<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/NCT02186600</url>
  </required_header>
  <id_info>
    <org_study_id>378-14</org_study_id>
    <nct_id>NCT02186600</nct_id>
  </id_info>
  <brief_title>Heartland Osteoporosis Prevention Study</brief_title>
  <acronym>HOPS</acronym>
  <official_title>Randomized Control Trial of Bone Loading Exercises Versus Risedronate on Bone Health in Post-Menopausal Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nebraska</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Creighton University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Nebraska</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to identify the best way to prevent bone loss in the first years&#xD;
      after menopause. The HOPS study will compare bone loss at 12 months in women: 1) who take&#xD;
      calcium and vitamin D only; 2) who take calcium and vitamin D plus the medication&#xD;
      &quot;risedronate&quot;; or 3) who take calcium and vitamin D plus participate in bone-loading&#xD;
      exercises. Our central hypothesis is that improvements in bone health will be greater in&#xD;
      women randomized to bone-loading exercises with calcium and vitamin D compared to women who&#xD;
      take calcium and vitamin D only or women who take calcium and vitamin D plus risedronate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This randomized controlled trial (RCT) will compare changes after 12 months in bone&#xD;
      structure, bone mineral density (BMD), and bone turnover in women with low bone mass who are&#xD;
      within 5 years of menopause. Women will be randomized to one control and 2 treatment groups&#xD;
      (n =103 per group): 1) calcium + vitamin D (CaD) alone (Control); 2) Bisphosphonate (BP) plus&#xD;
      optimal CaD (Risedronate); and 3) a bone loading exercise program plus optimal CaD&#xD;
      (Exercise). Our central hypothesis is that improvements in bone health will be greater in&#xD;
      subjects randomized to the exercise group compared to subjects in either the control or&#xD;
      risedronate groups. Specific Aims: Aims 1, 2, and 3 are to compare control, risedronate, and&#xD;
      exercise group subjects on changes in bone structure at the tibia and hip (measured by pQCT&#xD;
      and Hip Structural Analysis) (Aim 1) ; on changes in BMD at the total hip, femoral neck, and&#xD;
      spine (Aim 2); and on changes in serum markers of bone formation and resorption (Aim 3). In&#xD;
      addition, Aim 4 will explore relationships between adherence to exercise (% sessions&#xD;
      attended) or adherence to risedronate (% pills taken) and changes in bone structure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2015</start_date>
  <completion_date type="Actual">June 2019</completion_date>
  <primary_completion_date type="Actual">June 2019</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>Randomized to 3 treatment groups: Calcium + vitamin D only; risedronate and calcium + vitamin D; bone building exercises and calcium + vitamin D</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group.</measure>
    <time_frame>Baseline, 6, and 12 months</time_frame>
    <description>Change in Bone Strength Index (BSI) of the distal tibia based on randomization to Control, Risedronate, or Exercise group.&#xD;
BSI (mg2/mm4) at the 4% tibial site will be measured using peripheral quantitative computed tomography (pQCT).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group.</measure>
    <time_frame>Baseline,6, and 12 months</time_frame>
    <description>Bone mineral density is the gold standard for diagnosis of low bone mass and osteoporosis and will be measured at the spine using Dual Energy X-ray Absorptiometry (DXA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group.</measure>
    <time_frame>Baseline, 6, 12 months</time_frame>
    <description>Bone turnover is the process of removing old bone (resorption by osteoclasts) and replacing it with new bone (formation by osteoblasts). Menopause results in a brief period (~5 years) of accelerated turnover with resorption far exceeding formation. In this study, resorption will be measured by Serum NTx.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">276</enrollment>
  <condition>Osteopenia</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Women randomized to the control group will receive calcium and vitamin D intake for 12 months. Calcium intake will be determined by analyzing 3 day dietary intake of calcium at baseline and then prescribing calcium carbonate supplements to ensure women have ~1200 mg of calcium daily. Vitamin D intake will be determined using baseline measures of Serum 25 (OH) D. Subjects who have serum D levels of 30 ng/ml or greater will be prescribed 1,000 IU vitamin D3 daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU Vitamin D3; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU Vitamin D3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Risedronate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in the risedronate group will take 35 mg of the bisphosphonate &quot;risedronate&quot; weekly for 12 months plus CaD. They will be asked to follow the protocol for administration of risedronate including taking the medication upon arising in the morning with an 8 ounce glass of water, remaining upright for at least 30 minutes, and having no oral intake except water for at least 30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in the exercise group will participate in bone-loading exercises three times weekly in addition to taking CaD for 12 months. Women will exercise at community Young Men's Christian Association's fitness centers (YMCA) and exercises will be monitored by on-site Exercise Trainers. Exercises will consist of high-impact weight-bearing exercises (jogging with weighted vests) and resistance exercises for upper and lower extremities. Progressive increases in weight loads will be prescribed to provide maximal strength gains.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calcium Carbonate</intervention_name>
    <description>Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Exercise</arm_group_label>
    <arm_group_label>Risedronate</arm_group_label>
    <other_name>generic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D3</intervention_name>
    <description>Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Exercise</arm_group_label>
    <arm_group_label>Risedronate</arm_group_label>
    <other_name>generic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Risedronate</intervention_name>
    <description>Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.</description>
    <arm_group_label>Risedronate</arm_group_label>
    <other_name>Actonel</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Bone-loading exercises</intervention_name>
    <description>Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.</description>
    <arm_group_label>Exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women who are in their first 5 years of menopause&#xD;
&#xD;
          -  Have a T score between -1 and -2.49 at the femoral neck, total hip, or L1-L4 spine&#xD;
&#xD;
          -  Be 19 years of age or older&#xD;
&#xD;
          -  Have their health care provider's permission to enroll in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have osteoporosis&#xD;
&#xD;
          -  Have a 10 yr probability of hip fracture &gt;3% or major fracture &gt;20% based on results&#xD;
             of the fracture risk assessment (FRAX) tool&#xD;
&#xD;
          -  Currently take bisphosphonates, estrogen replacement therapy, glucocorticosteroids, or&#xD;
             other drugs affecting bone&#xD;
&#xD;
          -  Currently participate in a resistance training or high impact weight bearing exercise&#xD;
             program three or more times weekly&#xD;
&#xD;
          -  Weigh &gt;300 lbs&#xD;
&#xD;
          -  Have abnormal results for the following laboratory tests: serum 25(OH)D; serum&#xD;
             creatinine; serum calcium; parathyroid hormone (PTH); thyroid stimulating hormone&#xD;
             (TSH).&#xD;
&#xD;
          -  Have Paget's disease, heart disease, uncontrolled hypertension, renal disease, or&#xD;
             other concomitant conditions that prohibit participation in exercises, risedronate&#xD;
             therapy, or use of CaD supplements.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nancy L Waltman, PhD, APRN-NP</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nebraska</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Laura Bilek, PT, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nebraska</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198-4420</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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  <results_reference>
    <citation>Waltman N, Kupzyk KA, Flores LE, Mack LR, Lappe JM, Bilek LD. Bone-loading exercises versus risedronate for the prevention of osteoporosis in postmenopausal women with low bone mass: a randomized controlled trial. Osteoporos Int. 2022 Feb;33(2):475-486. doi: 10.1007/s00198-021-06083-2. Epub 2021 Sep 14.</citation>
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  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 7, 2014</study_first_submitted>
  <study_first_submitted_qc>July 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <results_first_submitted>February 2, 2022</results_first_submitted>
  <results_first_submitted_qc>June 23, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 27, 2023</results_first_posted>
  <last_update_submitted>June 23, 2023</last_update_submitted>
  <last_update_submitted_qc>June 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Low bone mass</keyword>
  <keyword>Post-menopausal women</keyword>
  <keyword>Bone mineral density</keyword>
  <keyword>Bone structure</keyword>
  <keyword>Bone turnover</keyword>
  <keyword>Bone-loading exercises</keyword>
  <keyword>calcium and vitamin D</keyword>
  <keyword>risedronate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bone Diseases, Metabolic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
    <mesh_term>Risedronic Acid</mesh_term>
    <mesh_term>Calcium Carbonate</mesh_term>
    <mesh_term>Calcium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 17, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT02186600/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 27, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT02186600/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Control</title>
          <description>Women randomized to the control group will receive calcium and vitamin D intake for 12 months. Calcium intake will be determined by analyzing 3 day dietary intake of calcium at baseline and then prescribing calcium carbonate supplements to ensure women have ~1200 mg of calcium daily. Vitamin D intake will be determined using baseline measures of Serum 25 (OH) D. Subjects who have serum D levels of 30 ng/ml or greater will be prescribed 1,000 IU vitamin D3 daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU Vitamin D3; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU Vitamin D3.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.</description>
        </group>
        <group group_id="P2">
          <title>Risedronate</title>
          <description>Subjects in the risedronate group will take 35 mg of the bisphosphonate &quot;risedronate&quot; weekly for 12 months plus CaD. They will be asked to follow the protocol for administration of risedronate including taking the medication upon arising in the morning with an 8 ounce glass of water, remaining upright for at least 30 minutes, and having no oral intake except water for at least 30 minutes.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Risedronate: Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.</description>
        </group>
        <group group_id="P3">
          <title>Exercise</title>
          <description>Subjects in the exercise group will participate in bone-loading exercises three times weekly in addition to taking CaD for 12 months. Women will exercise at community Young Men's Christian Association's fitness centers (YMCA) and exercises will be monitored by on-site Exercise Trainers. Exercises will consist of high-impact weight-bearing exercises (jogging with weighted vests) and resistance exercises for upper and lower extremities. Progressive increases in weight loads will be prescribed to provide maximal strength gains.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Bone-loading exercises: Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="93"/>
                <participants group_id="P2" count="91"/>
                <participants group_id="P3" count="92"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="77"/>
                <participants group_id="P2" count="78"/>
                <participants group_id="P3" count="72"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="20"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Control</title>
          <description>Women randomized to the control group will receive calcium and vitamin D intake for 12 months. Calcium intake will be determined by analyzing 3 day dietary intake of calcium at baseline and then prescribing calcium carbonate supplements to ensure women have ~1200 mg of calcium daily. Vitamin D intake will be determined using baseline measures of Serum 25 (OH) D. Subjects who have serum D levels of 30 ng/ml or greater will be prescribed 1,000 IU vitamin D3 daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU Vitamin D3; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU Vitamin D3.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.</description>
        </group>
        <group group_id="B2">
          <title>Risedronate</title>
          <description>Subjects in the risedronate group will take 35 mg of the bisphosphonate &quot;risedronate&quot; weekly for 12 months plus CaD. They will be asked to follow the protocol for administration of risedronate including taking the medication upon arising in the morning with an 8 ounce glass of water, remaining upright for at least 30 minutes, and having no oral intake except water for at least 30 minutes.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Risedronate: Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.</description>
        </group>
        <group group_id="B3">
          <title>Exercise</title>
          <description>Subjects in the exercise group will participate in bone-loading exercises three times weekly in addition to taking CaD for 12 months. Women will exercise at community Young Men's Christian Association's fitness centers (YMCA) and exercises will be monitored by on-site Exercise Trainers. Exercises will consist of high-impact weight-bearing exercises (jogging with weighted vests) and resistance exercises for upper and lower extremities. Progressive increases in weight loads will be prescribed to provide maximal strength gains.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Bone-loading exercises: Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.</description>
        </group>
        <group group_id="B4">
          <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="93"/>
            <count group_id="B2" value="91"/>
            <count group_id="B3" value="92"/>
            <count group_id="B4" value="276"/>
          </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="54.34" spread="3.30"/>
                    <measurement group_id="B2" value="54.53" spread="3.07"/>
                    <measurement group_id="B3" value="54.47" spread="3.11"/>
                    <measurement group_id="B4" value="54.4" spread="3.1"/>
                  </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="93"/>
                    <measurement group_id="B2" value="91"/>
                    <measurement group_id="B3" value="92"/>
                    <measurement group_id="B4" value="276"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="85"/>
                    <measurement group_id="B2" value="80"/>
                    <measurement group_id="B3" value="80"/>
                    <measurement group_id="B4" value="245"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="89"/>
                    <measurement group_id="B2" value="84"/>
                    <measurement group_id="B3" value="88"/>
                    <measurement group_id="B4" value="261"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Family History of Low Bone Mass or Osteoporosis</title>
          <description>Number of participants with a positive family history of osteoporosis.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="53"/>
                    <measurement group_id="B4" value="162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group.</title>
        <description>Change in Bone Strength Index (BSI) of the distal tibia based on randomization to Control, Risedronate, or Exercise group.&#xD;
BSI (mg2/mm4) at the 4% tibial site will be measured using peripheral quantitative computed tomography (pQCT).</description>
        <time_frame>Baseline, 6, and 12 months</time_frame>
        <population>Intent-to-treat</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Women randomized to the control group will receive calcium and vitamin D intake for 12 months. Calcium intake will be determined by analyzing 3 day dietary intake of calcium at baseline and then prescribing calcium carbonate supplements to ensure women have ~1200 mg of calcium daily. Vitamin D intake will be determined using baseline measures of Serum 25 (OH) D. Subjects who have serum D levels of 30 ng/ml or greater will be prescribed 1,000 IU vitamin D3 daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU Vitamin D3; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU Vitamin D3.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.</description>
          </group>
          <group group_id="O2">
            <title>Risedronate</title>
            <description>Subjects in the risedronate group will take 35 mg of the bisphosphonate &quot;risedronate&quot; weekly for 12 months plus CaD. They will be asked to follow the protocol for administration of risedronate including taking the medication upon arising in the morning with an 8 ounce glass of water, remaining upright for at least 30 minutes, and having no oral intake except water for at least 30 minutes.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Risedronate: Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.</description>
          </group>
          <group group_id="O3">
            <title>Exercise</title>
            <description>Subjects in the exercise group will participate in bone-loading exercises three times weekly in addition to taking CaD for 12 months. Women will exercise at community Young Men's Christian Association's fitness centers (YMCA) and exercises will be monitored by on-site Exercise Trainers. Exercises will consist of high-impact weight-bearing exercises (jogging with weighted vests) and resistance exercises for upper and lower extremities. Progressive increases in weight loads will be prescribed to provide maximal strength gains.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Bone-loading exercises: Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group.</title>
          <description>Change in Bone Strength Index (BSI) of the distal tibia based on randomization to Control, Risedronate, or Exercise group.&#xD;
BSI (mg2/mm4) at the 4% tibial site will be measured using peripheral quantitative computed tomography (pQCT).</description>
          <population>Intent-to-treat</population>
          <units>mg^2/mm^4</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="93"/>
                <count group_id="O2" value="91"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="85"/>
                    <count group_id="O2" value="85"/>
                    <count group_id="O3" value="87"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2098.7" spread="334.7"/>
                    <measurement group_id="O2" value="1993.3" spread="292.3"/>
                    <measurement group_id="O3" value="2001" spread="332.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 Months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="78"/>
                    <count group_id="O2" value="77"/>
                    <count group_id="O3" value="73"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2105.89" spread="322.822"/>
                    <measurement group_id="O2" value="1997.32" spread="307.103"/>
                    <measurement group_id="O3" value="1987.42" spread="300.136"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 Months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="72"/>
                    <count group_id="O2" value="70"/>
                    <count group_id="O3" value="67"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2107.2" spread="326.4"/>
                    <measurement group_id="O2" value="2014.2" spread="306.7"/>
                    <measurement group_id="O3" value="2009.2" spread="280.4"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Hierarchical linear modeling for intent-to-treat analysis to analyze time X group interactions, adjusted for baseline total body lean mass and height.</non_inferiority_desc>
            <p_value>0.7</p_value>
            <method>hierarchical linear modeling</method>
            <method_desc>controlled for total lean mass and height</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group.</title>
        <description>Bone mineral density is the gold standard for diagnosis of low bone mass and osteoporosis and will be measured at the spine using Dual Energy X-ray Absorptiometry (DXA).</description>
        <time_frame>Baseline,6, and 12 months</time_frame>
        <population>Intent to treat analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Women randomized to the control group will receive calcium and vitamin D intake for 12 months. Calcium intake will be determined by analyzing 3 day dietary intake of calcium at baseline and then prescribing calcium carbonate supplements to ensure women have ~1200 mg of calcium daily. Vitamin D intake will be determined using baseline measures of Serum 25 (OH) D. Subjects who have serum D levels of 30 ng/ml or greater will be prescribed 1,000 IU vitamin D3 daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU Vitamin D3; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU Vitamin D3.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.</description>
          </group>
          <group group_id="O2">
            <title>Risedronate</title>
            <description>Subjects in the risedronate group will take 35 mg of the bisphosphonate &quot;risedronate&quot; weekly for 12 months plus CaD. They will be asked to follow the protocol for administration of risedronate including taking the medication upon arising in the morning with an 8 ounce glass of water, remaining upright for at least 30 minutes, and having no oral intake except water for at least 30 minutes.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Risedronate: Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.</description>
          </group>
          <group group_id="O3">
            <title>Exercise</title>
            <description>Subjects in the exercise group will participate in bone-loading exercises three times weekly in addition to taking CaD for 12 months. Women will exercise at community Young Men's Christian Association's fitness centers (YMCA) and exercises will be monitored by on-site Exercise Trainers. Exercises will consist of high-impact weight-bearing exercises (jogging with weighted vests) and resistance exercises for upper and lower extremities. Progressive increases in weight loads will be prescribed to provide maximal strength gains.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Bone-loading exercises: Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group.</title>
          <description>Bone mineral density is the gold standard for diagnosis of low bone mass and osteoporosis and will be measured at the spine using Dual Energy X-ray Absorptiometry (DXA).</description>
          <population>Intent to treat analysis</population>
          <units>g/cm^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="93"/>
                <count group_id="O2" value="91"/>
                <count group_id="O3" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="91"/>
                    <count group_id="O3" value="92"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.889" spread="0.076"/>
                    <measurement group_id="O2" value="0.892" spread="0.06"/>
                    <measurement group_id="O3" value="0.886" spread="0.064"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 Months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="86"/>
                    <count group_id="O2" value="82"/>
                    <count group_id="O3" value="82"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".887" spread=".0755"/>
                    <measurement group_id="O2" value=".907" spread=".0666"/>
                    <measurement group_id="O3" value=".878" spread=".0619"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 Months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="91"/>
                    <count group_id="O3" value="92"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.885" spread="0.070"/>
                    <measurement group_id="O2" value="0.911" spread="0.070"/>
                    <measurement group_id="O3" value="0.885" spread="0.065"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>hierarchical linear modeling</non_inferiority_desc>
            <p_value>0.01</p_value>
            <method>hierarchical linear modeling</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group.</title>
        <description>Bone turnover is the process of removing old bone (resorption by osteoclasts) and replacing it with new bone (formation by osteoblasts). Menopause results in a brief period (~5 years) of accelerated turnover with resorption far exceeding formation. In this study, resorption will be measured by Serum NTx.</description>
        <time_frame>Baseline, 6, 12 months</time_frame>
        <population>Intention to treat for persons who had valid data at baseline</population>
        <group_list>
          <group group_id="O1">
            <title>Control</title>
            <description>Women randomized to the control group will receive calcium and vitamin D intake for 12 months. Calcium intake will be determined by analyzing 3 day dietary intake of calcium at baseline and then prescribing calcium carbonate supplements to ensure women have ~1200 mg of calcium daily. Vitamin D intake will be determined using baseline measures of Serum 25 (OH) D. Subjects who have serum D levels of 30 ng/ml or greater will be prescribed 1,000 IU vitamin D3 daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU Vitamin D3; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU Vitamin D3.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.</description>
          </group>
          <group group_id="O2">
            <title>Risedronate</title>
            <description>Subjects in the risedronate group will take 35 mg of the bisphosphonate &quot;risedronate&quot; weekly for 12 months plus CaD. They will be asked to follow the protocol for administration of risedronate including taking the medication upon arising in the morning with an 8 ounce glass of water, remaining upright for at least 30 minutes, and having no oral intake except water for at least 30 minutes.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Risedronate: Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.</description>
          </group>
          <group group_id="O3">
            <title>Exercise</title>
            <description>Subjects in the exercise group will participate in bone-loading exercises three times weekly in addition to taking CaD for 12 months. Women will exercise at community Young Men's Christian Association's fitness centers (YMCA) and exercises will be monitored by on-site Exercise Trainers. Exercises will consist of high-impact weight-bearing exercises (jogging with weighted vests) and resistance exercises for upper and lower extremities. Progressive increases in weight loads will be prescribed to provide maximal strength gains.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Bone-loading exercises: Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group.</title>
          <description>Bone turnover is the process of removing old bone (resorption by osteoclasts) and replacing it with new bone (formation by osteoblasts). Menopause results in a brief period (~5 years) of accelerated turnover with resorption far exceeding formation. In this study, resorption will be measured by Serum NTx.</description>
          <population>Intention to treat for persons who had valid data at baseline</population>
          <units>nanoMolar Bone Collagen Equivalents/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="78"/>
                <count group_id="O3" value="77"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.99" spread="4.22"/>
                    <measurement group_id="O2" value="14.31" spread="4.44"/>
                    <measurement group_id="O3" value="15.03" spread="5.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.16" spread="3.84"/>
                    <measurement group_id="O2" value="10.30" spread="3.93"/>
                    <measurement group_id="O3" value="13.36" spread="5.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 Months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.36" spread="3.48"/>
                    <measurement group_id="O2" value="11.42" spread="4.71"/>
                    <measurement group_id="O3" value="13.92" spread="5.84"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Hierarchical linear modeling</non_inferiority_desc>
            <p_value>&lt;0.007</p_value>
            <method>hierarchical linear modeling</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months for each participant</time_frame>
      <desc>At each study visit, participants were asked if they had any new health conditions or events. We had questionnaires that evaluated tolerance to the treatments which allowed us to communicate with those who experienced symptoms as a result of the intervention.</desc>
      <group_list>
        <group group_id="E1">
          <title>Control</title>
          <description>Women randomized to the control group will receive calcium and vitamin D intake for 12 months. Calcium intake will be determined by analyzing 3 day dietary intake of calcium at baseline and then prescribing calcium carbonate supplements to ensure women have ~1200 mg of calcium daily. Vitamin D intake will be determined using baseline measures of Serum 25 (OH) D. Subjects who have serum D levels of 30 ng/ml or greater will be prescribed 1,000 IU vitamin D3 daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU Vitamin D3; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU Vitamin D3.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.</description>
        </group>
        <group group_id="E2">
          <title>Risedronate</title>
          <description>Subjects in the risedronate group will take 35 mg of the bisphosphonate &quot;risedronate&quot; weekly for 12 months plus CaD. They will be asked to follow the protocol for administration of risedronate including taking the medication upon arising in the morning with an 8 ounce glass of water, remaining upright for at least 30 minutes, and having no oral intake except water for at least 30 minutes.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Risedronate: Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.</description>
        </group>
        <group group_id="E3">
          <title>Exercise</title>
          <description>Subjects in the exercise group will participate in bone-loading exercises three times weekly in addition to taking CaD for 12 months. Women will exercise at community Young Men's Christian Association's fitness centers (YMCA) and exercises will be monitored by on-site Exercise Trainers. Exercises will consist of high-impact weight-bearing exercises (jogging with weighted vests) and resistance exercises for upper and lower extremities. Progressive increases in weight loads will be prescribed to provide maximal strength gains.&#xD;
Calcium Carbonate: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)&#xD;
Vitamin D3: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.&#xD;
Bone-loading exercises: Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="91"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <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="9" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="91"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain or Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="91"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="93"/>
                <counts group_id="E2" events="13" subjects_affected="13" subjects_at_risk="91"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="92"/>
              </event>
              <event>
                <sub_title>Gi disturbances</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="91"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="92"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>muscle or joint pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="91"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="92"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Principal Investigator</name_or_title>
      <organization>University of Nebraska Medical Center, College of Allied Health Professions</organization>
      <phone>402-559-6923</phone>
      <email>lbilek@unmc.edu</email>
    </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/NCT02186600
org study id: 378-14
nct id: NCT02186600
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to identify the best way to prevent bone loss in the first years
      after menopause. The HOPS study will compare bone loss at 12 months in women: 1) who take
      calcium and vitamin D only; 2) who take calcium and vitamin D plus the medication
      "risedronate"; or 3) who take calcium and vitamin D plus participate in bone-loading
      exercises. Our central hypothesis is that improvements in bone health will be greater in
      women randomized to bone-loading exercises with calcium and vitamin D compared to women who
      take calcium and vitamin D only or women who take calcium and vitamin D plus risedronate.
This randomized controlled trial (RCT) will compare changes after 12 months in bone
      structure, bone mineral density (BMD), and bone turnover in women with low bone mass who are
      within 5 years of menopause. Women will be randomized to one control and 2 treatment groups
      (n =103 per group): 1) calcium + vitamin D (CaD) alone (Control); 2) Bisphosphonate (BP) plus
      optimal CaD (Risedronate); and 3) a bone loading exercise program plus optimal CaD
      (Exercise). Our central hypothesis is that improvements in bone health will be greater in
      subjects randomized to the exercise group compared to subjects in either the control or
      risedronate groups. Specific Aims: Aims 1, 2, and 3 are to compare control, risedronate, and
      exercise group subjects on changes in bone structure at the tibia and hip (measured by pQCT
      and Hip Structural Analysis) (Aim 1) ; on changes in BMD at the total hip, femoral neck, and
      spine (Aim 2); and on changes in serum markers of bone formation and resorption (Aim 3). In
      addition, Aim 4 will explore relationships between adherence to exercise (% sessions
      attended) or adherence to risedronate (% pills taken) and changes in bone structure.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized to 3 treatment groups: Calcium + vitamin D only; risedronate and calcium + vitamin D; bone building exercises and calcium + vitamin D
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group.
time frame: Baseline, 6, and 12 months
description: Change in Bone Strength Index (BSI) of the distal tibia based on randomization to Control, Risedronate, or Exercise group.
BSI (mg2/mm4) at the 4% tibial site will be measured using peripheral quantitative computed tomography (pQCT).
measure: Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group.
time frame: Baseline,6, and 12 months
description: Bone mineral density is the gold standard for diagnosis of low bone mass and osteoporosis and will be measured at the spine using Dual Energy X-ray Absorptiometry (DXA).
measure: Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group.
time frame: Baseline, 6, 12 months
description: Bone turnover is the process of removing old bone (resorption by osteoclasts) and replacing it with new bone (formation by osteoblasts). Menopause results in a brief period (~5 years) of accelerated turnover with resorption far exceeding formation. In this study, resorption will be measured by Serum NTx.
arm group label: Control
arm group type: Active Comparator
description: Women randomized to the control group will receive calcium and vitamin D intake for 12 months. Calcium intake will be determined by analyzing 3 day dietary intake of calcium at baseline and then prescribing calcium carbonate supplements to ensure women have ~1200 mg of calcium daily. Vitamin D intake will be determined using baseline measures of Serum 25 (OH) D. Subjects who have serum D levels of 30 ng/ml or greater will be prescribed 1,000 IU vitamin D3 daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU Vitamin D3; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU Vitamin D3.
arm group label: Risedronate
arm group type: Experimental
description: Subjects in the risedronate group will take 35 mg of the bisphosphonate "risedronate" weekly for 12 months plus CaD. They will be asked to follow the protocol for administration of risedronate including taking the medication upon arising in the morning with an 8 ounce glass of water, remaining upright for at least 30 minutes, and having no oral intake except water for at least 30 minutes.
arm group label: Exercise
arm group type: Experimental
description: Subjects in the exercise group will participate in bone-loading exercises three times weekly in addition to taking CaD for 12 months. Women will exercise at community Young Men's Christian Association's fitness centers (YMCA) and exercises will be monitored by on-site Exercise Trainers. Exercises will consist of high-impact weight-bearing exercises (jogging with weighted vests) and resistance exercises for upper and lower extremities. Progressive increases in weight loads will be prescribed to provide maximal strength gains.
intervention type: Drug
intervention name: Calcium Carbonate
description: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)
arm group label: Control
arm group label: Exercise
arm group label: Risedronate
other name: generic
intervention type: Drug
intervention name: Vitamin D3
description: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.
arm group label: Control
arm group label: Exercise
arm group label: Risedronate
other name: generic
intervention type: Drug
intervention name: Risedronate
description: Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.
arm group label: Risedronate
other name: Actonel
intervention type: Behavioral
intervention name: Bone-loading exercises
description: Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.
arm group label: Exercise
criteria: 
gender: Female
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Nancy L Waltman, PhD, APRN-NP
role: Principal Investigator
affiliation: University of Nebraska
last name: Laura Bilek, PT, PhD
role: Principal Investigator
affiliation: University of Nebraska
facility: 
country: United States
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responsible party type: Sponsor
mesh term: Bone Diseases, Metabolic
mesh term: Vitamin D
mesh term: Cholecalciferol
mesh term: Risedronic Acid
mesh term: Calcium Carbonate
mesh term: Calcium
sharing ipd: No
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