Biomarker Longitudinal Idiopathic Scoliosis Study: Predicting Growth in Idiopathic Scoliosis

Background: Growth has been theorized as one of the main risk factors for idiopathic scoliosis (IS) progression. Determining the amount and timing of growth is surprisingly challenging. Radiographic measures of skeletal maturity do not provide insight into the amount that individuals will grow. In addition, anthropometrics do not differentiate between early versus late growers. Biological measures have historically been nonspecific for growth, however, Collagen X Biomarker (CXM) is a direct measure of endochondral ossification and longitudinal bone growth. The aims of this study were (1) to determine the best anthropometric measure of growth in patients with idiopathic scoliosis (IS) and (2) to determine the best surrogate measure of height velocity. Methods: A prospective IRB-approved multicenter study of IS was followed every 6 months to measure anthropometrics and assess radiographic measures of skeletal maturity. Anthropometrics were assessed to determine linear measures of growth potential. Radiographs of the spine and hands were assessed for major curve magnitude (Cobb), Risser Sign (RS), Greulich and Pyle bone age (BA), Sanders Maturity Score (SMS), and Thumb Ossification Composite Index (TOCI). CXM levels were assessed with serial dried blood spots (DBS) collected on 3 consecutive days, every 1 to 2 months, based on SMS. Results: Two hundred fifty-four patients (193 female/61 male) with IS (Cobb ≥20) were recruited between 2018 and 2024. Average age at 12.9 years (range: 7 to 17), with the mean time of involvement 12 months (range: 1 to 63 mo). Standing height and height velocity (HtV) determined by standing height had the highest correlations with all other measures of length and length changes. CXM, SMS, RS, BA, TOCI, and age in months were all significant independent predictors of HtV. CXM accounted for the largest percentage of the explained variance in HtV at 50%. Multiple regression analysis was performed examining each measure independently and with the biomarker, and showed that the combination of CXM and RS explained the greatest amount of variance in height velocity at 55%. Conclusion: While there continues to be much that we do not know with regards to patient-specific measures of growth and growth potential, this study found that absolute height was the best measure of growth in adolescents with IS who are braced and CXM is the best measure of growth potential. Further study using advanced analytics will determine whether CXM in combination with other radiographic measures provides enhanced information from which to make clinical decisions regarding bracing and surgical intervention.