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)

Abstract 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 (β-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 were 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. β-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 β-CTX, PINP, OC and bone ALP varies with age and sex. β-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.