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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\n      \u003Ch2\u003ESummary\u003C\/h2\u003E\n      \u003Cp id=\u0022p-1\u0022\u003EThe efficacy and safety of the antiresorptive agent denosumab on bone mineral density and fracture rates were assessed in an open-label extension, crossover trial of the original 3-year, randomized, placebo-controlled Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months study. [FREEDOM; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00089791\u0026amp;atom=%2Fspmdc%2F11%2F13%2F12.atom\u0022\u003ENCT00089791\u003C\/a\u003E; Cummings SR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009].\u003C\/p\u003E\n   \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Emetabolic bone disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Emetabolic bone disease clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n      \u003Cp id=\u0022p-2\u0022\u003EThe efficacy and safety of the antiresorptive agent denosumab on bone mineral density (BMD) and fracture rates were assessed in an open-label extension, crossover trial of the original 3-year, randomized, placebo-controlled Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months study. [FREEDOM; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT00089791\u0026amp;atom=%2Fspmdc%2F11%2F13%2F12.atom\u0022\u003ENCT00089791\u003C\/a\u003E; Cummings SR et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2009].\u003C\/p\u003E\n      \u003Cp id=\u0022p-3\u0022\u003ESubjects were recruited for the 3-year extension of the trial if they had completed their Year 3 and had not missed more than 1 dose of the study medication (or placebo) during the trial. Of 5928 individuals who were eligible for the extension, 4550 (77%) elected to continue\u20142343 continued to receive denosumab and 2207 crossed over from placebo to denosumab. All participants received 60 mg of denosumab every 6 months, took supplemental calcium and vitamin D daily, and will be followed for 7 years in the extension\u2014therefore, up to 10 years of treatment with denosumab.\u003C\/p\u003E\n      \u003Cp id=\u0022p-4\u0022\u003ELead investigator Jacques Brown, MD, CHUQ-CHUL Research Centre, Laval University, Laval, Quebec, Canada, noted that both groups demonstrated a rapid and profound reduction of the resorption marker serum collagen type 1 crosslinked C-telopeptide (CTX) and a similar improvement in levels of the bone formation marker serum type 1 procollagen N-terminal (P1NP) after infusion, with the characteristic attenuation observed at the end of each dosing period.\u003C\/p\u003E\n      \u003Cp id=\u0022p-5\u0022\u003EParticipants in the extension phase exhibited continued improvement in BMD. There was a 6-year mean cumulative improvement of 15.2% at the lumbar spine and 7.5% at the total hip. The crossover group experienced a statistically significant (p\u0026lt;0.05) increase in BMD of 9.4% at the lumbar spine and 4.8% at the total hip, increases that were comparable with the denosumab-treated group during the initial 3-year FREEDOM trial.\u003C\/p\u003E\n      \u003Cp id=\u0022p-6\u0022\u003EThe annual rate of new vertebral and nonvertebral fractures in the long-term group remained low (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). In the crossover group, the rate of vertebral and nonvertebral fractures was much lower than in the placebo group of FREEDOM.\u003C\/p\u003E\n      \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\n         \u003Cdiv class=\u0022table-inline\u0022\u003E\n            \u003Cdiv class=\u0022callout\u0022\u003E\n               \u003Cspan\u003EView this table:\u003C\/span\u003E\n               \u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/12618\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/12618\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/12618\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\n            \u003C\/div\u003E\n         \u003C\/div\u003E\n         \u003Cdiv class=\u0022table-caption\u0022\u003E\n            \u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EAnnual Rate of New Vertebral and Nonvertebral Fractures.\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\n      \u003C\/div\u003E\n      \u003Cp id=\u0022p-8\u0022\u003EAdverse events per 100 subject years were similar between the crossover and extension groups. Two participants in the crossover group developed osteonecrosis of the jaw (ONJ), both of which resolved. Two participants in the follow-on group also developed ONJ, and both continue to be followed. There have been no reported atypical femur fractures in either group.\u003C\/p\u003E\n      \u003Cp id=\u0022p-9\u0022\u003E\u201cThe continued increase in bone mineral density was surprising,\u201d said Prof. Brown. \u201cWith an antiresorptive, we would expect at some point that bone mineral density would plateau; so, it is very surprising to still see a significant increase over 6 years,\u201d he concluded.\u003C\/p\u003E\n   \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/13\/12.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmw81\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzmw81\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}