in situ (DCIS)","volume":"48","author":"Farante","year":"2022","journal-title":"Eur J Surg Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2018.0012","article-title":"Breast cancer, version 4.2017, NCCN clinical practice guidelines in oncology","volume":"16","author":"Gradishar","year":"2018","journal-title":"J Natl Compr Canc Netw"},{"key":"B10","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/j.1524-4741.2011.01197.x","article-title":"ACR appropriateness criteria(\u00ae) ductal carcinoma in situ","volume":"18","author":"Moran","year":"2012","journal-title":"Breast J"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.2510","article-title":"Breast cancer mortality after a diagnosis of ductal carcinoma in situ","volume":"1","author":"Narod","year":"2015","journal-title":"JAMA Oncol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e24793","DOI":"10.1016\/j.heliyon.2024.e24793","article-title":"Benefit of adjuvant bisphosphonates in early breast cancer treated with contemporary systemic therapy: A meta-analysis of randomized control trials","volume":"10","author":"Mittal","year":"2024","journal-title":"Heliyon"},{"key":"B13","doi-asserted-by":"publisher","first-page":"Cd013451","DOI":"10.1002\/14651858.CD013451.pub2","article-title":"Bone-modifying agents for reducing bone loss in women with early and locally advanced breast cancer: a network meta-analysis","volume":"7","author":"Adams","year":"2024","journal-title":"Cochrane Database Syst Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s12609-018-0295-6","article-title":"Bone-modifying agents in early-stage and advanced breast cancer","volume":"10","author":"Heeke","year":"2018","journal-title":"Curr Breast Cancer Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbo.2014.02.001","article-title":"Zoledronic acid and atorvastatin inhibit \u03b1v\u03b23-mediated adhesion of breast cancer cells","volume":"3","author":"Wilke","year":"2014","journal-title":"J Bone Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdm249","article-title":"New developments of aminobisphosphonates: the double face of Janus","author":"Santini","year":"2007","journal-title":"Ann Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.035295","article-title":"Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid","volume":"302","author":"Wood","year":"2002","journal-title":"J Pharmacol Exp Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.3.482","article-title":"Zoledronic acid treatment of 5T2MM-bearing mice inhibits the development of myeloma bone disease: evidence for decreased osteolysis, tumor burden and angiogenesis, and increased survival","volume":"18","author":"Croucher","year":"2003","journal-title":"J Bone Mineral Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.08.017","article-title":"American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer","volume":"21","author":"Hillner","year":"2003","journal-title":"J Clin Oncol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"R52","DOI":"10.1186\/bcr1543","article-title":"In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells","volume":"8","author":"Ural","year":"2006","journal-title":"Breast Cancer Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"524","DOI":"10.3390\/biom13030524","article-title":"Molecular influence of the ATM protein in the treatment of human cells with different radioprotective drugs: comparisons between antioxidative and pro-episkevic strategies","volume":"13","author":"Restier-Verlet","year":"2023","journal-title":"Biomolecules"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-023-00560-7","article-title":"Effect of bisphosphonates and statins on the in vitro radiosensitivity of breast cancer cell lines","volume":"76","author":"Bodgi","year":"2024","journal-title":"Pharmacol Rep"},{"key":"B23","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s13058-015-0634-8","article-title":"Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence","volume":"17","author":"Santini","year":"2015","journal-title":"Breast Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/bcr2769","article-title":"Anti-tumor activity of bisphosphonates in preclinical models of breast cancer","volume":"12","author":"Holen","year":"2010","journal-title":"Breast Cancer Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2008.02.004","article-title":"Exploring the anti-tumor activity of bisphosphonates in early breast cancer","volume":"34","author":"Winter","year":"2008","journal-title":"Cancer Treat Rev"},{"key":"B26","doi-asserted-by":"publisher","first-page":"637976","DOI":"10.1155\/2013\/637976","article-title":"Bisphosphonates and cancer: what opportunities from nanotechnology","volume":"2013","author":"De Rosa","year":"2013","journal-title":"J Drug Delivery"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.1999.1131","article-title":"Bisphosphonates induce apoptosis in human breast cancer cell lines","volume":"82","author":"Senaratne","year":"2000","journal-title":"Br J cancer"},{"key":"B28","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1093\/jnci\/djz215","article-title":"Phase III randomized trial of bisphosphonates as adjuvant therapy in breast cancer: S0307","volume":"112","author":"Gralow","year":"2020","journal-title":"J Natl Cancer Inst"},{"key":"B29","doi-asserted-by":"publisher","first-page":"Cd003474","DOI":"10.1002\/14651858.CD003474.pub4","article-title":"Bisphosphonates and other bone agents for breast cancer","volume":"10","author":"O\u2019Carrigan","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/jrr\/rraa020","article-title":"Radiation therapy combined with bone-modifying agents ameliorates local control of osteolytic bone metastases in breast cancer","volume":"61","author":"Tanaka","year":"2020","journal-title":"J Radiat Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60908-4","article-title":"Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomized trials","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"B32","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1200\/JCO.21.02647","article-title":"Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: ASCO-OH (CCO) guideline update","volume":"40","author":"Eisen","year":"2022","journal-title":"J Clin Oncol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"104502","DOI":"10.1016\/j.breast.2025.104502","article-title":"Comparative analysis of Denosumab and Zoledronic acid in advanced breast cancer patients receiving CDK4\/6 inhibitors","volume":"82","author":"Scafetta","year":"2025","journal-title":"Breast"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/S0025-6196(11)60752-0","article-title":"Adverse effects of bisphosphonates: implications for osteoporosis management","volume":"84","author":"Kennel","year":"2009","journal-title":"Mayo Clin Proc"},{"key":"B35","article-title":"Bisphosphonate","volume-title":"StatPearls","author":"Ganesan","year":"2025"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-020-05567-9","article-title":"Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial","volume":"180","author":"van Hellemond","year":"2020","journal-title":"Breast Cancer Res Treat"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-17-0556","article-title":"Bisphosphonate use and risk of recurrence, second primary breast cancer, and breast cancer mortality in a population-based cohort of breast cancer patients","volume":"27","author":"Korde","year":"2018","journal-title":"Cancer Epidemiology Biomarkers Prev"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2014.3634","article-title":"Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid","volume":"174","author":"Hue","year":"2014","journal-title":"JAMA Intern Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djr399","article-title":"Bisphosphonate use after estrogen receptor\u2013positive breast cancer and risk of contralateral breast cancer","volume":"103","author":"Monsees","year":"2011","journal-title":"JNCI: J Natl Cancer Institute"},{"key":"B40","doi-asserted-by":"publisher","first-page":"593","DOI":"10.2147\/CLEP.S194056","article-title":"Bisphosphonates and primary breast cancer risk: an updated systematic review and meta-analysis involving 963,995 women","volume":"11","author":"Liu","year":"2019","journal-title":"Clin Epidemiol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"75","DOI":"10.2147\/BCTT.S16356","article-title":"Decreased risk of breast cancer associated with oral bisphosphonate therapy","volume":"4","author":"Mathew","year":"2012","journal-title":"Breast Cancer (Dove Med Press)"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.09.019","article-title":"ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer","volume":"32","author":"Gennari","year":"2021","journal-title":"Ann Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1725699\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T05:22:07Z","timestamp":1770614527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1725699\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":42,"alternative-id":["10.3389\/fonc.2026.1725699"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1725699","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]},"article-number":"1725699"}}