OsteoporosisEPIPEAKNCT06509776
Skeletal Maturation and Endocrine Health in Young Adults
An observational study of Osteoporosis and Sarcopenia, run by Holbaek Sygehus at 9 sites in Denmark.
Trial summary
Diseases which can be the result of poor lifestyle choices in adult life, such as osteoporosis, obesity or poor muscle mass (sarcopenia) can also be driven by heritable genetic factors. Read more about this study
- Who is it for?
- Ages 18 to 19 years
- Conditions the study is for
- Osteoporosis, Sarcopenia, Obesity
- How many people
- 2,000 participants
- Where
- 9 sitesDenmark
- Study dates
- 11 Nov 2024to Sep 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 19 years
- All sexes
- Adult
Study population: The Danish Personal Civil Registration will be used to identify all alive individuals born in Denmark in 2006 and 2007 using civil registration numbers. Invitations will be sent through secure e-mail (E-boks) in blocks until 2,000 participants have been reached. The study population will be selected with representative geographical distribution in Denmark.
Who may be able to join
- Individuals (n = 2000) born in Denmark in 2006 or 2007
- Are 18 years old and alive at the time of the clinical examination
Who cannot join
- Pregnancy or lactation
- No DBS samples available
- Lack of consent to use DBS samples or national health registries
- Emigration or disappearance
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
Denmark9 sites
Aalborg University Hospital, Department of Endocrinology
Aalborg, 9000
Aarhus University Hospital, Department of Endocrinology
Aarhus, 8200
Rigshospitalet, Department of Clinical Biochemistry and Endocrinology
Copenhagen, 2200
Bispebjerg and Frederiksberg Hospital, EEK, Parker Institute
Frederiksberg, 2000
Holbæk Hospital, Department of Medicine
Holbæk, 4300
Hvidovre Hospital, Department of Endocrinology
Hvidovre, 2650
Zealand University Hospital, Department of Medicine
Køge, 4600
Odense University Hospital, Department of Endocrinology
Odense, 5000
University of Southern Denmark, Department of Clinical Research
Odense, 5000
About this study
Official title: Early Life Determinants of Skeletal Maturation and Endocrine Health in Young Adults - A Nationwide Birth Cohort Study
Diseases which can be the result of poor lifestyle choices in adult life, such as osteoporosis, obesity or poor muscle mass (sarcopenia) can also be driven by heritable genetic factors. More surprisingly, perhaps, the genes we inherit from our parents can be modified as a result of influences that affected the health and pregnancy of our mothers and hence the environment experienced in the womb and at birth. The purpose of this study is to investigate which factors are needed for good bone health and hormonal health in young adulthood as well as good muscle mass and normal fat mass, and how this is influenced by factors before birth and by childhood health. Specifically, we will measure bone mass and body composition in young adults (18 years of age) and measure hormones in blood and in hair samples. The clinical visits will be available nationwide at several centers to make participation swift and easy for participants. The changes (known as epigenetic modification) to genes at birth will be studied in dried blood spot samples stored from birth 18 years ago in the Danish Serum Institute and we will use national health registers to identify factors during pregnancy and in childhood that contribute to health effects at age 18.
Read the detailed description
Population-based, nationwide, cross-sectional, clinical study with already available early life exposure data including bio banked neonatal biological samples. An embedded design using the full 2006+2007 birth cohorts is used to demonstrate external validity of the clinically assessed cohort. We will obtain the necessary ethics and regulatory approval and individual consent from the participants who are all aged 18.
The overall aim of the project addresses whether the following sets of potential determinants are associated with young adult hormonal status, lipids, bone turnover markers, bone mineral density (BMD), fat mass and lean body mass at age 18 years: a) maternal risk factors during preconception and pregnancy; b) risk factors at birth; c) neonatal epigenetic signature; d) childhood risk factors.
Aim 1 - Epigenetics - Is peak bone mass and body size influenced by epigenetic profile for endocrine signals at birth? From the second trimester of pregnancy and until early adulthood, bone is gradually developed and shaped, with longitudinal growth dominating the later stages of fetal life, infancy, and childhood. This is followed by a period of rapid bone mineral accrual occurring up to and during puberty, with bone mass accretion ultimately reaching a plateau in young adult life. It is strongly suggested by prior research that epigenetic variation at birth can result from differences in maternal health, lifestyle, nutrition, smoking and medication usage and result in long-term changes in gene expression and metabolism.
As existing childhood cohorts either lack BMD information, suffer from significant cohort attrition, and low recruitment success, there is an opportunity to instead use national invitations to recruit directly into an efficient endocrine and bone outcomes study and use already archived biological material from early infancy and register data and obtain individual study subject consent.
Aim 2 - Endocrine status in young adulthood - Does maternal medication use and health issues prior to pregnancy or in pregnancy affect endocrine health in young adults? This question will be addressed using data from Danish national registers. While it is straightforward to link binary events data e.g., malformations or paediatric admissions (eg epilepsy, diabetes, failure to thrive) to registry capture of their maternal exposures, we will be obtaining detailed information about continuous outcomes including endocrine serum biochemistry (thyroid axis, GH axis, PTH-vitamin D-calcium axis, lipids, HbA1c), hair cortisol levels (a cumulative serum cortisol metric) as well as body composition and bone density metrics.
Aim 3 - DXA measured muscle, fat mass and lipid status in young adults - Do suboptimal conditions prior to pregnancy, during pregnancy, birth, and childhood, such as lifestyle, poor health and low socioeconomics adversely influence establishment of healthy body composition and lipid status in young adulthood? Detailed register-based information prior to pregnancy, about pregnancy, birth and childhood health will be used to identify areas open to prevention. Detailed information will be obtained via the Danish national health registers.
Statistical consideration - With a study population of 2,000, the power (given α=0.05) available to detect a 0.2 SD effect on a continuous outcome such as PBM for a risk factor with a population prevalence of 20% is 90%. With inclusion of 1,500 subjects, the corresponding study power is 90% for detection of an effect size of 0.24 SD or 80% for detection of an effect size of 0.2 SD. The study needs this resolving power to be able to address multiple contributing factors and for the inclusion of factors in the model that may have a population prevalence below 20%. Less common factors would, even if powerful drivers of skeletal health, be somewhat less useful in population impact even if successfully modified.
Biological material - All material for use in the current project will be stored in a research biobank during the current study during its term. Any remaining material is transferred to biobank for future research with the approval of the Danish Data Protection Agency. The purpose of the biobank is to ensure validation of the analysis methods used over time. The participants must give consent to the storage of their biological material in the biobank. It is completely optional if the participants want to donate their excess biological material to the biobank and if they do not want this, it does not affect their participation in the study. For new research, new consent must be obtained, but the Scientific Ethics Committee can grant exemption from the consent requirement.
All material will be stored in compliance with Danish legislation on data protection.
24 mL of blood will be drawn. All blood samples are encoded so that all samples are anonymized, and the key is under special protection and only with access for authorized personnel. All extra material will be kept in the biobank.
To ensure uniformity between neonatal and adolescent samples, DBS will be created from the freshly drawn whole blood. DBS are created by spotting 3x75µL onto a cotton filter paper of the same type used in 2006-2007. The cards are left overnight at ambient temperatures then transferred to -20C for long term storage. DNA is be extracted from two 3.2mm disks excised from the DBS card, then purified using magnetic silica beads. Finally, concentrations are measured using intercalating dyes.
All hair samples (minimum 20 mg per participant) will be encoded so that all samples are pseudonymised, and the key is under special protection and only with access for authorized personnel. All hair samples will be used in the analyses, and then discarded.
- Conditions
- Osteoporosis, Sarcopenia, Obesity, Cardiovascular Diseases
- Keywords
- Bone and Bones, Bone mineralization, Bone mineral density, Bone density, Endocrinology, Hormones, Thyroid Hormones, Parathyroid Hormone, Puberty, Adolescent, Glucocorticoids, Genetics, Human Genetics, Epigenomics, Neonatal Screening, Body Composition, Cohort Study, Epidemiology, Phenotype
- Medical subject headings
- Osteoporosis, Sarcopenia, Obesity, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Population sample | Random subsample of all 17-18-year-old individuals in Denmark, i.e. live births from year 2006 and 2007. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone Mineral Density of Spine, Hip and Whole-body
The Dual-energy X-ray Absorptiometry (DXA) measures the bone mineral density (BMD) of the spine, hip and whole-body.
Measured: Baseline
Bone Mineral Density of Spine, Hip and Whole-body
The Dual-energy X-ray Absorptiometry (DXA) measures the bone mineral density (BMD) of the spine, hip and whole-body.
Measured: 2 years
Bone Area of Spine, Hip and Whole-body
The Dual-energy X-ray Absorptiometry (DXA) measures the bone area (BA) of the spine, hip and whole-body.
Measured: Baseline
Bone Area of Spine, Hip and Whole-body
The Dual-energy X-ray Absorptiometry (DXA) measures the bone area (BA) of the spine, hip and whole-body.
Measured: 2 years
Bone Mineral Content of Spine, Hip and Whole-body
The Dual-energy X-ray Absorptiometry (DXA) measures the bone mineral content (BMC) in the spine, hip and whole-body.
Measured: Baseline
Bone Mineral Content of Spine, Hip and Whole-body
The Dual-energy X-ray Absorptiometry (DXA) measures the bone mineral content (BMC) in the spine, hip and whole-body.
Measured: 2 years
Secondary outcomes (23)
Total Body Lean Mass
The Dual-energy X-ray Absorptiometry (DXA) measures the whole-body densitometry, providing information on total body lean mass in kg.
Measured: Baseline
Total Body Lean Mass
The Dual-energy X-ray Absorptiometry (DXA) measures the whole-body densitometry, providing information on total body lean mass in kg.
Measured: 2 years
Total Body Fat Mass
The Dual-energy X-ray Absorptiometry (DXA) measures the whole-body densitometry, providing information on total body fat mass in kg.
Measured: Baseline
Total Body Fat Mass
The Dual-energy X-ray Absorptiometry (DXA) measures the whole-body densitometry, providing information on total body fat mass in kg.
Measured: 2 years
High-Resolution Peripheral Quantitative Computed Tomography of The Distal Radius and Tibia
High-resolution peripheral quantitative computed tomography (HRpQCT) of the distal radius and tibia will provide structural information including cortical thickness, trabecular number, trabecular thickness and volumetric bone mineral density (vBMD)
Measured: Baseline
High-Resolution Peripheral Quantitative Computed Tomography of The Distal Radius and Tibia
High-resolution peripheral quantitative computed tomography (HRpQCT) of the distal radius and tibia will provide structural information including cortical thickness, trabecular number, trabecular thickness and volumetric bone mineral density (vBMD)
Measured: 2 years
Body Weight
Weight will be measured to the nearest 0.1 kg on an electronic scale with participants wearing light clothing. Measurement will be carried out barefoot.
Measured: Baseline
Body Weight
Weight will be measured to the nearest 0.1 kg on an electronic scale with participants wearing light clothing. Measurement will be carried out barefoot.
Measured: 2 years
Height
Height will be measured to the nearest 0.5 cm using a portable stadiometer. Measurement will be carried out barefoot
Measured: Baseline
Height
Height will be measured to the nearest 0.5 cm using a portable stadiometer. Measurement will be carried out barefoot
Measured: 2 years
Body Mass Index
Body Mass Index (BMI) will be calculated based on the participant's weight and height
Measured: Baseline
Body Mass Index
Body Mass Index (BMI) will be calculated based on the participant's weight and height
Measured: 2 years
Waist Circumference
The waist circumference will be measured using a measuring tape to the nearest 0.5 cm. At least two measurements will be performed and a third will be made if the two differs by more than 1 cm
Measured: Baseline
Waist Circumference
The waist circumference will be measured using a measuring tape to the nearest 0.5 cm. At least two measurements will be performed and a third will be made if the two differs by more than 1 cm
Measured: 2 years
Hip Circumference
The hip circumference will be measured using a measuring tape to the nearest 0.5 cm. At least two measurements will be performed and a third will be made if the two differs by more than 1 cm
Measured: Baseline
Hip Circumference
The hip circumference will be measured using a measuring tape to the nearest 0.5 cm. At least two measurements will be performed and a third will be made if the two differs by more than 1 cm
Measured: 2 years
Waist-Hip Ratio
The waist-hip ratio is calculated using the waist and hip circumference
Measured: Baseline
Waist-Hip Ratio
The waist-hip ratio is calculated using the waist and hip circumference
Measured: 2 years
Endocrine Status
Blood will be drawn for plasma analyses for endocrine status
Measured: Baseline
Endocrine Status and Bone Markers of Bone Metabolism
Blood will be drawn for plasma analyses for endocrine status and biomarkers of bone metabolism (PINP and CTX)
Measured: Baseline
Hair Cortisol Concentrations
The hair samples will be cut from the posterior apex as close to the scalp as possible (minimum 20 mg per participant). Cortisol extracted from the hair will be analysed via the Elisa method
Measured: Baseline
Blood Pressure
Resting blood pressure will be measured
Measured: Baseline
Blood Pressure
Resting blood pressure will be measured
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2024
- Study start11 Nov 2024
- Primary completionSep 2026 (estimated)
- Study completionSep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for OsteoporosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Holbaek Sygehus
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital, Aalborg University Hospital, University of Southern Denmark, University Hospital Bispebjerg and Frederiksberg, Zealand University Hospital, Odense University Hospital, Copenhagen University Hospital, Rigshospitalet, Statens Serum Institut, Hvidovre University Hospital
- Responsible party
- Sponsor
- Investigators
- Bo Abrahamsen, MD, PhD, Study chair, OPEN, University of Southern Denmark, Odense and Department of Medicine 1, Holbæk Hospital, HolbækKatrine H Rubin, MHS, PhD, Principal investigator, OPEN, Department of Clinical Research, University of Southern Denmark and Odense University HospitalBente Langdahl, MD, PhD, Principal investigator, Department of Clinical Medicine and Department of Endocrinology and Diabetes, Aarhus UniversityPeter Vestergaard, MD, PhD, Principal investigator, Faculty of Medicine, Aalborg University and Department of Endocrinology, Aalborg University HospitalBerit L Heitmann, DMD, PhD, Principal investigator, The Parker Institute, Frederiksberg Hospital, FrederiksbergMina N Händel, Msc, PhD, Principal investigator, The Parker Institute, Frederiksberg Hospital, FrederiksbergCharlotte L Tofteng, MD, PhD, Principal investigator, Department of CIinical Medicine, Endocrinology, Zealand University Hospital, KøgePernille Bach-Mortensen, MD, PhD, Principal investigator, Department of Endocrinology, Amager and Hvidovre Hospital, Hvidovre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06509776
- Sponsor's protocol ID
- S-20230105
- Other IDs
- NNF22OC0080437, 21-B-0436
- Acronym
- EPIPEAK
- Status last verified
- Jan 2025
- First submitted
- 15 Jul 2024
- Last updated
- 10 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Yu XH, Wei YY, Zeng P, Lei SF. Birth weight is positively associated with adult osteoporosis risk: observational and Mendelian randomization studies. J Bone Miner Res. 2021 Aug;36(8):1469-1480. doi: 10.1002/jbmr.4316. Epub 2021 Jun 9.
PubMed 34105796Curtis EM, Fuggle NR, Cooper C, Harvey NC. Epigenetic regulation of bone mass. Best Pract Res Clin Endocrinol Metab. 2022 Mar;36(2):101612. doi: 10.1016/j.beem.2021.101612. Epub 2022 Jan 4.
PubMed 35120798Krstic N, Bishop N, Curtis B, Cooper C, Harvey N, Lilycrop K, Murray R, Owen R, Reilly G, Skerry T, Borg S. Early life vitamin D depletion and mechanical loading determine methylation changes in the RUNX2, RXRA, and osterix promoters in mice. Genes Nutr. 2022 May 26;17(1):7. doi: 10.1186/s12263-022-00711-0.
PubMed 35619053Reppe S, Lien TG, Hsu YH, Gautvik VT, Olstad OK, Yu R, Bakke HG, Lyle R, Kringen MK, Glad IK, Gautvik KM. Distinct DNA methylation profiles in bone and blood of osteoporotic and healthy postmenopausal women. Epigenetics. 2017 Aug;12(8):674-687. doi: 10.1080/15592294.2017.1345832. Epub 2017 Jun 26.
PubMed 28650214Williams GR, Bassett JHD. Thyroid diseases and bone health. J Endocrinol Invest. 2018 Jan;41(1):99-109. doi: 10.1007/s40618-017-0753-4. Epub 2017 Aug 29.
PubMed 28853052Cardoso I, Specht IO, Thorsteinsdottir F, Thorbek MJ, Keller A, Stougaard M, Cohen AS, Handel MN, Kristensen LE, Heitmann BL. Vitamin D Concentrations at Birth and the Risk of Rheumatoid Arthritis in Early Adulthood: A Danish Population-Based Case-Cohort Study. Nutrients. 2022 Jan 20;14(3):447. doi: 10.3390/nu14030447.
PubMed 35276806Handel MN, Frederiksen P, Cohen A, Cooper C, Heitmann BL, Abrahamsen B. Neonatal vitamin D status from archived dried blood spots and future risk of fractures in childhood: results from the D-tect study, a population-based case-cohort study. Am J Clin Nutr. 2017 Jul;106(1):155-161. doi: 10.3945/ajcn.116.145599. Epub 2017 May 17.
PubMed 28515065Jensen CB, Lundqvist M, Sorensen TIA, Heitmann BL. Neonatal Vitamin D Levels in Relation to Risk of Overweight at 7 Years in the Danish D-Tect Case-Cohort Study. Obes Facts. 2017;10(3):273-283. doi: 10.1159/000471881. Epub 2017 Jun 10.
PubMed 28601865Keller A, Thorsteinsdottir F, Stougaard M, Cardoso I, Frederiksen P, Cohen AS, Vaag A, Jacobsen R, Heitmann BL. Vitamin D concentrations from neonatal dried blood spots and the risk of early-onset type 2 diabetes in the Danish D-tect case-cohort study. Diabetologia. 2021 Jul;64(7):1572-1582. doi: 10.1007/s00125-021-05450-2. Epub 2021 May 24.
PubMed 34028586Keller A, Frederiksen P, Handel MN, Jacobsen R, McGrath JJ, Cohen AS, Heitmann BL. Environmental and individual predictors of 25-hydroxyvitamin D concentrations in Denmark measured from neonatal dried blood spots: the D-tect study. Br J Nutr. 2019 Mar 14;121(5):567-575. doi: 10.1017/S0007114518003604. Epub 2019 Jan 30.
PubMed 30526709Keller A, Handel MN, Frederiksen P, Jacobsen R, Cohen AS, McGrath JJ, Heitmann BL. Concentration of 25-hydroxyvitamin D from neonatal dried blood spots and the relation to gestational age, birth weight and Ponderal Index: the D-tect study. Br J Nutr. 2018 Jun;119(12):1416-1423. doi: 10.1017/S0007114518000879. Epub 2018 Apr 25.
PubMed 29690937Thorsteinsdottir F, Cardoso I, Keller A, Stougaard M, Frederiksen P, Cohen AS, Maslova E, Jacobsen R, Backer V, Heitmann BL. Neonatal Vitamin D Status and Risk of Asthma in Childhood: Results from the D-Tect Study. Nutrients. 2020 Mar 21;12(3):842. doi: 10.3390/nu12030842.
PubMed 32245170Dugue PA, English DR, MacInnis RJ, Jung CH, Bassett JK, FitzGerald LM, Wong EM, Joo JE, Hopper JL, Southey MC, Giles GG, Milne RL. Reliability of DNA methylation measures from dried blood spots and mononuclear cells using the HumanMethylation450k BeadArray. Sci Rep. 2016 Jul 26;6:30317. doi: 10.1038/srep30317.
PubMed 27457678Staunstrup NH, Starnawska A, Nyegaard M, Christiansen L, Nielsen AL, Borglum A, Mors O. Genome-wide DNA methylation profiling with MeDIP-seq using archived dried blood spots. Clin Epigenetics. 2016 Jul 26;8:81. doi: 10.1186/s13148-016-0242-1. eCollection 2016.
PubMed 27462375Ghantous A, Saffery R, Cros MP, Ponsonby AL, Hirschfeld S, Kasten C, Dwyer T, Herceg Z, Hernandez-Vargas H. Optimized DNA extraction from neonatal dried blood spots: application in methylome profiling. BMC Biotechnol. 2014 Jul 1;14:60. doi: 10.1186/1472-6750-14-60.
PubMed 24980254
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Life Determinants of Skeletal Maturation and Endocrine Health in Young Adults - A Nationwide Birth Cohort Study
- ClinicalTrials.gov ID
- NCT06509776
- Acronym / sponsor ID
- EPIPEAK / S-20230105
- Conditions
- Osteoporosis, Sarcopenia, Obesity, Cardiovascular Diseases
- Keywords
- Bone and Bones, Bone mineralization, Bone mineral density, Bone density, Endocrinology, Hormones, Thyroid Hormones, Parathyroid Hormone
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Holbaek SygehusUniversity, hospital or other
- Collaborators
- Aarhus University Hospital, Aalborg University Hospital, University of Southern Denmark, University Hospital Bispebjerg and Frederiksberg, Zealand University Hospital, Odense University Hospital, Copenhagen University Hospital, Rigshospitalet, Statens Serum Institut, Hvidovre University Hospital
- Study start
- 11 Nov 2024 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2031 (estimated)
- First posted
- 19 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Diseases which can be the result of poor lifestyle choices in adult life, such as osteoporosis, obesity or poor muscle mass (sarcopenia) can also be driven by heritable genetic factors. More surprisingly, perhaps, the genes we inherit from our parents can be modified as a result of influences that affected the health and pregnancy of our mothers and hence the environment experienced in the womb and at birth. The purpose of this study is to investigate which factors are needed for good bone health and hormonal health in young adulthood as well as good muscle mass and normal fat mass, and how this is influenced by factors before birth and by childhood health. Specifically, we will measure bone mass and body composition in young adults (18 years of age) and measure hormones in blood and in hair samples. The clinical visits will be available nationwide at several centers to make participation swift and easy for participants. The changes (known as epigenetic modification) to genes at birth will be studied in dried blood spot samples stored from birth 18 years ago in the Danish Serum Institute and we will use national health registers to identify factors during pregnancy and in childhood that contribute to health effects at age 18.
Detailed description
Population-based, nationwide, cross-sectional, clinical study with already available early life exposure data including bio banked neonatal biological samples. An embedded design using the full 2006+2007 birth cohorts is used to demonstrate external validity of the clinically assessed cohort. We will obtain the necessary ethics and regulatory approval and individual consent from the participants who are all aged 18.
The overall aim of the project addresses whether the following sets of potential determinants are associated with young adult hormonal status, lipids, bone turnover markers, bone mineral density (BMD), fat mass and lean body mass at age 18 years: a) maternal risk factors during preconception and pregnancy; b) risk factors at birth; c) neonatal epigenetic signature; d) childhood risk factors.
Aim 1 - Epigenetics - Is peak bone mass and body size influenced by epigenetic profile for endocrine signals at birth? From the second trimester of pregnancy and until early adulthood, bone is gradually developed and shaped, with longitudinal growth dominating the later stages of fetal life, infancy, and childhood. This is followed by a period of rapid bone mineral accrual occurring up to and during puberty, with bone mass accretion ultimately reaching a plateau in young adult life. It is strongly suggested by prior research that epigenetic variation at birth can result from differences in maternal health, lifestyle, nutrition, smoking and medication usage and result in long-term changes in gene expression and metabolism.
As existing childhood cohorts either lack BMD information, suffer from significant cohort attrition, and low recruitment success, there is an opportunity to instead use national invitations to recruit directly into an efficient endocrine and bone outcomes study and use already archived biological material from early infancy and register data and obtain individual study subject consent.
Aim 2 - Endocrine status in young adulthood - Does maternal medication use and health issues prior to pregnancy or in pregnancy affect endocrine health in young adults? This question will be addressed using data from Danish national registers. While it is straightforward to link binary events data e.g., malformations or paediatric admissions (eg epilepsy, diabetes, failure to thrive) to registry capture of their maternal exposures, we will be obtaining detailed information about continuous outcomes including endocrine serum biochemistry (thyroid axis, GH axis, PTH-vitamin D-calcium axis, lipids, HbA1c), hair cortisol levels (a cumulative serum cortisol metric) as well as body composition and bone density metrics.
Aim 3 - DXA measured muscle, fat mass and lipid status in young adults - Do suboptimal conditions prior to pregnancy, during pregnancy, birth, and childhood, such as lifestyle, poor health and low socioeconomics adversely influence establishment of healthy body composition and lipid status in young adulthood? Detailed register-based information prior to pregnancy, about pregnancy, birth and childhood health will be used to identify areas open to prevention. Detailed information will be obtained via the Danish national health registers.
Statistical consideration - With a study population of 2,000, the power (given α=0.05) available to detect a 0.2 SD effect on a continuous outcome such as PBM for a risk factor with a population prevalence of 20% is 90%. With inclusion of 1,500 subjects, the corresponding study power is 90% for detection of an effect size of 0.24 SD or 80% for detection of an effect size of 0.2 SD. The study needs this resolving power to be able to address multiple contributing factors and for the inclusion of factors in the model that may have a population prevalence below 20%. Less common factors would, even if powerful drivers of skeletal health, be somewhat less useful in population impact even if successfully modified.
Biological material - All material for use in the current project will be stored in a research biobank during the current study during its term. Any remaining material is transferred to biobank for future research with the approval of the Danish Data Protection Agency. The purpose of the biobank is to ensure validation of the analysis methods used over time. The participants must give consent to the storage of their biological material in the biobank. It is completely optional if the participants want to donate their excess biological material to the biobank and if they do not want this, it does not affect their participation in the study. For new research, new consent must be obtained, but the Scientific Ethics Committee can grant exemption from the consent requirement.
All material will be stored in compliance with Danish legislation on data protection.
24 mL of blood will be drawn. All blood samples are encoded so that all samples are anonymized, and the key is under special protection and only with access for authorized personnel. All extra material will be kept in the biobank.
To ensure uniformity between neonatal and adolescent samples, DBS will be created from the freshly drawn whole blood. DBS are created by spotting 3x75µL onto a cotton filter paper of the same type used in 2006-2007. The cards are left overnight at ambient temperatures then transferred to -20C for long term storage. DNA is be extracted from two 3.2mm disks excised from the DBS card, then purified using magnetic silica beads. Finally, concentrations are measured using intercalating dyes.
All hair samples (minimum 20 mg per participant) will be encoded so that all samples are pseudonymised, and the key is under special protection and only with access for authorized personnel. All hair samples will be used in the analyses, and then discarded.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Population sample | – | –Random subsample of all 17-18-year-old individuals in Denmark, i.e. live births from year 2006 and 2007. |
Who may qualify
- Ages
- 18 to 19 years
- Sex
- All
- Age groups
- Adult
- Study population
- The Danish Personal Civil Registration will be used to identify all alive individuals born in Denmark in 2006 and 2007 using civil registration numbers. Invitations will be sent through secure e-mail (E-boks) in blocks until 2,000 participants have been reached. The study population will be selected with representative geographical distribution in Denmark.
Key inclusion criteria (2 listed)
- Individuals (n = 2000) born in Denmark in 2006 or 2007
- Are 18 years old and alive at the time of the clinical examination
Key exclusion criteria (4 listed)
- Pregnancy or lactation
- No DBS samples available
- Lack of consent to use DBS samples or national health registries
- Emigration or disappearance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Bone Mineral Density of Spine, Hip and Whole-body
Time frame: Baseline
The Dual-energy X-ray Absorptiometry (DXA) measures the bone mineral density (BMD) of the spine, hip and whole-body.
Bone Mineral Density of Spine, Hip and Whole-body
Time frame: 2 years
The Dual-energy X-ray Absorptiometry (DXA) measures the bone mineral density (BMD) of the spine, hip and whole-body.
Bone Area of Spine, Hip and Whole-body
Time frame: Baseline
The Dual-energy X-ray Absorptiometry (DXA) measures the bone area (BA) of the spine, hip and whole-body.
Bone Area of Spine, Hip and Whole-body
Time frame: 2 years
The Dual-energy X-ray Absorptiometry (DXA) measures the bone area (BA) of the spine, hip and whole-body.
Bone Mineral Content of Spine, Hip and Whole-body
Time frame: Baseline
The Dual-energy X-ray Absorptiometry (DXA) measures the bone mineral content (BMC) in the spine, hip and whole-body.
Bone Mineral Content of Spine, Hip and Whole-body
Time frame: 2 years
The Dual-energy X-ray Absorptiometry (DXA) measures the bone mineral content (BMC) in the spine, hip and whole-body.
23 secondary outcomes
Total Body Lean Mass
Time frame: Baseline
Total Body Lean Mass
Time frame: 2 years
Total Body Fat Mass
Time frame: Baseline
Total Body Fat Mass
Time frame: 2 years
High-Resolution Peripheral Quantitative Computed Tomography of The Distal Radius and Tibia
Time frame: Baseline
High-Resolution Peripheral Quantitative Computed Tomography of The Distal Radius and Tibia
Time frame: 2 years
Body Weight
Time frame: Baseline
Body Weight
Time frame: 2 years
Height
Time frame: Baseline
Height
Time frame: 2 years
Body Mass Index
Time frame: Baseline
Body Mass Index
Time frame: 2 years
Waist Circumference
Time frame: Baseline
Waist Circumference
Time frame: 2 years
Hip Circumference
Time frame: Baseline
Hip Circumference
Time frame: 2 years
Waist-Hip Ratio
Time frame: Baseline
Waist-Hip Ratio
Time frame: 2 years
Endocrine Status
Time frame: Baseline
Endocrine Status and Bone Markers of Bone Metabolism
Time frame: Baseline
Hair Cortisol Concentrations
Time frame: Baseline
Blood Pressure
Time frame: Baseline
Blood Pressure
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2025.
- Background: PubMed 34105796Yu XH, Wei YY, Zeng P, Lei SF. Birth weight is positively associated with adult osteoporosis risk: observational and Mendelian randomization studies. J Bone Miner Res. 2021 Aug;36(8):1469-1480. doi: 10.1002/jbmr.4316. Epub 2021 Jun 9.
- Background: PubMed 35120798Curtis EM, Fuggle NR, Cooper C, Harvey NC. Epigenetic regulation of bone mass. Best Pract Res Clin Endocrinol Metab. 2022 Mar;36(2):101612. doi: 10.1016/j.beem.2021.101612. Epub 2022 Jan 4.
- Background: PubMed 35619053Krstic N, Bishop N, Curtis B, Cooper C, Harvey N, Lilycrop K, Murray R, Owen R, Reilly G, Skerry T, Borg S. Early life vitamin D depletion and mechanical loading determine methylation changes in the RUNX2, RXRA, and osterix promoters in mice. Genes Nutr. 2022 May 26;17(1):7. doi: 10.1186/s12263-022-00711-0.
- Background: PubMed 28650214Reppe S, Lien TG, Hsu YH, Gautvik VT, Olstad OK, Yu R, Bakke HG, Lyle R, Kringen MK, Glad IK, Gautvik KM. Distinct DNA methylation profiles in bone and blood of osteoporotic and healthy postmenopausal women. Epigenetics. 2017 Aug;12(8):674-687. doi: 10.1080/15592294.2017.1345832. Epub 2017 Jun 26.
- Background: PubMed 28853052Williams GR, Bassett JHD. Thyroid diseases and bone health. J Endocrinol Invest. 2018 Jan;41(1):99-109. doi: 10.1007/s40618-017-0753-4. Epub 2017 Aug 29.
- Background: PubMed 35276806Cardoso I, Specht IO, Thorsteinsdottir F, Thorbek MJ, Keller A, Stougaard M, Cohen AS, Handel MN, Kristensen LE, Heitmann BL. Vitamin D Concentrations at Birth and the Risk of Rheumatoid Arthritis in Early Adulthood: A Danish Population-Based Case-Cohort Study. Nutrients. 2022 Jan 20;14(3):447. doi: 10.3390/nu14030447.
- Background: PubMed 28515065Handel MN, Frederiksen P, Cohen A, Cooper C, Heitmann BL, Abrahamsen B. Neonatal vitamin D status from archived dried blood spots and future risk of fractures in childhood: results from the D-tect study, a population-based case-cohort study. Am J Clin Nutr. 2017 Jul;106(1):155-161. doi: 10.3945/ajcn.116.145599. Epub 2017 May 17.
- Background: PubMed 28601865Jensen CB, Lundqvist M, Sorensen TIA, Heitmann BL. Neonatal Vitamin D Levels in Relation to Risk of Overweight at 7 Years in the Danish D-Tect Case-Cohort Study. Obes Facts. 2017;10(3):273-283. doi: 10.1159/000471881. Epub 2017 Jun 10.
- Background: PubMed 34028586Keller A, Thorsteinsdottir F, Stougaard M, Cardoso I, Frederiksen P, Cohen AS, Vaag A, Jacobsen R, Heitmann BL. Vitamin D concentrations from neonatal dried blood spots and the risk of early-onset type 2 diabetes in the Danish D-tect case-cohort study. Diabetologia. 2021 Jul;64(7):1572-1582. doi: 10.1007/s00125-021-05450-2. Epub 2021 May 24.
- Background: PubMed 30526709Keller A, Frederiksen P, Handel MN, Jacobsen R, McGrath JJ, Cohen AS, Heitmann BL. Environmental and individual predictors of 25-hydroxyvitamin D concentrations in Denmark measured from neonatal dried blood spots: the D-tect study. Br J Nutr. 2019 Mar 14;121(5):567-575. doi: 10.1017/S0007114518003604. Epub 2019 Jan 30.
- Background: PubMed 29690937Keller A, Handel MN, Frederiksen P, Jacobsen R, Cohen AS, McGrath JJ, Heitmann BL. Concentration of 25-hydroxyvitamin D from neonatal dried blood spots and the relation to gestational age, birth weight and Ponderal Index: the D-tect study. Br J Nutr. 2018 Jun;119(12):1416-1423. doi: 10.1017/S0007114518000879. Epub 2018 Apr 25.
- Background: PubMed 32245170Thorsteinsdottir F, Cardoso I, Keller A, Stougaard M, Frederiksen P, Cohen AS, Maslova E, Jacobsen R, Backer V, Heitmann BL. Neonatal Vitamin D Status and Risk of Asthma in Childhood: Results from the D-Tect Study. Nutrients. 2020 Mar 21;12(3):842. doi: 10.3390/nu12030842.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bo Abrahamsen, MD, PhD study chair
OPEN, University of Southern Denmark, Odense and Department of Medicine 1, Holbæk Hospital, Holbæk
Katrine H Rubin, MHS, PhD principal investigator
OPEN, Department of Clinical Research, University of Southern Denmark and Odense University Hospital
Bente Langdahl, MD, PhD principal investigator
Department of Clinical Medicine and Department of Endocrinology and Diabetes, Aarhus University
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Osteoporosis and Sarcopenia, run by Holbaek Sygehus at 9 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 10 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone Mineral Density of Spine, Hip and Whole-body (time frame: Baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06509776, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2025.