<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/NCT02997033</url>
  </required_header>
  <id_info>
    <org_study_id>2013/1090</org_study_id>
    <nct_id>NCT02997033</nct_id>
  </id_info>
  <brief_title>SIBlos EXtension Study (SIBEX)</brief_title>
  <official_title>Longitudinal Extension Phase of Sibling Pair Linkage Analysis of Bone Mineral Density / Geometry and Sex Steroid and Thyroid Status in Healthy Young Men</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Ghent</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Ghent</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Population-based, longitudinal cohort study designed to evaluate changes in bone mineral&#xD;
      density, bone geometry, body composition, parameters reflecting muscle force, and sex steroid&#xD;
      status in healthy young men, as well as their interactions, over a period of +-10 years.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Osteoporosis is a common disorder affecting both sexes, with a lifetime risk of sustaining a&#xD;
      fragility fracture at age 50 y estimated at 40-50% in women and 13-22% in men. The&#xD;
      age-specific fracture risk in men is about half that in women, which results in part from the&#xD;
      achievement of a higher bone mass in men, in particular of larger bone size during growth.&#xD;
      Bone size, mass and strength in the elderly depend on the accrual and loss of bone through&#xD;
      time. Not only from an epidemiological but also from a potentially preventive viewpoint, it&#xD;
      is important to understand the determinants of the components and to identify risk and&#xD;
      protective factors for bone accrual or loss through life.&#xD;
&#xD;
      Hormonal status in men, e.g. gonadal and thyroid hormone levels, has a wide range of effects&#xD;
      on different body compartments. For both thyroid and gonadal steroid levels, there exists a&#xD;
      wide inter-individual variation, even among healthy young men. Up till now, it is not clear&#xD;
      whether this variation represents true differences in hormonal exposure or whether it&#xD;
      represents an inter-individual variation in hormonal responsiveness. Since prevalence of both&#xD;
      thyroid disorders and age- and obesity-associated hypogonadism is rather high, it is relevant&#xD;
      to assess determinant and clinical correlates of the between-subject variation in sex steroid&#xD;
      and thyroid hormone status.&#xD;
&#xD;
      Our research department therefore undertook a cross-sectional, population-based study in&#xD;
      healthy men aged 25-45 years with the aim to investigate determinants of peak bone mass and&#xD;
      between-subject variation in gonadal and thyroid hormone status (SIBLOS study). In total,&#xD;
      1114 men were recruited from 2002 till 2009. Herein, we focused on genetic determinants&#xD;
      (SNPs, single nucleotide polymorphisms) contributing to between-subject differences in bone&#xD;
      mass, as well as on the interrelationship between body composition, bone mass, density and&#xD;
      size, lifestyle and hormonal status (sex steroids, thyroid hormones). In addition, we&#xD;
      assessed determinants of sex steroid and thyroid hormone status, again focusing on genetic&#xD;
      polymorphisms, body composition and lifestyle factors. The investigations in the SIBLOS study&#xD;
      have been performed using state-of-the-art technology such as dual-energy X-ray&#xD;
      absorptiometry and peripheral quantitative computed tomography for evaluating bone, muscle&#xD;
      and body composition parameters; assessment of anthropometric parameters by well-trained&#xD;
      personnel; validated questionnaires regarding lifestyle, physical activity and calcium&#xD;
      intake; the use of liquid gas chromatography / mass spectrometry for assessing serum hormonal&#xD;
      levels; using KASPar technology for genotyping after a high-yield DNA extraction procedure.&#xD;
&#xD;
      From this cross-sectional study, for example, following results have emerged:&#xD;
&#xD;
        -  Estradiol seems to be the main sex steroid associated with bone mineral density and bone&#xD;
           geometry, whereas testosterone was weakly associated with parameters reflecting muscle&#xD;
           strength. In addition, serum estradiol levels might modulate the impact of physical&#xD;
           activity on bone size at the tibia.&#xD;
&#xD;
        -  Smokers presented with a higher prevalence of previous fractures, especially if they&#xD;
           started smoking at younger age. This could be partly explained by the observation of&#xD;
           lower bone mineral density and a thinner cortex in smokers.&#xD;
&#xD;
        -  Physical activity, muscle mass and parameters reflecting muscle force are strongly&#xD;
           associated with bone size; whereas fat mass displayed an inverse association with bone&#xD;
           mass and size.&#xD;
&#xD;
        -  Birth weight is associated with higher testosterone levels at adult age; in addition&#xD;
           weight gain higher/lower than expected during life associated with lower/higher&#xD;
           testosterone levels at adult age.&#xD;
&#xD;
        -  Serum levels of sex-hormone binding globulin are positively associated with bone size in&#xD;
           adult men.&#xD;
&#xD;
        -  Higher serum thyroid hormone levels are associated with lower bone mineral density and&#xD;
           cortical bone area.&#xD;
&#xD;
        -  A less favorable body composition (higher fat and lower muscle mass) and insulin&#xD;
           resistance are associated with higher serum thyroid hormone concentrations.&#xD;
&#xD;
        -  Serum thyroid hormone levels are influenced by SNPs in the monocarboxylate transporter&#xD;
           (MCT)-8 gene.&#xD;
&#xD;
        -  Testosterone serum levels are associated with genetic polymorphisms in the genes&#xD;
           encoding for the androgen receptor and sex-hormone binding globulin.&#xD;
&#xD;
      Our initial analyses in this SIBLOS population are cross-sectional. Although revealing, this,&#xD;
      as any, cross-sectional study has limitations, mainly because the associations do not allow&#xD;
      conclusions about direction nor causality. To add prospective elements to the acquired data&#xD;
      and to investigate changes over time, we plan to perform a longitudinal follow-up in this&#xD;
      study population (SIBEX - SIBlos EXtension study), and as in the mean time knowledge has&#xD;
      increased and new questions have emerged, additional investigations are intended. The general&#xD;
      aims of this follow-up study include the evaluation of changes in bone mineral density, bone&#xD;
      geometry, body composition, parameters reflecting muscle force and sex steroid status in&#xD;
      healthy young men, +-10 years after their initial evaluation in the SIBLOS cohort.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2014</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 12, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in bone mineral density</measure>
    <time_frame>ten years</time_frame>
    <description>Change in bone mineral density vs. baseline (= study visit in SIBLOS study)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in sex steroid levels</measure>
    <time_frame>ten years</time_frame>
    <description>Change in sex steroid levels vs. baseline (= study visit in SIBLOS study)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in body composition</measure>
    <time_frame>ten years</time_frame>
    <description>Change in body composition vs. baseline (= study visit in SIBLOS study)</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">709</enrollment>
  <condition>Bone Density</condition>
  <condition>Gonadal Steroid Hormones</condition>
  <condition>Thyroid Hormones</condition>
  <arm_group>
    <arm_group_label>Total study cohort</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No intervention</intervention_name>
    <description>No intervention</description>
    <arm_group_label>Total study cohort</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      -  Venous blood sampling after overnight fast, with whole blood, serum and plasma samples&#xD;
           to be retained&#xD;
&#xD;
        -  Second void urine samples to be retained&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Participants of the first SIBLOS study (recruited between 2002 and 2009)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Full participation in the first SIBLOS study&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unwillingness or inability to participate&#xD;
&#xD;
          -  Medication or disease known to affect bone metabolism, body composition and/or sex&#xD;
             steroid metabolism:&#xD;
&#xD;
          -  malignancy (previous or current)&#xD;
&#xD;
          -  systemic diseases (auto-immune and rheumatoid pathology, ankylosing spondylitis)&#xD;
&#xD;
          -  previous or current systemic use of glucocorticoids for more than 3 months,&#xD;
             irrespective or dose&#xD;
&#xD;
          -  use of glucocorticoid injections in previous 3 months&#xD;
&#xD;
          -  use of inhalation glucocorticoids more than 500 µg / day&#xD;
&#xD;
          -  previous or current thyroxin therapy (Graves disease, thyroidectomy)&#xD;
&#xD;
          -  current insulin use for diabetes mellitus&#xD;
&#xD;
          -  previous or current (anti-) androgen treatment or treated hypogonadism&#xD;
&#xD;
          -  previous or current anti-epileptic drugs (phenytoin, valproate, carbamazepine,&#xD;
             oxcarbazepine/carbamazepine, primidone)&#xD;
&#xD;
          -  previous or current hyperthyroidism&#xD;
&#xD;
          -  previous or current hyperparathyroidism or serum calcaemia &lt; 8.5 or &gt; 11 mg/dL&#xD;
&#xD;
          -  hypocalcaemia (corrected for albumin, confirmed in 2 measurements)&#xD;
&#xD;
          -  cystic fibrosis&#xD;
&#xD;
          -  orchidectomy irrespective of underlying cause&#xD;
&#xD;
          -  history of immobilisation &gt; 3 months or immobilisation &gt; 4 weeks within previous 6&#xD;
             months&#xD;
&#xD;
          -  previous or current history of eating disorder&#xD;
&#xD;
          -  serum creatinine &gt; 2 mg% (estimated creatinine clearance &lt; 35 mL/min)&#xD;
&#xD;
          -  known diseases affecting growth, collagen, bone development or body composition (OI,&#xD;
             otosclerosis, AIDS, ...)&#xD;
&#xD;
          -  previous or current gastrointestinal malabsorption (gastrectomy, Crohn's disease,&#xD;
             ulcerative colitis, coeliac disease, haemochromatosis)&#xD;
&#xD;
          -  alcoholism (&gt; 42 units per week)&#xD;
&#xD;
          -  organ transplant recipients&#xD;
&#xD;
          -  previous or current treatment for osteoporosis&#xD;
&#xD;
          -  previous treatment for cryptorchidism irrespective of age&#xD;
&#xD;
          -  current varicocoele or treatment for varicocoele after the age of 25 years (no&#xD;
             exclusion if testosterone level in blood is normal)&#xD;
&#xD;
          -  BMI &gt; 42.3 kg/m²&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruno Lapauw, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Ghent</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ghent University Hospital, Dept. of Endocrinology</name>
      <address>
        <city>Ghent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <citation>Kaptoge S, da Silva JA, Brixen K, Reid DM, Kroger H, Nielsen TL, Andersen M, Hagen C, Lorenc R, Boonen S, de Vernejoul MC, Stepan JJ, Adams J, Kaufman JM, Reeve J. Geographical variation in DXA bone mineral density in young European men and women. Results from the Network in Europe on Male Osteoporosis (NEMO) study. Bone. 2008 Aug;43(2):332-339. doi: 10.1016/j.bone.2008.04.001. Epub 2008 Apr 16.</citation>
    <PMID>18519175</PMID>
  </reference>
  <reference>
    <citation>Bogaert V, Taes Y, Konings P, Van Steen K, De Bacquer D, Goemaere S, Zmierczak H, Crabbe P, Kaufman JM. Heritability of blood concentrations of sex-steroids in relation to body composition in young adult male siblings. Clin Endocrinol (Oxf). 2008 Jul;69(1):129-35. doi: 10.1111/j.1365-2265.2008.03173.x.</citation>
    <PMID>18598274</PMID>
  </reference>
  <reference>
    <citation>Lapauw BM, Taes Y, Bogaert V, Vanbillemont G, Goemaere S, Zmierczak HG, De Bacquer D, Kaufman JM. Serum estradiol is associated with volumetric BMD and modulates the impact of physical activity on bone size at the age of peak bone mass: a study in healthy male siblings. J Bone Miner Res. 2009 Jun;24(6):1075-85. doi: 10.1359/jbmr.081260.</citation>
    <PMID>19113912</PMID>
  </reference>
  <reference>
    <citation>Vanbillemont G, Bogaert V, De Bacquer D, Lapauw B, Goemaere S, Toye K, Van Steen K, Taes Y, Kaufman JM. Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men. Clin Endocrinol (Oxf). 2009 Feb;70(2):303-10. doi: 10.1111/j.1365-2265.2008.03365.x. Epub 2008 Aug 4.</citation>
    <PMID>18681858</PMID>
  </reference>
  <reference>
    <citation>Bogaert V, Vanbillemont G, Taes Y, De Bacquer D, Deschepper E, Van Steen K, Kaufman JM. Small effect of the androgen receptor gene GGN repeat polymorphism on serum testosterone levels in healthy men. Eur J Endocrinol. 2009 Jul;161(1):171-7. doi: 10.1530/EJE-09-0123. Epub 2009 Apr 21.</citation>
    <PMID>19383805</PMID>
  </reference>
  <reference>
    <citation>Taes YE, Lapauw B, Vanbillemont G, Bogaert V, De Bacquer D, Zmierczak H, Goemaere S, Kaufman JM. Fat mass is negatively associated with cortical bone size in young healthy male siblings. J Clin Endocrinol Metab. 2009 Jul;94(7):2325-31. doi: 10.1210/jc.2008-2501. Epub 2009 Apr 28.</citation>
    <PMID>19401374</PMID>
  </reference>
  <reference>
    <citation>Taes Y, Lapauw B, Vanbillemont G, Bogaert V, De Bacquer D, Goemaere S, Zmierczak H, Kaufman JM. Early smoking is associated with peak bone mass and prevalent fractures in young, healthy men. J Bone Miner Res. 2010 Feb;25(2):379-87. doi: 10.1359/jbmr.090809.</citation>
    <PMID>19653814</PMID>
  </reference>
  <reference>
    <citation>Vanbillemont G, Lapauw B, Bogaert V, De Naeyer H, De Bacquer D, Ruige J, Kaufman JM, Taes YE. Birth weight in relation to sex steroid status and body composition in young healthy male siblings. J Clin Endocrinol Metab. 2010 Apr;95(4):1587-94. doi: 10.1210/jc.2009-2149. Epub 2010 Feb 3.</citation>
    <PMID>20130068</PMID>
  </reference>
  <reference>
    <citation>Taes Y, Lapauw B, Griet V, De Bacquer D, Goemaere S, Zmierczak H, Kaufman JM. Prevalent fractures are related to cortical bone geometry in young healthy men at age of peak bone mass. J Bone Miner Res. 2010 Jun;25(6):1433-40. doi: 10.1002/jbmr.17.</citation>
    <PMID>20200932</PMID>
  </reference>
  <reference>
    <citation>Vanbillemont G, Lapauw B, Bogaert V, Goemaere S, Zmierczak HG, Taes Y, Kaufman JM. Sex hormone-binding globulin as an independent determinant of cortical bone status in men at the age of peak bone mass. J Clin Endocrinol Metab. 2010 Apr;95(4):1579-86. doi: 10.1210/jc.2009-2189. Epub 2010 Feb 4.</citation>
    <PMID>20133463</PMID>
  </reference>
  <reference>
    <citation>Roef G, Lapauw B, Goemaere S, Zmierczak H, Fiers T, Kaufman JM, Taes Y. Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass. Eur J Endocrinol. 2011 Jun;164(6):1027-34. doi: 10.1530/EJE-10-1113. Epub 2011 Mar 10.</citation>
    <PMID>21393448</PMID>
  </reference>
  <reference>
    <citation>Vanbillemont G, Lapauw B, De Naeyer H, Roef G, Kaufman JM, Taes YE. Sex hormone-binding globulin at the crossroad of body composition, somatotropic axis and insulin/glucose homeostasis in young healthy men. Clin Endocrinol (Oxf). 2012 Jan;76(1):111-8. doi: 10.1111/j.1365-2265.2011.04155.x.</citation>
    <PMID>21711374</PMID>
  </reference>
  <reference>
    <citation>Boudin E, Piters E, Fransen E, Nielsen TL, Andersen M, Roef G, Taes Y, Brixen K, Van Hul W. Association study of common variants in the sFRP1 gene region and parameters of bone strength and body composition in two independent healthy Caucasian male cohorts. Mol Genet Metab. 2012 Mar;105(3):508-15. doi: 10.1016/j.ymgme.2011.11.189. Epub 2011 Nov 23.</citation>
    <PMID>22178351</PMID>
  </reference>
  <reference>
    <citation>Boudin E, Piters E, Nielsen TL, Andersen M, Roef G, Taes Y, Brixen K, Van Hul W. Single nucleotide polymorphisms in sFRP4 are associated with bone and body composition related parameters in Danish but not in Belgian men. Mol Genet Metab. 2012 Jul;106(3):366-74. doi: 10.1016/j.ymgme.2012.04.021. Epub 2012 May 2.</citation>
    <PMID>22608881</PMID>
  </reference>
  <reference>
    <citation>Roef G, Lapauw B, Goemaere S, Zmierczak HG, Toye K, Kaufman JM, Taes Y. Body composition and metabolic parameters are associated with variation in thyroid hormone levels among euthyroid young men. Eur J Endocrinol. 2012 Nov;167(5):719-26. doi: 10.1530/EJE-12-0447. Epub 2012 Sep 6.</citation>
    <PMID>22956557</PMID>
  </reference>
  <reference>
    <citation>Van Camp JK, Beckers S, Zegers D, Boudin E, Nielsen TL, Andersen M, Roef G, Taes Y, Brixen K, Van Hul W. Genetic association study of WNT10B polymorphisms with BMD and adiposity parameters in Danish and Belgian males. Endocrine. 2013 Aug;44(1):247-54. doi: 10.1007/s12020-012-9869-7. Epub 2013 Jan 17.</citation>
    <PMID>23325361</PMID>
  </reference>
  <reference>
    <citation>Roef GL, Rietzschel ER, De Meyer T, Bekaert S, De Buyzere ML, Van daele C, Toye K, Kaufman JM, Taes YE. Associations between single nucleotide polymorphisms in thyroid hormone transporter genes (MCT8, MCT10 and OATP1C1) and circulating thyroid hormones. Clin Chim Acta. 2013 Oct 21;425:227-32. doi: 10.1016/j.cca.2013.08.017. Epub 2013 Aug 24.</citation>
    <PMID>23978482</PMID>
  </reference>
  <reference>
    <citation>Roef G, Taes Y, Toye K, Goemaere S, Fiers T, Verstraete A, Kaufman JM. Heredity and lifestyle in the determination of between-subject variation in thyroid hormone levels in euthyroid men. Eur J Endocrinol. 2013 Oct 21;169(6):835-44. doi: 10.1530/EJE-13-0265. Print 2013 Dec.</citation>
    <PMID>24086088</PMID>
  </reference>
  <reference>
    <citation>De Naeyer H, Bogaert V, De Spaey A, Roef G, Vandewalle S, Derave W, Taes Y, Kaufman JM. Genetic variations in the androgen receptor are associated with steroid concentrations and anthropometrics but not with muscle mass in healthy young men. PLoS One. 2014 Jan 23;9(1):e86235. doi: 10.1371/journal.pone.0086235. eCollection 2014.</citation>
    <PMID>24465978</PMID>
  </reference>
  <reference>
    <citation>Gysel T, Calders P, Cambier D, Roman de Mettelinge T, Kaufman JM, Taes Y, Zmierczak HG, Goemaere S. Association between insulin resistance, lean mass and muscle torque/force in proximal versus distal body parts in healthy young men. J Musculoskelet Neuronal Interact. 2014 Mar;14(1):41-9.</citation>
    <PMID>24583539</PMID>
  </reference>
  <reference>
    <citation>Verroken C, Zmierczak HG, Goemaere S, Kaufman JM, Lapauw B. Association of Jumping Mechanography-Derived Indices of Muscle Function with Tibial Cortical Bone Geometry. Calcif Tissue Int. 2016 May;98(5):446-55. doi: 10.1007/s00223-015-0094-2. Epub 2015 Dec 16.</citation>
    <PMID>26671019</PMID>
  </reference>
  <reference>
    <citation>Verroken C, Zmierczak HG, Goemaere S, Kaufman JM, Lapauw B. Maternal age at childbirth is associated with offspring insulin sensitivity: a cross-sectional study in adult male siblings. Clin Endocrinol (Oxf). 2017 Jan;86(1):52-59. doi: 10.1111/cen.13253. Epub 2016 Nov 2.</citation>
    <PMID>27726168</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 14, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 19, 2016</study_first_posted>
  <last_update_submitted>February 7, 2023</last_update_submitted>
  <last_update_submitted_qc>February 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bone</keyword>
  <keyword>Sex steroids</keyword>
  <keyword>Body composition</keyword>
  <keyword>Men</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT02997033
org study id: 2013/1090
nct id: NCT02997033
lead sponsor: 
has dmc: No
Population-based, longitudinal cohort study designed to evaluate changes in bone mineral
      density, bone geometry, body composition, parameters reflecting muscle force, and sex steroid
      status in healthy young men, as well as their interactions, over a period of +-10 years.
Osteoporosis is a common disorder affecting both sexes, with a lifetime risk of sustaining a
      fragility fracture at age 50 y estimated at 40-50% in women and 13-22% in men. The
      age-specific fracture risk in men is about half that in women, which results in part from the
      achievement of a higher bone mass in men, in particular of larger bone size during growth.
      Bone size, mass and strength in the elderly depend on the accrual and loss of bone through
      time. Not only from an epidemiological but also from a potentially preventive viewpoint, it
      is important to understand the determinants of the components and to identify risk and
      protective factors for bone accrual or loss through life.

      Hormonal status in men, e.g. gonadal and thyroid hormone levels, has a wide range of effects
      on different body compartments. For both thyroid and gonadal steroid levels, there exists a
      wide inter-individual variation, even among healthy young men. Up till now, it is not clear
      whether this variation represents true differences in hormonal exposure or whether it
      represents an inter-individual variation in hormonal responsiveness. Since prevalence of both
      thyroid disorders and age- and obesity-associated hypogonadism is rather high, it is relevant
      to assess determinant and clinical correlates of the between-subject variation in sex steroid
      and thyroid hormone status.

      Our research department therefore undertook a cross-sectional, population-based study in
      healthy men aged 25-45 years with the aim to investigate determinants of peak bone mass and
      between-subject variation in gonadal and thyroid hormone status (SIBLOS study). In total,
      1114 men were recruited from 2002 till 2009. Herein, we focused on genetic determinants
      (SNPs, single nucleotide polymorphisms) contributing to between-subject differences in bone
      mass, as well as on the interrelationship between body composition, bone mass, density and
      size, lifestyle and hormonal status (sex steroids, thyroid hormones). In addition, we
      assessed determinants of sex steroid and thyroid hormone status, again focusing on genetic
      polymorphisms, body composition and lifestyle factors. The investigations in the SIBLOS study
      have been performed using state-of-the-art technology such as dual-energy X-ray
      absorptiometry and peripheral quantitative computed tomography for evaluating bone, muscle
      and body composition parameters; assessment of anthropometric parameters by well-trained
      personnel; validated questionnaires regarding lifestyle, physical activity and calcium
      intake; the use of liquid gas chromatography / mass spectrometry for assessing serum hormonal
      levels; using KASPar technology for genotyping after a high-yield DNA extraction procedure.

      From this cross-sectional study, for example, following results have emerged:

        -  Estradiol seems to be the main sex steroid associated with bone mineral density and bone
           geometry, whereas testosterone was weakly associated with parameters reflecting muscle
           strength. In addition, serum estradiol levels might modulate the impact of physical
           activity on bone size at the tibia.

        -  Smokers presented with a higher prevalence of previous fractures, especially if they
           started smoking at younger age. This could be partly explained by the observation of
           lower bone mineral density and a thinner cortex in smokers.

        -  Physical activity, muscle mass and parameters reflecting muscle force are strongly
           associated with bone size; whereas fat mass displayed an inverse association with bone
           mass and size.

        -  Birth weight is associated with higher testosterone levels at adult age; in addition
           weight gain higher/lower than expected during life associated with lower/higher
           testosterone levels at adult age.

        -  Serum levels of sex-hormone binding globulin are positively associated with bone size in
           adult men.

        -  Higher serum thyroid hormone levels are associated with lower bone mineral density and
           cortical bone area.

        -  A less favorable body composition (higher fat and lower muscle mass) and insulin
           resistance are associated with higher serum thyroid hormone concentrations.

        -  Serum thyroid hormone levels are influenced by SNPs in the monocarboxylate transporter
           (MCT)-8 gene.

        -  Testosterone serum levels are associated with genetic polymorphisms in the genes
           encoding for the androgen receptor and sex-hormone binding globulin.

      Our initial analyses in this SIBLOS population are cross-sectional. Although revealing, this,
      as any, cross-sectional study has limitations, mainly because the associations do not allow
      conclusions about direction nor causality. To add prospective elements to the acquired data
      and to investigate changes over time, we plan to perform a longitudinal follow-up in this
      study population (SIBEX - SIBlos EXtension study), and as in the mean time knowledge has
      increased and new questions have emerged, additional investigations are intended. The general
      aims of this follow-up study include the evaluation of changes in bone mineral density, bone
      geometry, body composition, parameters reflecting muscle force and sex steroid status in
      healthy young men, +-10 years after their initial evaluation in the SIBLOS cohort.
observational model: Cohort
time perspective: Prospective
measure: Change in bone mineral density
time frame: ten years
description: Change in bone mineral density vs. baseline (= study visit in SIBLOS study)
measure: Change in sex steroid levels
time frame: ten years
description: Change in sex steroid levels vs. baseline (= study visit in SIBLOS study)
measure: Change in body composition
time frame: ten years
description: Change in body composition vs. baseline (= study visit in SIBLOS study)
arm group label: Total study cohort
intervention type: Other
intervention name: No intervention
description: No intervention
arm group label: Total study cohort
-  Venous blood sampling after overnight fast, with whole blood, serum and plasma samples
           to be retained

        -  Second void urine samples to be retained
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 25 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Bruno Lapauw, M.D., Ph.D.
role: Principal Investigator
affiliation: University Ghent
facility: 
country: Belgium
citation: Kaptoge S, da Silva JA, Brixen K, Reid DM, Kroger H, Nielsen TL, Andersen M, Hagen C, Lorenc R, Boonen S, de Vernejoul MC, Stepan JJ, Adams J, Kaufman JM, Reeve J. Geographical variation in DXA bone mineral density in young European men and women. Results from the Network in Europe on Male Osteoporosis (NEMO) study. Bone. 2008 Aug;43(2):332-339. doi: 10.1016/j.bone.2008.04.001. Epub 2008 Apr 16.
PMID: 18519175
citation: Bogaert V, Taes Y, Konings P, Van Steen K, De Bacquer D, Goemaere S, Zmierczak H, Crabbe P, Kaufman JM. Heritability of blood concentrations of sex-steroids in relation to body composition in young adult male siblings. Clin Endocrinol (Oxf). 2008 Jul;69(1):129-35. doi: 10.1111/j.1365-2265.2008.03173.x.
PMID: 18598274
citation: Lapauw BM, Taes Y, Bogaert V, Vanbillemont G, Goemaere S, Zmierczak HG, De Bacquer D, Kaufman JM. Serum estradiol is associated with volumetric BMD and modulates the impact of physical activity on bone size at the age of peak bone mass: a study in healthy male siblings. J Bone Miner Res. 2009 Jun;24(6):1075-85. doi: 10.1359/jbmr.081260.
PMID: 19113912
citation: Vanbillemont G, Bogaert V, De Bacquer D, Lapauw B, Goemaere S, Toye K, Van Steen K, Taes Y, Kaufman JM. Polymorphisms of the SHBG gene contribute to the interindividual variation of sex steroid hormone blood levels in young, middle-aged and elderly men. Clin Endocrinol (Oxf). 2009 Feb;70(2):303-10. doi: 10.1111/j.1365-2265.2008.03365.x. Epub 2008 Aug 4.
PMID: 18681858
citation: Bogaert V, Vanbillemont G, Taes Y, De Bacquer D, Deschepper E, Van Steen K, Kaufman JM. Small effect of the androgen receptor gene GGN repeat polymorphism on serum testosterone levels in healthy men. Eur J Endocrinol. 2009 Jul;161(1):171-7. doi: 10.1530/EJE-09-0123. Epub 2009 Apr 21.
PMID: 19383805
citation: Taes YE, Lapauw B, Vanbillemont G, Bogaert V, De Bacquer D, Zmierczak H, Goemaere S, Kaufman JM. Fat mass is negatively associated with cortical bone size in young healthy male siblings. J Clin Endocrinol Metab. 2009 Jul;94(7):2325-31. doi: 10.1210/jc.2008-2501. Epub 2009 Apr 28.
PMID: 19401374
citation: Taes Y, Lapauw B, Vanbillemont G, Bogaert V, De Bacquer D, Goemaere S, Zmierczak H, Kaufman JM. Early smoking is associated with peak bone mass and prevalent fractures in young, healthy men. J Bone Miner Res. 2010 Feb;25(2):379-87. doi: 10.1359/jbmr.090809.
PMID: 19653814
citation: Vanbillemont G, Lapauw B, Bogaert V, De Naeyer H, De Bacquer D, Ruige J, Kaufman JM, Taes YE. Birth weight in relation to sex steroid status and body composition in young healthy male siblings. J Clin Endocrinol Metab. 2010 Apr;95(4):1587-94. doi: 10.1210/jc.2009-2149. Epub 2010 Feb 3.
PMID: 20130068
citation: Taes Y, Lapauw B, Griet V, De Bacquer D, Goemaere S, Zmierczak H, Kaufman JM. Prevalent fractures are related to cortical bone geometry in young healthy men at age of peak bone mass. J Bone Miner Res. 2010 Jun;25(6):1433-40. doi: 10.1002/jbmr.17.
PMID: 20200932
citation: Vanbillemont G, Lapauw B, Bogaert V, Goemaere S, Zmierczak HG, Taes Y, Kaufman JM. Sex hormone-binding globulin as an independent determinant of cortical bone status in men at the age of peak bone mass. J Clin Endocrinol Metab. 2010 Apr;95(4):1579-86. doi: 10.1210/jc.2009-2189. Epub 2010 Feb 4.
PMID: 20133463
citation: Roef G, Lapauw B, Goemaere S, Zmierczak H, Fiers T, Kaufman JM, Taes Y. Thyroid hormone status within the physiological range affects bone mass and density in healthy men at the age of peak bone mass. Eur J Endocrinol. 2011 Jun;164(6):1027-34. doi: 10.1530/EJE-10-1113. Epub 2011 Mar 10.
PMID: 21393448
citation: Vanbillemont G, Lapauw B, De Naeyer H, Roef G, Kaufman JM, Taes YE. Sex hormone-binding globulin at the crossroad of body composition, somatotropic axis and insulin/glucose homeostasis in young healthy men. Clin Endocrinol (Oxf). 2012 Jan;76(1):111-8. doi: 10.1111/j.1365-2265.2011.04155.x.
PMID: 21711374
citation: Boudin E, Piters E, Fransen E, Nielsen TL, Andersen M, Roef G, Taes Y, Brixen K, Van Hul W. Association study of common variants in the sFRP1 gene region and parameters of bone strength and body composition in two independent healthy Caucasian male cohorts. Mol Genet Metab. 2012 Mar;105(3):508-15. doi: 10.1016/j.ymgme.2011.11.189. Epub 2011 Nov 23.
PMID: 22178351
citation: Boudin E, Piters E, Nielsen TL, Andersen M, Roef G, Taes Y, Brixen K, Van Hul W. Single nucleotide polymorphisms in sFRP4 are associated with bone and body composition related parameters in Danish but not in Belgian men. Mol Genet Metab. 2012 Jul;106(3):366-74. doi: 10.1016/j.ymgme.2012.04.021. Epub 2012 May 2.
PMID: 22608881
citation: Roef G, Lapauw B, Goemaere S, Zmierczak HG, Toye K, Kaufman JM, Taes Y. Body composition and metabolic parameters are associated with variation in thyroid hormone levels among euthyroid young men. Eur J Endocrinol. 2012 Nov;167(5):719-26. doi: 10.1530/EJE-12-0447. Epub 2012 Sep 6.
PMID: 22956557
citation: Van Camp JK, Beckers S, Zegers D, Boudin E, Nielsen TL, Andersen M, Roef G, Taes Y, Brixen K, Van Hul W. Genetic association study of WNT10B polymorphisms with BMD and adiposity parameters in Danish and Belgian males. Endocrine. 2013 Aug;44(1):247-54. doi: 10.1007/s12020-012-9869-7. Epub 2013 Jan 17.
PMID: 23325361
citation: Roef GL, Rietzschel ER, De Meyer T, Bekaert S, De Buyzere ML, Van daele C, Toye K, Kaufman JM, Taes YE. Associations between single nucleotide polymorphisms in thyroid hormone transporter genes (MCT8, MCT10 and OATP1C1) and circulating thyroid hormones. Clin Chim Acta. 2013 Oct 21;425:227-32. doi: 10.1016/j.cca.2013.08.017. Epub 2013 Aug 24.
PMID: 23978482
citation: Roef G, Taes Y, Toye K, Goemaere S, Fiers T, Verstraete A, Kaufman JM. Heredity and lifestyle in the determination of between-subject variation in thyroid hormone levels in euthyroid men. Eur J Endocrinol. 2013 Oct 21;169(6):835-44. doi: 10.1530/EJE-13-0265. Print 2013 Dec.
PMID: 24086088
citation: De Naeyer H, Bogaert V, De Spaey A, Roef G, Vandewalle S, Derave W, Taes Y, Kaufman JM. Genetic variations in the androgen receptor are associated with steroid concentrations and anthropometrics but not with muscle mass in healthy young men. PLoS One. 2014 Jan 23;9(1):e86235. doi: 10.1371/journal.pone.0086235. eCollection 2014.
PMID: 24465978
citation: Gysel T, Calders P, Cambier D, Roman de Mettelinge T, Kaufman JM, Taes Y, Zmierczak HG, Goemaere S. Association between insulin resistance, lean mass and muscle torque/force in proximal versus distal body parts in healthy young men. J Musculoskelet Neuronal Interact. 2014 Mar;14(1):41-9.
PMID: 24583539
citation: Verroken C, Zmierczak HG, Goemaere S, Kaufman JM, Lapauw B. Association of Jumping Mechanography-Derived Indices of Muscle Function with Tibial Cortical Bone Geometry. Calcif Tissue Int. 2016 May;98(5):446-55. doi: 10.1007/s00223-015-0094-2. Epub 2015 Dec 16.
PMID: 26671019
citation: Verroken C, Zmierczak HG, Goemaere S, Kaufman JM, Lapauw B. Maternal age at childbirth is associated with offspring insulin sensitivity: a cross-sectional study in adult male siblings. Clin Endocrinol (Oxf). 2017 Jan;86(1):52-59. doi: 10.1111/cen.13253. Epub 2016 Nov 2.
PMID: 27726168
responsible party type: Sponsor
mesh term: Thyroid Diseases