TY - JOUR

T1 - Reference intervals in Danish children and adolescents for bone turnover markers 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)

AU - Diemar, Sarah Seberg

AU - Lylloff, Louise

AU - Rønne, Maria Sode

AU - Møllehave, Line Tang

AU - Heidemann, Malene

AU - Thuesen, Betina Heinsbæk

AU - Johannesen, Jesper

AU - Schou, Anders J

AU - Husby, Steffen

AU - Wedderkopp, Niels

AU - Mølgaard, Christian

AU - Jørgensen, Niklas Rye

N1 - CURIS 2021 NEXS 074 (In Progress / May 2021)

PY - 2021

Y1 - 2021

N2 - 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 were 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.

AB - 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 were 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.

KW - Faculty of Science

KW - Bone turnover markers

KW - Carboxy-terminal cross-linked telopeptide of type I collagen

KW - Pro-collagen type I N-terminal propeptide

KW - Osteocalcin

KW - Adolescents

KW - Children

U2 - 10.1016/j.bone.2021.115879

DO - 10.1016/j.bone.2021.115879

M3 - Journal article

C2 - 33561588

VL - 146

JO - Bone

JF - Bone

SN - 8756-3282

M1 - 115879

ER -