Sarah Seberg Diemar1, Louise Lylloff2, Maria Sode Rønne3, Line Tang Møllehave4, Malene Heidemann3, Betina Heinsbæk Thuesen4, Jesper Johannesen5, Anders J Schou3, Steffen Husby6, Niels Wedderkopp7, Christian Mølgaard8, Niklas Rye Jørgensen9. 1. Department of Clinical Biochemistry, Rigshospitalet, Valdemar Hansens Vej 1-23, 2600 Glostrup, Denmark. Electronic address: sarah.seberg.diemar@regionh.dk. 2. Department of Clinical Biochemistry, Regional Hospital West Jutland, Gl. Landevej 61, 7400 Herning, Denmark. 3. Hans Christian Andersen Children's Hospital, Odense University Hospital, Kløvervænget 23C, 5000 Odense, Denmark. 4. Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark. 5. Department of Children and Adolescents, Copenhagen University Hospital Herlev, Borgmester Ib Juuls Vej 1, 2730 Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark. 6. Hans Christian Andersen Children's Hospital, Odense University Hospital, Kløvervænget 23C, 5000 Odense, Denmark; Clinical Institute, University of Southern Denmark, Campusvej 55, 5000 Odense, Denmark. 7. Research Unit for Exercise Epidemiology, Centre of Research in Childhood Health, Department of Regional Health Research, University of Southern Denmark, Campusvej 55, 5000 Odense, Denmark; Department of Orthopaedics, Hospital of Southwest Jutland, Finsensgade 35, 6700 Esbjerg, Denmark. 8. Hans Christian Andersen Children's Hospital, Odense University Hospital, Kløvervænget 23C, 5000 Odense, Denmark; Clinical Institute, University of Southern Denmark, Campusvej 55, 5000 Odense, Denmark; Department of Nutrition, Exercise and Sports, University of Copenhagen, Nørre Allé 51, 2200 Copenhagen, Denmark. 9. Department of Clinical Biochemistry, Rigshospitalet, Valdemar Hansens Vej 1-23, 2600 Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark.
Abstract
PURPOSE: Bone turnover markers (BTM) are gaining ground in clinical practice but to fully use their potential there is a need for establishing valid reference intervals (RI). Consequently, the purpose of the study was to establish general RI as well as suggested clinical RI for carboxy-terminal cross-linked telopeptide of type I collagen (β-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP) in children and adolescents. METHOD: BTM were measured on Danish children and adolescents participating in the CHAMPS-study DK. A total of 762 participants were included (8-18 years, 50.4% girls) contributing a total of 1410 study visits. The RI was calculated based on 2-years age spans. Participants with biochemical signs of metabolic bone disease were excluded. RESULTS: The differences in RI between age groups clearly reflect changes in growth with an initial increase in BTM, greatest in boys, and a subsequent decrease most pronounced in girls. β-CTX and PINP are markers most affected by these changes, compared to OC and bone ALP. The suggested clinical 95% RI included participants with vitamin D insufficiency but no biochemical signs of metabolic bone disease which did not markedly alter the RI. CONCLUSION: RI for β-CTX, PINP, OC and bone ALP varies with age and sex. β-CTX and PINP which reflect bone resorption and formation processes are mostly affected by these changes. We suggest a set of clinically applicable 95% RI for the four BTM to heighten the usefulness and generalizability of the RI.
PURPOSE: Bone turnover markers (BTM) are gaining ground in clinical practice but to fully use their potential there is a need for establishing valid reference intervals (RI). Consequently, the purpose of the study was to establish general RI as well as suggested clinical RI for carboxy-terminal cross-linked telopeptide of type I collagen (β-CTX), pro-collagen type I N-terminal propeptide (PINP), osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP) in children and adolescents. METHOD: BTM were measured on Danish children and adolescents participating in the CHAMPS-study DK. A total of 762 participants were included (8-18 years, 50.4% girls) contributing a total of 1410 study visits. The RI was calculated based on 2-years age spans. Participants with biochemical signs of metabolic bone disease were excluded. RESULTS: The differences in RI between age groups clearly reflect changes in growth with an initial increase in BTM, greatest in boys, and a subsequent decrease most pronounced in girls. β-CTX and PINP are markers most affected by these changes, compared to OC and bone ALP. The suggested clinical 95% RI included participants with vitamin Dinsufficiency but no biochemical signs of metabolic bone disease which did not markedly alter the RI. CONCLUSION: RI for β-CTX, PINP, OC and bone ALP varies with age and sex. β-CTX and PINP which reflect bone resorption and formation processes are mostly affected by these changes. We suggest a set of clinically applicable 95% RI for the four BTM to heighten the usefulness and generalizability of the RI.
Keywords:
Bone turnover markers; Carboxy-terminal cross-linked telopeptide of type I collagen; Children; Osteocalcin; Pro-collagen type I N-terminal propeptide; Reference interval
Authors: Jakob Rempe; Björn E Rosengren; Lars Jehpsson; Per Swärd; Magnus Dencker; Magnus K Karlsson Journal: Front Physiol Date: 2022-04-07 Impact factor: 4.566