Longitudinal Circulating Procollagen-markers PRO-C1 and PRO-C2 Reflect Pubertal Growth Spurt in Healthy Adolescents

Area of Science:

• Pediatric endocrinology
• Biomarker discovery
• Skeletal development

Background:

• Growth hormone (GH) and IGF-I stimulate epiphyseal growth plate development.
• Serum IGF-I is a standard marker for GH treatment efficacy and safety in children.
• IGF-I provides limited guidance for non-GHD children, necessitating novel biomarkers for linear growth.

Purpose of the Study:

• To evaluate the association between linear growth during pubertal transition and circulating levels of procollagen type I (PRO-C1) and type II (PRO-C2).
• To establish reference intervals for PRO-C1 and PRO-C2 in healthy children and adolescents.
• To assess PRO-C1 and PRO-C2 as potential biomarkers for endogenous and GH-induced linear growth.

Main Methods:

• Analysis of 1700 serum samples from 213 healthy children and adolescents (aged 5-16 years) from the Copenhagen Puberty study.
• Assessment of peak height velocity (PHV), pubertal development, IGF-I, sex-steroids, PRO-C1, and PRO-C2.
• Determination of PRO-C1 and PRO-C2 in short children born small-for-gestational-age (SGA) before and after GH treatment.

Main Results:

• Established age-, sex-, and puberty-related reference intervals for PRO-C1 and PRO-C2.
• PRO-C1 and PRO-C2 levels significantly increased with age and pubertal development.
• PRO-C1 and PRO-C2 peaked at the time of PHV, preceding IGF-I and sex-steroids, and were associated with increased height SDS and velocity.
• GH treatment significantly increased PRO-C1 and PRO-C2 levels in prepubertal children.

Conclusions:

• PRO-C1 and PRO-C2 levels longitudinally track normal and disordered growth patterns.
• PRO-C1 and PRO-C2 are proposed as potential biomarkers for monitoring endogenous and GH-induced linear growth.
• These novel biomarkers may offer improved guidance for clinicians in assessing pediatric growth.