Abstract
Children and adolescents have high bone turnover marker (BTM) levels due to high growth velocity and rapid bone turnover. Pediatric normative values for BTMs reflecting bone formation and resorption are vital for timely assessment of healthy bone turnover, investigating skeletal diseases, or monitoring treatment outcomes. Optimally, clinically feasible measurement protocols for BTMs would be validated and measurable in both urine and serum. We aimed to (a) establish sex- and age-specific reference intervals for urinary and serum total and carboxylated osteocalcin (OC) in 7- to 19-year-old healthy Finnish children and adolescents (n = 172), (b) validate these against standardized serum and urinary BTMs, and (c) assess the impact of anthropometry, pubertal status, and body composition on the OC values. All OC values in addition to other BTMs increased with puberty and correlated with pubertal growth, which occurred and declined earlier in girls than in boys. The mean serum total and carboxylated OC and urinary OC values and percentiles for sex-specific age categories and pubertal stages were established. Correlation between serum and urinary OC was weak, especially in younger boys, but improved with increasing age. The independent determinants for OC varied, the urinary OC being the most robust while age, height, weight, and plasma parathyroid hormone (PTH) influenced serum total and carboxylated OC values. Body composition parameters had no influence on any of the OC values. In children and adolescents, circulating and urinary OC reflect more accurately growth status than bone mineral density (BMD) or body composition. Thus, validity of OC, similar to other BTMs, as a single marker of bone turnover, remains limited. Yet, serum and urinary OC similarly to other BTMs provide a valuable supplementary tool when assessing longitudinal changes in bone health with repeat measurements, in combination with other clinically relevant parameters.
Highlights
Normal pediatric reference ranges for bone turnover markers (BTMs), reflecting bone formation and resorption, are a prerequisite for timely assessment of metabolic bone disorders and monitoring of response to therapy or disease progression [1]
Participation in this study, which was designed to assess the relationship between Vitamin D and aspects of bone health, was voluntary and invitation letters were given by the teachers to the pupils and their parents
All those willing to participate were included. This current study included a total of 172 subjects from the original cohort, 106 girls and 66 boys, who presented with normal bone mineral density (BMD), i.e., whole body (WB) BMD Z-score between −2.0 and +2.0, and had data for clinical characteristics, including puberty stage and at least sufficient serum samples for OC analysis
Summary
Normal pediatric reference ranges for bone turnover markers (BTMs), reflecting bone formation and resorption, are a prerequisite for timely assessment of metabolic bone disorders and monitoring of response to therapy or disease progression [1]. The subsequent increase in BTMs should coincide with the pubertal growth spurt while increased variation in BTM levels demonstrates correlation with growth velocity. This fluctuation surges during pubertal years due to considerable changes in absolute measured concentrations of both formation and resorption markers with age [10,11,12]. Any longitudinal measurement to distinguish between normal and abnormal bone turnover in a growing child necessitates comparison against pediatric normative reference curves
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