Correlation of collagen X biomarker (CXM) with peak height velocity and radiographic measures of growth in idiopathic scoliosis

Abstract

Study design

Prospective comparative study.

Objectives

Evaluate the correlation of CXM with established measures of growth. Theoretically higher CXM levels would correlate with rapid longitudinal bone growth and lower levels with growth cessation.

Summary

Assessment of growth status in patients with pediatric spinal deformity is critical. The current gold standards for assessing skeletal maturity are based on radiographic measures and have large standard errors (SE). Type X collagen (COLX) is produced in the growing physis during enchondral ossification. CXM is a COLX breakdown product that can be measured in blood products. CXM, thus, is a direct measure of enchondral ossification.

Methods

IRB-approved prospective study. Q6mo anthropometrics and spine PA biplanar slot scanner images including the hand were assessed for major Cobb, Risser score (RS), triradiate cartilage status (TRC), Greulich and Pyle bone age (BA), and Sanders Score (SS). Serial dried blood spots (DBS) to obtain CXM levels were collected 3 consecutive days Q1–2 months based on SS.

Results

47 idiopathic scoliosis patients, Cobb ≥ 20 were enrolled. Mean enrollment age was 11.8 years (range 7.1–16.6 years). 3103 DBS samples were assayed in quadruplicate. CXM results were highly reproducible with a 3% intraassay coefficient of variation (CV), and 12% interassay CV%. The CXM 3-day average was significantly correlated with BA R = 0.9, p < 0.001, RS R = 0.6, p < 0.001, SS R = 0.7, p < 0.001 and with height R = 0.7, p < 0.001. No patient with a CXM level < 5 ng/ml had remaining growth.

Conclusion

CXM is the first identifiable biomarker specific to longitudinal bone growth. Early results indicate that it is a patient-specific, real-time measure of growth velocity with high correlation to the established anthropometric and radiographic measures of growth. It is predictive of cessation of growth. It is highly reproducible with a low SE. Long-term follow-up is required to determine the ability of CXM to guide clinical decision-making.

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Funding

POSNA Research Startup Grant; Shriners Hospital for Children Directed Research Grant.

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Authors

Contributions

MCW: Conception/design, data acquisition, analysis, interpretation, drafted/revised work, and approved final version. RC: Conception/design, data acquisition, analysis, interpretation, drafted/revised work, and approved final version. SS: Conception/design, data acquisition, analysis, interpretation, drafted/revised work, and approved final version. WH: Conception/design, interpretation, drafted/revised work, and approved final version. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Michelle Cameron Welborn.

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Conflict of interest

Dr. Welborn reports grants from POSNA, grants from Shriners Hospital for Children, during the conduct of the study; personal fees and other from Depuy Synthes, personal fees from Nuvasive, personal fees from Stryker/K2M, outside the submitted work. Mr. Coghlan reports grants from POSNA, grants from Shriners Hospital for Children, during the conduct of the study; personal fees from BioMarin, personal fees from Therachon, personal fees from QED therapeutics outside the submitted work. Dr. Sienko reports grants from POSNA, grants from Shriners Hospital for Children, during the conduct of the study. Dr. Horton reports grants from POSNA, grants from Shriners Hospital for Children, during the conduct of the study; personal fees from Biomarin, personal fees from Ascendis Pharma, personal fees from Theracon, personal fees from QED Therapeutics, personal fees from Relay Therapeutics, outside the submitted work.

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This is a Western IRB approved study.

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Informed consent was obtained from all patients and their parents.

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Welborn, M.C., Coghlan, R., Sienko, S. et al. Correlation of collagen X biomarker (CXM) with peak height velocity and radiographic measures of growth in idiopathic scoliosis. Spine Deform (2021). https://doi.org/10.1007/s43390-020-00262-7

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Keywords

  • Growth
  • Scoliosis
  • Sskeletal maturity
  • Growth potential
  • Collagen X
  • Biomarker