<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/NCT03027557</url>
  </required_header>
  <id_info>
    <org_study_id>180987</org_study_id>
    <secondary_id>2016-001510-20</secondary_id>
    <nct_id>NCT03027557</nct_id>
  </id_info>
  <brief_title>Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet.</brief_title>
  <acronym>DENOCINA</acronym>
  <official_title>Treatment of Primary Hyperparathyroidism With Denosumab and Cinacalcet.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peter Vestergaard</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Aalborg University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Aalborg University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The only known cure for primary hyperparathyroidism is surgical removal of one or more&#xD;
      parathyroid glands. Some patients however, do not fulfill criteria for surgery or do not want&#xD;
      to undergo a procedure due to fear of the associated risks. Therefore a medical alternative&#xD;
      is warranted.&#xD;
&#xD;
      This study aims to evaluate the effects of Denosumab alone, and in combination with&#xD;
      Cinacalcet, as a medical treatment for patients suffering from primary hyperparathyroidism,&#xD;
      with mild osteoporosis. To the best of our knowledge no previously reported randomized&#xD;
      controlled trial has investigated the use of denosumab in primary hyperparathyroidism.&#xD;
&#xD;
      60 patients will be enrolled in three different treatment-groups: 20 receiving both Denosumab&#xD;
      and Cinacalcet, 20 Denosumab and placebo and 20 placebo and placebo. Patients included do not&#xD;
      meet the criteria for, or have no wish for a surgical procedure.&#xD;
&#xD;
      By combining the two drugs, this study could possibly contribute to the discovery of a&#xD;
      realistic medical alternative to surgery. It is expected that the therapy will be able to&#xD;
      both control s-calcium and s-intact parathyroid hormone (iPTH), and simultaneously enhance&#xD;
      bone-structure. The therapy thus has the potential of preventing fractures and possibly other&#xD;
      long-term effects of primary hyperparathyroidism such as formation of kidney stones, and&#xD;
      coronary calcification. Another objective of this project is to investigate whether the&#xD;
      combined therapy can facilitate an actual reset of the Calcium-sensing receptor, and thereby&#xD;
      de facto cure the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background/Context:&#xD;
&#xD;
      This project deals with medical treatment of primary hyperparathyroidism. The only cure&#xD;
      currently available is surgical removal of one or more parathyroid glands, but this option is&#xD;
      neither feasible, nor desirable in all patients with the diagnosis.&#xD;
&#xD;
      Today a major group of patients are being diagnosed by coincidence with biochemical&#xD;
      blood-screening, and are therefore in an asymptomatic state of the disease at the time of&#xD;
      diagnosis. Long term studies show that these patients over time often have progression in&#xD;
      their disease, and develop complications such as osteoporosis. Thus a medical alternative is&#xD;
      warranted.&#xD;
&#xD;
      Previous studies have investigated the effects of well known antiresorptive drugs such as&#xD;
      bisphosphonates, as well as estrogen-related compounds. These drugs have had effects on&#xD;
      particularly bone mineral density (BMD) and biochemical bone-turnover markers, but have been&#xD;
      able only transiently to lower blood-calcium levels. Combined with too many unwanted&#xD;
      side-effects and a high prevalence of contraindications for a large proportion of the&#xD;
      patients needing treatment, these drugs have not provided a realistic alternative to surgery.&#xD;
&#xD;
      Treatment today generally follows the international consensus for treatment of asymptomatic&#xD;
      patients with primary hyperparathyroidism. Briefly this includes watchful waiting with&#xD;
      biannual control-sessions for indication of surgery, screening for kidney&#xD;
      stones/nephrolithiasis, osteoporosis and s-calcium - and s-iPTH levels.&#xD;
&#xD;
      This randomized controlled trial involves the drugs Cinacalcet og Denosumab. Denosumab has&#xD;
      previously been shown to greatly improve BMD, lower s-calcium, lower the rate of&#xD;
      bone-turnover and prevent osteoporotic fractures in several populations with different&#xD;
      diseases, but has never been tested in a published randomized controlled trial in patients&#xD;
      with primary hyperparathyroidism.&#xD;
&#xD;
      Cinacalcet has been proved able to lower s-iPTH, lower s-Calcium and thereby relieve symptoms&#xD;
      of hypercalcaemia caused by primary hyperparathyroidism. It does not however, lower the rate&#xD;
      of bone turnover, and it has not been show to improve BMD.&#xD;
&#xD;
      By combining the two drugs, this study could possibly contribute to the discovery of a&#xD;
      realistic medical alternative to surgery. It is expected that the therapy will be able to&#xD;
      both control s-calcium and s-iPTH, and simultaneously enhance bone-structure. The therapy&#xD;
      thus has the potential of preventing fractures and possibly other long-term effects of&#xD;
      primary hyperparathyroidism such as formation of kidney stones, and coronary calcification.&#xD;
      Another objective of this project is to investigate whether the combined therapy can&#xD;
      facilitate an actual reset of the Calcium-sensing receptor, and thereby de facto cure the&#xD;
      disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">September 12, 2019</completion_date>
  <primary_completion_date type="Actual">April 1, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Lumbar Spine Bone Mineral Density</measure>
    <time_frame>Baseline,one year</time_frame>
    <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Total Hip Bone Mineral Density</measure>
    <time_frame>Baseline,one year</time_frame>
    <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Femoral Neck Bone Mineral Density</measure>
    <time_frame>Baseline,one year</time_frame>
    <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in 1/3 Forearm Bone Mineral Density</measure>
    <time_frame>Baseline,one year</time_frame>
    <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage Change in Lumbar Spine Bone Mineral Density</measure>
    <time_frame>Baseline,one year</time_frame>
    <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage Change in Total Hip Bone Mineral Density</measure>
    <time_frame>Baseline,one year</time_frame>
    <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage Change in Femoral Neck Bone Mineral Density</measure>
    <time_frame>Baseline,one year</time_frame>
    <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage Change in 1/3 Forearm Bone Mineral Density</measure>
    <time_frame>Baseline,one year</time_frame>
    <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Volumetric BMD for the Lumbar Spine.</measure>
    <time_frame>Baseline, one year</time_frame>
    <description>Measured at baseline and after one year by QCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean P-calcium During Treatment.</measure>
    <time_frame>Monthly up to one year.</time_frame>
    <description>Blood samples were acquired once every 4 weeks for safety-purposes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in P-carboxy-terminal Collagen Crosslinks (CTX)</measure>
    <time_frame>Change from baseline at 48 weeks reported.</time_frame>
    <description>p-CTX, change from baseline at 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Agatstons Score Final</measure>
    <time_frame>Baseline, one year</time_frame>
    <description>Simultaneously with QCT-measurements coronary calcification was be assessed. Agatston score is a score based on the extent of coronary artery calcification calculated on the amount of plaque observed in a CT scan. A score of zero indicates absence of coronary calcium, 1-10: minimal calcification, 11-100 mild calcification, 101-400 moderate calcification, &gt;400 severe calcification.&#xD;
Thus the score increases with increasing level of calcification in the coronary vessels.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients With Nephrolithiasis Final Scan.</measure>
    <time_frame>Patients with nephrolithiasis at one year reported.</time_frame>
    <description>Number of subjects w. renal stones at final scan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients With Pancreas-calcifications Final Scan.</measure>
    <time_frame>Patients with pancreas-calcifications at one year reported.</time_frame>
    <description>By QCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reset of the Calcium Sensing Receptor?</measure>
    <time_frame>2 weeks after termination of medication.</time_frame>
    <description>Measured from effect on s-calcium and PTH weeks after termination of IMP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vertebral Fracture Assessment - Final Scan</measure>
    <time_frame>Patients with vertebral fractures at one year reported.</time_frame>
    <description>Number of participants with vertebral fractures as assessed by VFA at final scan.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change MDI-score</measure>
    <time_frame>Baseline, 6 mths, one year.</time_frame>
    <description>Major Depression Inventory (MDI)-score, Baseline, 6 months, one year (week 52)., change between baseline and 1 year reported.&#xD;
The Major Depression Inventory (MDI) is a mood questionnaire developed by the World Health Organization. To calculate the total score, a sum of ten individual items (each with an individual score between 0-5, with 0 indicating absence of a symptom and 5 indicating constant presence of a given symptom) is used. A higher score signifies deeper depression with 50 being the maximum score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Reactions.</measure>
    <time_frame>Monthly up to one year.</time_frame>
    <description>All participants filled in questionnaires regarding symptoms related to the treatment.&#xD;
Results are reported in the Adverse Events section.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone Mineral Content</measure>
    <time_frame>Baseline, one year</time_frame>
    <description>Measured at baseline and after one year at the lumbar spine and distal 1/3 of the non-dominant antebrachii.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Cortical Width.</measure>
    <time_frame>Baseline, one year.</time_frame>
    <description>Measured at baseline and after one year at the distal non-dominant antebrachii.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Volumetric BMD for the Distal Forearm.</measure>
    <time_frame>Baseline, one year</time_frame>
    <description>Measured at baseline and after one year by QCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change in Volumetric BMD for the Lumbar Spine.</measure>
    <time_frame>Baseline, one year</time_frame>
    <description>Measured at baseline and after one year by QCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change in Volumetric BMD for the Distal Forearm.</measure>
    <time_frame>Baseline, one year</time_frame>
    <description>Measured at baseline and after one year by QCT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean p-PTH During Treatment.</measure>
    <time_frame>Monthly up to one year.</time_frame>
    <description>Blood samples were acquired once every 4 weeks for safety-purposes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean p-Phosphate During Treatment.</measure>
    <time_frame>Monthly up to one year.</time_frame>
    <description>Blood samples were acquired once every 4 weeks for safety-purposes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in p-N-terminal Propeptide of Type I Procollagen (p-P1NP).</measure>
    <time_frame>Change from baseline at 48 weeks reported.</time_frame>
    <description>p-P1NP, change from baseline at 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in P-osteocalcin.</measure>
    <time_frame>Change from baseline at 48 weeks reported.</time_frame>
    <description>p-osteocalcin, change from baseline at 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in S-bone-specific Alkaline Phosphatase (BAP).</measure>
    <time_frame>Change from baseline at 48 weeks reported.</time_frame>
    <description>S-Bone specific alkaline phosphatase, change from baseline at 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in p-Tartrate-resistant Acid Phosphatase 5b (Trap5b).</measure>
    <time_frame>Change from baseline at 48 weeks reported.</time_frame>
    <description>P-Trap5b, change from baseline at 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in p-Sclerostin.</measure>
    <time_frame>Change from baseline at 48 weeks reported.</time_frame>
    <description>P-Sclerostin, change from baseline at 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in P-fibroblast Growth Factor 23 (FGF23).</measure>
    <time_frame>Change from baseline at 48 weeks reported.</time_frame>
    <description>P-FGF23 , change from baseline at 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in p-25-vitamin D</measure>
    <time_frame>Change from baseline at 48 weeks reported.</time_frame>
    <description>P-25-vitD , change from baseline at 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in s-1,25-vitamin D</measure>
    <time_frame>Change from baseline at 48 weeks reported.</time_frame>
    <description>S-1,25-vitD, change from baseline at 48 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients With Nephrocalcinosis, Final Scan.</measure>
    <time_frame>Baseline, one year</time_frame>
    <description>Number of subjects w. renal calcifications at final scan.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Safety Measures</measure>
    <time_frame>Monthly up to one year.</time_frame>
    <description>Biochemical measures of changes in liver, infection, kidney and electrolyte-status and urinary excretion of calcium.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">46</enrollment>
  <condition>Primary Hyperparathyroidism</condition>
  <condition>Parathyroid Adenoma</condition>
  <condition>Parathyroid Hyperplasia</condition>
  <arm_group>
    <arm_group_label>Combined treatment.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 subjects will be treated with combined 60mg denosumab bi-annually , 30 mg cinacalcet daily and 50 micrograms vitamin-D daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Monotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 subjects will receive 60mg denosumab bi-annually, placebo and 50 micrograms vitamin-D daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>20 subjects will receive a saline injection bi-annually (blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cinacalcet 30 mg Tablet</intervention_name>
    <description>Participants in one arm will receive 30 mg cinacalcet each day.</description>
    <arm_group_label>Combined treatment.</arm_group_label>
    <other_name>Mimpara</other_name>
    <other_name>Sensipar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Denosumab Inj 60 mg/ml</intervention_name>
    <description>Participants in two arms will receive 60 mg Denosumab biannually.</description>
    <arm_group_label>Combined treatment.</arm_group_label>
    <arm_group_label>Monotherapy</arm_group_label>
    <other_name>Prolia</other_name>
    <other_name>Xgeva</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo tablets</intervention_name>
    <description>Participants in two arms will receive one placebo-tablet each day.</description>
    <arm_group_label>Monotherapy</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Saline Injection (Placebo)</intervention_name>
    <description>Participants in one arm will receive saline injections as placebo for denosumab.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Sodium Chloride (NaCl) Fresenius &quot;Kabi&quot;</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women of 18 years of age or older.&#xD;
&#xD;
          -  T-score by Dual X-ray Absorptiometry (DXA) between -1,0 og -3,5&#xD;
&#xD;
          -  Patients from The North Jutland Region diagnosed with primary hyperparathyroidism at&#xD;
             the Department of Endocrinology, Aalborg University Hospital. (Hypercalcaemia measured&#xD;
             at two different time-points and simultaneous elevated/inappropriately high PTH, and&#xD;
             exclusion of differential diagnosis.)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medical history of diseases leading to hypercalcaemia other than Primary&#xD;
             Hyperparathyroidism.&#xD;
&#xD;
          -  Patients being treated with Denosumab or Cinacalcet prior to inclusion or previously&#xD;
             treated with Denosumab or Cinacalcet.&#xD;
&#xD;
          -  Moderately - Severely decreased liver function (alanine aminotransferase &gt;250u/l,&#xD;
             gamma-glutamyl transferase&gt;150u/l, Bilirubin &gt;30)&#xD;
&#xD;
          -  Acute myocardial infarction or apoplexia in the 3 months before inclusion.&#xD;
&#xD;
          -  Medical record of heart failure&#xD;
&#xD;
          -  Risk factors of prolonged corrected QT interval (QTc).&#xD;
&#xD;
          -  Open lesions from oral surgery.&#xD;
&#xD;
          -  Primary diseases of the bone other than osteoporosis.&#xD;
&#xD;
          -  Patients suffering from kidney disease or renal failure.&#xD;
&#xD;
          -  Patients under treatment with thiazide or lithium.&#xD;
&#xD;
          -  Medical record of generalized seizures or epilepsy.&#xD;
&#xD;
          -  Active malignant disease.&#xD;
&#xD;
          -  Known allergies towards the specified medicinal products (IMPs).&#xD;
&#xD;
          -  Pregnancy or breastfeeding.&#xD;
&#xD;
          -  Fertile women who do not agree to the usage of effective contraception.&#xD;
&#xD;
          -  Other circumstances, evaluated by the responsible investigator, making the subject&#xD;
             unsuitable for participation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Julius Simoni Leere, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Aalborg University and Aalborg University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Peter Vestergaard, DMSc</last_name>
    <role>Study Director</role>
    <affiliation>Aalborg University and Aalborg University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aalborg University Hospital</name>
      <address>
        <city>Aalborg</city>
        <zip>9000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>January 16, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <results_first_submitted>July 24, 2020</results_first_submitted>
  <results_first_submitted_qc>May 1, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 25, 2021</results_first_posted>
  <last_update_submitted>May 1, 2021</last_update_submitted>
  <last_update_submitted_qc>May 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Aalborg University Hospital</investigator_affiliation>
    <investigator_full_name>Peter Vestergaard</investigator_full_name>
    <investigator_title>Professor, DMSc, Consultant</investigator_title>
  </responsible_party>
  <keyword>Primary Hyperparathyroidism</keyword>
  <keyword>Parathyroid Adenoma</keyword>
  <keyword>Parathyroid Hyperplasia</keyword>
  <keyword>Cinacalcet</keyword>
  <keyword>Denosumab</keyword>
  <keyword>Drug Therapy</keyword>
  <keyword>Bone Mineral Density</keyword>
  <keyword>Calcium</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenoma</mesh_term>
    <mesh_term>Parathyroid Neoplasms</mesh_term>
    <mesh_term>Hyperparathyroidism</mesh_term>
    <mesh_term>Hyperparathyroidism, Primary</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Denosumab</mesh_term>
    <mesh_term>Cinacalcet</mesh_term>
  </intervention_browse>
  <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>May 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT03027557/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Combined Treatment.</title>
          <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
        </group>
        <group group_id="P2">
          <title>Denosumab Monotherapy</title>
          <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Combined Treatment.</title>
          <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
        </group>
        <group group_id="B2">
          <title>Denosumab Monotherapy</title>
          <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</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="15"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="15"/>
            <count group_id="B4" value="46"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65.1" spread="13.2"/>
                    <measurement group_id="B2" value="65.4" spread="8.8"/>
                    <measurement group_id="B3" value="68.0" spread="7.0"/>
                    <measurement group_id="B4" value="66.15" spread="9.7"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Denmark</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>T-score Lumbar Spine (LS) by Dual X-ray Absorptiometry (DXA)</title>
          <description>Baseline Bone mineral density (BMD) at lumbar spine (L2-L4) T-score. The T-score is the number of units that the bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates osteoporosis</description>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-1.9" spread="0.93"/>
                    <measurement group_id="B2" value="-2.0" spread="0.68"/>
                    <measurement group_id="B3" value="-1.3" spread="0.85"/>
                    <measurement group_id="B4" value="-1.7" spread="0.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>T-score TH (by DXA)</title>
          <description>Baseline Bone mineral density (BMD) at Total Hip (TH) T-score. The T-score is the number of units that the bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates osteoporosis.</description>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-1.4" spread="0.5"/>
                    <measurement group_id="B2" value="-1.4" spread="0.6"/>
                    <measurement group_id="B3" value="-1.1" spread="0.5"/>
                    <measurement group_id="B4" value="-1.3" spread="0.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>T-score FN (by DXA)</title>
          <description>Baseline Bone mineral density (BMD) at Femoral Neck (FN) T-score. The T-score is the number of units that the bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates osteoporosis.</description>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-2.0" spread="0.7"/>
                    <measurement group_id="B2" value="-1.9" spread="0.7"/>
                    <measurement group_id="B3" value="-1.7" spread="0.6"/>
                    <measurement group_id="B4" value="-1.88" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>T-score 1/3 FA (by DXA)</title>
          <description>Baseline Bone mineral density (BMD) at 1/3 distal forearm (1/3 FA)T-score. The T-score is the number of units that the bone density is above or below the average. -1 and above-bone density is considered normal; Between -1 and -2.5-is a sign of osteopenia, a condition in which bone density is below normal and may lead to osteoporosis. -2.5 and below-indicates osteoporosis.</description>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-2.4" spread="1.2"/>
                    <measurement group_id="B2" value="-2.4" spread="1.2"/>
                    <measurement group_id="B3" value="-2.8" spread="0.9"/>
                    <measurement group_id="B4" value="-2.5" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Volumetric Bone Mineral Density (vBMD) LS</title>
          <description>Baseline lumbar spine BMD by quantitative computed tomography (QCT)</description>
          <units>mg/cm^3</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="96.4" spread="28.1"/>
                    <measurement group_id="B2" value="99.7" spread="24.0"/>
                    <measurement group_id="B3" value="94.2" spread="25.4"/>
                    <measurement group_id="B4" value="96.9" spread="25.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>vBMD distal forearm</title>
          <description>Bone Mineral Density at the distal forearm by QCT</description>
          <units>mg/cm^3</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="183.5" spread="32.0"/>
                    <measurement group_id="B2" value="194.9" spread="37.6"/>
                    <measurement group_id="B3" value="181.4" spread="35.5"/>
                    <measurement group_id="B4" value="192.6" spread="34.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cortical width</title>
          <description>Baseline cortical Width of the distal forearm.</description>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.23" spread="0.5"/>
                    <measurement group_id="B2" value="1.19" spread="0.5"/>
                    <measurement group_id="B3" value="1.14" spread="0.4"/>
                    <measurement group_id="B4" value="1.2" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Nephrolithiasis</title>
          <description>Subjects with nephrolithiasis at baseline</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Nephrocalcinosis</title>
          <description>Subjects with nephrocalcinosis at baseline</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pancreas calcifications</title>
          <description>Subjects with pancreatic calcifications at baseline</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fracture by Vertebral Fracture Assessment (VFA)</title>
          <description>Subjects with vertebral fractures by VFA at baseline</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <description>Body Mass Index at baseline</description>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.7" spread="3.5"/>
                    <measurement group_id="B2" value="27.4" spread="4.8"/>
                    <measurement group_id="B3" value="28.4" spread="3.9"/>
                    <measurement group_id="B4" value="27.8" spread="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ionized Calcium</title>
          <description>Baseline ionized calcium levels.</description>
          <units>mmol/l</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.39" spread="0.08"/>
                    <measurement group_id="B2" value="1.39" spread="0.078"/>
                    <measurement group_id="B3" value="1.39" spread="0.08"/>
                    <measurement group_id="B4" value="1.39" spread="0.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>P-Parathyroid Hormone (PTH)</title>
          <description>Baseline Parathyroid Hormone level.</description>
          <units>pmol/l</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12.1" spread="6.2"/>
                    <measurement group_id="B2" value="13.1" spread="6.4"/>
                    <measurement group_id="B3" value="11.2" spread="4.3"/>
                    <measurement group_id="B4" value="12.1" spread="5.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Agatston Score</title>
          <description>Agatston score is a score based on the extent of coronary artery calcification calculated on the amount of plaque observed in a CT scan. A score of zero indicates absence of coronary calcium, 1-10: minimal calcification, 11-100 mild calcification, 101-400 moderate calcification, &gt;400 severe calcification.&#xD;
Thus the score increases with increasing level of calcification in the coronary vessels.</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.9" lower_limit="0.7" upper_limit="25.9"/>
                    <measurement group_id="B2" value="10.1" lower_limit="0.3" upper_limit="470.3"/>
                    <measurement group_id="B3" value="55.7" lower_limit="6.8" upper_limit="144.6"/>
                    <measurement group_id="B4" value="15.5" lower_limit="0.65" upper_limit="129.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>U-Calcium</title>
          <description>Baseline urine calcium excretion per day.</description>
          <units>mg/d</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="338" lower_limit="159" upper_limit="419"/>
                    <measurement group_id="B2" value="276" lower_limit="218" upper_limit="555"/>
                    <measurement group_id="B3" value="314" lower_limit="222" upper_limit="373"/>
                    <measurement group_id="B4" value="284" lower_limit="218" upper_limit="393"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>U-Phosphorous</title>
          <description>Baseline daily excretion of phosphorous in urine.</description>
          <units>mmol/d</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.5" lower_limit="25.7" upper_limit="33.6"/>
                    <measurement group_id="B2" value="32.2" lower_limit="26.5" upper_limit="37.0"/>
                    <measurement group_id="B3" value="35.2" lower_limit="23.6" upper_limit="39.5"/>
                    <measurement group_id="B4" value="32.0" lower_limit="25.6" upper_limit="37.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>P-Phosphorous</title>
          <description>Baseline p-phosphorous.</description>
          <units>mmol/l</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0.77" spread="0.15"/>
                    <measurement group_id="B2" value="0.77" spread="0.16"/>
                    <measurement group_id="B3" value="0.79" spread="0.12"/>
                    <measurement group_id="B4" value="0.78" spread="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Major Depression Inventory score</title>
          <description>The Major Depression Inventory (MDI) is a mood questionnaire developed by the World Health Organization. To calculate the total score, a sum of ten individual items (each with an individual score between 0-5, with 0 indicating absence of a symptom and 5 indicating constant presence of a given symptom) is used. A higher score signifies deeper depression with 50 being the maximum score.</description>
          <units>MDI-points</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="15"/>
                    <count group_id="B2" value="16"/>
                    <count group_id="B3" value="15"/>
                    <count group_id="B4" value="46"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5" lower_limit="2" upper_limit="11"/>
                    <measurement group_id="B2" value="5" lower_limit="1.5" upper_limit="8.5"/>
                    <measurement group_id="B3" value="5" lower_limit="2" upper_limit="7"/>
                    <measurement group_id="B4" value="5" lower_limit="2" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Lumbar Spine Bone Mineral Density</title>
        <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
        <time_frame>Baseline,one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Lumbar Spine Bone Mineral Density</title>
          <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan.</population>
          <units>g/cm^2</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.030" spread="0.009"/>
                    <measurement group_id="O2" value="0.042" spread="0.009"/>
                    <measurement group_id="O3" value="-0.016" spread="0.007"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>&lt; 0.00001</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Total Hip Bone Mineral Density</title>
        <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
        <time_frame>Baseline,one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total Hip Bone Mineral Density</title>
          <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed.</population>
          <units>g/cm^2</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.027" spread="0.006"/>
                    <measurement group_id="O2" value="0.021" spread="0.003"/>
                    <measurement group_id="O3" value="-0.013" spread="0.006"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>&lt; 0.00001</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Femoral Neck Bone Mineral Density</title>
        <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
        <time_frame>Baseline,one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Femoral Neck Bone Mineral Density</title>
          <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed.</population>
          <units>g/cm^2</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.023" spread="0.006"/>
                    <measurement group_id="O2" value="0.020" spread="0.005"/>
                    <measurement group_id="O3" value="-0.007" spread="0.006"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.0019</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in 1/3 Forearm Bone Mineral Density</title>
        <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
        <time_frame>Baseline,one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group did not provide results for this analysis as he/she experienced a wrist fracture prior to the final scan.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in 1/3 Forearm Bone Mineral Density</title>
          <description>Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group did not provide results for this analysis as he/she experienced a wrist fracture prior to the final scan.</population>
          <units>g/cm^2</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.005" spread="0.003"/>
                    <measurement group_id="O2" value="0.005" spread="0.003"/>
                    <measurement group_id="O3" value="-0.005" spread="0.004"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.096</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage Change in Lumbar Spine Bone Mineral Density</title>
        <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
        <time_frame>Baseline,one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in Lumbar Spine Bone Mineral Density</title>
          <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan.</population>
          <units>% change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" spread="1.1"/>
                    <measurement group_id="O2" value="5.1" spread="1.1"/>
                    <measurement group_id="O3" value="-1.8" spread="0.8"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.0001</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage Change in Total Hip Bone Mineral Density</title>
        <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
        <time_frame>Baseline,one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in Total Hip Bone Mineral Density</title>
          <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed.</population>
          <units>% change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.45" spread="0.72"/>
                    <measurement group_id="O2" value="2.64" spread="0.41"/>
                    <measurement group_id="O3" value="-1.50" spread="0.72"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>&lt; 0.00001</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage Change in Femoral Neck Bone Mineral Density</title>
        <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
        <time_frame>Baseline,one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in Femoral Neck Bone Mineral Density</title>
          <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the placebo group did not provide results for this analysis as he/she had had a hip-replacement performed.</population>
          <units>% change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.70" spread="0.98"/>
                    <measurement group_id="O2" value="3.03" spread="0.86"/>
                    <measurement group_id="O3" value="-0.78" spread="0.9"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.0027</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage Change in 1/3 Forearm Bone Mineral Density</title>
        <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
        <time_frame>Baseline,one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group did not provide results for this analysis as he/she experienced a wrist fracture prior to the final scan.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in 1/3 Forearm Bone Mineral Density</title>
          <description>Percentage change of Bone Mineral Density after one year of treatment from baseline.&#xD;
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group did not provide results for this analysis as he/she experienced a wrist fracture prior to the final scan.</population>
          <units>% change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.94" spread="0.7"/>
                    <measurement group_id="O2" value="0.88" spread="0.5"/>
                    <measurement group_id="O3" value="-0.91" spread="0.7"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.081</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Volumetric BMD for the Lumbar Spine.</title>
        <description>Measured at baseline and after one year by QCT.</description>
        <time_frame>Baseline, one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. Another scan could not be included due to a technical problems with the image analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Volumetric BMD for the Lumbar Spine.</title>
          <description>Measured at baseline and after one year by QCT.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. Another scan could not be included due to a technical problems with the image analysis.</population>
          <units>mg/cm^3</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.93" spread="2.15"/>
                    <measurement group_id="O2" value="5.35" spread="1.91"/>
                    <measurement group_id="O3" value="-2.56" spread="1.6"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>= 0.0071</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean P-calcium During Treatment.</title>
        <description>Blood samples were acquired once every 4 weeks for safety-purposes.</description>
        <time_frame>Monthly up to one year.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean P-calcium During Treatment.</title>
          <description>Blood samples were acquired once every 4 weeks for safety-purposes.</description>
          <units>mmol/l</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <units_analyzed>p-calcium measurements</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>p-calcium measurements</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="210"/>
                <count group_id="O2" value="240"/>
                <count group_id="O3" value="224"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.28" spread="0.007"/>
                    <measurement group_id="O2" value="1.38" spread="0.006"/>
                    <measurement group_id="O3" value="1.40" spread="0.004"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.0001</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in P-carboxy-terminal Collagen Crosslinks (CTX)</title>
        <description>p-CTX, change from baseline at 48 weeks.</description>
        <time_frame>Change from baseline at 48 weeks reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in P-carboxy-terminal Collagen Crosslinks (CTX)</title>
          <description>p-CTX, change from baseline at 48 weeks.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>% change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-48.7" lower_limit="-73.2" upper_limit="-15.8"/>
                    <measurement group_id="O2" value="-58.2" lower_limit="-76.7" upper_limit="-44.3"/>
                    <measurement group_id="O3" value="11.8" lower_limit="1.96" upper_limit="40.0"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.0001</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Agatstons Score Final</title>
        <description>Simultaneously with QCT-measurements coronary calcification was be assessed. Agatston score is a score based on the extent of coronary artery calcification calculated on the amount of plaque observed in a CT scan. A score of zero indicates absence of coronary calcium, 1-10: minimal calcification, 11-100 mild calcification, 101-400 moderate calcification, &gt;400 severe calcification.&#xD;
Thus the score increases with increasing level of calcification in the coronary vessels.</description>
        <time_frame>Baseline, one year</time_frame>
        <population>Some participant from the combined and placebo groups could not be included in the analysis because they had coronary stents.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Agatstons Score Final</title>
          <description>Simultaneously with QCT-measurements coronary calcification was be assessed. Agatston score is a score based on the extent of coronary artery calcification calculated on the amount of plaque observed in a CT scan. A score of zero indicates absence of coronary calcium, 1-10: minimal calcification, 11-100 mild calcification, 101-400 moderate calcification, &gt;400 severe calcification.&#xD;
Thus the score increases with increasing level of calcification in the coronary vessels.</description>
          <population>Some participant from the combined and placebo groups could not be included in the analysis because they had coronary stents.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0" lower_limit="0.0" upper_limit="78.1"/>
                    <measurement group_id="O2" value="24.3" lower_limit="0.7" upper_limit="602.1"/>
                    <measurement group_id="O3" value="117.8" lower_limit="6.8" upper_limit="182.6"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>= 0.38</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patients With Nephrolithiasis Final Scan.</title>
        <description>Number of subjects w. renal stones at final scan.</description>
        <time_frame>Patients with nephrolithiasis at one year reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Patients With Nephrolithiasis Final Scan.</title>
          <description>Number of subjects w. renal stones at final scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patients With Pancreas-calcifications Final Scan.</title>
        <description>By QCT.</description>
        <time_frame>Patients with pancreas-calcifications at one year reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Patients With Pancreas-calcifications Final Scan.</title>
          <description>By QCT.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Reset of the Calcium Sensing Receptor?</title>
        <description>Measured from effect on s-calcium and PTH weeks after termination of IMP</description>
        <time_frame>2 weeks after termination of medication.</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Vertebral Fracture Assessment - Final Scan</title>
        <description>Number of participants with vertebral fractures as assessed by VFA at final scan.</description>
        <time_frame>Patients with vertebral fractures at one year reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Vertebral Fracture Assessment - Final Scan</title>
          <description>Number of participants with vertebral fractures as assessed by VFA at final scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change MDI-score</title>
        <description>Major Depression Inventory (MDI)-score, Baseline, 6 months, one year (week 52)., change between baseline and 1 year reported.&#xD;
The Major Depression Inventory (MDI) is a mood questionnaire developed by the World Health Organization. To calculate the total score, a sum of ten individual items (each with an individual score between 0-5, with 0 indicating absence of a symptom and 5 indicating constant presence of a given symptom) is used. A higher score signifies deeper depression with 50 being the maximum score.</description>
        <time_frame>Baseline, 6 mths, one year.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final collection of MDI-questionnaires.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change MDI-score</title>
          <description>Major Depression Inventory (MDI)-score, Baseline, 6 months, one year (week 52)., change between baseline and 1 year reported.&#xD;
The Major Depression Inventory (MDI) is a mood questionnaire developed by the World Health Organization. To calculate the total score, a sum of ten individual items (each with an individual score between 0-5, with 0 indicating absence of a symptom and 5 indicating constant presence of a given symptom) is used. A higher score signifies deeper depression with 50 being the maximum score.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final collection of MDI-questionnaires.</population>
          <units>MDI-score</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-4.0" upper_limit="1.0"/>
                    <measurement group_id="O2" value="-0.5" lower_limit="-4.5" upper_limit="1.0"/>
                    <measurement group_id="O3" value="0.0" lower_limit="-3.0" upper_limit="0.0"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.83</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adverse Reactions.</title>
        <description>All participants filled in questionnaires regarding symptoms related to the treatment.&#xD;
Results are reported in the Adverse Events section.</description>
        <time_frame>Monthly up to one year.</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bone Mineral Content</title>
        <description>Measured at baseline and after one year at the lumbar spine and distal 1/3 of the non-dominant antebrachii.</description>
        <time_frame>Baseline, one year</time_frame>
        <population>Data were not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Bone Mineral Content</title>
          <description>Measured at baseline and after one year at the lumbar spine and distal 1/3 of the non-dominant antebrachii.</description>
          <population>Data were not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Cortical Width.</title>
        <description>Measured at baseline and after one year at the distal non-dominant antebrachii.</description>
        <time_frame>Baseline, one year.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group experienced a wrist fracture prior to the final scan and was excluded. 4 patients did not provide data for the analysis due to errors in the technique of the obtained images.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Cortical Width.</title>
          <description>Measured at baseline and after one year at the distal non-dominant antebrachii.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group experienced a wrist fracture prior to the final scan and was excluded. 4 patients did not provide data for the analysis due to errors in the technique of the obtained images.</population>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" spread="0.1"/>
                    <measurement group_id="O2" value="0.02" spread="0.08"/>
                    <measurement group_id="O3" value="0.04" spread="0.05"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>&gt;0.05</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Volumetric BMD for the Distal Forearm.</title>
        <description>Measured at baseline and after one year by QCT.</description>
        <time_frame>Baseline, one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group experienced a wrist fracture prior to the final scan and was excluded. 5 patients did not provide data for the analysis due to errors in the technique of the obtained images.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Volumetric BMD for the Distal Forearm.</title>
          <description>Measured at baseline and after one year by QCT.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group experienced a wrist fracture prior to the final scan and was excluded. 5 patients did not provide data for the analysis due to errors in the technique of the obtained images.</population>
          <units>mg/cm^3</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" spread="2.1"/>
                    <measurement group_id="O2" value="9.6" spread="3.7"/>
                    <measurement group_id="O3" value="-1.1" spread="4.6"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>= 0.0077</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change in Volumetric BMD for the Lumbar Spine.</title>
        <description>Measured at baseline and after one year by QCT.</description>
        <time_frame>Baseline, one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. Another scan could not be included due to a technical problems with the image analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in Volumetric BMD for the Lumbar Spine.</title>
          <description>Measured at baseline and after one year by QCT.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. Another scan could not be included due to a technical problems with the image analysis.</population>
          <units>% change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.18" spread="3.14"/>
                    <measurement group_id="O2" value="5.66" spread="1.85"/>
                    <measurement group_id="O3" value="-2.94" spread="1.96"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.011</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change in Volumetric BMD for the Distal Forearm.</title>
        <description>Measured at baseline and after one year by QCT.</description>
        <time_frame>Baseline, one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group experienced a wrist fracture prior to the final scan and was excluded. 5 patients did not provide data for the analysis due to errors in the technique of the obtained images.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in Volumetric BMD for the Distal Forearm.</title>
          <description>Measured at baseline and after one year by QCT.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final scan. One participant from the denosumab group experienced a wrist fracture prior to the final scan and was excluded. 5 patients did not provide data for the analysis due to errors in the technique of the obtained images.</population>
          <units>% change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="13"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.53" spread="1.2"/>
                    <measurement group_id="O2" value="5.2" spread="1.0"/>
                    <measurement group_id="O3" value="-0.74" spread="2.6"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>= 0.011</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean p-PTH During Treatment.</title>
        <description>Blood samples were acquired once every 4 weeks for safety-purposes.</description>
        <time_frame>Monthly up to one year.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean p-PTH During Treatment.</title>
          <description>Blood samples were acquired once every 4 weeks for safety-purposes.</description>
          <units>pmol/l</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <units_analyzed>p-PTH measurements</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>p-PTH measurements</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="211"/>
                <count group_id="O2" value="240"/>
                <count group_id="O3" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.0" lower_limit="11.1" upper_limit="12.9"/>
                    <measurement group_id="O2" value="13.4" lower_limit="12.7" upper_limit="14.2"/>
                    <measurement group_id="O3" value="9.9" lower_limit="9.5" upper_limit="10.4"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.0001</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean p-Phosphate During Treatment.</title>
        <description>Blood samples were acquired once every 4 weeks for safety-purposes.</description>
        <time_frame>Monthly up to one year.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean p-Phosphate During Treatment.</title>
          <description>Blood samples were acquired once every 4 weeks for safety-purposes.</description>
          <units>pmol/l</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <units_analyzed>p-phosphate measurements</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="15"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>p-phosphate measurements</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="211"/>
                <count group_id="O2" value="240"/>
                <count group_id="O3" value="225"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.83" spread="0.013"/>
                    <measurement group_id="O2" value="0.76" spread="0.012"/>
                    <measurement group_id="O3" value="0.083" spread="0.011"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>&lt; 0.00001</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in p-N-terminal Propeptide of Type I Procollagen (p-P1NP).</title>
        <description>p-P1NP, change from baseline at 48 weeks.</description>
        <time_frame>Change from baseline at 48 weeks reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in p-N-terminal Propeptide of Type I Procollagen (p-P1NP).</title>
          <description>p-P1NP, change from baseline at 48 weeks.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>% change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-63.1" lower_limit="-66.9" upper_limit="-57.2"/>
                    <measurement group_id="O2" value="-66.1" lower_limit="-75.9" upper_limit="-55.4"/>
                    <measurement group_id="O3" value="17.8" lower_limit="-11.0" upper_limit="31.5"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.0001</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in P-osteocalcin.</title>
        <description>p-osteocalcin, change from baseline at 48 weeks.</description>
        <time_frame>Change from baseline at 48 weeks reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in P-osteocalcin.</title>
          <description>p-osteocalcin, change from baseline at 48 weeks.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>% change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-60.0" lower_limit="-69.8" upper_limit="-36.9"/>
                    <measurement group_id="O2" value="-58.9" lower_limit="-66.9" upper_limit="-49.0"/>
                    <measurement group_id="O3" value="7.0" lower_limit="-0.9" upper_limit="36.9"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.0001</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in S-bone-specific Alkaline Phosphatase (BAP).</title>
        <description>S-Bone specific alkaline phosphatase, change from baseline at 48 weeks.</description>
        <time_frame>Change from baseline at 48 weeks reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in S-bone-specific Alkaline Phosphatase (BAP).</title>
          <description>S-Bone specific alkaline phosphatase, change from baseline at 48 weeks.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>% change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-40.0" lower_limit="-46.3" upper_limit="-24.1"/>
                    <measurement group_id="O2" value="-46.3" lower_limit="-51.5" upper_limit="-38.4"/>
                    <measurement group_id="O3" value="9.7" lower_limit="-7.9" upper_limit="32.5"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.0001</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in p-Tartrate-resistant Acid Phosphatase 5b (Trap5b).</title>
        <description>P-Trap5b, change from baseline at 48 weeks.</description>
        <time_frame>Change from baseline at 48 weeks reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in p-Tartrate-resistant Acid Phosphatase 5b (Trap5b).</title>
          <description>P-Trap5b, change from baseline at 48 weeks.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>% change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-27.8" lower_limit="-34.1" upper_limit="-2.3"/>
                    <measurement group_id="O2" value="-36.7" lower_limit="-51.8" upper_limit="-16.4"/>
                    <measurement group_id="O3" value="2.3" lower_limit="-4.9" upper_limit="19.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in p-Sclerostin.</title>
        <description>P-Sclerostin, change from baseline at 48 weeks.</description>
        <time_frame>Change from baseline at 48 weeks reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in p-Sclerostin.</title>
          <description>P-Sclerostin, change from baseline at 48 weeks.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>% change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.0" lower_limit="3.1" upper_limit="21.1"/>
                    <measurement group_id="O2" value="6.5" lower_limit="0.9" upper_limit="15.9"/>
                    <measurement group_id="O3" value="4.8" lower_limit="-2.3" upper_limit="13.9"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.5</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in P-fibroblast Growth Factor 23 (FGF23).</title>
        <description>P-FGF23 , change from baseline at 48 weeks.</description>
        <time_frame>Change from baseline at 48 weeks reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in P-fibroblast Growth Factor 23 (FGF23).</title>
          <description>P-FGF23 , change from baseline at 48 weeks.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>% change</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.8" lower_limit="0.0" upper_limit="52.9"/>
                    <measurement group_id="O2" value="20.4" lower_limit="-13.6" upper_limit="58.2"/>
                    <measurement group_id="O3" value="28.0" lower_limit="-25.9" upper_limit="64.7"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.85</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in p-25-vitamin D</title>
        <description>P-25-vitD , change from baseline at 48 weeks.</description>
        <time_frame>Change from baseline at 48 weeks reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in p-25-vitamin D</title>
          <description>P-25-vitD , change from baseline at 48 weeks.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>nmol/l</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.1" lower_limit="13.3" upper_limit="32.6"/>
                    <measurement group_id="O2" value="16.0" lower_limit="4.1" upper_limit="22.0"/>
                    <measurement group_id="O3" value="21.2" lower_limit="8.2" upper_limit="30.5"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.22</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in s-1,25-vitamin D</title>
        <description>S-1,25-vitD, change from baseline at 48 weeks.</description>
        <time_frame>Change from baseline at 48 weeks reported.</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in s-1,25-vitamin D</title>
          <description>S-1,25-vitD, change from baseline at 48 weeks.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>pmol/l</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5" lower_limit="-4.0" upper_limit="35.0"/>
                    <measurement group_id="O2" value="4.5" lower_limit="-15.0" upper_limit="25.5"/>
                    <measurement group_id="O3" value="26.0" lower_limit="14.0" upper_limit="36.0"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>= 0.18</p_value>
            <method>Kruskal-Wallis</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patients With Nephrocalcinosis, Final Scan.</title>
        <description>Number of subjects w. renal calcifications at final scan.</description>
        <time_frame>Baseline, one year</time_frame>
        <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Combined Treatment.</title>
            <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
          </group>
          <group group_id="O2">
            <title>Denosumab Monotherapy</title>
            <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Patients With Nephrocalcinosis, Final Scan.</title>
          <description>Number of subjects w. renal calcifications at final scan.</description>
          <population>One participant from the combined treatment-group was not included in the analysis due to withdrawal before the final blood-sampling.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Safety Measures</title>
        <description>Biochemical measures of changes in liver, infection, kidney and electrolyte-status and urinary excretion of calcium.</description>
        <time_frame>Monthly up to one year.</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected for each participant from baseline until two weeks after treatment-cessation, up to 1 year.</time_frame>
      <desc>Adverse events were collected at each visit using a adverse event questionnaire as well as assessment by a study-physician.</desc>
      <group_list>
        <group group_id="E1">
          <title>Combined Treatment.</title>
          <description>15 subjects were treated with combined 60mg denosumab every six months, 30 mg cinacalcet daily and 50 micrograms vitamin-D3 daily.</description>
        </group>
        <group group_id="E2">
          <title>Denosumab Monotherapy</title>
          <description>16 subjects received 60 mg denosumab every six months, placebo and 50 micrograms vitamin-D daily.</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>15 subjects will receive a saline injection every six months(blinded), placebo-tablets and 50 micrograms vitamin-D daily.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <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="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Polycythaemia Vera</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina, Unstable</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Inflammatory Bowel Disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erysipelas</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (Unspecified)</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="13" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="7" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E3" events="17" subjects_affected="3" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="33" subjects_affected="6" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="18" subjects_affected="7" subjects_at_risk="15"/>
                <counts group_id="E2" events="21" subjects_affected="9" subjects_at_risk="16"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="15"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="5" subjects_affected="2" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="12" subjects_affected="5" subjects_at_risk="15"/>
                <counts group_id="E2" events="20" subjects_affected="6" subjects_at_risk="16"/>
                <counts group_id="E3" events="5" subjects_affected="4" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="14" subjects_affected="6" subjects_at_risk="15"/>
                <counts group_id="E2" events="17" subjects_affected="6" subjects_at_risk="16"/>
                <counts group_id="E3" events="20" subjects_affected="3" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="12" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Paraesthesia, hands</sub_title>
                <counts group_id="E1" events="36" subjects_affected="6" subjects_at_risk="15"/>
                <counts group_id="E2" events="15" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" events="20" subjects_affected="4" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Paraesthesia, feet</sub_title>
                <counts group_id="E1" events="17" subjects_affected="4" subjects_at_risk="15"/>
                <counts group_id="E2" events="27" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" events="23" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="5" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Coughing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="9" subjects_affected="4" subjects_at_risk="16"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="15"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Leg edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E2" events="7" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="15"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <limitations_and_caveats>Important limitations are the relatively small number of study-participants, and the lack of a cinacalcet monotherapy-arm.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Professor Peter Vestergaard</name_or_title>
      <organization>Aalborg University Hospital</organization>
      <phone>+45 97 66 36 00</phone>
      <email>p.vestergaard@rn.dk</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/NCT03027557
org study id: 180987
secondary id: 2016-001510-20
nct id: NCT03027557
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The only known cure for primary hyperparathyroidism is surgical removal of one or more
      parathyroid glands. Some patients however, do not fulfill criteria for surgery or do not want
      to undergo a procedure due to fear of the associated risks. Therefore a medical alternative
      is warranted.

      This study aims to evaluate the effects of Denosumab alone, and in combination with
      Cinacalcet, as a medical treatment for patients suffering from primary hyperparathyroidism,
      with mild osteoporosis. To the best of our knowledge no previously reported randomized
      controlled trial has investigated the use of denosumab in primary hyperparathyroidism.

      60 patients will be enrolled in three different treatment-groups: 20 receiving both Denosumab
      and Cinacalcet, 20 Denosumab and placebo and 20 placebo and placebo. Patients included do not
      meet the criteria for, or have no wish for a surgical procedure.

      By combining the two drugs, this study could possibly contribute to the discovery of a
      realistic medical alternative to surgery. It is expected that the therapy will be able to
      both control s-calcium and s-intact parathyroid hormone (iPTH), and simultaneously enhance
      bone-structure. The therapy thus has the potential of preventing fractures and possibly other
      long-term effects of primary hyperparathyroidism such as formation of kidney stones, and
      coronary calcification. Another objective of this project is to investigate whether the
      combined therapy can facilitate an actual reset of the Calcium-sensing receptor, and thereby
      de facto cure the disease.
Background/Context:

      This project deals with medical treatment of primary hyperparathyroidism. The only cure
      currently available is surgical removal of one or more parathyroid glands, but this option is
      neither feasible, nor desirable in all patients with the diagnosis.

      Today a major group of patients are being diagnosed by coincidence with biochemical
      blood-screening, and are therefore in an asymptomatic state of the disease at the time of
      diagnosis. Long term studies show that these patients over time often have progression in
      their disease, and develop complications such as osteoporosis. Thus a medical alternative is
      warranted.

      Previous studies have investigated the effects of well known antiresorptive drugs such as
      bisphosphonates, as well as estrogen-related compounds. These drugs have had effects on
      particularly bone mineral density (BMD) and biochemical bone-turnover markers, but have been
      able only transiently to lower blood-calcium levels. Combined with too many unwanted
      side-effects and a high prevalence of contraindications for a large proportion of the
      patients needing treatment, these drugs have not provided a realistic alternative to surgery.

      Treatment today generally follows the international consensus for treatment of asymptomatic
      patients with primary hyperparathyroidism. Briefly this includes watchful waiting with
      biannual control-sessions for indication of surgery, screening for kidney
      stones/nephrolithiasis, osteoporosis and s-calcium - and s-iPTH levels.

      This randomized controlled trial involves the drugs Cinacalcet og Denosumab. Denosumab has
      previously been shown to greatly improve BMD, lower s-calcium, lower the rate of
      bone-turnover and prevent osteoporotic fractures in several populations with different
      diseases, but has never been tested in a published randomized controlled trial in patients
      with primary hyperparathyroidism.

      Cinacalcet has been proved able to lower s-iPTH, lower s-Calcium and thereby relieve symptoms
      of hypercalcaemia caused by primary hyperparathyroidism. It does not however, lower the rate
      of bone turnover, and it has not been show to improve BMD.

      By combining the two drugs, this study could possibly contribute to the discovery of a
      realistic medical alternative to surgery. It is expected that the therapy will be able to
      both control s-calcium and s-iPTH, and simultaneously enhance bone-structure. The therapy
      thus has the potential of preventing fractures and possibly other long-term effects of
      primary hyperparathyroidism such as formation of kidney stones, and coronary calcification.
      Another objective of this project is to investigate whether the combined therapy can
      facilitate an actual reset of the Calcium-sensing receptor, and thereby de facto cure the
      disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in Lumbar Spine Bone Mineral Density
time frame: Baseline,one year
description: Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
measure: Change in Total Hip Bone Mineral Density
time frame: Baseline,one year
description: Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
measure: Change in Femoral Neck Bone Mineral Density
time frame: Baseline,one year
description: Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
measure: Change in 1/3 Forearm Bone Mineral Density
time frame: Baseline,one year
description: Change of Bone Mineral Density after one year of treatment from baseline. Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
measure: Percentage Change in Lumbar Spine Bone Mineral Density
time frame: Baseline,one year
description: Percentage change of Bone Mineral Density after one year of treatment from baseline.
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
measure: Percentage Change in Total Hip Bone Mineral Density
time frame: Baseline,one year
description: Percentage change of Bone Mineral Density after one year of treatment from baseline.
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
measure: Percentage Change in Femoral Neck Bone Mineral Density
time frame: Baseline,one year
description: Percentage change of Bone Mineral Density after one year of treatment from baseline.
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
measure: Percentage Change in 1/3 Forearm Bone Mineral Density
time frame: Baseline,one year
description: Percentage change of Bone Mineral Density after one year of treatment from baseline.
Measured with Dual-energy X-ray absorptiometry (DXA)-scan.
measure: Change in Volumetric BMD for the Lumbar Spine.
time frame: Baseline, one year
description: Measured at baseline and after one year by QCT.
measure: Mean P-calcium During Treatment.
time frame: Monthly up to one year.
description: Blood samples were acquired once every 4 weeks for safety-purposes.
measure: Percent Change From Baseline in P-carboxy-terminal Collagen Crosslinks (CTX)
time frame: Change from baseline at 48 weeks reported.
description: p-CTX, change from baseline at 48 weeks.
measure: Median Agatstons Score Final
time frame: Baseline, one year
description: Simultaneously with QCT-measurements coronary calcification was be assessed. Agatston score is a score based on the extent of coronary artery calcification calculated on the amount of plaque observed in a CT scan. A score of zero indicates absence of coronary calcium, 1-10: minimal calcification, 11-100 mild calcification, 101-400 moderate calcification, >400 severe calcification.
Thus the score increases with increasing level of calcification in the coronary vessels.
measure: Patients With Nephrolithiasis Final Scan.
time frame: Patients with nephrolithiasis at one year reported.
description: Number of subjects w. renal stones at final scan.
measure: Patients With Pancreas-calcifications Final Scan.
time frame: Patients with pancreas-calcifications at one year reported.
description: By QCT.
measure: Reset of the Calcium Sensing Receptor?
time frame: 2 weeks after termination of medication.
description: Measured from effect on s-calcium and PTH weeks after termination of IMP
measure: Vertebral Fracture Assessment - Final Scan
time frame: Patients with vertebral fractures at one year reported.
description: Number of participants with vertebral fractures as assessed by VFA at final scan.
measure: Change MDI-score
time frame: Baseline, 6 mths, one year.
description: Major Depression Inventory (MDI)-score, Baseline, 6 months, one year (week 52)., change between baseline and 1 year reported.
The Major Depression Inventory (MDI) is a mood questionnaire developed by the World Health Organization. To calculate the total score, a sum of ten individual items (each with an individual score between 0-5, with 0 indicating absence of a symptom and 5 indicating constant presence of a given symptom) is used. A higher score signifies deeper depression with 50 being the maximum score.
measure: Adverse Reactions.
time frame: Monthly up to one year.
description: All participants filled in questionnaires regarding symptoms related to the treatment.
Results are reported in the Adverse Events section.
measure: Bone Mineral Content
time frame: Baseline, one year
description: Measured at baseline and after one year at the lumbar spine and distal 1/3 of the non-dominant antebrachii.
measure: Change in Cortical Width.
time frame: Baseline, one year.
description: Measured at baseline and after one year at the distal non-dominant antebrachii.
measure: Change in Volumetric BMD for the Distal Forearm.
time frame: Baseline, one year
description: Measured at baseline and after one year by QCT.
measure: Percentage Change in Volumetric BMD for the Lumbar Spine.
time frame: Baseline, one year
description: Measured at baseline and after one year by QCT.
measure: Percentage Change in Volumetric BMD for the Distal Forearm.
time frame: Baseline, one year
description: Measured at baseline and after one year by QCT.
measure: Mean p-PTH During Treatment.
time frame: Monthly up to one year.
description: Blood samples were acquired once every 4 weeks for safety-purposes.
measure: Mean p-Phosphate During Treatment.
time frame: Monthly up to one year.
description: Blood samples were acquired once every 4 weeks for safety-purposes.
measure: Percent Change From Baseline in p-N-terminal Propeptide of Type I Procollagen (p-P1NP).
time frame: Change from baseline at 48 weeks reported.
description: p-P1NP, change from baseline at 48 weeks.
measure: Percent Change From Baseline in P-osteocalcin.
time frame: Change from baseline at 48 weeks reported.
description: p-osteocalcin, change from baseline at 48 weeks.
measure: Percent Change From Baseline in S-bone-specific Alkaline Phosphatase (BAP).
time frame: Change from baseline at 48 weeks reported.
description: S-Bone specific alkaline phosphatase, change from baseline at 48 weeks.
measure: Percent Change From Baseline in p-Tartrate-resistant Acid Phosphatase 5b (Trap5b).
time frame: Change from baseline at 48 weeks reported.
description: P-Trap5b, change from baseline at 48 weeks.
measure: Percent Change From Baseline in p-Sclerostin.
time frame: Change from baseline at 48 weeks reported.
description: P-Sclerostin, change from baseline at 48 weeks.
measure: Percent Change From Baseline in P-fibroblast Growth Factor 23 (FGF23).
time frame: Change from baseline at 48 weeks reported.
description: P-FGF23 , change from baseline at 48 weeks.
measure: Changes in p-25-vitamin D
time frame: Change from baseline at 48 weeks reported.
description: P-25-vitD , change from baseline at 48 weeks.
measure: Changes in s-1,25-vitamin D
time frame: Change from baseline at 48 weeks reported.
description: S-1,25-vitD, change from baseline at 48 weeks.
measure: Patients With Nephrocalcinosis, Final Scan.
time frame: Baseline, one year
description: Number of subjects w. renal calcifications at final scan.
measure: Safety Measures
time frame: Monthly up to one year.
description: Biochemical measures of changes in liver, infection, kidney and electrolyte-status and urinary excretion of calcium.
arm group label: Combined treatment.
arm group type: Experimental
description: 20 subjects will be treated with combined 60mg denosumab bi-annually , 30 mg cinacalcet daily and 50 micrograms vitamin-D daily.
arm group label: Monotherapy
arm group type: Active Comparator
description: 20 subjects will receive 60mg denosumab bi-annually, placebo and 50 micrograms vitamin-D daily.
arm group label: Placebo
arm group type: Placebo Comparator
description: 20 subjects will receive a saline injection bi-annually (blinded), placebo-tablets and 50 micrograms vitamin-D daily.
intervention type: Drug
intervention name: Cinacalcet 30 mg Tablet
description: Participants in one arm will receive 30 mg cinacalcet each day.
arm group label: Combined treatment.
other name: Mimpara
other name: Sensipar
intervention type: Drug
intervention name: Denosumab Inj 60 mg/ml
description: Participants in two arms will receive 60 mg Denosumab biannually.
arm group label: Combined treatment.
arm group label: Monotherapy
other name: Prolia
other name: Xgeva
intervention type: Other
intervention name: Placebo tablets
description: Participants in two arms will receive one placebo-tablet each day.
arm group label: Monotherapy
arm group label: Placebo
intervention type: Other
intervention name: Saline Injection (Placebo)
description: Participants in one arm will receive saline injections as placebo for denosumab.
arm group label: Placebo
other name: Sodium Chloride (NaCl) Fresenius "Kabi"
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Julius Simoni Leere, MD
role: Principal Investigator
affiliation: Aalborg University and Aalborg University Hospital
last name: Peter Vestergaard, DMSc
role: Study Director
affiliation: Aalborg University and Aalborg University Hospital
facility: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Aalborg University Hospital
investigator full name: Peter Vestergaard
investigator title: Professor, DMSc, Consultant
mesh term: Adenoma
mesh term: Parathyroid Neoplasms
mesh term: Hyperparathyroidism
mesh term: Hyperparathyroidism, Primary
mesh term: Hyperplasia
mesh term: Denosumab
mesh term: Cinacalcet
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Important limitations are the relatively small number of study-participants, and the lack of a cinacalcet monotherapy-arm.
point of contact: 