<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01732770</url>
  </required_header>
  <id_info>
    <org_study_id>20110153</org_study_id>
    <secondary_id>2012-001821-28</secondary_id>
    <nct_id>NCT01732770</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis</brief_title>
  <official_title>A Randomized Double-blind Study to Evaluate the Safety and Efficacy of Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amgen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will compare the effectiveness of denosumab treatment every 6 months with once&#xD;
      yearly zoledronic acid treatment on bone mineral density (BMD) at various skeletal sites.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 7, 2012</start_date>
  <completion_date type="Actual">January 7, 2015</completion_date>
  <primary_completion_date type="Actual">January 7, 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis</measure>
    <time_frame>Baseline and Month 12</time_frame>
    <description>Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis</measure>
    <time_frame>Baseline and Month 12</time_frame>
    <description>BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis</measure>
    <time_frame>Baseline and Month 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis</measure>
    <time_frame>Baseline and Month 12</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">643</enrollment>
  <condition>Post Menopausal Osteoporosis</condition>
  <arm_group>
    <arm_group_label>Denosumab 60 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received denosumab 60 mg subcutaneous injection once every 6 months for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Zoledronic Acid 5 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants received zoledronic acid 5 mg by intravenous infusion on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Denosumab</intervention_name>
    <description>Denosumab 60 mg administered by subcutaneous injection once every 6 months.</description>
    <arm_group_label>Denosumab 60 mg</arm_group_label>
    <other_name>Prolia®</other_name>
    <other_name>AMG 162</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zoledronic Acid</intervention_name>
    <description>Zoledronic acid 5 mg administered by intravenous infusion once a year</description>
    <arm_group_label>Zoledronic Acid 5 mg</arm_group_label>
    <other_name>Reclast</other_name>
    <other_name>Aclasta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo to Denosumab</intervention_name>
    <description>Administered by subcutaneous injection once every 6 months</description>
    <arm_group_label>Zoledronic Acid 5 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo to Zoledronic Acid</intervention_name>
    <description>Administered by intravenous infusion once a year</description>
    <arm_group_label>Denosumab 60 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ambulatory postmenopausal women.&#xD;
&#xD;
          -  Age 55 years or older&#xD;
&#xD;
          -  Subject has provided informed consent prior to any study specific procedures&#xD;
&#xD;
          -  Received oral bisphosphonate therapy for osteoporosis at least 2 years prior to&#xD;
             screening visit&#xD;
&#xD;
          -  Screening BMD (g/cm²) values at the lumbar spine, total hip or femoral neck values of&#xD;
             equal to or less than those listed in the protocol.&#xD;
&#xD;
          -  At least 2 lumbar vertebrae and one hip must be evaluable by dual energy x-ray&#xD;
             absorptiometry (DXA) at the screening visit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received other osteoporosis treatment or bone active treatment&#xD;
&#xD;
          -  Evidence of history of any of the following:&#xD;
&#xD;
               -  hyperthyroidism (stable on antithyroid therapy is allowed)&#xD;
&#xD;
               -  hypothyroidism (stable on thyroid replacement therapy is allowed)&#xD;
&#xD;
               -  hypo- or hyperparathyroidism&#xD;
&#xD;
               -  hypo- or hypercalcemia based on the central laboratory reference ranges&#xD;
&#xD;
               -  Recent tooth extraction (within 6 months of screening visit)&#xD;
&#xD;
               -  Paget disease of bone (subject report or chart review)&#xD;
&#xD;
               -  other bone diseases which affect bone metabolism (eg, osteopetrosis, osteogenesis&#xD;
                  imperfecta) (chart review)&#xD;
&#xD;
          -  Abnormalities of the following per central laboratory reference ranges:&#xD;
&#xD;
               -  vitamin D deficiency (25[OH] vitamin D level &lt; 20 ng/mL), repletion will be&#xD;
                  allowed and subjects may be re-screened&#xD;
&#xD;
               -  hypercalcemia&#xD;
&#xD;
               -  elevated transaminases ≥ 2.0 x upper limits of normal (ULN)&#xD;
&#xD;
          -  History of any solid organ or bone marrow transplant&#xD;
&#xD;
          -  Malignancy (except nonmelanoma skin cancers, cervical or breast ductal carcinoma in&#xD;
             situ) within the last 5 years&#xD;
&#xD;
          -  Known intolerance to calcium or vitamin D supplements&#xD;
&#xD;
          -  Self-reported alcohol or drug abuse within 12 months prior to screening&#xD;
&#xD;
          -  Currently receiving treatment in another investigational device or drug study, or less&#xD;
             than 30 days since ending treatment on another investigational device or drug study(s)&#xD;
&#xD;
          -  History or evidence of any other clinically significant disorder, condition or disease&#xD;
             that in the opinion of the Investigator or Amgen physician, if consulted, would pose a&#xD;
             risk to subject safety or interfere with the study evaluation, procedures or&#xD;
             completion&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lakewood</city>
        <state>Colorado</state>
        <zip>80227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Longmont</city>
        <state>Colorado</state>
        <zip>80501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hagerstown</city>
        <state>Maryland</state>
        <zip>21740</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48236</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>West Haverstraw</city>
        <state>New York</state>
        <zip>10993</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77074</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Maroubra</city>
        <state>New South Wales</state>
        <zip>2035</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Penrith</city>
        <state>New South Wales</state>
        <zip>2750</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>St Leonards</city>
        <state>New South Wales</state>
        <zip>2065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Box Hill</city>
        <state>Victoria</state>
        <zip>3128</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Geelong</city>
        <state>Victoria</state>
        <zip>3220</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brussels</city>
        <zip>1050</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brussel</city>
        <zip>1090</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bruxelles</city>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bruxelles</city>
        <zip>1020</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Genk</city>
        <zip>3600</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Liège</city>
        <zip>4020</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Merksem</city>
        <zip>2170</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Tessenderlo</city>
        <zip>3980</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Wilrijk</city>
        <zip>2610</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Yvoir</city>
        <zip>5530</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 4Z6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 2Y9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5C 2T2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M9W 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Quebec</city>
        <zip>G1V 3M7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Aalborg</city>
        <zip>9000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ballerup</city>
        <zip>2750</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Vejle</city>
        <zip>7100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bialystok</city>
        <zip>15-879</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kraków</city>
        <zip>31-501</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Torun</city>
        <zip>87-100</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Warszawa</city>
        <zip>01-192</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Granada</city>
        <state>Andalucía</state>
        <zip>18012</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <state>Cataluña</state>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <state>Cataluña</state>
        <zip>08041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Canada</country>
    <country>Denmark</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.amgentrials.com</url>
    <description>AmgenTrials clinical trials website</description>
  </link>
  <reference>
    <citation>Miller PD, Pannacciulli N, Brown JP, Czerwinski E, Nedergaard BS, Bolognese MA, Malouf J, Bone HG, Reginster JY, Singer A, Wang C, Wagman RB, Cummings SR. Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. J Clin Endocrinol Metab. 2016 Aug;101(8):3163-70. doi: 10.1210/jc.2016-1801. Epub 2016 Jun 6.</citation>
    <PMID>27270237</PMID>
  </reference>
  <reference>
    <citation>Miller PD, Pannacciulli N, Malouf-Sierra J, Singer A, Czerwinski E, Bone HG, Wang C, Huang S, Chines A, Lems W, Brown JP. Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates. Osteoporos Int. 2020 Jan;31(1):181-191. doi: 10.1007/s00198-019-05233-x. Epub 2019 Nov 28.</citation>
    <PMID>31776637</PMID>
  </reference>
  <reference>
    <citation>Chotiyarnwong P, McCloskey E, Eastell R, McClung MR, Gielen E, Gostage J, McDermott M, Chines A, Huang S, Cummings SR. A Pooled Analysis of Fall Incidence From Placebo-Controlled Trials of Denosumab. J Bone Miner Res. 2020 Jun;35(6):1014-1021. doi: 10.1002/jbmr.3972. Epub 2020 Apr 2.</citation>
    <PMID>31999376</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 26, 2012</study_first_posted>
  <results_first_submitted>December 9, 2015</results_first_submitted>
  <results_first_submitted_qc>December 17, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 25, 2016</results_first_posted>
  <last_update_submitted>March 2, 2020</last_update_submitted>
  <last_update_submitted_qc>March 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoporosis</mesh_term>
    <mesh_term>Osteoporosis, Postmenopausal</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Zoledronic Acid</mesh_term>
    <mesh_term>Denosumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at 37 centers in Belgium, Denmark, Poland, Spain, Canada, United States of America, and Australia. The first participant enrolled on 07 November 2012 and the last participant enrolled on 15 January 2014.</recruitment_details>
      <pre_assignment_details>Participants were randomized in a 1:1 allocation ratio to receive either denosumab or zoledronic acid. Randomization was stratified by screening serum type I collagen C-telopeptide (sCTX) values (&lt; 0.3 ng/mL, 0.3 to 0.5 ng/mL).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Zoledronic Acid 5 mg Q12M</title>
          <description>Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.</description>
        </group>
        <group group_id="P2">
          <title>Denosumab 60 mg Q6M</title>
          <description>Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="322"/>
                <participants group_id="P2" count="321"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Study Treatment</title>
              <participants_list>
                <participants group_id="P1" count="320"/>
                <participants group_id="P2" count="320"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="312"/>
                <participants group_id="P2" count="313"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Decision by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Zoledronic Acid 5 mg Q12M</title>
          <description>Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.</description>
        </group>
        <group group_id="B2">
          <title>Denosumab 60 mg Q6M</title>
          <description>Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="322"/>
            <count group_id="B2" value="321"/>
            <count group_id="B3" value="643"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.5" spread="7.7"/>
                    <measurement group_id="B2" value="68.5" spread="7.1"/>
                    <measurement group_id="B3" value="69.0" spread="7.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="322"/>
                    <measurement group_id="B2" value="321"/>
                    <measurement group_id="B3" value="643"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="314"/>
                    <measurement group_id="B2" value="309"/>
                    <measurement group_id="B3" value="623"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Screening serum CTX</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt; 0.3 ng/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="242"/>
                    <measurement group_id="B2" value="239"/>
                    <measurement group_id="B3" value="481"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥ 0.3 ng/mL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="78"/>
                    <measurement group_id="B2" value="82"/>
                    <measurement group_id="B3" value="160"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Missing</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Lumbar Spine Bone Mineral Density (BMD) T-score</title>
          <description>BMD was measured using dual-energy x-ray absorptiometry (DXA) of the lumbar spine. The T-score is a comparison of a person's bone density with that of a healthy 30-year-old of the same sex. Lower scores (more negative) mean lower bone density: A T-score of -2.5 or lower qualifies as osteoporosis and a T-score of -1.0 to -2.5 signifies osteopenia, meaning below-normal bone density without full osteoporosis.</description>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-2.64" spread="0.86"/>
                    <measurement group_id="B2" value="-2.74" spread="0.83"/>
                    <measurement group_id="B3" value="-2.69" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Total Hip BMD T-score</title>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-1.93" spread="0.80"/>
                    <measurement group_id="B2" value="-1.93" spread="0.74"/>
                    <measurement group_id="B3" value="-1.93" spread="0.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Femoral Neck BMD T-score</title>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-2.17" spread="0.68"/>
                    <measurement group_id="B2" value="-2.17" spread="0.66"/>
                    <measurement group_id="B3" value="-2.17" spread="0.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Prior Oral Bisphosphonate Duration</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6.35" spread="3.68"/>
                    <measurement group_id="B2" value="6.21" spread="3.84"/>
                    <measurement group_id="B3" value="6.28" spread="3.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Historical Fractures</title>
          <description>An osteoporotic fracture is defined as a reported fracture excluding skull fracture, facial bones fracture, fingers fracture and toes fracture, fractures with high trauma severity, and pathological fractures.</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Any prior fracture</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="159"/>
                    <measurement group_id="B2" value="169"/>
                    <measurement group_id="B3" value="328"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Prior osteoporotic fracture</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="121"/>
                    <measurement group_id="B2" value="120"/>
                    <measurement group_id="B3" value="241"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kg/m²</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.31" spread="4.18"/>
                    <measurement group_id="B2" value="24.27" spread="3.99"/>
                    <measurement group_id="B3" value="24.29" spread="4.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis</title>
        <description>Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility.</description>
        <time_frame>Baseline and Month 12</time_frame>
        <population>The primary efficacy analysis set includes all randomized participants who have a baseline BMD measurement and at least one postbaseline BMD measurement. Any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, last observation carried forward [LOCF]).</population>
        <group_list>
          <group group_id="O1">
            <title>Zoledronic Acid 5 mg Q12M</title>
            <description>Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab 60 mg Q6M</title>
            <description>Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis</title>
          <description>Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility.</description>
          <population>The primary efficacy analysis set includes all randomized participants who have a baseline BMD measurement and at least one postbaseline BMD measurement. Any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, last observation carried forward [LOCF]).</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="312"/>
                <count group_id="O2" value="314"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" lower_limit="0.7" upper_limit="1.5"/>
                    <measurement group_id="O2" value="3.2" lower_limit="2.8" upper_limit="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A step-down sequential testing procedure was used in order to maintain the overall type I error rate at 5% for the tests of primary and secondary BMD endpoints. For the non-inferiority analysis the 1-sided significance level was 2.5%.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence (legacy)</non_inferiority_type>
            <non_inferiority_desc>The lower bound of the 2-sided 95% confidence interval (CI) of (denosumab - zoledronic acid) was compared with the non-inferiority margin of -0.46% for assessing non-inferiority.</non_inferiority_desc>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <method_desc>The model included treatment, screening sCTX, baseline BMD, DXA machine type (Hologic or Lunar), and baseline BMD-by-machine type interaction.</method_desc>
            <param_type>Treatment Difference</param_type>
            <param_value>2.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.6</ci_lower_limit>
            <ci_upper_limit>2.6</ci_upper_limit>
            <estimate_desc>Treatment difference = denosumab - zoledronic acid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis</title>
        <description>BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility.</description>
        <time_frame>Baseline and Month 12</time_frame>
        <population>The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF).</population>
        <group_list>
          <group group_id="O1">
            <title>Zoledronic Acid 5 mg Q12M</title>
            <description>Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab 60 mg Q6M</title>
            <description>Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis</title>
          <description>BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility.</description>
          <population>The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF).</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="309"/>
                <count group_id="O2" value="311"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" lower_limit="0.3" upper_limit="0.8"/>
                    <measurement group_id="O2" value="1.9" lower_limit="1.7" upper_limit="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A step-down sequential testing procedure was used in order to maintain the overall type I error rate at 5% for the tests of primary and secondary BMD endpoints. For the non-inferiority analysis the 1-sided significance level was 2.5%.</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence (legacy)</non_inferiority_type>
            <non_inferiority_desc>The lower bound of the 2-sided 95% CI) of (denosumab - zoledronic acid) was compared with the non-inferiority margin of -0.51% for assessing non-inferiority.</non_inferiority_desc>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <method_desc>The model included treatment, screening sCTX, baseline BMD, DXA machine type (Hologic or Lunar), and baseline BMD-by-machine type interaction.</method_desc>
            <param_type>Treatment Difference</param_type>
            <param_value>1.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.0</ci_lower_limit>
            <ci_upper_limit>1.7</ci_upper_limit>
            <estimate_desc>Treatment difference = denosumab - zoledronic acid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis</title>
        <time_frame>Baseline and Month 12</time_frame>
        <population>The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF).</population>
        <group_list>
          <group group_id="O1">
            <title>Zoledronic Acid 5 mg Q12M</title>
            <description>Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab 60 mg Q6M</title>
            <description>Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis</title>
          <population>The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF).</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="312"/>
                <count group_id="O2" value="314"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" lower_limit="0.7" upper_limit="1.5"/>
                    <measurement group_id="O2" value="3.2" lower_limit="2.8" upper_limit="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A step-down sequential testing procedure was used in order to maintain the overall type I error rate at 5% for the tests of primary and secondary BMD endpoints. For the superiority analysis the 2-sided significance level was 5%.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <method_desc>The model included treatment, screening sCTX, baseline BMD, DXA machine type (Hologic or Lunar), and baseline BMD-by-machine type interaction.</method_desc>
            <param_type>Treatment Difference</param_type>
            <param_value>2.1</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.6</ci_lower_limit>
            <ci_upper_limit>2.6</ci_upper_limit>
            <estimate_desc>Treatment difference = denosumab - zoledronic acid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis</title>
        <time_frame>Baseline and Month 12</time_frame>
        <population>The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF).</population>
        <group_list>
          <group group_id="O1">
            <title>Zoledronic Acid 5 mg Q12M</title>
            <description>Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab 60 mg Q6M</title>
            <description>Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis</title>
          <population>The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF).</population>
          <units>percent change</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="309"/>
                <count group_id="O2" value="311"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" lower_limit="0.3" upper_limit="0.8"/>
                    <measurement group_id="O2" value="1.9" lower_limit="1.7" upper_limit="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>A step-down sequential testing procedure was used in order to maintain the overall type I error rate at 5% for the tests of primary and secondary BMD endpoints. For the superiority analysis the 2-sided significance level was 5%.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>ANCOVA</method>
            <method_desc>The model included treatment, screening sCTX, baseline BMD, DXA machine type (Hologic or Lunar), and baseline BMD-by-machine type interaction.</method_desc>
            <param_type>Treatment Difference</param_type>
            <param_value>1.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.0</ci_lower_limit>
            <ci_upper_limit>1.7</ci_upper_limit>
            <estimate_desc>Treatment difference = denosumab - zoledronic acid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <desc>Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.</desc>
      <group_list>
        <group group_id="E1">
          <title>Zoledronic Acid 5 mg Q12M</title>
          <description>Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.</description>
        </group>
        <group group_id="E2">
          <title>Denosumab 60 mg Q6M</title>
          <description>Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Goitre</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diverticulum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Gastrointestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Drug interaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Autoimmune hepatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Vulval abscess</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Radius fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Intervertebral disc disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Breast cancer female</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Colon cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Lung adenocarcinoma stage I</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Lung neoplasm malignant</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Malignant melanoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Non-small cell lung cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Pituitary tumour benign</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Pleomorphic adenoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Uterine leiomyoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Cystocele</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Rectocele</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Uterine prolapse</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Knee operation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Tendon operation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Varicose vein operation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Peripheral artery thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="320"/>
              </event>
              <event>
                <sub_title>Varicose vein</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="320"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="320"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Amgen Inc.</organization>
      <phone>866-572-6436</phone>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01732770
org study id: 20110153
secondary id: 2012-001821-28
nct id: NCT01732770
lead sponsor: 
has dmc: No
This study will compare the effectiveness of denosumab treatment every 6 months with once
      yearly zoledronic acid treatment on bone mineral density (BMD) at various skeletal sites.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis
time frame: Baseline and Month 12
description: Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility.
measure: Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis
time frame: Baseline and Month 12
description: BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility.
measure: Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis
time frame: Baseline and Month 12
measure: Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis
time frame: Baseline and Month 12
arm group label: Denosumab 60 mg
arm group type: Experimental
description: Participants received denosumab 60 mg subcutaneous injection once every 6 months for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.
arm group label: Zoledronic Acid 5 mg
arm group type: Active Comparator
description: Participants received zoledronic acid 5 mg by intravenous infusion on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.
intervention type: Biological
intervention name: Denosumab
description: Denosumab 60 mg administered by subcutaneous injection once every 6 months.
arm group label: Denosumab 60 mg
other name: Prolia®
other name: AMG 162
intervention type: Drug
intervention name: Zoledronic Acid
description: Zoledronic acid 5 mg administered by intravenous infusion once a year
arm group label: Zoledronic Acid 5 mg
other name: Reclast
other name: Aclasta
intervention type: Drug
intervention name: Placebo to Denosumab
description: Administered by subcutaneous injection once every 6 months
arm group label: Zoledronic Acid 5 mg
intervention type: Drug
intervention name: Placebo to Zoledronic Acid
description: Administered by intravenous infusion once a year
arm group label: Denosumab 60 mg
criteria: 
gender: Female
minimum age: 55 Years
maximum age: N/A
healthy volunteers: No
last name: MD
role: Study Director
affiliation: Amgen
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country: Australia
country: Belgium
country: Canada
country: Denmark
country: Poland
country: Spain
country: United States
url: http://www.amgentrials.com
description: AmgenTrials clinical trials website
citation: Miller PD, Pannacciulli N, Brown JP, Czerwinski E, Nedergaard BS, Bolognese MA, Malouf J, Bone HG, Reginster JY, Singer A, Wang C, Wagman RB, Cummings SR. Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. J Clin Endocrinol Metab. 2016 Aug;101(8):3163-70. doi: 10.1210/jc.2016-1801. Epub 2016 Jun 6.
PMID: 27270237
citation: Miller PD, Pannacciulli N, Malouf-Sierra J, Singer A, Czerwinski E, Bone HG, Wang C, Huang S, Chines A, Lems W, Brown JP. Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates. Osteoporos Int. 2020 Jan;31(1):181-191. doi: 10.1007/s00198-019-05233-x. Epub 2019 Nov 28.
PMID: 31776637
citation: Chotiyarnwong P, McCloskey E, Eastell R, McClung MR, Gielen E, Gostage J, McDermott M, Chines A, Huang S, Cummings SR. A Pooled Analysis of Fall Incidence From Placebo-Controlled Trials of Denosumab. J Bone Miner Res. 2020 Jun;35(6):1014-1021. doi: 10.1002/jbmr.3972. Epub 2020 Apr 2.
PMID: 31999376
responsible party type: Sponsor
mesh term: Osteoporosis
mesh term: Osteoporosis, Postmenopausal
mesh term: Zoledronic Acid
mesh term: Denosumab
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