Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population
Abstract
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.
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In men (n = 21), 5% displayed lower PINP and 14% displayed lower CTX.
“In men (n = 21), 5% displayed lower PINP and 14% displayed lower CTX.”
In women (n = 24), all baseline BTM measurements of PINP and CTX were within reference values.
“In women (n = 24), all baseline BTM measurements of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were within reference values.”
Sex- and age-adjusted measures of bone status in chronic, obese, antipsychotic-treated patients appeared comparable to the reference population.
“Sex- and age-adjusted measures of bone status in chronic, obese, antipsychotic-treated patients appeared comparable to the reference population.”
Cites
STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT
Martin Bland, J., & Altman, D. (1986) · The Lancet · doi:10.1016/s0140-6736(86)90837-8 · Cited by 47,965 · see citing works
Beckett, A. H., Rowland, M., & TURNER, P. (1965) · The Lancet · doi:10.1016/s0140-6736(65)91037-8 · Cited by 16,917 · see citing works
for the IOF-IFCC Bone Marker Standards Working Group, Vasikaran, S., Eastell, R., Bruyère, O., Foldes, A. J., Garnero, P., Griesmacher, A., McClung, M., Morris, H. A., Silverman, S., et al. (2011) · Osteoporosis International · doi:10.1007/s00198-010-1501-1 · Cited by 1,212 · see citing works
Exercise for preventing and treating osteoporosis in postmenopausal women
Howe, T. E., Shea, B., Dawson, L., Downie, F., Murray, A., Ross, C., Harbour, R., Caldwell, L. M., & Creed, G. (2011) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd000333.pub2 · Cited by 1,090 · see citing works
SALTIN, B., & GRIMBY, G. (1968) · Circulation · doi:10.1161/01.cir.38.6.1104 · Cited by 1,015 · see citing works
Bauer, D. C., Black, D. M., Garnero, P., Hochberg, M. C., Ott, S. M., Orloff, J. J., Thompson, D. E., Ewing, S. K., Delmas, P. D., & for the Fracture Intervention Trial Study Group (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040512 · Cited by 403 · see citing works
Vasikaran, S. D., Cooper, C. C., Eastell, R., Griesmacher, A., Morris, H. A., Trenti, T., & Kanis, J. А. (2011) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2011.602 · Cited by 380 · see citing works
Effects of Training on Bone Mass in Older Adults
Gómez‐Cabello, A., Ara, I., González‐Agüero, A., Casajús, J. A., & Vicente‐Rodríguez, G. (2012) · Sports Medicine · doi:10.2165/11597670-000000000-00000 · Cited by 337 · see citing works
Bone turnover markers: use in osteoporosis
Naylor, K. E., & Eastell, R. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2012.86 · Cited by 263 · see citing works
Solberg, H. E. (1987) · Clinica Chimica Acta · doi:10.1016/0009-8981(87)90224-5 · Cited by 226 · see citing works
Physical activity protects against coronary death and deaths from all causes in middle-aged men
Rosengren, A., & Wilhelmsen, L. (1997) · Annals of Epidemiology · doi:10.1016/s1047-2797(96)00106-8 · Cited by 224 · see citing works
Solberg, H. E. (1987) · PubMed · Cited by 210 · see citing works
A Meta-Analysis of Reference Markers of Bone Turnover for Prediction of Fracture
IFCC-IOF Joint Working Group on Standardisation of Biochemical Markers of Bone Turnover, Johansson, H., Odén, A., Kanis, J. А., McCloskey, E. V., Morris, H. A., Cooper, C. C., & Vasikaran, S. D. (2014) · Calcified Tissue International · doi:10.1007/s00223-014-9842-y · Cited by 185 · see citing works
Bauer, D. C., Krege, J. H., Lane, N. E., Leary, E., Libanati, C. R., Miller, P. D., Myers, G. L., Silverman, S., Vesper, H. W., Lee, D., et al. (2012) · Osteoporosis International · doi:10.1007/s00198-012-2049-z · Cited by 159 · see citing works
Clinical usefulness of bone turnover marker concentrations in osteoporosis
Morris, H. A., Eastell, R., Jørgensen, N. R., Cavalier, E., Vasikaran, S. D., Chubb, S. A. P., Kanis, J. А., Cooper, C. C., & Makris, K. (2016) · Clinica Chimica Acta · doi:10.1016/j.cca.2016.06.036 · Cited by 131 · see citing works
Self-citationReference intervals for serum concentrations of three bone turnover markers for men and women
Michelsen, J., Wallaschofski, H., Friedrich, N., Spielhagen, C., Rettig, R., Ittermann, T., Nauck, M. A., & Hannemann, A. (2013) · Bone · doi:10.1016/j.bone.2013.09.010 · Cited by 127 · see citing works
Cohort Profile: The Health2006 cohort, Research Centre for Prevention and Health
Thuesen, B. H., Cerqueira, C., Aadahl, M., Ebstrup, J. F., Toft, U., Thyssen, J. P., Fenger, R. V., Hersoug, L., Elberling, J., Pedersen, O. B., et al. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dyt009 · Cited by 100 · see citing works
Self-citationAge-related reference intervals for bone turnover markers from an Australian reference population
Jenkins, N., Black, M. B., Paul, E. M., Pasco, J. A., Kotowicz, M. A., & Schneider, H. G. (2013) · Bone · doi:10.1016/j.bone.2013.04.003 · Cited by 81 · see citing works
Ardawi, M. M., Maimani, A. A., Bahksh, T. M., Rouzi, A. A., Qari, M. H., & Raddadi, R. M. (2010) · Bone · doi:10.1016/j.bone.2010.07.017 · Cited by 67 · see citing works
Screening for celiac disease in Danish adults
Horwitz, A., Skaaby, T., Kårhus, L. L., et al. (2015) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2015.1010571 · Cited by 59 · see citing works
Li, M., Li, Y., Deng, W., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103841 · Cited by 58 · see citing works
Morovat, A., Catchpole, A., Meurisse, A., Carlisi, A., Bekaert, A.-C., Rousselle, O., Paddon, M., James, T., & Cavalier, E. (2013) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2012-0531 · Cited by 51 · see citing works
(2010) · doi:10.1309/ajcpq4n7brzqvhal · Cited by 46 · see citing works
Laboratory reproducibility of biochemical markers of bone turnover in clinical practice
Schafer, A. L., Vittinghoff, E., Ramachandran, R., Mahmoudi, N., & Bauer, D. C. (2009) · Osteoporosis International · doi:10.1007/s00198-009-0974-2 · Cited by 45 · see citing works
Bone turnover markers in Spanish adult men
Olmos, J. M., Hernández, J. L., Martínez, J., et al. (2010) · Clinica Chimica Acta · doi:10.1016/j.cca.2010.06.010 · Cited by 42 · see citing works
Reference intervals for bone turnover markers in Spanish premenopausal women
Guañabens, N., Filella, X., Monegal, A., Gómez‐Vaquero, C., Bonet, M., Buquet, D., Casado, E., Cerdá, D., Erra, A., Martinez, S., et al. (2015) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2015-0162 · Cited by 37 · see citing works
Gossiel, F., Finigan, J., Jacques, R., Reid, D. M., Felsenberg, D., Roux, C., Glueer, C., & Eastell, R. (2014) · BoneKEy Reports · doi:10.1038/bonekey.2014.68 · Cited by 28 · see citing works
Comparison of results from commercial assays for plasma CTX: The need for harmonization
Chubb, S. A. P., Mandelt, C., & Vasikaran, S. D. (2015) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2015.03.002 · Cited by 25 · see citing works
Bone turnover markers: Defining a therapeutic target
Chubb, S. A. P., Byrnes, E., Manning, L. A., et al. (2016) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2016.09.010 · Cited by 14 · see citing works
Wheater, G., Goodrum, C., Tuck, S. P., Datta, H. K., & van Laar, J. M. (2014) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2013-0934 · Cited by 12 · see citing works
Fenger, R. V., Vidal, C., González‐Quintela, A., et al. (2014) · BMJ Open · doi:10.1136/bmjopen-2013-003933 · Cited by 3 · see citing works
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Cited by
Sorted by citations
Use of bone turnover markers in postmenopausal osteoporosis
Eastell, R., & Szulc, P. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(17)30184-5 · Cited by 594 · see citing works
Bone turnover, calcium homeostasis, and vitamin D status in Danish vegans
Hansen, T. H., Madsen, M. T. B., Jørgensen, N. R., Cohen, A. S., Hansen, T., Vestergaard, H., Pedersen, O., & Allin, K. H. (2018) · European Journal of Clinical Nutrition · doi:10.1038/s41430-017-0081-y · Cited by 62 · see citing works
Self-citationEriksson, R., Broberg, B. V., Ishøy, P. L., Bak, N., Andersen, U. B., Jørgensen, N. R., Knop, F. K., & Ebdrup, B. H. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00781 · Cited by 26 · see citing works
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- Authors
- Jørgensen, N. R., Møllehave, L. T., Hansen, Y. B. L., Quardon, N., Lylloff, L., & Linneberg, A.
- Affiliations
- University of Southern Denmark (DK)
- Capital Region of Denmark (DK)
- Rigshospitalet (DK)
- Hvidovre Hospital (DK)
- University of Copenhagen (DK)
- Corresponding author
- Jørgensen, N. R.
- Venue
- Osteoporosis International
- Published
- 2017-04-28
- Volume
- 28
- Issue
- 7
- Pages
- 2103-2113
- ISSN
- 0937-941X (ISSN-L)
- 1433-2965
- OpenAlex
- W2609433149
- Cited by
- 72
- References
- 31
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 7 · 2023: 6 · 2022: 3 · 2021: 13 · 2020: 12 · 2019: 8 · 2018: 9 · 2017: 3
- FWCI
- 9.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Osteoporosis International (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- bone turnover markers, C-terminal telopeptide of type I collagen, P1NP, bone-specific alkaline phosphatase, reference values, assay agreement, assay harmonization, osteoporosis treatment monitoring, sex-specific reference values, Danish population
- MeSH terms
- Adult, Aged, Aging, Blood Chemical Analysis, Blood Specimen Collection, Female, Glomerular Filtration Rate, Humans, Life Style, Male, Middle Aged, Peptide Fragments, Peptides, Procollagen, Reference Values, Sex Characteristics, Vitamin D, Reproducibility of Results, Biomarkers, Body Mass Index, Bone Remodeling, Collagen Type I, Young Adult
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