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

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. 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.