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Collagen X Marker Levels are Decreased in Individuals with Achondroplasia

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Abstract

Collagen X marker (CXM) is a degradation fragment of collagen type X. It is a real-time biomarker of height velocity with established norms. Plasma C-type natriuretic peptide (CNP) and NTproCNP levels have also been found to correlate with growth velocity in the general population and are elevated in individuals with achondroplasia compared with age- and sex-matched controls. Collagen X marker levels in people with fibroblast growth factor receptor 3 (FGFR3)-opathies have never been systematically measured. The objective of this study was to measure CXM in a population of dwarfism caused by FGFR3-opathies. Using the same cohort in which CNP and NTproCNP levels were previously measured, archived serum aliquots from 63 children with achondroplasia, six with hypochondroplasia, and two with thanatophoric dysplasia had CXM concentrations measured. Results were plotted against age- and sex-specific norms, and standard deviation scores were plotted for comparison between clinical diagnoses. CXM levels were significantly decreased (p < 0.0001) in children with achondroplasia compared with age- and sex-matched controls. Temporal patterns of change in CXM levels were sex-dependent. As the FGFR3 pathway was more constitutively active, CXM levels decreased. New tools are emerging to study impact of skeletal dysplasia on growth plate regulation and function.

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Data Availability

Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all the families who participated in this research. This new insight into biomarkers in FGFR3-opathies would not be possible without their contribution. This work was supported in part by the Growing Stronger Foundation, developmental funds from Nemours, and Shriners Hospital research grant. Work was additionally funded by NIH (Grant R21AR065657 WAH), and the Bill and Melinda Gates Foundation (Grant OPP1106834 WAH).

Funding

This work was supported in part by the Growing Stronger Foundation, developmental funds from Nemours, and Shriners Hospital research grant. Work was additionally funded by NIH (Grant R21AR065657 WAH), and the Bill and Melinda Gates Foundation (Grant OPP1106834 WAH).

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Authors and Affiliations

  1. Nemours Children’s Hospital, Delaware, 1600 Rockland Road, Wilmington, DE, 19803, USA

    Ricki S. Carroll, Angela L. Duker, William G. Mackenzie, Colleen P. Ditro, Cassondra J. Brown & Michael B. Bober

  2. Thomas Jefferson University, Philadelphia, PA, USA

    Ricki S. Carroll, William G. Mackenzie, David A. O’Connell & Michael B. Bober

  3. Nemours Children’s Hospital, Jacksonville, Jacksonville, FL, USA

    Robert C. Olney

  4. Shriners Hospital for Children, Portland, OR, USA

    Ryan F. Coghlan, William A. Horton & Brian Johnstone

  5. Oregon Health & Science University, Portland, OR, USA

    William A. Horton & Brian Johnstone

  6. University of Otago, Christchurch, New Zealand

    Eric A. Espiner & Timothy C. R. Prickett

Authors
  1. Ricki S. Carroll
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  2. Robert C. Olney
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  3. Angela L. Duker
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  4. Ryan F. Coghlan
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  5. William G. Mackenzie
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  6. Colleen P. Ditro
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  7. Cassondra J. Brown
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  8. David A. O’Connell
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  9. William A. Horton
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  10. Brian Johnstone
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  11. Eric A. Espiner
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  12. Timothy C. R. Prickett
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  13. Michael B. Bober
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Contributions

RSC guarantor, data acquisition, interpretation, writing, RCO study design, data analysis, interpretation, writing, ALD data acquisition, interpretation, writing, RFC data acquisition, WGM study design, data acquisition, CPD data acquisition, CJB data acquisition, DAC data analysis, interpretation, WAH data acquisition, data analysis, BJ data acquisition, data analysis, EAE study design, interpretation, writing, TCRP study design, interpretation, writing, MBB study design, data acquisition, data analysis, interpretation, writing.

Corresponding author

Correspondence to Ricki S. Carroll.

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Conflicts of interest

CJB, ALD, BJ, DAO’C, RCO have no disclosure information relevant to this work. CPD received lecture fees from BioMarin. RFC & WAH are inventors on a patent entitled, “Type X collagen assay and methods of use thereof,” filed by Shriners Hospital for Children. EAE & TCRP have filed a patent entitled, “Assessment of skeletal growth using measurements of NT-CNP peptides.” MBB, RFC, WAH, have consulted for TherAchon/Pfizer and QED. MBB, RFC, EAE, WAH, WGM have consulted for BioMarin. WAH has consulted for Relay Therapeutics.

MBB, WAH have consulted for Ascendis. MBB and RSC receive research funding from Biomarin, TherAchon/Pfizer, Ascendis, and QED.

Ethical Approval

The original study was approved by the Nemours Florida Institutional Review Board. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed Consent

All children had written parental permission obtained. Parental permission forms included authorization to archive and use blood samples for future research studies.

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Carroll, R.S., Olney, R.C., Duker, A.L. et al. Collagen X Marker Levels are Decreased in Individuals with Achondroplasia. Calcif Tissue Int 111, 66–72 (2022). https://doi.org/10.1007/s00223-022-00966-0

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  • DOI: https://doi.org/10.1007/s00223-022-00966-0

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