Reference values for cross-linked C-telopeptide of type 1 collagen and pro-collagen type1 N-terminal propeptide in children and adolescents: Results from the Canadian Health Measures Survey

Introduction: Procollagen type 1 N-propeptide (P1NP) and carboxy-terminal telopeptide of type 1 collagen (CTX) are bone turnover markers for diagnosing and monitoring metabolic bone diseases and growth disorders. This study aimed to establish representative reference ranges for CTX and P1NP, as measured with an IDS-iSYS system, in Canadian children and adolescents. Methods: Serum levels of CTX and P1NP were measured in participants of the Canadian Health Measures Survey, a nationally representative study. The LMSP method, using Box–Cox power exponential distribution to accommodate kurtosis in the distribution, was employed to estimate age- and sex-specific reference curves and parameters for Z-score calculation. In addition, non-parametric analysis was utilized to establish 95 % reference intervals for two-year age brackets. Reference curves were generated based on the cohort aged 6 to 27 years, and reference intervals were calculated based on the age range 6 to 20 years. Results: The cohort included 1840 participants for CTX (51.6 % males) and 4069 for P1NP (50.5 % males). Reference ranges for age and sex showed the expected patterns with peaks at the age of puberty (earlier in females than males). As the aim of the study was to present representative reference data, results were provided based on the entire study population regardless of ethnicity and health status. Results obtained in the most common ethnicity (‘white’) and in the subgroup of ‘healthy white’ study participants were similar. Conclusion: This study establishes age- and sex-specific reference values for serum concentrations of CTX and P1NP in Canadian individuals from 6 to 20 years of age. These results have the potential to enhance diagnostic accuracy and inform bone health clinical decision-making for this population.