Skip to main content
Erschienen in: Osteoporosis International 7/2017

28.04.2017 | Original Article

Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population

verfasst von: N. R. Jørgensen, L. T. Møllehave, Y. B. L. Hansen, N. Quardon, L. Lylloff, A. Linneberg

Erschienen in: Osteoporosis International | Ausgabe 7/2017

Einloggen, um Zugang zu erhalten

Abstract

Summary

Bone turnover markers are used for monitoring osteoporosis treatment. Therefore, we evaluated the agreement between different assays for CTX and PINP and established reference intervals in a cohort of 2300 individuals. We found poor agreement between assays and different reference intervals. This highlights the importance of harmonization of the assays.

Introduction

Two reference markers for bone turnover have been proposed: CTX bone resorption and P1NP for bone formation. The purpose of the current study was to establish reference intervals for the two markers in a Danish cohort and to determine the agreement on the two platforms.

Methods

Fasting sera from 2308 individuals (1250 males and 1058 females, age range 24–76 years) participating in the Health2006 study were analyzed for CTX and P1NP using the automated IDS-iSYS analyzer and the automated Cobas e411 analyzer. Participants in anti-osteoporotic treatment were excluded, while subjects on hormonal contraceptives were included.

Results

There was significant disagreement between both the two P1NP assays with a mean difference of −3 μg/L (LoA −19 to 14) (p < 0.001) and the two CTX assays with a mean difference of 13 ng/L (LoA−187 to 214) (p < 0.001). For CTX, there was a systematic bias: at low values, Cobas measured a higher value than iSYS and at higher concentrations, iSYS measured increasingly higher values than Cobas. Based on the results, we propose three reference intervals for each sex: 25–29, 30–39, and 40–80 years for men, and 25–29, >30 (pre-menopausal), and >30 years (post-menopausal) for women.

Conclusions

There is significant disagreement between the IDS-iSYS and Roche Cobas assays for both reference markers. Consequently, the reference intervals for an adult, healthy population are different depending on the analysis method used. Therefore, repeated measurements of patient samples used for monitoring of treatment should be done on the same assay. Moreover, assay-specific reference intervals should be used. Harmonization of assays for BTM is highly warranted.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Naylor K, Eastell R (2012) Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol 8:379–389CrossRefPubMed Naylor K, Eastell R (2012) Bone turnover markers: use in osteoporosis. Nat Rev Rheumatol 8:379–389CrossRefPubMed
2.
Zurück zum Zitat Vasikaran S, Eastell R, Bruyere O, Foldes AJ, Garnero P, Griesmacher A, McClung M, Morris HA, Silverman S, Trenti T, Wahl DA, Cooper C, Kanis JA (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22:391–420CrossRefPubMed Vasikaran S, Eastell R, Bruyere O, Foldes AJ, Garnero P, Griesmacher A, McClung M, Morris HA, Silverman S, Trenti T, Wahl DA, Cooper C, Kanis JA (2011) Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int 22:391–420CrossRefPubMed
3.
Zurück zum Zitat Johansson H, Oden A, Kanis JA, McCloskey EV, Morris HA, Cooper C, Vasikaran S (2014) A meta-analysis of reference markers of bone turnover for prediction of fracture. Calcif Tissue Int 94:560–567CrossRefPubMed Johansson H, Oden A, Kanis JA, McCloskey EV, Morris HA, Cooper C, Vasikaran S (2014) A meta-analysis of reference markers of bone turnover for prediction of fracture. Calcif Tissue Int 94:560–567CrossRefPubMed
5.
Zurück zum Zitat Bauer DC, Black DM, Garnero P, Hochberg M, Ott S, Orloff J, Thompson DE, Ewing SK, Delmas PD (2004) Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res 19:1250–1258CrossRefPubMed Bauer DC, Black DM, Garnero P, Hochberg M, Ott S, Orloff J, Thompson DE, Ewing SK, Delmas PD (2004) Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res 19:1250–1258CrossRefPubMed
6.
Zurück zum Zitat 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 49:1271–1274CrossRefPubMed 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 49:1271–1274CrossRefPubMed
7.
Zurück zum Zitat Bauer D, Krege J, Lane N, Leary E, Libanati C, Miller P, Myers G, Silverman S, Vesper HW, Lee D, Payette M, Randall S (2012) National Bone Health Alliance Bone Turnover Marker Project: current practices and the need for US harmonization, standardization, and common reference ranges. Osteoporos Int 23:2425–2433CrossRefPubMedPubMedCentral Bauer D, Krege J, Lane N, Leary E, Libanati C, Miller P, Myers G, Silverman S, Vesper HW, Lee D, Payette M, Randall S (2012) National Bone Health Alliance Bone Turnover Marker Project: current practices and the need for US harmonization, standardization, and common reference ranges. Osteoporos Int 23:2425–2433CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Guañabens N, Filella X, Monegal A, Gómez-Vaquero C, Bonet M, Buquet D, Casado E, Cerdá D, Erra A, Martinez S, Montalá N, Pitarch C, Kanterewicz E, Sala M, Surís X, Torres F, LabOscat Study Group (2016) Reference intervals for bone turnover markers in Spanish premenopausal women. Clin Chem Lab Med 54:293–303CrossRefPubMed Guañabens N, Filella X, Monegal A, Gómez-Vaquero C, Bonet M, Buquet D, Casado E, Cerdá D, Erra A, Martinez S, Montalá N, Pitarch C, Kanterewicz E, Sala M, Surís X, Torres F, LabOscat Study Group (2016) Reference intervals for bone turnover markers in Spanish premenopausal women. Clin Chem Lab Med 54:293–303CrossRefPubMed
10.
Zurück zum Zitat Thuesen BH, Cerqueira C, Aadahl M, Ebstrup JF, Toft U, Thyssen JP, Fenger RV, Hersoug LG, Elberling J, Pedersen O, Hansen T, Johansen JD, Jorgensen T, Linneberg A (2014) Cohort profile: the Health2006 cohort, research centre for prevention and health. Int J Epidemiol 43:568–575CrossRefPubMed Thuesen BH, Cerqueira C, Aadahl M, Ebstrup JF, Toft U, Thyssen JP, Fenger RV, Hersoug LG, Elberling J, Pedersen O, Hansen T, Johansen JD, Jorgensen T, Linneberg A (2014) Cohort profile: the Health2006 cohort, research centre for prevention and health. Int J Epidemiol 43:568–575CrossRefPubMed
11.
Zurück zum Zitat Fenger RV, Vidal C, Gonzalez-Quintela A, Husemoen LL, Skaaby T, Aadahl M, Linneberg A (2014) The association of the ‘additional height index’ with atopic diseases, non-atopic asthma, ischaemic heart disease and mortality: a population-based study. BMJ Open 4(2):e003933. doi:10.1136/bmjopen-2013-003933 CrossRefPubMedPubMedCentral Fenger RV, Vidal C, Gonzalez-Quintela A, Husemoen LL, Skaaby T, Aadahl M, Linneberg A (2014) The association of the ‘additional height index’ with atopic diseases, non-atopic asthma, ischaemic heart disease and mortality: a population-based study. BMJ Open 4(2):e003933. doi:10.​1136/​bmjopen-2013-003933 CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Horwitz A, Skaaby T, Karhus LL, Schwarz P, Jorgensen T, Rumessen JJ, Linneberg A (2015) Screening for celiac disease in Danish adults. Scand J Gastroenterol 50:824–831CrossRefPubMedPubMedCentral Horwitz A, Skaaby T, Karhus LL, Schwarz P, Jorgensen T, Rumessen JJ, Linneberg A (2015) Screening for celiac disease in Danish adults. Scand J Gastroenterol 50:824–831CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Rosengren A, Wilhelmsen L (1997) Physical activity protects against coronary death and deaths from all causes in middle-aged men. Evidence from a 20-year follow-up of the primary prevention study in Goteborg. Ann Epidemiol 7:69–75CrossRefPubMed Rosengren A, Wilhelmsen L (1997) Physical activity protects against coronary death and deaths from all causes in middle-aged men. Evidence from a 20-year follow-up of the primary prevention study in Goteborg. Ann Epidemiol 7:69–75CrossRefPubMed
14.
Zurück zum Zitat Saltin B, Grimby G (1968) Physiological analysis of middle-aged and old former athletes. Comparison with still active athletes of the same ages. Circulation 38:1104–1115CrossRefPubMed Saltin B, Grimby G (1968) Physiological analysis of middle-aged and old former athletes. Comparison with still active athletes of the same ages. Circulation 38:1104–1115CrossRefPubMed
15.
Zurück zum Zitat Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310CrossRefPubMed Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:307–310CrossRefPubMed
16.
Zurück zum Zitat Solberg HE (1987) International Federation of Clinical Chemistry. Scientific committee, clinical section. Expert Panel on Theory of Reference Values and International Committee for Standardization in Haematology Standing Committee on Reference Values. Approved recommendation (1986) on the theory of reference values. Part 1. The concept of reference values. Clin Chim Acta 165:111–118CrossRefPubMed Solberg HE (1987) International Federation of Clinical Chemistry. Scientific committee, clinical section. Expert Panel on Theory of Reference Values and International Committee for Standardization in Haematology Standing Committee on Reference Values. Approved recommendation (1986) on the theory of reference values. Part 1. The concept of reference values. Clin Chim Acta 165:111–118CrossRefPubMed
17.
Zurück zum Zitat Solberg HE (1987) International Federation of Clinical Chemistry (IFCC), scientific committee, clinical section, Expert Panel on Theory of Reference Values, and International Committee for Standardization in Haematology (ICSH), Standing Committee on Reference Values. Approved recommendation (1986) on the theory of reference values. Part 1. The concept of reference values. J Clin Chem Clin Biochem 25:337–342PubMed Solberg HE (1987) International Federation of Clinical Chemistry (IFCC), scientific committee, clinical section, Expert Panel on Theory of Reference Values, and International Committee for Standardization in Haematology (ICSH), Standing Committee on Reference Values. Approved recommendation (1986) on the theory of reference values. Part 1. The concept of reference values. J Clin Chem Clin Biochem 25:337–342PubMed
18.
Zurück zum Zitat Chubb SA, Mandelt CD, Vasikaran SD (2015) Comparison of results from commercial assays for plasma CTX: the need for harmonization. Clin Biochem 48:519–524CrossRefPubMed Chubb SA, Mandelt CD, Vasikaran SD (2015) Comparison of results from commercial assays for plasma CTX: the need for harmonization. Clin Biochem 48:519–524CrossRefPubMed
19.
Zurück zum Zitat Wheater G, Goodrum C, Tuck SP, Datta HK, van Laar JM (2014) Method-specific differences in beta-isomerised carboxy-terminal cross-linking telopeptide of type I collagen and procollagen type I amino-terminal propeptide using two fully automated immunoassays. Clin Chem Lab Med 52:e135–e138CrossRefPubMed Wheater G, Goodrum C, Tuck SP, Datta HK, van Laar JM (2014) Method-specific differences in beta-isomerised carboxy-terminal cross-linking telopeptide of type I collagen and procollagen type I amino-terminal propeptide using two fully automated immunoassays. Clin Chem Lab Med 52:e135–e138CrossRefPubMed
20.
Zurück zum Zitat Schafer AL, Vittinghoff E, Ramachandran R, Mahmoudi N, Bauer DC (2010) Laboratory reproducibility of biochemical markers of bone turnover in clinical practice. Osteoporos Int 21:439–445CrossRefPubMed Schafer AL, Vittinghoff E, Ramachandran R, Mahmoudi N, Bauer DC (2010) Laboratory reproducibility of biochemical markers of bone turnover in clinical practice. Osteoporos Int 21:439–445CrossRefPubMed
21.
Zurück zum Zitat Michelsen J, Wallaschofski H, Friedrich N, Spielhagen C, Rettig R, Ittermann T, Nauck M, Hannemann A (2013) Reference intervals for serum concentrations of three bone turnover markers for men and women. Bone 57:399–404CrossRefPubMed Michelsen J, Wallaschofski H, Friedrich N, Spielhagen C, Rettig R, Ittermann T, Nauck M, Hannemann A (2013) Reference intervals for serum concentrations of three bone turnover markers for men and women. Bone 57:399–404CrossRefPubMed
22.
Zurück zum Zitat Morovat A, Catchpole A, Meurisse A, Carlisi A, Bekaert AC, Rousselle O, Paddon M, James T, Cavalier E (2013) IDS iSYS automated intact procollagen-1-N-terminus pro-peptide assay: method evaluation and reference intervals in adults and children. Clin Chem Lab Med 51:2009–2018CrossRefPubMed Morovat A, Catchpole A, Meurisse A, Carlisi A, Bekaert AC, Rousselle O, Paddon M, James T, Cavalier E (2013) IDS iSYS automated intact procollagen-1-N-terminus pro-peptide assay: method evaluation and reference intervals in adults and children. Clin Chem Lab Med 51:2009–2018CrossRefPubMed
24.
Zurück zum Zitat Jenkins N, Black M, Paul E, Pasco JA, Kotowicz MA, Schneider HG (2013) Age-related reference intervals for bone turnover markers from an Australian reference population. Bone 55:271–276CrossRefPubMed Jenkins N, Black M, Paul E, Pasco JA, Kotowicz MA, Schneider HG (2013) Age-related reference intervals for bone turnover markers from an Australian reference population. Bone 55:271–276CrossRefPubMed
25.
Zurück zum Zitat Olmos JM, Hernandez JL, Martinez J, Pariente E, Llorca J, Gonzalez-Macias J (2010) Bone turnover markers in Spanish adult men the Camargo cohort study. Clin Chim Acta 411:1511–1515CrossRefPubMed Olmos JM, Hernandez JL, Martinez J, Pariente E, Llorca J, Gonzalez-Macias J (2010) Bone turnover markers in Spanish adult men the Camargo cohort study. Clin Chim Acta 411:1511–1515CrossRefPubMed
27.
Zurück zum Zitat Ardawi MS, Maimani AA, Bahksh TA, Rouzi AA, Qari MH, Raddadi RM (2010) Reference intervals of biochemical bone turnover markers for Saudi Arabian women: a cross-sectional study. Bone 47:804–814CrossRefPubMed Ardawi MS, Maimani AA, Bahksh TA, Rouzi AA, Qari MH, Raddadi RM (2010) Reference intervals of biochemical bone turnover markers for Saudi Arabian women: a cross-sectional study. Bone 47:804–814CrossRefPubMed
29.
Zurück zum Zitat Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G. (2011) Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev CD000333: doi: 10.1002/14651858.CD000333.pub2 Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G. (2011) Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev CD000333: doi: 10.​1002/​14651858.​CD000333.​pub2
30.
Zurück zum Zitat Gomez-Cabello A, Ara I, Gonzalez-Aguero A, Casajus JA, Vicente-Rodriguez G (2012) Effects of training on bone mass in older adults: a systematic review. Sports Med 42:301–325CrossRefPubMed Gomez-Cabello A, Ara I, Gonzalez-Aguero A, Casajus JA, Vicente-Rodriguez G (2012) Effects of training on bone mass in older adults: a systematic review. Sports Med 42:301–325CrossRefPubMed
Metadaten
Titel
Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population
verfasst von
N. R. Jørgensen
L. T. Møllehave
Y. B. L. Hansen
N. Quardon
L. Lylloff
A. Linneberg
Publikationsdatum
28.04.2017
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 7/2017
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-017-4026-z

Weitere Artikel der Ausgabe 7/2017

Osteoporosis International 7/2017 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.