{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:43:03Z","timestamp":1792896183726,"version":"4.5.0"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Osaka Foundation for the Prevention of Cancer and Cardiovascular Diseases","award":["A2023-4"],"award-info":[{"award-number":["A2023-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background: Bone metastasis is associated with a poor prognosis. Bone-modifying agents (BMA) are commonly used for the prevention or treatment of skeletal-related events (SRE) in patients with bone metastasis; however, whether or not treatment with BMA improves survival remains unclear. In this study, we investigated whether BMA was involved in post-bone metastasis survival. Methods: A total of 539 cancer patients were retrospectively analyzed to identify significant independent factors in post-bone metastasis survival. Results: Among the overall population, patients with the following cancers had a median survival longer than 24 months: thyroid, 97.2 months; breast, 51.5 months; prostate, 47.2 months; and kidney, 38.8 months. In contrast, median post-bone metastasis survival was significantly shorter in gastrointestinal (GI) (6.5 months), head and neck (6.3 months), and urinary tract (3.4 months) cancers. In non-small cell lung cancer (NSCLC), the log-rank test demonstrated that the epidermal growth factor receptor (EGFR) mutation was a significant factor for post-bone metastasis survival: EGFR mutation (\u2212) n = 67, median post-bone metastasis survival 11.5 months (95% CI: 6.0\u201315.2); EGFR mutation (+) n = 39, median post-bone metastasis survival 28.8 months (95% CI: 18.1\u201335.7) (p &lt; 0.05). Intriguingly, treatment with BMA was a significant positive prognostic factor: BMA (\u2212) n = 203, median post-bone metastasis survival 7.8 months (95% CI: 5.8\u201312.5); BMA (+) n = 336, median post-bone metastasis survival 21.9 months (95% CI: 16.1\u201326.4) (p &lt; 0.001). Moreover, the Cox proportional hazards model showed that this was particularly evident in cancer types with poor prognosis such as GI cancer (hazard ratio [HR]: 0.62, 95% CI: 0.40\u20130.95; p &lt; 0.05) and NSCLC without the epidermal growth factor receptor (EGFR) mutation (HR: 0.56, 95% CI: 0.34\u20130.91; p &lt; 0.05). Conclusions: Treatment with BMA is recommended not only for the prevention and\/or treatment of SRE, but also may have a positive impact on post-bone metastasis survival, particularly in cancers with typically poor post-bone metastasis survival such as GI cancer and NSCLC without the EGFR mutation.<\/jats:p>","DOI":"10.3390\/curroncol32010042","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T10:00:01Z","timestamp":1736935201000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of Bone-Modifying Agents on Post-Bone Metastasis Survival Across Cancer Types"],"prefix":"10.3390","volume":"32","author":[{"given":"Hironari","family":"Tamiya","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, Osaka International Cancer Institute, Osaka 541-8567, Japan"},{"name":"Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2000-7472","authenticated-orcid":false,"given":"Kazumi","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Nakahashi-Kato","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurika","family":"Kosuga-Tsujimoto","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiyo","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3073-0595","authenticated-orcid":false,"given":"Toru","family":"Wakamatsu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1248-9520","authenticated-orcid":false,"given":"Shigeki","family":"Kakunaga","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Takenaka","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka International Cancer Institute, Osaka 541-8567, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"482","DOI":"10.21037\/atm.2020.03.55","article-title":"Incidence of Patients with Bone Metastases at Diagnosis of Solid Tumors in Adults: A Large Population-Based Study","volume":"8","author":"Huang","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hernandez, R.K., Wade, S.W., Reich, A., Pirolli, M., Liede, A., and Lyman, G.H. (2018). Incidence of Bone Metastases in Patients with Solid Tumors: Analysis of Oncology Electronic Medical Records in the United States. BMC Cancer, 18.","DOI":"10.1186\/s12885-017-3922-0"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.juro.2010.03.034","article-title":"Skeletal Related Events, Bone Metastasis and Survival of Prostate Cancer: A Population Based Cohort Study in Denmark (1999 to 2007)","volume":"184","author":"Jensen","year":"2010","journal-title":"J. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/pcan.2011.7","article-title":"Mortality Following Bone Metastasis and Skeletal-Related Events among Men with Prostate Cancer: A Population-Based Analysis of US Medicare Beneficiaries, 1999\u20132006","volume":"14","author":"Sathiakumar","year":"2011","journal-title":"Prostate Cancer Prostatic Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s10549-011-1475-5","article-title":"Survival in Breast Cancer Patients with Bone Metastases and Skeletal-Related Events: A Population-Based Cohort Study in Denmark (1999\u20132007)","volume":"129","author":"Yong","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s10585-014-9648-3","article-title":"Features and Prognostic Impact of Distant Metastasis in Patients with Stage IV Lung Adenocarcinoma Harboring EGFR Mutations: Importance of Bone Metastasis","volume":"31","author":"Fujimoto","year":"2014","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1038\/sj.bjc.6602551","article-title":"Zoledronic Acid Significantly Improves Pain Scores and Quality of Life in Breast Cancer Patients with Bone Metastases: A Randomised, Crossover Study of Community vs Hospital Bisphosphonate Administration","volume":"92","author":"Wardley","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1210\/clinem\/dgae214","article-title":"Survival Outcome and Optimal Candidates of Primary Tumor Resection for Patients with Metastatic Medullary Thyroid Cancer","volume":"109","author":"Liu","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4103\/0973-1482.181177","article-title":"Colorectal Cancer Presenting as Bone Metastasis","volume":"13","author":"Garg","year":"2017","journal-title":"J. Cancer Res. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3346\/jkms.2024.39.e293","article-title":"Sites of Metastasis and Survival in Metastatic Renal Cell Carcinoma: Results from the Korean Renal Cancer Study Group Database","volume":"39","author":"Lee","year":"2024","journal-title":"J. Korean Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"378","DOI":"10.2105\/AJPH.87.3.378","article-title":"Disability in Activities of Daily Living: Patterns of Change and a Hierarchy of Disability","volume":"87","author":"Dunlop","year":"1997","journal-title":"Am. J. Public Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ctrv.2017.10.006","article-title":"Disability in Activities of Daily Living among Adults with Cancer: A Systematic Review and Meta-Analysis","volume":"61","author":"Neo","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10147-023-02312-2","article-title":"Cancer May Accelerate Locomotive Syndrome and Deteriorate Quality of Life: A Single-Centre Cross-Sectional Study of Locomotive Syndrome in Cancer Patients","volume":"28","author":"Hirahata","year":"2023","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1056\/NEJMoa1612674","article-title":"Osimertinib or Platinum\u2013Pemetrexed in EGFR T790M\u2013Positive Lung Cancer","volume":"376","author":"Mok","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus Chemotherapy for PD-L1\u2013Positive Non\u2013Small-Cell Lung Cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.amjmed.2023.11.018","article-title":"Medication-Related Osteonecrosis of the Jaw: A Cross-Sectional Study on the Prevalence of Cutaneous Manifestations and the Primary Care Physician\u2019s Role in Its Early Diagnosis","volume":"137","author":"Whitefield","year":"2024","journal-title":"Am. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.annonc.2020.07.019","article-title":"Bone Health in Cancer: ESMO Clinical Practice Guidelines","volume":"31","author":"Coleman","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_18","first-page":"283","article-title":"Surgical Treatment for Bisphosphonate-Related Atypical Femoral Fracture: A Systematic Review","volume":"9","author":"Ebrahimpour","year":"2021","journal-title":"Arch. Bone Jt. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5255","DOI":"10.1111\/odi.15066","article-title":"Clinical and Radiologic Treatment Outcomes of Implant Presence Tirggered-MRONJ: Systematic Review of Literature","volume":"30","author":"Nisi","year":"2024","journal-title":"Oral Dis."},{"key":"ref_20","first-page":"1314","article-title":"Role of Bone-Modifying Agents in Advanced Cancer","volume":"9","author":"Desautels","year":"2020","journal-title":"Ann. Cardiothorac. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1016\/j.clinthera.2020.05.019","article-title":"Denosumab Versus Zoledronic Acid in the Prevention of Skeletal-Related Events in Vulnerable Cancer Patients: A Meta-Analysis of Randomized, Controlled Trials","volume":"42","author":"Chen","year":"2020","journal-title":"Clin. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1200\/JCO.2005.05.116","article-title":"Zoledronic Acid Significantly Reduces Skeletal Complications Compared with Placebo in Japanese Women with Bone Metastases from Breast Cancer: A Randomized, Placebo-Controlled Trial","volume":"23","author":"Kohno","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_23","first-page":"CD003474","article-title":"Bisphosphonates and Other Bone Agents for Breast Cancer","volume":"2017","author":"Wong","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5132","DOI":"10.1200\/JCO.2010.29.7101","article-title":"Denosumab Compared with Zoledronic Acid for the Treatment of Bone Metastases in Patients with Advanced Breast Cancer: A Randomized, Double-Blind Study","volume":"28","author":"Stopeck","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the Freely Available Easy-to-Use Software \u2018EZR\u2019 for Medical Statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1007\/s11255-014-0824-9","article-title":"Docetaxel with or without Zoledronic Acid for Castration-Resistant Prostate Cancer","volume":"46","author":"Pan","year":"2014","journal-title":"Int. Urol. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"915","DOI":"10.6004\/jnccn.2020.7668","article-title":"Bone Metastases, Skeletal-Related Events, and Survival in Patients with Metastatic Non\u2013Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors","volume":"19","author":"Qin","year":"2021","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1097\/JTO.0b013e31826aec2b","article-title":"Overall Survival Improvement in Patients with Lung Cancer and Bone Metastases Treated with Denosumab Versus Zoledronic Acid: Subgroup Analysis from a Randomized Phase 3 Study","volume":"7","author":"Scagliotti","year":"2012","journal-title":"J. Thorac. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100301","DOI":"10.1016\/j.jbo.2020.100301","article-title":"Incidence of Atypical Femoral Fractures in the Treatment of Bone Metastasis: An Alert Report","volume":"23","author":"Kaku","year":"2020","journal-title":"J. Bone Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/S1470-2045(19)30456-5","article-title":"Progress in Cancer Survival, Mortality, and Incidence in Seven High-Income Countries 1995\u20132014 (ICBP SURVMARK-2): A Population-Based Study","volume":"20","author":"Arnold","year":"2019","journal-title":"Lancet. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hong, S., Youk, T., Lee, S.J., Kim, K.M., and Vajdic, C.M. (2020). Bone Metastasis and Skeletal-Related Events in Patients with Solid Cancer: A Korean Nationwide Health Insurance Database Study. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0234927"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e016022","DOI":"10.1136\/bmjopen-2017-016022","article-title":"Survival after Bone Metastasis by Primary Cancer Type: A Danish Population-Based Cohort Study","volume":"7","author":"Svensson","year":"2017","journal-title":"BMJ Open"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s11999-007-0051-0","article-title":"Predictors of Survival in Patients with Bone Metastasis of Lung Cancer","volume":"466","author":"Sugiura","year":"2008","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bulfamante, A.M., Lori, E., Bellini, M.I., Bolis, E., Lozza, P., Castellani, L., Saibene, A.M., Pipolo, C., Fuccillo, E., and Rosso, C. (2022). Advanced Differentiated Thyroid Cancer: A Complex Condition Needing a Tailored Approach. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.954759"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kanaoka, K., Sumikawa, H., Oyamada, S., Tamiya, A., Inagaki, Y., Taniguchi, Y., Nakao, K., Matsuda, Y., and Okishio, K. (2023). Osteoblastic Bone Reaction in Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutation Treated with Osimertinib. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11360-w"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"446","DOI":"10.2214\/AJR.19.21656","article-title":"Diagnostic Value of Whole-Body DWI With Background Body Suppression Plus Calculation of Apparent Diffusion Coefficient at 3 T Versus 18 F-FDG PET\/CT for Detection of Bone Metastases","volume":"214","author":"Sun","year":"2020","journal-title":"Am. J. Roentgenol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1002\/jmri.27596","article-title":"Metastatic Diffusion Volume Based on Apparent Diffusion Coefficient as a Prognostic Factor in Castration-Resistant Prostate Cancer","volume":"54","author":"Yamamoto","year":"2021","journal-title":"J. Magn. Reson. Imaging"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/1\/42\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:29:23Z","timestamp":1759919363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/1\/42"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["curroncol32010042"],"URL":"https:\/\/doi.org\/10.3390\/curroncol32010042","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]}}}