<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/NCT03040765</url>
  </required_header>
  <id_info>
    <org_study_id>16441/16</org_study_id>
    <nct_id>NCT03040765</nct_id>
  </id_info>
  <brief_title>Denosumab Versus Zoledronic Acid in Thalassemia-Induced Osteoporosis</brief_title>
  <acronym>DOHA</acronym>
  <official_title>Denosumab Versus Zoledronic Acid for Patients With Beta-Thalassemia Major-Induced Osteoporosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hamad Medical Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hamad Medical Corporation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to compare the two medications Denosumab and Zoledronic Acid For Patients With&#xD;
      Beta Thalassemia Major Induced Osteoporosis. Patients with B-thalassemia major induce&#xD;
      osteoporosis will undergo baseline assessment of the bone densitometry by Dual-energy X-ray&#xD;
      absorptiometry scan as a standard of care by the radiology department, then a blood test for&#xD;
      bone specific Alkaline phosphatase and type-1 Carboxy Telopeptide will be measured by the&#xD;
      chemistry lab.&#xD;
&#xD;
      Patients with B-Thalassemia Major induced osteoporosis, who are 18 years of age or more and&#xD;
      willing to participate in the study will be enrolled after consenting by the primary&#xD;
      investigator in hematology outpatient clinic. Patients with osteoporosis will receive one of&#xD;
      the two medications, at the end of the year Dual-energy X-ray absorptiometry scan will be&#xD;
      done to compare the response of the two medications. The potential risks include the&#xD;
      drug-related side effects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite the significant improvements in the therapeutic management of beta thalassemia major&#xD;
      (BTM) over the past few decades, osteoporosis is still a common finding, even in optimally&#xD;
      treated patients. The relationships between bone mineral densities (BMD) and several clinical&#xD;
      characteristics or hematological markers have been described. Chronic anemia, bone marrow&#xD;
      expansion due to ineffective erythropoiesis, iron toxicity, calcium and zinc deficiencies,&#xD;
      low vitamin D levels and endocrine complications have been suggested to contribute to the&#xD;
      etiology of bone diseases in BTM. Nevertheless, the complex etiological mechanisms of this&#xD;
      heterogeneous osteopathy remain incompletely clarified. A complex mechanism controls bone&#xD;
      remodeling in human. This mechanism includes the receptor activator of nuclear factor kappa B&#xD;
      ligand (RANKL), its natural receptor (RANK) and osteoprotegerin (OPG). The RANK/RANKL pathway&#xD;
      is an essential to promote osteoclast formation and activation and prolongs osteoclast&#xD;
      survival.&#xD;
&#xD;
      OPG acts as a decoy receptor for RANKL and prevents its interaction with RANK thereby&#xD;
      inhibiting osteoclast formation, function, and survival. Alteration of the RANK/RANKL/OPG&#xD;
      system for increased osteoclastic activity and enhanced osteoblastic dysfunction is proposed&#xD;
      as an important mechanism in the etiology of osteoporosis in BTM. Hypogonadism, a common&#xD;
      finding in BTM, is associated with enhanced RANKL activity. The sex steroid hormones,&#xD;
      androgen, and estrogens, via their respective nuclear receptors, regulate BMD in humans and&#xD;
      mice. Testosterone is likely to have direct and indirect inhibitory effects on human&#xD;
      osteoclast formation and bone resorption. Animal model and cell culture studies suggest a&#xD;
      direct inhibitory effect of androgens on the OPG/RANKL cytokines system. In human&#xD;
      osteoblastic cells, testosterone and 5-dihydrotestosterone mediate an androgen&#xD;
      receptor-induced specific inhibition of OPG messenger ribonucleic acid (mRNA) expression.&#xD;
      Androgens have also been shown to block RANKL-induced osteoclastic formation while RANKL&#xD;
      expression was found to be up-regulated in osteoblastic cells from androgen&#xD;
      receptor-deficient mice. The effect of oestradiol (E2) on osteoclast precursors and&#xD;
      osteoclasts seems to be mediated by osteoblastic cells. Inhibitory effect of E2 is associated&#xD;
      with the stimulated secretion of OPG by osteoblasts. Previous studies have focused on the&#xD;
      characteristics of thalassemic patients with osteoporosis and their response to therapy with&#xD;
      bisphosphonate. Because RANK-RANKL and OPG play a significant role in bone resorption and&#xD;
      seem to be the principal implicated mechanism for the development of osteoporosis in BTM, we&#xD;
      will conduct this prospective study to evaluate the anti-RANKL denosumab versus zoledronic&#xD;
      acid on TM-induced osteoporosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    failed to recruit eligible subjects&#xD;
  </why_stopped>
  <start_date type="Actual">May 14, 2018</start_date>
  <completion_date type="Actual">April 8, 2019</completion_date>
  <primary_completion_date type="Actual">April 8, 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with a 50 percent or greater reduction in type-1 collagen carboxy telopeptide from the baseline</measure>
    <time_frame>12 months</time_frame>
    <description>Number of patients with a 50 percent or greater reduction in type-1 collagen carboxy telopeptide from the baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with a 50 percent or greater improvement in Dual-energy X-ray absorptiometry scan from the baseline</measure>
    <time_frame>12 months</time_frame>
    <description>Number of patients with a 50 percent or greater improvement in Dual-energy X-ray absorptiometry scan from the baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>12 months</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Thalassemia Majors (Beta-Thalassemia Major)</condition>
  <condition>Osteoporosis</condition>
  <arm_group>
    <arm_group_label>Denosumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Denosumab 60 MG/ML Prefilled Syringe&#xD;
Denosumab Dose: 60 milligrams, subcutaneous injection, every 6 months (twice a year)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Zoledronic Acid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Zoledronic Acid 5Mg/Bag 100Ml Inj&#xD;
Zoledronic acid will be 5 milligrams, Intravenous injection, once a year</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Denosumab 60 MG/ML Prefilled Syringe</intervention_name>
    <description>Denosumab 60 MG/ML will be administered to 20 patients with b-thalassemia major</description>
    <arm_group_label>Denosumab</arm_group_label>
    <other_name>Prolia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zoledronic Acid 5Mg/Bag 100Ml Inj</intervention_name>
    <description>Zoledronic Acid 5Mg/Bag 100Ml Inj will be administered to 20 patients with b-thalassemia major</description>
    <arm_group_label>Zoledronic Acid</arm_group_label>
    <other_name>Aclasta</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing to participate in the study&#xD;
&#xD;
          -  Age 18 years old or older&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance Status less than or equal 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age less than 18 years old&#xD;
&#xD;
          -  Not willing to participate in the study&#xD;
&#xD;
          -  Vulnerable subjects or Eastern Cooperative Oncology Group Performance Status 3 or 4&#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>Mohamed Yassin</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hamad Medical Corporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Center for Cancer Care &amp; Research (NCCCR)</name>
      <address>
        <city>Doha</city>
        <country>Qatar</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Qatar</country>
  </location_countries>
  <reference>
    <citation>Baldini M, Forti S, Marcon A, Ulivieri FM, Orsatti A, Tampieri B, Airaghi L, Zanaboni L, Cappellini MD. Endocrine and bone disease in appropriately treated adult patients with beta-thalassemia major. Ann Hematol. 2010 Dec;89(12):1207-13. doi: 10.1007/s00277-010-1007-0. Epub 2010 Jun 26.</citation>
    <PMID>20582415</PMID>
  </reference>
  <reference>
    <citation>Scacchi M, Danesi L, Cattaneo A, Valassi E, Pecori Giraldi F, Argento C, D'Angelo E, Mirra N, Carnelli V, Zanaboni L, Tampieri B, Cappellini MD, Cavagnini F. Bone demineralization in adult thalassaemic patients: contribution of GH and IGF-I at different skeletal sites. Clin Endocrinol (Oxf). 2008 Aug;69(2):202-7. doi: 10.1111/j.1365-2265.2008.03191.x. Epub 2008 Jan 21.</citation>
    <PMID>18221395</PMID>
  </reference>
  <reference>
    <citation>Kyriakou A, Savva SC, Savvides I, Pangalou E, Ioannou YS, Christou S, Skordis N. Gender differences in the prevalence and severity of bone disease in thalassaemia. Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:116-22.</citation>
    <PMID>19337164</PMID>
  </reference>
  <reference>
    <citation>Voskaridou E, Terpos E. Pathogenesis and management of osteoporosis in thalassemia. Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:86-93.</citation>
    <PMID>19337161</PMID>
  </reference>
  <reference>
    <citation>Pietrapertosa AC, Minenna G, Colella SM, Santeramo TM, Renni R, D'Amore M. Osteoprotegerin and RANKL in the pathogenesis of osteoporosis in patients with thalassaemia major. Panminerva Med. 2009 Mar;51(1):17-23.</citation>
    <PMID>19352306</PMID>
  </reference>
  <reference>
    <citation>Mahachoklertwattana P, Pootrakul P, Chuansumrit A, Choubtum L, Sriphrapradang A, Sirisriro R, Rajatanavin R. Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes. J Bone Miner Metab. 2006;24(2):146-52. doi: 10.1007/s00774-005-0661-0.</citation>
    <PMID>16502122</PMID>
  </reference>
  <reference>
    <citation>Aslan I, Canatan D, Balta N, Kacar G, Dorak C, Ozsancak A, Oguz N, Cosan R. Bone mineral density in thalassemia major patients from antalya, Turkey. Int J Endocrinol. 2012;2012:573298. doi: 10.1155/2012/573298. Epub 2012 Jun 20.</citation>
    <PMID>22778734</PMID>
  </reference>
  <reference>
    <citation>Pincelli AI, Masera N, Tavecchia L, Perotti M, Perra S, Mariani R, Piperno A, Mancia G, Grassi G, Masera G. GH deficiency in adult B-thalassemia major patients and its relationship with IGF-1 production. Pediatr Endocrinol Rev. 2011 Mar;8 Suppl 2:284-9.</citation>
    <PMID>21705979</PMID>
  </reference>
  <reference>
    <citation>Pirinccioglu AG, Akpolat V, Koksal O, Haspolat K, Soker M. Bone mineral density in children with beta-thalassemia major in Diyarbakir. Bone. 2011 Oct;49(4):819-23. doi: 10.1016/j.bone.2011.07.014. Epub 2011 Jul 23.</citation>
    <PMID>21798385</PMID>
  </reference>
  <reference>
    <citation>Skordis N, Ioannou YS, Kyriakou A, Savva SC, Efstathiou E, Savvides I, Christou S. Effect of bisphosphonate treatment on bone mineral density in patients with thalassaemia major. Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:144-8.</citation>
    <PMID>19337169</PMID>
  </reference>
  <reference>
    <citation>Soliman AT, El Banna N, Abdel Fattah M, ElZalabani MM, Ansari BM. Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data. Metabolism. 1998 May;47(5):541-8. doi: 10.1016/s0026-0495(98)90237-2.</citation>
    <PMID>9591744</PMID>
  </reference>
  <reference>
    <citation>Mahachoklertwattana P, Chuansumrit A, Sirisriro R, Choubtum L, Sriphrapradang A, Rajatanavin R. Bone mineral density, biochemical and hormonal profiles in suboptimally treated children and adolescents with beta-thalassaemia disease. Clin Endocrinol (Oxf). 2003 Mar;58(3):273-9. doi: 10.1046/j.1365-2265.2003.01707.x.</citation>
    <PMID>12608931</PMID>
  </reference>
  <reference>
    <citation>Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008 May 15;473(2):139-46. doi: 10.1016/j.abb.2008.03.018. Epub 2008 Mar 25.</citation>
    <PMID>18395508</PMID>
  </reference>
  <reference>
    <citation>Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2008 Apr;29(2):155-92. doi: 10.1210/er.2007-0014. Epub 2007 Dec 5.</citation>
    <PMID>18057140</PMID>
  </reference>
  <reference>
    <citation>Pepene CE, Crisan N, Coman I. Elevated serum receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in late-onset male hypogonadism. Clin Invest Med. 2011 Aug 1;34(4):E232. doi: 10.25011/cim.v34i4.15365.</citation>
    <PMID>21810381</PMID>
  </reference>
  <reference>
    <citation>Michael H, Harkonen PL, Vaananen HK, Hentunen TA. Estrogen and testosterone use different cellular pathways to inhibit osteoclastogenesis and bone resorption. J Bone Miner Res. 2005 Dec;20(12):2224-32. doi: 10.1359/JBMR.050803. Epub 2005 Aug 1.</citation>
    <PMID>16294275</PMID>
  </reference>
  <reference>
    <citation>Hofbauer LC, Hicok KC, Chen D, Khosla S. Regulation of osteoprotegerin production by androgens and anti-androgens in human osteoblastic lineage cells. Eur J Endocrinol. 2002 Aug;147(2):269-73. doi: 10.1530/eje.0.1470269.</citation>
    <PMID>12153751</PMID>
  </reference>
  <reference>
    <citation>Grundt A, Grafe IA, Liegibel U, Sommer U, Nawroth P, Kasperk C. Direct effects of osteoprotegerin on human bone cell metabolism. Biochem Biophys Res Commun. 2009 Nov 20;389(3):550-5. doi: 10.1016/j.bbrc.2009.09.026. Epub 2009 Sep 11.</citation>
    <PMID>19748486</PMID>
  </reference>
  <reference>
    <citation>Huber DM, Bendixen AC, Pathrose P, Srivastava S, Dienger KM, Shevde NK, Pike JW. Androgens suppress osteoclast formation induced by RANKL and macrophage-colony stimulating factor. Endocrinology. 2001 Sep;142(9):3800-8. doi: 10.1210/endo.142.9.8402.</citation>
    <PMID>11517156</PMID>
  </reference>
  <reference>
    <citation>Kawano H, Sato T, Yamada T, Matsumoto T, Sekine K, Watanabe T, Nakamura T, Fukuda T, Yoshimura K, Yoshizawa T, Aihara K, Yamamoto Y, Nakamichi Y, Metzger D, Chambon P, Nakamura K, Kawaguchi H, Kato S. Suppressive function of androgen receptor in bone resorption. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9416-21. doi: 10.1073/pnas.1533500100. Epub 2003 Jul 18.</citation>
    <PMID>12872002</PMID>
  </reference>
  <reference>
    <citation>Gorny G, Shaw A, Oursler MJ. IL-6, LIF, and TNF-alpha regulation of GM-CSF inhibition of osteoclastogenesis in vitro. Exp Cell Res. 2004 Mar 10;294(1):149-58. doi: 10.1016/j.yexcr.2003.11.009.</citation>
    <PMID>14980510</PMID>
  </reference>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>January 22, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>December 10, 2019</last_update_submitted>
  <last_update_submitted_qc>December 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Osteoporosis</keyword>
  <keyword>Beta-Thalassemia Major</keyword>
  <keyword>Denosumab</keyword>
  <keyword>Zoledronic Acid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoporosis</mesh_term>
    <mesh_term>Thalassemia</mesh_term>
    <mesh_term>beta-Thalassemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Zoledronic Acid</mesh_term>
    <mesh_term>Denosumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03040765
org study id: 16441/16
nct id: NCT03040765
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study is to compare the two medications Denosumab and Zoledronic Acid For Patients With
      Beta Thalassemia Major Induced Osteoporosis. Patients with B-thalassemia major induce
      osteoporosis will undergo baseline assessment of the bone densitometry by Dual-energy X-ray
      absorptiometry scan as a standard of care by the radiology department, then a blood test for
      bone specific Alkaline phosphatase and type-1 Carboxy Telopeptide will be measured by the
      chemistry lab.

      Patients with B-Thalassemia Major induced osteoporosis, who are 18 years of age or more and
      willing to participate in the study will be enrolled after consenting by the primary
      investigator in hematology outpatient clinic. Patients with osteoporosis will receive one of
      the two medications, at the end of the year Dual-energy X-ray absorptiometry scan will be
      done to compare the response of the two medications. The potential risks include the
      drug-related side effects
Despite the significant improvements in the therapeutic management of beta thalassemia major
      (BTM) over the past few decades, osteoporosis is still a common finding, even in optimally
      treated patients. The relationships between bone mineral densities (BMD) and several clinical
      characteristics or hematological markers have been described. Chronic anemia, bone marrow
      expansion due to ineffective erythropoiesis, iron toxicity, calcium and zinc deficiencies,
      low vitamin D levels and endocrine complications have been suggested to contribute to the
      etiology of bone diseases in BTM. Nevertheless, the complex etiological mechanisms of this
      heterogeneous osteopathy remain incompletely clarified. A complex mechanism controls bone
      remodeling in human. This mechanism includes the receptor activator of nuclear factor kappa B
      ligand (RANKL), its natural receptor (RANK) and osteoprotegerin (OPG). The RANK/RANKL pathway
      is an essential to promote osteoclast formation and activation and prolongs osteoclast
      survival.

      OPG acts as a decoy receptor for RANKL and prevents its interaction with RANK thereby
      inhibiting osteoclast formation, function, and survival. Alteration of the RANK/RANKL/OPG
      system for increased osteoclastic activity and enhanced osteoblastic dysfunction is proposed
      as an important mechanism in the etiology of osteoporosis in BTM. Hypogonadism, a common
      finding in BTM, is associated with enhanced RANKL activity. The sex steroid hormones,
      androgen, and estrogens, via their respective nuclear receptors, regulate BMD in humans and
      mice. Testosterone is likely to have direct and indirect inhibitory effects on human
      osteoclast formation and bone resorption. Animal model and cell culture studies suggest a
      direct inhibitory effect of androgens on the OPG/RANKL cytokines system. In human
      osteoblastic cells, testosterone and 5-dihydrotestosterone mediate an androgen
      receptor-induced specific inhibition of OPG messenger ribonucleic acid (mRNA) expression.
      Androgens have also been shown to block RANKL-induced osteoclastic formation while RANKL
      expression was found to be up-regulated in osteoblastic cells from androgen
      receptor-deficient mice. The effect of oestradiol (E2) on osteoclast precursors and
      osteoclasts seems to be mediated by osteoblastic cells. Inhibitory effect of E2 is associated
      with the stimulated secretion of OPG by osteoblasts. Previous studies have focused on the
      characteristics of thalassemic patients with osteoporosis and their response to therapy with
      bisphosphonate. Because RANK-RANKL and OPG play a significant role in bone resorption and
      seem to be the principal implicated mechanism for the development of osteoporosis in BTM, we
      will conduct this prospective study to evaluate the anti-RANKL denosumab versus zoledronic
      acid on TM-induced osteoporosis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with a 50 percent or greater reduction in type-1 collagen carboxy telopeptide from the baseline
time frame: 12 months
description: Number of patients with a 50 percent or greater reduction in type-1 collagen carboxy telopeptide from the baseline
measure: Number of patients with a 50 percent or greater improvement in Dual-energy X-ray absorptiometry scan from the baseline
time frame: 12 months
description: Number of patients with a 50 percent or greater improvement in Dual-energy X-ray absorptiometry scan from the baseline
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 12 months
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
arm group label: Denosumab
arm group type: Active Comparator
description: Denosumab 60 MG/ML Prefilled Syringe
Denosumab Dose: 60 milligrams, subcutaneous injection, every 6 months (twice a year)
arm group label: Zoledronic Acid
arm group type: Active Comparator
description: Zoledronic Acid 5Mg/Bag 100Ml Inj
Zoledronic acid will be 5 milligrams, Intravenous injection, once a year
intervention type: Drug
intervention name: Denosumab 60 MG/ML Prefilled Syringe
description: Denosumab 60 MG/ML will be administered to 20 patients with b-thalassemia major
arm group label: Denosumab
other name: Prolia
intervention type: Drug
intervention name: Zoledronic Acid 5Mg/Bag 100Ml Inj
description: Zoledronic Acid 5Mg/Bag 100Ml Inj will be administered to 20 patients with b-thalassemia major
arm group label: Zoledronic Acid
other name: Aclasta
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mohamed Yassin
role: Principal Investigator
affiliation: Hamad Medical Corporation
facility: 
country: Qatar
citation: Baldini M, Forti S, Marcon A, Ulivieri FM, Orsatti A, Tampieri B, Airaghi L, Zanaboni L, Cappellini MD. Endocrine and bone disease in appropriately treated adult patients with beta-thalassemia major. Ann Hematol. 2010 Dec;89(12):1207-13. doi: 10.1007/s00277-010-1007-0. Epub 2010 Jun 26.
PMID: 20582415
citation: Scacchi M, Danesi L, Cattaneo A, Valassi E, Pecori Giraldi F, Argento C, D'Angelo E, Mirra N, Carnelli V, Zanaboni L, Tampieri B, Cappellini MD, Cavagnini F. Bone demineralization in adult thalassaemic patients: contribution of GH and IGF-I at different skeletal sites. Clin Endocrinol (Oxf). 2008 Aug;69(2):202-7. doi: 10.1111/j.1365-2265.2008.03191.x. Epub 2008 Jan 21.
PMID: 18221395
citation: Kyriakou A, Savva SC, Savvides I, Pangalou E, Ioannou YS, Christou S, Skordis N. Gender differences in the prevalence and severity of bone disease in thalassaemia. Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:116-22.
PMID: 19337164
citation: Voskaridou E, Terpos E. Pathogenesis and management of osteoporosis in thalassemia. Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:86-93.
PMID: 19337161
citation: Pietrapertosa AC, Minenna G, Colella SM, Santeramo TM, Renni R, D'Amore M. Osteoprotegerin and RANKL in the pathogenesis of osteoporosis in patients with thalassaemia major. Panminerva Med. 2009 Mar;51(1):17-23.
PMID: 19352306
citation: Mahachoklertwattana P, Pootrakul P, Chuansumrit A, Choubtum L, Sriphrapradang A, Sirisriro R, Rajatanavin R. Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes. J Bone Miner Metab. 2006;24(2):146-52. doi: 10.1007/s00774-005-0661-0.
PMID: 16502122
citation: Aslan I, Canatan D, Balta N, Kacar G, Dorak C, Ozsancak A, Oguz N, Cosan R. Bone mineral density in thalassemia major patients from antalya, Turkey. Int J Endocrinol. 2012;2012:573298. doi: 10.1155/2012/573298. Epub 2012 Jun 20.
PMID: 22778734
citation: Pincelli AI, Masera N, Tavecchia L, Perotti M, Perra S, Mariani R, Piperno A, Mancia G, Grassi G, Masera G. GH deficiency in adult B-thalassemia major patients and its relationship with IGF-1 production. Pediatr Endocrinol Rev. 2011 Mar;8 Suppl 2:284-9.
PMID: 21705979
citation: Pirinccioglu AG, Akpolat V, Koksal O, Haspolat K, Soker M. Bone mineral density in children with beta-thalassemia major in Diyarbakir. Bone. 2011 Oct;49(4):819-23. doi: 10.1016/j.bone.2011.07.014. Epub 2011 Jul 23.
PMID: 21798385
citation: Skordis N, Ioannou YS, Kyriakou A, Savva SC, Efstathiou E, Savvides I, Christou S. Effect of bisphosphonate treatment on bone mineral density in patients with thalassaemia major. Pediatr Endocrinol Rev. 2008 Oct;6 Suppl 1:144-8.
PMID: 19337169
citation: Soliman AT, El Banna N, Abdel Fattah M, ElZalabani MM, Ansari BM. Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data. Metabolism. 1998 May;47(5):541-8. doi: 10.1016/s0026-0495(98)90237-2.
PMID: 9591744
citation: Mahachoklertwattana P, Chuansumrit A, Sirisriro R, Choubtum L, Sriphrapradang A, Rajatanavin R. Bone mineral density, biochemical and hormonal profiles in suboptimally treated children and adolescents with beta-thalassaemia disease. Clin Endocrinol (Oxf). 2003 Mar;58(3):273-9. doi: 10.1046/j.1365-2265.2003.01707.x.
PMID: 12608931
citation: Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008 May 15;473(2):139-46. doi: 10.1016/j.abb.2008.03.018. Epub 2008 Mar 25.
PMID: 18395508
citation: Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev. 2008 Apr;29(2):155-92. doi: 10.1210/er.2007-0014. Epub 2007 Dec 5.
PMID: 18057140
citation: Pepene CE, Crisan N, Coman I. Elevated serum receptor activator of nuclear factor kappa B ligand and osteoprotegerin levels in late-onset male hypogonadism. Clin Invest Med. 2011 Aug 1;34(4):E232. doi: 10.25011/cim.v34i4.15365.
PMID: 21810381
citation: Michael H, Harkonen PL, Vaananen HK, Hentunen TA. Estrogen and testosterone use different cellular pathways to inhibit osteoclastogenesis and bone resorption. J Bone Miner Res. 2005 Dec;20(12):2224-32. doi: 10.1359/JBMR.050803. Epub 2005 Aug 1.
PMID: 16294275
citation: Hofbauer LC, Hicok KC, Chen D, Khosla S. Regulation of osteoprotegerin production by androgens and anti-androgens in human osteoblastic lineage cells. Eur J Endocrinol. 2002 Aug;147(2):269-73. doi: 10.1530/eje.0.1470269.
PMID: 12153751
citation: Grundt A, Grafe IA, Liegibel U, Sommer U, Nawroth P, Kasperk C. Direct effects of osteoprotegerin on human bone cell metabolism. Biochem Biophys Res Commun. 2009 Nov 20;389(3):550-5. doi: 10.1016/j.bbrc.2009.09.026. Epub 2009 Sep 11.
PMID: 19748486
citation: Huber DM, Bendixen AC, Pathrose P, Srivastava S, Dienger KM, Shevde NK, Pike JW. Androgens suppress osteoclast formation induced by RANKL and macrophage-colony stimulating factor. Endocrinology. 2001 Sep;142(9):3800-8. doi: 10.1210/endo.142.9.8402.
PMID: 11517156
citation: Kawano H, Sato T, Yamada T, Matsumoto T, Sekine K, Watanabe T, Nakamura T, Fukuda T, Yoshimura K, Yoshizawa T, Aihara K, Yamamoto Y, Nakamichi Y, Metzger D, Chambon P, Nakamura K, Kawaguchi H, Kato S. Suppressive function of androgen receptor in bone resorption. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9416-21. doi: 10.1073/pnas.1533500100. Epub 2003 Jul 18.
PMID: 12872002
citation: Gorny G, Shaw A, Oursler MJ. IL-6, LIF, and TNF-alpha regulation of GM-CSF inhibition of osteoclastogenesis in vitro. Exp Cell Res. 2004 Mar 10;294(1):149-58. doi: 10.1016/j.yexcr.2003.11.009.
PMID: 14980510
responsible party type: Sponsor
mesh term: Osteoporosis
mesh term: Thalassemia
mesh term: beta-Thalassemia
mesh term: Zoledronic Acid
mesh term: Denosumab
sharing ipd: Undecided