Serum CrossLaps: Pediatric Reference Intervals from Birth to 19 Years of Age

Abstract

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 …