Objective: A major prerequisite for using bone turnover markers (BTM) in children and adolescents is sex- and age-specific reference curves enabling calculation of Z-scores. Consequently, the purpose of this study was to establish sex- and age-specific reference curves for BTM and to examine the association between BTM Z-scores and change in total body less head bone mineral density (TBLH BMD).

Method: BTM were measured in Danish children and adolescents participating in the CHAMPS-study DK. 758 participants aged 8–17 years were included (50.3 % girls) contributing to a total of 1378 serum samples for determination of bone-specific alkaline phosphatase (bone ALP), carboxy-terminal cross-linked telopeptide of type I collagen (β-CTX), osteocalcin (OC) and pro-collagen type I N-terminal propeptide (PINP). Reference curves for all four BTM were developed using generalized additive models for location, scale and shape. The association between BTM Z-score and change in TBLH BMD was assessed in 523 participants.

Results: Reference curves for bone ALP, β-CTX, OC and PINP enabling calculation of Z-scores were constructed. BTM levels peak between the age of 11 to 12 years in girls and 13 to 14 years in boys, corresponding to the age at peak height velocity. BTM Z-scores were positively associated with change in TBLH BMD Z-score in regression analyses (p < 0.01), but only explained a small portion of the variance in TBLH BMD Z-score change (R² between 0.022 and 0.034).

Conclusion: BTM in children and adolescents vary widely with age and sex, favoring the use of Z-scores. Baseline BTM Z-scores are associated to the change in TBLH BMD Z-score.