Background: Children and adolescents have high bone turnover marker (BTM) levels due to high skeletal growth velocity and rapid bone turnover. Paediatric normative values are vital for differentiating between normal and abnormal bone turnover, investigating skeletal diseases in children or monitoring responses to bone treatment. We aimed to establish sex- and age-specific BTM reference intervals in healthy children and adolescents and to assess the variation by anthropometric variables, pubertal status and fat percentage (fat%) on urinary (uOC), serum total (sOC) and carboxylated (cOC) osteocalcin values.
Methods: Clinical characteristics, serum and urinary samples, and fat% (DEXA) data from a cross-sectional cohort were available for a total of 175 healthy, 7-18 year old Finnish children and adolescents with normal bone mineral density (Z score between -2 and +2); 107 girls (mean age 13.8) and 68 boys (mean age 12.5). Two-site immunoassays were used to measure sOC, cOC and creatinine-adjusted uOC mid-molecular fragments.
Results: BTMs increased with puberty, correlated with pubertal growth which occurred and declined earlier in girls (after 11 years) vs. boys (14 years). The mean values and percentiles for total sOC, cOC, and uOC for sex-specific age categories and pubertal stages (pre-, mid- and post-puberty) were established. There was limited correlation between sOC and uOC, especially in younger boys, driven by age categories with progressively improving correlation with increasing age. The determinants for sOC, cOC and uOC varied; the uOC being most robust while age, height, weight, vitamin D status and PTH influenced sOC and cOC. Body fat% had no influence on sOC, cOC or uOC.
Conclusion: In young children (age < 11) circulating OC reflects more growth status than bone metabolism. Thus its validity, similar to other BTMs, as a determinant of healthy bone status is limited.
Disclosure: The authors declared no competing interests. Päivi M Paldánius is a shareholder and employee of Novartis Pharmaceuticals. This study was supported by grants from the Finnish Pediatric Research Foundation, the Sigrid Juselius Foundation, the Folkhälsan Research Foundation, the Academy of Finland and the Helsinki University Hospital Research Funds.