Reference intervals in Danish children and adolescents for bone turnover markers carboxy-terminal cross-linked telopeptide of type I collagen (β-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP)

Purpose: Bone turnover markers (BTM) are gaining ground in clinical practice but to fully use their potential there is a need for establishing valid reference intervals (RI). Consequently, the purpose of the study was to establish general RI as well as suggested clinical RI for carboxy-terminal cross-linked telopeptide of type I collagen (beta-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP) in children and adolescents. Method: BTM were measured on Danish children and adolescents participating in the CHAMPS-study DK. A total of 762 participants were included (8-18 years, 50.4% girls) contributing a total of 1410 study visits. The RI was calculated based on 2-years age spans. Participants with biochemical signs of metabolic bone disease were excluded. Results: The differences in RI between age groups clearly reflect changes in growth with an initial increase in BTM, greatest in boys, and a subsequent decrease most pronounced in girls. beta-CTX and PINP are markers most affected by these changes, compared to OC and bone ALP. The suggested clinical 95% RI included participants with vitamin D insufficiency but no biochemical signs of metabolic bone disease which did not markedly alter the RI. Conclusion: RI for beta-CTX, PINP, OC and bone ALP varies with age and sex. beta-CTX and PINP which reflect bone resorption and formation processes are mostly affected by these changes. We suggest a set of clinically applicable 95% RI for the four BTM to heighten the usefulness and generalizability of the RI.