{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:08:52Z","timestamp":1777597732172,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Aromatase inhibitors (AI) are extensively used as adjuvant endocrine therapy in post-menopausal women with hormone receptor-positive early breast cancer (HR+ EBC), but their impact on bone health is not negligible. This work aimed to assess bone loss, fracture incidence, and risk factors associated with these events, as well as the prognostic influence of fractures. We have conducted a retrospective cohort study of women with HR+ EBC under adjuvant therapy with AI, during a 3-year period. Four-hundred-and-fifty-one eligible women were reviewed (median age 68 years). Median time under AI was 40 months. A fracture event occurred in 8.4%, mostly in the radium and femoral neck and in older women (mean 74 vs. 68 years, p = 0.006). Age (OR 1.01, 95% CI 1.01\u20131.07, p = 0.024) and time under AI (OR 1.02, 95% CI 1.00\u20131.04, p = 0.037) were independent predictors of fracture, with a fair discrimination (AUC 0.71). Analysis of disease-free survival according to fracture event varied between groups, disfavoring the fracture cohort (at 73 months, survival 78.6%, 95% CI, 47.6\u201392.4 vs. 95.6%, 95% CI, 91.2\u201397.8, p = 0.027). The multivariate model confirmed the prognostic impact of fracture occurrence (adjusted HR of 3.17, 95% CI 1.10\u20139.11; p = 0.032). Bone health is often forgotten, despite its great impact in survivorship. Our results validate the pathophysiologic link between EBC and bone metabolism, which translates into EBC recurrence. Further research in this area may help refine these findings. Moreover, early identification of women at higher risk for fractures is warranted.<\/jats:p>","DOI":"10.3390\/curroncol28020104","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T21:02:34Z","timestamp":1614373354000},"page":"1067-1076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["From Theory to Practice: Bone Health in Women with Early Breast Cancer Treated with Aromatase Inhibitors"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9568-238X","authenticated-orcid":false,"given":"Leonor","family":"Vasconcelos de Matos","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Hospital de S\u00e3o Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6655-0986","authenticated-orcid":false,"given":"Leonor","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de S\u00e3o Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9891-8009","authenticated-orcid":false,"given":"Maria Teresa","family":"Neves","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de S\u00e3o Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e1tima","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de S\u00e3o Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mafalda","family":"Baleiras","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de S\u00e3o Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de S\u00e3o Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6724-899X","authenticated-orcid":false,"given":"Pedro","family":"Giesteira Cotovio","sequence":"additional","affiliation":[{"name":"CEAUL, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiago","family":"Dias Domingues","sequence":"additional","affiliation":[{"name":"CEAUL, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Malheiro","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de S\u00e3o Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisbon, Portugal"},{"name":"Department of Medical Oncology, Hospital Cuf Tejo, 1350-353 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Pl\u00e1cido","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de S\u00e3o Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Helena","family":"Miranda","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de S\u00e3o Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital de S\u00e3o Francisco Xavier, Centro Hospitalar de Lisboa Ocidental, 1449-005 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"v8","DOI":"10.1093\/annonc\/mdv298","article-title":"Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"26","author":"Senkus","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/S0140-6736(15)61074-1","article-title":"Aromatase inhibitors versus tamoxifen in early breast cancer: Patient-level meta-analysis of the randomised trials","volume":"386","author":"Bradley","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/bcr1757","article-title":"Effects of steroidal and nonsteroidal aromatase inhibitors on markers of bone turnover in healthy postmenopausal women","volume":"9","author":"Goss","year":"2007","journal-title":"Breast Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S0002-9343(03)00127-X","article-title":"The effects of adjuvant chemotherapy on bone density in postmenopausal women with early breast cancer","volume":"114","author":"Greep","year":"2003","journal-title":"Am. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s10549-005-3803-0","article-title":"Changes on bone mineral density after adjuvant treatment in women with non-metastatic breast cancer","volume":"93","author":"Llanos","year":"2005","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5769","DOI":"10.1200\/JCO.2006.07.2793","article-title":"Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer","volume":"24","author":"Walshe","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/0360-3016(92)90895-O","article-title":"Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer","volume":"23","author":"Pierce","year":"1992","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1093\/annonc\/mdv617","article-title":"Adjuvant bisphosphonates in early breast cancer: Consensus guidance for clinical practice from a European Panel","volume":"27","author":"Hadji","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jbo.2017.03.001","article-title":"Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG","volume":"7","author":"Hadji","year":"2017","journal-title":"J. Bone Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1093\/annonc\/mdu103","article-title":"Bone health in cancer patients: ESMO clinical practice guidelines","volume":"25","author":"Coleman","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1200\/JCO.2016.70.7257","article-title":"Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: A Cancer Care Ontario and American Society of Clinical Oncology clinical practice guideline","volume":"35","author":"Fletcher","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ctrv.2016.10.004","article-title":"Bone health in the elderly cancer patient: A SIOG position paper","volume":"51","author":"Body","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.ctrv.2008.03.007","article-title":"Guidance for the management of breast cancer treatment-induced bone loss: A consensus position statement from a UK Expert Group","volume":"34","author":"Reid","year":"2008","journal-title":"Cancer Treat. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1158\/1078-0432.CCR-10-1595","article-title":"Cancer Therapy: Clinical Cancer Therapy Associated Bone Loss: Implications for Hip Fractures in Mid-Life Women with Breast Cancer","volume":"17","author":"Edwards","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chang, C., Chen, S., and Liu, C. (2015). Fracture Risk and Adjuvant Therapies in Young Breast Cancer Patients: A Population- Based Study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130725"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1093\/annonc\/mdu008","article-title":"Fracture incidence after 3 years of aromatase inhibitor therapy","volume":"25","author":"Bouvard","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0140-6736(15)60995-3","article-title":"Adjuvant denosumab in breast cancer (ABCSG-18): A multicentre, randomised, double-blind, placebo-controlled trial","volume":"386","author":"Gnant","year":"2015","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/annonc\/mds277","article-title":"Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): Final 60-month results","volume":"24","author":"Coleman","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10549-009-0332-2","article-title":"Immediate versus delayed zoledronic acid for prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen-N03CC","volume":"117","author":"Hines","year":"2009","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1093\/annonc\/mdp033","article-title":"Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial","volume":"20","author":"Rabaglio","year":"2009","journal-title":"Ann. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1001\/jama.2009.50","article-title":"Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women","volume":"301","author":"Bliuc","year":"2009","journal-title":"JAMA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.critrevonc.2008.07.013","article-title":"Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis","volume":"69","author":"Hadji","year":"2009","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1093\/jnci\/djr242","article-title":"Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: A systematic review and meta-analysis","volume":"103","author":"Amir","year":"2011","journal-title":"Natl. Cancer Inst."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1093\/annonc\/mdz173","article-title":"Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up\u2020","volume":"30","author":"Cardoso","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1093\/annonc\/mdu222","article-title":"\u201cThe dilemmas of breast cancer treatment and increased fracture risk\u201d by Malik","volume":"25","author":"Bouvard","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1159\/000499931","article-title":"St. Gallen\/Vienna 2019: A brief summary of the consensus discussion on the optimal primary breast cancer treatment","volume":"14","author":"Balic","year":"2019","journal-title":"Breast Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"449","DOI":"10.21037\/gs.2018.08.03","article-title":"Extended duration of adjuvant aromatase inhibitor in breast cancer: A meta-analysis of randomized controlled trials","volume":"7","author":"Clement","year":"2018","journal-title":"Gland Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10549-019-05464-w","article-title":"Efficacy and toxicity of extended aromatase inhibitors after adjuvant aromatase inhibitors-containing therapy for hormone-receptor-positive breast cancer: A literature-based meta-analysis of randomized trials","volume":"179","author":"Qian","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s10549-007-9698-1","article-title":"Letrozole in the extended adjuvant setting: MA.17","volume":"105","author":"Goss","year":"2007","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_30","first-page":"1","article-title":"Osteoblasts are \u201ceducated\u201d by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis 06 Biological Sciences 0601 Biochemistry and Cell Biology 11 Medical and Health","volume":"21","author":"Kolb","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/S0140-6736(15)60908-4","article-title":"Adjuvant bisphosphonate treatment in early breast cancer: Meta-analyses of individual patient data from randomised trials","volume":"386","author":"Coleman","year":"2015","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/S1470-2045(14)70302-X","article-title":"Adjuvant zoledronic acid in patients with early breast cancer: Final efficacy analysis of the AZURE (BIG 01\/04) randomised open-label phase 3 trial","volume":"15","author":"Coleman","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/annonc\/mdu544","article-title":"Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: Final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12","volume":"26","author":"Gnant","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s11864-018-0535-z","article-title":"Adjuvant Bisphosphonate Therapy in Postmenopausal Breast Cancer","volume":"19","author":"Strobl","year":"2018","journal-title":"Curr. Treat. Options Oncol."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/2\/104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:29:39Z","timestamp":1760160579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/28\/2\/104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,26]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["curroncol28020104"],"URL":"https:\/\/doi.org\/10.3390\/curroncol28020104","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,26]]}}}