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We report pediatric age- and sex-specific 95% reference intervals for procollagen type I C-terminal propeptide (PICP), the cross-linked C-terminal telopeptide of type I collagen (ICTP), and procollagen type III N-terminal propeptide (P3NP), measured in plasma from 302 schoolchildren (156 boys, 146 girls) ages 4 ‐19 years. All three markers displayed a significant variation with age (ANOVA P

During childhood growth, bone undergoes extensive modeling involving separate osteoblastic and osteoclastic processes. Markers of bone formation and resorption circulate at higher concentrations in children than in adults, parallel the childhood growth curve, and correlate with height velocity (1)(2). Not only do these markers provide insight into the pathophysiology of bone turnover during growth, but they also give an early surrogate measure of its response to treatment. The markers of bone formation are all measured in plasma, and their use as markers of growth and bone formation in children is well established (1)(2). However, most markers of bone resorption have traditionally been measured in urine. In infants and children, the practical difficulties associated with urine collection are compounded by marked circadian variation and high within-individual biological variation in urinary markers. Results are generally expressed in relation to creatinine, itself subject to considerable biological variation and changing with age as muscle mass increases. There is therefore a need for a sensitive and specific marker of bone resorption that can be measured in plasma and directly compared with markers of bone formation measured in the same sample. Serum CrossLapsTM is a promising new marker for bone resorption (3), but its application in children has been hampered by lack of suitable reference data. Here we report age- and sex-related reference data for serum CrossLaps in children from birth to 19 years of age. Surplus plasma remaining after routine biochemical tests had been completed was retrieved from 59 neonates, infants, and children (37 males) who presented with various minor conditions that were considered not to have either a short- or long-term effect on growth. Children with systemic disease or intercurrent infections were specifically excluded. Samples were fully anonymized and stored at −70 °C until analysis. We analyzed stored plasma …

Type I collagen is the predominant collagen in bone and soft tissue. The rate of synthesis of type I collagen can be assessed by measuring plasma concentrations of the C-terminal (PICP) and N-terminal (PINP) propeptides released during extracellular processing of its procollagen precursor (1). However, the propeptides have different clearance routes, PICP being cleared by mannose receptors (2) and PINP by scavenger receptors (3) in liver endothelial cells. Clearance of PICP may be modulated by the hormonal milieu, whereas scavenger receptors apparently are not influenced by hormones (4)(5). Within-individual biological variability is similar for PICP and PINP (6), but PINP displays greater dynamic changes than PICP in response to disease and interventions (7)(8). PINP has been shown to be a useful marker of bone formation in adults (7)(8)(9)(10)(11)(12). During childhood growth, markers of bone turnover circulate at higher concentrations than in adults and correlate with height velocity (13)(14). These markers have been used to investigate bone dynamics in childhood disorders of bone and growth (13)(14)(15), but a lack of appropriate reference data has hampered use of PINP in pediatrics. Here, we report age- and sex-related reference data for plasma PINP in children from birth to 19 years of age. We also investigated the relationship between PINP and PICP to determine whether their relative clearance rates differ through childhood and adolescence. Surplus plasma remaining after routine biochemical tests had been completed was retrieved for 43 neonates, infants, and children (23 males) younger than 5 years, who presented with various minor conditions that were considered not to have either a short- or long-term effect on growth; children with systemic disease or concurrent infections were excluded. Samples were deidentified and stored at …