Bone formation and resorption markers at 7 years of age: Relations with growth and bone mineralization

PLoS One. 2019 Aug 22;14(8):e0219423. doi: 10.1371/journal.pone.0219423. eCollection 2019.

Abstract

Purpose: We aimed to describe bone formation and resorption markers in generally healthy prepubertal children using total alkaline phosphatase (tALP), osteocalcin (OC) and β-isomerized C-terminal telopeptides of type I collagen (β-CTx) serum concentrations and to estimate markers' correlations with anthropometric growth (height, weight, body mass index and trajectories of weight gain) as well as bone mineral content (BMC) and areal density (aBMD).

Methods: We assessed 395 7-year-old children from the Generation XXI cohort with tALP, OC and β-CTx concentrations determined from a fasting venous blood sample and BMC/aBMD measured by dual-energy X-ray absorptiometry. Gender-specific reference intervals for tALP, OC and β-CTx in 7-year-old children were established by calculating the 2.5th and 97.5th percentiles. Pearson and partial correlation coefficients (controlling for sex, age, body size and season) between bone markers and growth measures were computed.

Results: tALP increased with height (rpartial controlled for sex = 0.26, 95%CI: 0.17, 0.35), was higher in overweight than in healthy weight children, and in children who gained weight above average during infancy. No correlations were found between OC or β-CTx and growth. In girls, OC was slightly correlated with subtotal BMC (rpartial = 0.22, 95%CI: 0.08, 0.35), subtotal aBMD (rpartial = 0.20, 95%CI: 0.06, 0.33) and lumbar spine aBMD (rpartial = 0.23, 95%CI: 0.09, 0.36). tALP and β-CTx were not correlated with any of the DXA-derived bone measures.

Conclusion: This study contributed to the description of bone turnover at 7 years of age and suggested that bone metabolism markers measured in a single point in time have limited ability to describe anthropometric growth and overall bone status in generally healthy prepubertal children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Alkaline Phosphatase / blood
  • Biomarkers / blood
  • Body Mass Index
  • Bone Density / physiology
  • Bone Remodeling / physiology
  • Bone Resorption / metabolism*
  • Calcification, Physiologic / physiology
  • Child
  • Child Development / physiology
  • Cohort Studies
  • Collagen Type I / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Osteocalcin / blood
  • Osteogenesis / physiology*
  • Peptides / blood
  • Portugal
  • Prospective Studies
  • Reference Values

Substances

  • BGLAP protein, human
  • Biomarkers
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Alkaline Phosphatase

Grants and funding

This study was funded by the European Regional Development Fund (ERDF), through the Operational Programme Competitiveness and Internationalization, and national funding from the Foundation for Science and Technology (FCT) - Portuguese Ministry of Science, Technology and Higher Education - under the projects “STEPACHE - Raízes pediátricas da resposta ampliada à dor: das influências contextuais à estratificação do risco (POCI-01-0145-FEDER-029087; PTDC/SAU-EPI/29087/2017); “BioAdversity: Como a adversidade social na infância condiciona a saúde: A biologia da adversidade social” (POCI-01-0145-FEDER-016838; PTDC/DTP-EPI/1687/2014); “PathMOB: Risco cardiometabólico na infância: desde o início da vida ao fim da infância” (POCI-01-0145-FEDER-016837; PTDC/DTP-EPI/3306/2014) and "Qualidade e dinâmica ósseas na infância: as alterações antropométricas longitudinais fazem diferença?" (EXPL/DTP-EPI/0280/2012). This work was also supported by the Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; UID/DTP/04750/2019), by Administração Regional de Saúde Norte (Regional Department of Ministry of Health) and Fundação Calouste Gulbenkian. This research was also supported by the PhD Grant SFRH/BD/92370/2013 (Teresa Monjardino) co-funded by the FCT and Human Potential Operating Program of the European Social Fund (POPH/FSE Program) and by the FCT Investigator contract IF/01060/2015 (Ana Cristina Santos). This study is also a result of the project “DOCnet: Diabetes & obesity at the crossroads between Oncological and Cardiovascular diseases – a system analysis NETwork towards precision medicine” (NORTE-01-0145-FEDER-000003), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the ERDF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.