{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T04:40:38Z","timestamp":1771476038849,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2008,5,1]],"date-time":"2008-05-01T00:00:00Z","timestamp":1209600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Learning Objectives<\/jats:title>\n                  <jats:p>After reading this article, the reader should be able to: Monitor for and treat to prevent bone loss in postmenopausal breast cancer patients receiving an aromatase inhibitor.Describe the methodology of the Z-FAST and ZO-FAST clinical trials.Discuss the effectiveness and tolerability of zoledronic acid when administrated to prevent bone loss associated with aromatase inhibitors.<\/jats:p>\n                  <jats:p>CME This article is available for continuing medical education credit at CME.TheOncologist.com<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Background.<\/jats:title>\n                  <jats:p>The interim (12-month) results of two similarly designed, ongoing studies (the Zometa\u00ae-Femara\u00ae Adjuvant Synergy Trials [Z-FAST and ZO-FAST]) suggest that zoledronic acid (4 mg intravenously every 6 months) when initiated with adjuvant letrozole increases bone mineral density (BMD) of the lumbar spine (LS) in postmenopausal women with early-stage breast cancer compared with patients who receive zoledronic acid only when bone loss became clinically significant or a fragility fracture occurred.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods.<\/jats:title>\n                  <jats:p>An integrated analysis was performed to maximize the value of the large pool of data from the two studies in answering clinically relevant questions. The primary objective was to compare the change in LS BMD at month 12. Secondary objectives included comparing (a) the change in total hip (TH) BMD, (b) changes in bone turnover marker concentrations, (c) time to disease recurrence, and (d) safety at month 12.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Findings.<\/jats:title>\n                  <jats:p>The integrated analysis included 1,667 patients. At month 12, LS BMD was 5.2% higher in the upfront group than in the delayed group; TH BMD was 3.5% higher. N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 21.3% and 12.8% in the upfront group and increased by 21.7% and 24.9% in the delayed group, respectively (p &amp;lt; .0001 for intergroup comparisons). Fewer patients receiving upfront zoledronic acid experienced disease recurrence than patients in the delayed group\u2014seven patients (0.84%) versus 17 patients (1.9%) (p = .0401). Fracture rates were similar. No confirmed osteonecrosis of the jaw was reported.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions.<\/jats:title>\n                  <jats:p>The results of this analysis strengthen the statistical validity of the preliminary results of the Z-FAST and ZO-FAST studies, showing that upfront zoledronic acid prevents aromatase inhibitor\u2013associated bone loss more effectively than delayed-start zoledronic acid in postmenopausal women with early-stage breast cancer receiving letrozole. Additionally, disease recurrence appears to be lower with upfront zoledronic acid, but further follow-up is needed to confirm these interim results.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2007-0206","type":"journal-article","created":{"date-parts":[[2008,5,30]],"date-time":"2008-05-30T20:53:48Z","timestamp":1212180828000},"page":"503-514","source":"Crossref","is-referenced-by-count":141,"title":["Integrated Analysis of Zoledronic Acid for Prevention of Aromatase Inhibitor\u2013Associated Bone Loss in Postmenopausal Women with Early Breast Cancer Receiving Adjuvant Letrozole"],"prefix":"10.1093","volume":"13","author":[{"given":"Adam","family":"Brufsky","sequence":"first","affiliation":[{"name":"a Magee-Womens Hospital, Pittsburgh, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Bundred","sequence":"additional","affiliation":[{"name":"b University Hospital of South Manchester NHS Foundation Trust, Academic Department of Surgery, Education and Research Center, Wythenshawe, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Coleman","sequence":"additional","affiliation":[{"name":"c Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary","family":"Lambert-Falls","sequence":"additional","affiliation":[{"name":"d South Carolina Oncology Associates, Columbia, South Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raul","family":"Mena","sequence":"additional","affiliation":[{"name":"e East Valley Hematology & Oncology Medical Group, Burbank, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peyman","family":"Hadji","sequence":"additional","affiliation":[{"name":"f Philipps-Universit\u00e4t Marburg, University Hospital of Giessen and Marburg, GmbH, Marburg, Department of Gynecology, Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixian","family":"Jin","sequence":"additional","affiliation":[{"name":"g Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Schenk","sequence":"additional","affiliation":[{"name":"g Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solveig","family":"Ericson","sequence":"additional","affiliation":[{"name":"g Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edith A.","family":"Perez","sequence":"additional","affiliation":[{"name":"h Mayo Clinic Jacksonville, Jacksonville, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,5,1]]},"reference":[{"key":"2021122208421938600_R1","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1200\/JCO.2006.08.8617","article-title":"Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: Update of study BIG 1\u201398","volume":"25","author":"Coates","year":"2007","journal-title":"J Clin Oncol"},{"key":"2021122208421938600_R2","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S0140-6736(05)67059-6","article-title":"Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: Combined results of ABCSG trial 8 and ARNO 95 trial","volume":"366","author":"Jakesz","year":"2005","journal-title":"Lancet"},{"key":"2021122208421938600_R3","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S0140-6736(07)60200-1","article-title":"Survival and safety of exemestane versus tamoxifen after 2\u20133 years' tamoxifen treatment (Intergroup Exemestane Study): A randomised controlled trial","volume":"369","author":"Coombes","year":"2007","journal-title":"Lancet"},{"key":"2021122208421938600_R4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0140-6736(04)17666-6","article-title":"; ATAC Trialists' Group. 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