Skeletal Maturation and Endocrine Health in Young Adults

NCT06509776 | Enrolling By Invitation

• 3 other identifiers: S-20230105NNF22OC008043721-B-0436
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 9

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  2 years

Secondary Outcomes (23)

• Total Body Lean Mass

  Baseline

• Total Body Lean Mass

  2 years

• Total Body Fat Mass

  Baseline

• Total Body Fat Mass

  2 years

• High-Resolution Peripheral Quantitative Computed Tomography of The Distal Radius and Tibia

  Baseline

Other Outcomes (3)

• Self-reported Stress

  Baseline

• Self-reported Sleep

  Baseline

• Self-reported Hearing

  Baseline

Study Arms (1)

Population sample

Random subsample of all 17-18-year-old individuals in Denmark, i.e. live births from year 2006 and 2007.

Eligibility Criteria

• Age: 18 Years - 19 Years
• Sex: all
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

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.

You may qualify if:

• Individuals (n = 2000) born in Denmark in 2006 or 2007
• Are 18 years old and alive at the time of the clinical examination

You may not qualify if:

• Pregnancy or lactation
• No DBS samples available
• Lack of consent to use DBS samples or national health registries
• Emigration or disappearance

Sponsors & Collaborators

• Holbaek Sygehus: lead
• Aarhus University Hospital: collaborator
• Aalborg University Hospital: collaborator
• University of Southern Denmark: collaborator
• University Hospital Bispebjerg and Frederiksberg: collaborator
• Zealand University Hospital: collaborator
• Odense University Hospital: collaborator
• Rigshospitalet, Denmark: collaborator
• Statens Serum Institut: collaborator
• Hvidovre University Hospital: collaborator

Study Sites (9)

Aalborg University Hospital, Department of Endocrinology

Aalborg, 9000, Denmark

Location

Aarhus University Hospital, Department of Endocrinology

Aarhus, 8200, Denmark

Location

Rigshospitalet, Department of Clinical Biochemistry and Endocrinology

Copenhagen, 2200, Denmark

Location

Bispebjerg and Frederiksberg Hospital, EEK, Parker Institute

Frederiksberg, 2000, Denmark

Location

Holbæk Hospital, Department of Medicine

Holbæk, 4300, Denmark

Location

Hvidovre Hospital, Department of Endocrinology

Hvidovre, 2650, Denmark

Location

Zealand University Hospital, Department of Medicine

Køge, 4600, Denmark

Location

Odense University Hospital, Department of Endocrinology

Odense, 5000, Denmark

Location

University of Southern Denmark, Department of Clinical Research

Odense, 5000, Denmark

Location

Related Publications (29)

• 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.

  PMID: 34105796 BACKGROUND

• Curtis 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.

  PMID: 35120798 BACKGROUND

• Krstic 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.

  PMID: 35619053 BACKGROUND

• Reppe 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.

  PMID: 28650214 BACKGROUND

• Williams 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.

  PMID: 28853052 BACKGROUND

• Cardoso 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.

  PMID: 35276806 BACKGROUND

• Handel 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.

  PMID: 28515065 BACKGROUND

• Jensen 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.

  PMID: 28601865 BACKGROUND

• Keller 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.

  PMID: 34028586 BACKGROUND

• Keller 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.

  PMID: 30526709 BACKGROUND

• Keller 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.

  PMID: 29690937 BACKGROUND

• Thorsteinsdottir 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.

  PMID: 32245170 BACKGROUND

• Dugue 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.

  PMID: 27457678 BACKGROUND

• Staunstrup 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.

  PMID: 27462375 BACKGROUND

• Ghantous 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.

  PMID: 24980254 BACKGROUND

• Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, O'Karma M, Wallace TC, Zemel BS. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016 Apr;27(4):1281-1386. doi: 10.1007/s00198-015-3440-3. Epub 2016 Feb 8.

  PMID: 26856587 BACKGROUND

• Hannon E, Schendel D, Ladd-Acosta C, Grove J, Hansen CS, Hougaard DM, Bresnahan M, Mors O, Hollegaard MV, Baekvad-Hansen M, Hornig M, Mortensen PB, Borglum AD, Werge T, Pedersen MG, Nordentoft M; iPSYCH-Broad ASD Group; Buxbaum JD, Daniele Fallin M, Bybjerg-Grauholm J, Reichenberg A, Mill J. Variable DNA methylation in neonates mediates the association between prenatal smoking and birth weight. Philos Trans R Soc Lond B Biol Sci. 2019 Apr 15;374(1770):20180120. doi: 10.1098/rstb.2018.0120.

  PMID: 30966880 BACKGROUND

• Gicquel C, El-Osta A, Le Bouc Y. Epigenetic regulation and fetal programming. Best Pract Res Clin Endocrinol Metab. 2008 Feb;22(1):1-16. doi: 10.1016/j.beem.2007.07.009.

  PMID: 18279777 BACKGROUND

• Jensen KH, Riis KR, Abrahamsen B, Handel MN. Nutrients, Diet, and Other Factors in Prenatal Life and Bone Health in Young Adults: A Systematic Review of Longitudinal Studies. Nutrients. 2020 Sep 19;12(9):2866. doi: 10.3390/nu12092866.

  PMID: 32961712 BACKGROUND

• Harvey N, Dennison E, Cooper C. Osteoporosis: a lifecourse approach. J Bone Miner Res. 2014 Sep;29(9):1917-25. doi: 10.1002/jbmr.2286.

  PMID: 24861883 BACKGROUND

• Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008 Jul 3;359(1):61-73. doi: 10.1056/NEJMra0708473. No abstract available.

  PMID: 18596274 BACKGROUND

• Lillycrop K, Murray R, Cheong C, Teh AL, Clarke-Harris R, Barton S, Costello P, Garratt E, Cook E, Titcombe P, Shunmuganathan B, Liew SJ, Chua YC, Lin X, Wu Y, Burdge GC, Cooper C, Inskip HM, Karnani N, Hopkins JC, Childs CE, Chavez CP, Calder PC, Yap F, Lee YS, Chong YS, Melton PE, Beilin L, Huang RC, Gluckman PD, Harvey N, Hanson MA, Holbrook JD; EpiGen Consortium; Godfrey KM. ANRIL Promoter DNA Methylation: A Perinatal Marker for Later Adiposity. EBioMedicine. 2017 May;19:60-72. doi: 10.1016/j.ebiom.2017.03.037. Epub 2017 Apr 26.

  PMID: 28473239 BACKGROUND

• Godfrey KM, Costello PM, Lillycrop KA. The developmental environment, epigenetic biomarkers and long-term health. J Dev Orig Health Dis. 2015 Oct;6(5):399-406. doi: 10.1017/S204017441500121X. Epub 2015 May 28.

  PMID: 26017068 BACKGROUND

• Block T, El-Osta A. Epigenetic programming, early life nutrition and the risk of metabolic disease. Atherosclerosis. 2017 Nov;266:31-40. doi: 10.1016/j.atherosclerosis.2017.09.003. Epub 2017 Sep 5.

  PMID: 28950165 BACKGROUND

• Godfrey KM, Costello PM, Lillycrop KA. Development, Epigenetics and Metabolic Programming. Nestle Nutr Inst Workshop Ser. 2016;85:71-80. doi: 10.1159/000439488. Epub 2016 Apr 18.

  PMID: 27088334 BACKGROUND

• Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies JL, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, Hanson MA. Epigenetic gene promoter methylation at birth is associated with child's later adiposity. Diabetes. 2011 May;60(5):1528-34. doi: 10.2337/db10-0979. Epub 2011 Apr 6.

  PMID: 21471513 BACKGROUND

• Godfrey KM, Lillycrop KA, Burdge GC, Gluckman PD, Hanson MA. Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease. Pediatr Res. 2007 May;61(5 Pt 2):5R-10R. doi: 10.1203/pdr.0b013e318045bedb.

  PMID: 17413851 BACKGROUND

• Hollegaard MV, Grauholm J, Norgaard-Pedersen B, Hougaard DM. DNA methylome profiling using neonatal dried blood spot samples: a proof-of-principle study. Mol Genet Metab. 2013 Apr;108(4):225-31. doi: 10.1016/j.ymgme.2013.01.016. Epub 2013 Feb 1.

  PMID: 23422032 BACKGROUND

• Handel MN, Jorgensen NR, Bybjerg-Grauholm J, Jansen RB, Eiken P, Tofteng CL, Hermann AP, Bach-Mortensen P, Heitmann BL, Rubin KH, Langdahl BL, Vestergaard P, Abrahamsen B. Early life determinants of skeletal maturation, body composition and endocrine health in young adults (EPIPEAK): protocol for a nationwide birth cohort study. BMJ Open. 2025 Oct 23;15(10):e101632. doi: 10.1136/bmjopen-2025-101632.

  PMID: 41130671 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood will be drawn for plasma analyses for endocrine status and biomarkers of bone metabolism (outcomes). Hair samples will be collected for cortisol (outcomes). Already collected neonatal blood samples will be measured for genetic and epigenetic profiles (predictors).

MeSH Terms

Conditions

Osteoporosis; Sarcopenia; Obesity; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Body Weight

Study Officials

• Bo Abrahamsen, MD, PhD

  OPEN, University of Southern Denmark, Odense and Department of Medicine 1, Holbæk Hospital, Holbæk

  STUDY CHAIR

• Katrine H Rubin, MHS, PhD

  OPEN, Department of Clinical Research, University of Southern Denmark and Odense University Hospital

  PRINCIPAL INVESTIGATOR

• Bente Langdahl, MD, PhD

  Department of Clinical Medicine and Department of Endocrinology and Diabetes, Aarhus University

  PRINCIPAL INVESTIGATOR

• Peter Vestergaard, MD, PhD

  Faculty of Medicine, Aalborg University and Department of Endocrinology, Aalborg University Hospital

  PRINCIPAL INVESTIGATOR

• Berit L Heitmann, DMD, PhD

  The Parker Institute, Frederiksberg Hospital, Frederiksberg

  PRINCIPAL INVESTIGATOR

• Mina N Händel, Msc, PhD

  The Parker Institute, Frederiksberg Hospital, Frederiksberg

  PRINCIPAL INVESTIGATOR

• Charlotte L Tofteng, MD, PhD

  Department of CIinical Medicine, Endocrinology, Zealand University Hospital, Køge

  PRINCIPAL INVESTIGATOR

• Pernille Bach-Mortensen, MD, PhD

  Department of Endocrinology, Amager and Hvidovre Hospital, Hvidovre

  PRINCIPAL INVESTIGATOR

• Pernille Hermann, MD, PhD

  Department of Endocrinology, Odense University Hospital, Odense

  PRINCIPAL INVESTIGATOR

• Niklas R Jørgensen, MD, PhD

  Department of Clinical Biochemistry and Centre of Diagnostic Investigation,Rigshospitalet Copenhagen

  PRINCIPAL INVESTIGATOR

• Jonas Bybjerg-Grauholm, MSE

  Danish Center for Neonatal Screening, Statens Serum Institut, Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2024
• First Posted: July 19, 2024
• Study Start: November 11, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2031
• Last Updated: January 10, 2025

Record last verified: 2025-01

Locations

DK (9)