Abstract
Summary
The aim of this study was to assess the relationships between both a marker of bone formation and a marker of bone turnover and age, sex, and pubertal stage in a group (n = 439) of healthy children and adolescents. These reference data should be instrumental in interpretation of results.
Introduction
The skeletal system has high metabolic activity. In children, bone markers may be useful in diagnostics and treatment management of skeletal diseases but there could be difficulties with interpretation of results. Compared with adults, children have elevated bone marker levels due to high skeletal growth velocity and rapid bone turnover. Thus, valid age- and sex-specific reference data should be obtained for each pediatric population living in a particular climate and with a similar lifestyle. The aim of this study was to assess the relationships between both a marker of bone formation (procollagen type I N-terminal propeptide [PINP]) and a marker of bone turnover (osteocalcin [OC]) and age, sex, and pubertal stage in a group of healthy children and adolescents.
Methods
Four hundred thirty-nine healthy Caucasian children participated. Their height, weight, and pubertal stage were recorded. Fasting PINP and OC were measured using a morning blood sample.
Results
The highest levels of PINP were observed during the first year of life. There is no OC postnatal peak, but levels are higher than the adult reference interval throughout childhood. OC peaks with the pubertal growth spurt at second–third Tanner stage of breast development in girls and at second–third Tanner stage of genital development in boys. PINP peaks during second–third Tanner stage of breast development in girls and at third Tanner stage of genital development in boys.
Conclusion
This study provides reference data for OC and PINP in healthy Caucasian children from a Central European population.
Similar content being viewed by others
References
van Coeverden SCCM, Netelenbos JC, de Ridder CM, Roos JC, Popp-Snijders C, Delemarre-van de Waal HA (2002) Bone metabolism markers and bone mass in healthy pubertal boys and girls. Clin Endocrinol 57:107–116
Szulc P, Seeman E, Delmas PD (2000) Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 11:281–294
Yang L, Grey V (2006) Pediatric reference intervals for bone markers. Clin Biochem 39:561–568
Huang Y, Eapen E, Steele S, Grey V (2011) Establishment of reference intervals for bone markers in children and adolescents. Clin Biochem 44(10–11):771–778
Eastell R, Mallinak N, Weiss S, Ettinger M, Pettinger M, Cain D, Fressland K, Chesnut C 3rd (2000) Biological variability of serum and urinary N-telopeptides of type I collagen in postmenopausal women. J Bone Miner Res 15(3):594–598
Schonau E, Rauch F (1997) Markers of bone and collagen metabolism problems and perspectives in paediatrics. Horm Res 48(Suppl 5):50–59
van der Sluis IM, Hop WC, van Leeuwen JPTM, Pols HAP, de Muinck Keizer-Schrama SM (2002) A cross-sectional study on biochemical parameters of bone turnover and vitamin D metabolites in healthy Dutch children and young adults. Horm Res 57:170–179
Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, Kanis JA (2011) International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med 49(8):1271–1274
Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44(235):291–303
Marshall WA, Tanner JM (1970) Variations in pattern of pubertal changes in boys. Arch Dis Child 45(239):13–23
Saggese G, Baroncelli GI, Bertelloni S, Cinquanta L, DiNero G (1994) Twenty four-hour osteocalcin, carboxyterminal propeptide of type I procollagen, and aminoterminal propeptide of type III procollagen rhythms in normal and growth-retarded children. Pediatr Res 35:409–415
Schmidt-Gayk H, Spanuth E, Kötting J, Bartl R, Felsenberg D, Pfeilschifter J, Raue F, Roth HJ (2004) Performance evaluation of automated assays for beta-crosslaps, N-Mid-osteocalcin and intact parathyroid hormone (BIOROSE Multicenter Study). Clin Chem Lab Med 42/1/:90–95
Manjón Llorente G, Fernández-Espuelas C, González López JM, Ruiz-Echarri MP, Baldellou Vázquez A (2004) Normal values of bone turnover markers in childhood. [Article in Spanish] An Pediatr (Barc) 60(4):330–336
Rauchenzauner M, Schmid A, Heinz-Erian P, Kapelari K, Falkemsammer G, Griesmacher A, Finkenstedt G, Högler W (2007) Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years. J Clin Endocrinol Metab 92:443–449
Gilsanz V, Chalfant J, Kalkwarf H, Zemel B, Lappe J, Oberfield S, Shepherd J, Wren T, Winer K (2011) Age at onset of puberty predicts bone mass in young adulthood. J Pediatr 158(1):52–57
Akesson K (1995) Biochemical markers of bone turnover. A review. Act Orthop Scand 66:376–386
Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G (1996) Increased bone formation in osteocalcin-deficient mice. Nature 382:448–452
Henck C, Skjaerbaek C, Wolthers OD (1998) Diurnal rhytm of serum osteocalcin in normal children. Acta Paediatr 87:930–932
Cioffi M, Molinari AM, Gazzero P, Di Finizio B, Fratta M, Deufemia A, Puca GA (1997) Serum osteocalcin in 1634 healthy children. Clin Chem 43(3):543–545
Sen AT, Derman O, Kinik E (2000) The relationship between osteocalcin levels and sexual stages of puberty in male children. Turk J Pediatr 42(4):281–285
Yilmaz D, Betül E, Bilgin E, Gümüşer G, Onur E, Pinar ED (2005) Bone mineral density in girls and boys at different pubertal stages: relation with gonadal steroids, bone formation markers, and growth parameters. J Bone Miner Metab 23:476–482
Kirmani S, Atkinson EJ, Melton LJ 3rd, Riggs BL, Amin S, Khosla S (2011) Relationship of testosterone and osteocalcin levels during growth. J Bone Miner Res 26:2212–2216
Brandt J, Frederiksen JK, Jensen CH, Teisner B (2001) The N- and C-terminal propeptides of human procollagen type 1 (P1NP and P1CP): molecular heterogeneity and assay technology. In: Eastell R, Baumann M, Hoyle NR, Wieczorek L (eds) Bone markers—biochemical and clinical perspectives. Dunitz, London, pp 73–81
Wolthers OD, Heuck C, Heickendorff L (2001) Diurnal variations in serum and urine markers of type I and type III collagen turnover in children. Clin Chem 47(9):1721–1722
Tähtelä R, Turpeinen M, Sorva R, Karonen SL (1997) The aminoterminal propeptide of type I procollagen: evaluation of a commercial radioimmunoassay kit and values in healthy subjects. Clin Biochem 30(1):35–40
Crofton PM, Evans N, Taylor MRH, Holland CV (2004) Procollagen type I amino-terminal propeptide: pediatric reference data and relationship with procollagen type I carboxyl-terminal propeptide. Clin Chem 50/11/:2173–2176
Jürimäe J, Pomerants T, Tillmann V, Jürimäe T (2009) Bone metabolism markers and ghrelin in boys at different stages of sexual maturity. Acta Pediatr 98(5):892–896
Blumsohn A, Naylor KE, Timm W, Eagleton AC, Hannon RA, Eastell R (2003) Absence of marked seasonal change in bone turnover: a longitudinal and multicenter cross-sectional study. J Bone Miner Res 18:1274–1281
Munday K, Ginty F, Fulford A, Bates CJ (2006) Relationships between biochemical bone turnover markers, season, and inflammatory status indices in prepubertal Gambian boys. Calcif Tissue Int 79(1):15–21
Clowes JA, Hannon RA, Yap TS, Hoyle NR, Blumsohn A, Eastell R (2002) Effect of feeding on bone turnover markers and its impact on biological variability of measurements. Bone 30 /6/:886–890
Schou AJ, Heuck C, Wolthers OD (2003) Vitamin D supplementation to healthy children does not affect serum osteocalcin or markers of type I collagen turnover. Acta Paediatr 92(7):797–801
Hill KM, Laing EM, Hausman DB, Acton A, Martin BR, McCabe GP, Weaver CM, Lewis RD, Peacock M (2012) Bone turnover is not influenced by serum 25-hydroxyvitamin D in pubertal healthy black and white children. Bone 51(4):795–799
Acknowledgments
This study is supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00179906. The author thanks Roche Diagnostics GmbH for providing the PINP and osteocalcin assays used in this study. The author is grateful to Ian McColl MD, Ph.D. for the assistance with the manuscript. The author is grateful to Dr. Eva Cermakova for the statistical evaluation.
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bayer, M. Reference values of osteocalcin and procollagen type I N-propeptide plasma levels in a healthy Central European population aged 0–18 years. Osteoporos Int 25, 729–736 (2014). https://doi.org/10.1007/s00198-013-2485-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-013-2485-4