{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:54:00Z","timestamp":1791291240975,"version":"4.3.0"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2011,11,23]],"date-time":"2011-11-23T00:00:00Z","timestamp":1322006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The 3-year FREEDOM trial assessed the efficacy and safety of 60\u2009mg denosumab every 6 months for the treatment of postmenopausal women with osteoporosis. Participants who completed the FREEDOM trial were eligible to enter an extension to continue the evaluation of denosumab efficacy and safety for up to 10 years. For the extension results presented here, women from the FREEDOM denosumab group had 2 more years of denosumab treatment (long-term group) and those from the FREEDOM placebo group had 2 years of denosumab exposure (cross-over group). We report results for bone turnover markers (BTMs), bone mineral density (BMD), fracture rates, and safety. A total of 4550 women enrolled in the extension (2343 long-term; 2207 cross-over). Reductions in BTMs were maintained (long-term group) or occurred rapidly (cross-over group) following denosumab administration. In the long-term group, lumbar spine and total hip BMD increased further, resulting in 5-year gains of 13.7% and 7.0%, respectively. In the cross-over group, BMD increased at the lumbar spine (7.7%) and total hip (4.0%) during the 2-year denosumab treatment. Yearly fracture incidences for both groups were below rates observed in the FREEDOM placebo group and below rates projected for a \u201cvirtual untreated twin\u201d cohort. Adverse events did not increase with long-term denosumab administration. Two adverse events in the cross-over group were adjudicated as consistent with osteonecrosis of the jaw. Five-year denosumab treatment of women with postmenopausal osteoporosis maintained BTM reduction and increased BMD, and was associated with low fracture rates and a favorable risk\/benefit profile. \u00a9 2012 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.1479","type":"journal-article","created":{"date-parts":[[2011,11,23]],"date-time":"2011-11-23T10:31:46Z","timestamp":1322044306000},"page":"694-701","source":"Crossref","is-referenced-by-count":282,"title":["Five years of denosumab exposure in women with postmenopausal osteoporosis: Results from the first two years of the FREEDOM extension"],"prefix":"10.1093","volume":"27","author":[{"given":"Socrates","family":"Papapoulos","sequence":"first","affiliation":[{"name":"Department of Endocrinology & Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Chapurlat","sequence":"additional","affiliation":[{"name":"INSERM UMR 1033, Universit\u00e9 de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Libanati","sequence":"additional","affiliation":[{"name":"Amgen Inc., Thousand Oaks, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luisa","family":"Brandi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques P","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Medicine, Laval University and Rheumatology Division, CHUQ Research Centre, Laval University, Quebec City, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Czerwi\u0144ski","sequence":"additional","affiliation":[{"name":"Krakow Medical Center, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Antoine","family":"Krieg","sequence":"additional","affiliation":[{"name":"Bone and Joint Department, University Hospital of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zulema","family":"Man","sequence":"additional","affiliation":[{"name":"Endocrinology Division, Centro TIEMPO, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Mellstr\u00f6m","sequence":"additional","affiliation":[{"name":"Osteoporosis Clinic, Center for Bone Research, Sahlgrenska University Hospital, G\u00f6teborg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebasti\u00e3o C","family":"Radominski","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Universidade Federal do Paran\u00e1, Curitiba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Yves","family":"Reginster","sequence":"additional","affiliation":[{"name":"Bone and Cartilage Metabolism Unit, University of Li\u00e8ge, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Resch","sequence":"additional","affiliation":[{"name":"Medical Department II, St. Vincent Hospital, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A Rom\u00e1n","family":"Ivorra","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Hospital Universitario La Fe, Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Roux","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Cochin Hospital, Paris 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