{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:20:49Z","timestamp":1792545649665,"version":"4.5.0"},"reference-count":36,"publisher":"Elsevier BV","issue":"16","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","ejcancer.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Cancer"],"published-print":{"date-parts":[[2012,11]]},"DOI":"10.1016\/j.ejca.2012.08.002","type":"journal-article","created":{"date-parts":[[2012,9,10]],"date-time":"2012-09-10T13:16:01Z","timestamp":1347282961000},"page":"3082-3092","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":502,"title":["Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials"],"prefix":"10.1016","volume":"48","clinical-trial-number":[{"clinical-trial-number":"nct00321464","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00321620","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct00330759","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Allan","family":"Lipton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Fizazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison T.","family":"Stopeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet E.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise A.","family":"Yardley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Siena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Maroto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Clemens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Bilynskyy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veena","family":"Charu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Beuzeboc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Viniegra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlei","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada","family":"Braun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susie","family":"Jun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"8","key":"10.1016\/j.ejca.2012.08.002_b0005","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.ctrv.2010.04.003","article-title":"Metastasis and bone loss: advancing treatment and prevention","volume":"36","author":"Coleman","year":"2010","journal-title":"Cancer Treat Rev"},{"issue":"20 Pt. 2","key":"10.1016\/j.ejca.2012.08.002_b0010","doi-asserted-by":"crossref","first-page":"6243s","DOI":"10.1158\/1078-0432.CCR-06-0931","article-title":"Clinical features of metastatic bone disease and risk of skeletal morbidity","volume":"12","author":"Coleman","year":"2006","journal-title":"Clin Cancer Res"},{"issue":"1","key":"10.1016\/j.ejca.2012.08.002_b0015","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":"Norgaard","year":"2010","journal-title":"J Urol"},{"issue":"5\u20136","key":"10.1016\/j.ejca.2012.08.002_b0020","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1159\/000082923","article-title":"The cost of treatment of skeletal-related events in patients with bone metastases from lung cancer","volume":"67","author":"Delea","year":"2004","journal-title":"Oncology"},{"issue":"8","key":"10.1016\/j.ejca.2012.08.002_b0025","first-page":"879","article-title":"Impact of skeletal complications on patients\u2019 quality of life, mobility, and functional independence","volume":"16","author":"Costa","year":"2008","journal-title":"Support Care Cancer"},{"issue":"5","key":"10.1016\/j.ejca.2012.08.002_b0030","first-page":"317","article-title":"The cost of treating skeletal-related events in patients with prostate cancer","volume":"14","author":"Lage","year":"2008","journal-title":"Am J Manag Care"},{"issue":"9","key":"10.1016\/j.ejca.2012.08.002_b0035","first-page":"693","article-title":"Payer costs for inpatient treatment of pathologic fracture, surgery to bone, and spinal cord compression among patients with multiple myeloma or bone metastasis secondary to prostate or breast cancer","volume":"16","author":"Barlev","year":"2010","journal-title":"J Manag Care Pharm"},{"issue":"6","key":"10.1016\/j.ejca.2012.08.002_b0040","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1200\/JCO.1998.16.6.2038","article-title":"Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. Protocol 19 Aredia Breast Cancer Study Group","volume":"16","author":"Hortobagyi","year":"1998","journal-title":"J Clin Oncol"},{"issue":"3","key":"10.1016\/j.ejca.2012.08.002_b0045","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1200\/JCO.1999.17.3.846","article-title":"Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group","volume":"17","author":"Theriault","year":"1999","journal-title":"J Clin Oncol"},{"issue":"5","key":"10.1016\/j.ejca.2012.08.002_b0050","first-page":"377","article-title":"Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial","volume":"7","author":"Rosen","year":"2001","journal-title":"Cancer J"},{"issue":"19","key":"10.1016\/j.ejca.2012.08.002_b0055","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1093\/jnci\/94.19.1458","article-title":"A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma","volume":"94","author":"Saad","year":"2002","journal-title":"J Natl Cancer Inst"},{"issue":"16","key":"10.1016\/j.ejca.2012.08.002_b0060","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1200\/JCO.2003.04.105","article-title":"Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial \u2013 the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group","volume":"21","author":"Rosen","year":"2003","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2012.08.002_b0065","unstructured":"Zometa (zoledronic acid) injection, concentrate for intravenous infusion [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2009."},{"issue":"6","key":"10.1016\/j.ejca.2012.08.002_b0070","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1002\/cncr.22904","article-title":"Prevalence of Renal Insufficiency in cancer patients and implications for anticancer drug management: the renal insufficiency and anticancer medications (IRMA) study","volume":"110","author":"Launay-Vacher","year":"2007","journal-title":"Cancer"},{"issue":"2","key":"10.1016\/j.ejca.2012.08.002_b0075","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(00)81569-X","article-title":"Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation","volume":"93","author":"Lacey","year":"1998","journal-title":"Cell"},{"issue":"3","key":"10.1016\/j.ejca.2012.08.002_b0080","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1210\/endo.139.3.5837","article-title":"Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG\/OCIF inhibits osteoclastogenesis in vitro","volume":"139","author":"Yasuda","year":"1998","journal-title":"Endocrinology"},{"issue":"7","key":"10.1016\/j.ejca.2012.08.002_b0085","first-page":"2587","article-title":"Prostate cancer cells\u2013osteoblast interaction shifts expression of growth\/survival-related genes in prostate cancer and reduces expression of osteoprotegerin in osteoblasts","volume":"9","author":"Fizazi","year":"2003","journal-title":"Clin Cancer Res"},{"issue":"1","key":"10.1016\/j.ejca.2012.08.002_b0090","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1136\/jcp.2005.026534","article-title":"Expression of osteoprotegerin (OPG), TNF related apoptosis inducing ligand (TRAIL), and receptor activator of nuclear factor kappaB ligand (RANKL) in human breast tumours","volume":"59","author":"Van Poznak","year":"2006","journal-title":"J Clin Pathol"},{"issue":"4","key":"10.1016\/j.ejca.2012.08.002_b0095","first-page":"1436","article-title":"Expression of receptor activator of nuclear factor kappaB ligand on bone marrow plasma cells correlates with osteolytic bone disease in patients with multiple myeloma","volume":"9","author":"Heider","year":"2003","journal-title":"Clin Cancer Res"},{"issue":"2","key":"10.1016\/j.ejca.2012.08.002_b0100","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s10585-007-9127-1","article-title":"Inhibition of RANKL blocks skeletal tumor progression and improves survival in a mouse model of breast cancer bone metastasis","volume":"25","author":"Canon","year":"2008","journal-title":"Clin Exp Metastasis"},{"issue":"28","key":"10.1016\/j.ejca.2012.08.002_b0105","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1200\/JCO.2007.11.8604","article-title":"Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases","volume":"25","author":"Lipton","year":"2007","journal-title":"J Clin Oncol"},{"issue":"30","key":"10.1016\/j.ejca.2012.08.002_b0110","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.1200\/JCO.2008.16.3832","article-title":"Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer","volume":"26","author":"Ellis","year":"2008","journal-title":"J Clin Oncol"},{"issue":"10","key":"10.1016\/j.ejca.2012.08.002_b0115","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1200\/JCO.2008.19.2146","article-title":"Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates","volume":"27","author":"Fizazi","year":"2009","journal-title":"J Clin Oncol"},{"issue":"8","key":"10.1016\/j.ejca.2012.08.002_b0120","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1056\/NEJMoa0809003","article-title":"Denosumab in men receiving androgen-deprivation therapy for prostate cancer","volume":"361","author":"Smith","year":"2009","journal-title":"N Engl J Med"},{"issue":"35","key":"10.1016\/j.ejca.2012.08.002_b0125","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":"10.1016\/j.ejca.2012.08.002_b0130","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0140-6736(10)62344-6","article-title":"A randomised, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in men with castration-resistant prostate cancer","volume":"377","author":"Fizazi","year":"2011","journal-title":"Lancet"},{"issue":"9","key":"10.1016\/j.ejca.2012.08.002_b0135","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1200\/JCO.2010.31.3304","article-title":"A randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma","volume":"29","author":"Henry","year":"2011","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.ejca.2012.08.002_b0140","unstructured":"XGEVA (denosumab) injection, for subcutaneous use, [prescribing information]. Thousand Oaks, CA: Amgen Inc.; 2012."},{"issue":"5","key":"10.1016\/j.ejca.2012.08.002_b0145","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1093\/annonc\/mdr435","article-title":"Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases","volume":"23","author":"Saad","year":"2012","journal-title":"Ann Oncol"},{"issue":"8","key":"10.1016\/j.ejca.2012.08.002_b0150","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1001\/jama.299.8.937","article-title":"Spinal cord compression in patients with advanced metastatic cancer: \u201call I care about is walking and living my life\u201d","volume":"299","author":"Abrahm","year":"2008","journal-title":"JAMA"},{"issue":"7","key":"10.1016\/j.ejca.2012.08.002_b0155","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1191\/0269216305pm1079oa","article-title":"Painful bone metastases: a prospective observational cohort study","volume":"19","author":"Clare","year":"2005","journal-title":"Palliat Med"},{"issue":"6","key":"10.1016\/j.ejca.2012.08.002_b0160","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1634\/theoncologist.5-6-463","article-title":"Management of bone metastases","volume":"5","author":"Coleman","year":"2000","journal-title":"Oncologist"},{"issue":"4","key":"10.1016\/j.ejca.2012.08.002_b0165","doi-asserted-by":"crossref","first-page":"712","DOI":"10.3111\/13696998.2012.675380","article-title":"Cost-effectiveness of denosumab vs zoledronic acid for prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States","volume":"15","author":"Stopeck","year":"2012","journal-title":"J Med Econ"},{"issue":"3","key":"10.1016\/j.ejca.2012.08.002_b0170","doi-asserted-by":"crossref","first-page":"E83","DOI":"10.3816\/CGC.2009.n.029","article-title":"Drug management of prostate cancer: prevalence and consequences of renal insufficiency","volume":"7","author":"Launay-Vacher","year":"2009","journal-title":"Clin Genitourin Cancer"},{"issue":"6","key":"10.1016\/j.ejca.2012.08.002_b0175","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/cncr.22504","article-title":"The risk of renal impairment in hormone-refractory prostate cancer patients with bone metastases treated with zoledronic acid","volume":"109","author":"Oh","year":"2007","journal-title":"Cancer"},{"issue":"4","key":"10.1016\/j.ejca.2012.08.002_b0185","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1159\/000209246","article-title":"Pathophysiology of calcium and phosphate metabolism impairment in chronic kidney disease","volume":"27","author":"Cozzolino","year":"2009","journal-title":"Blood Purif"}],"container-title":["European Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S095980491200617X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S095980491200617X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T20:18:13Z","timestamp":1760732293000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S095980491200617X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11]]},"references-count":36,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["S095980491200617X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejca.2012.08.002","relation":{},"ISSN":["0959-8049"],"issn-type":[{"value":"0959-8049","type":"print"}],"subject":[],"published":{"date-parts":[[2012,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: A combined analysis of 3 pivotal, randomised, phase 3 trials","name":"articletitle","label":"Article Title"},{"value":"European Journal of Cancer","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejca.2012.08.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2012 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}