Abstract
Background
Biochemical bone turnover markers (BTM) are useful tools to assess bone remodeling at the cellular level. N-terminal propeptide of type I procollagen (PINP) has been recommended as a reference marker for bone formation in research studies.
Methods
We describe the results of a multicenter study for routine clinical laboratory assays for PINP in serum and plasma. Four centers (Athens, Greece [GR], Copenhagen, Denmark [DK], Liege, Belgium [BE] and Sheffield, United Kingdom [UK]) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers’ instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method and the concordance correlation coefficient for PINP values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods.
Results
We showed that both EDTA plasma and serum were suitable for PINP determination. We observed a significant proportional bias between Orion radioimmunoassay and the automated methods for PINP (Roche Cobas and IDS iSYS), which both gave very similar results. The multivariate model did not improve the excellent correlation that was observed between the methods.
Conclusions
Harmonization of PINP assays is possible by applying a correction factor or correctly assigning the values of the calibrators. This work will benefit from further collaboration between assays manufacturers and clinical laboratory professionals.
Acknowledgments
We acknowledge the support of Roche Diagnostics International Ltd, Immunodiagnostics Systems Holdings plc and Orion Diagnostica Oy for financial support and supply of reagents, calibrators and internal quality control specimens for the PINP assays.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden: a report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 2013;8:136.10.1007/s11657-013-0136-1Search in Google Scholar PubMed PubMed Central
2. Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, et al. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine Position on bone marker standards in osteoporosis. Clin Chem Lab Med 2011;49:1271–4.10.1515/CCLM.2011.602Search in Google Scholar PubMed
3. Diez-Perez A, Naylor KE, Abrahamsen B, Agnusdei D, Brandi ML, Cooper C, et al. International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates. Osteoporos Int 2017;28:767–74.10.1007/s00198-017-3906-6Search in Google Scholar PubMed PubMed Central
4. Koivula MK, Risteli L, Risteli J. Measurement of aminoterminal propeptide of type I procollagen (PINP) in serum. Clin Biochem 2012;45:920–7.10.1016/j.clinbiochem.2012.03.023Search in Google Scholar PubMed
5. Szulc P, Naylor K, Hoyle NR, Eastell R, Leary ET. Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliancerecommendations to standardize sample handling and patient preparation to reduce pre-analytical variability. Osteoporos Int 2017;28:2541–56.10.1007/s00198-017-4082-4Search in Google Scholar PubMed
6. Cavalier E, Lukas P, Carlisi A, Gadisseur R, Delanaye P. Aminoterminal propeptide of type I procollagen (PINP) in chronic kidney disease patients: the assay matters. Clin Chim Acta 2013;425:117–8.10.1016/j.cca.2013.07.016Search in Google Scholar PubMed
7. Koivula MK, Ruotsalainen V, Björkman M, Nurmenniemi S, Ikäheimo R, Savolainen K, et al. Difference between total and intact assays for N-terminal propeptide of type I procollagen reflects degradation of pN-collagen rather than denaturation of intact propeptide. Ann Clin Biochem 2010;47:67–71.10.1258/acb.2009.009110Search in Google Scholar PubMed
8. Marin L, Koivula MK, Jukkola-Vuorinen A, Leino A, Risteli J. Comparison of total and intact aminoterminal propeptide of type I procollagen assays in patients with breast cancer with or without bone metastases. Ann Clin Biochem 2011;48:447–51.10.1258/acb.2011.011040Search in Google Scholar PubMed
9. Wheater G, Goodrum C, Tuck SP, Datta HK, van Laar JM. Method-specific differences in β-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 2014;52:135–8.10.1515/cclm-2013-0934Search in Google Scholar PubMed
10. Koivula MK, Richardson J, Leino A, Valleala H, Griffiths K, Barnes A, et al. Validation of an automated intact N-terminal propeptide of type I procollagen (PINP) assay. Clin Biochem 2010;43:1453–7.10.1016/j.clinbiochem.2010.09.019Search in Google Scholar PubMed
11. Jørgensen NR, Møllehave LT, Hansen YB, Quardon N, Lylloff L, Linneberg A. Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population. Osteoporos Int 2017;28:2103–13.10.1007/s00198-017-4026-zSearch in Google Scholar
12. Morovat A, Catchpole A, Meurisse A, Carlisi A, Bekaert A-C, Rousselle O, et al. IDS iSYS automated intact procollagen-1-N-terminus pro-peptide assay: method evaluation and reference intervals in adults and children. Clin Chem Lab Med 2013;51:2009–18.10.1515/cclm-2012-0531Search in Google Scholar
13. Garnero P, Vergnaud P, Hoyle N. Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin Chem 2008;54:188–96.10.1373/clinchem.2007.094953Search in Google Scholar
14. Genant HK, Grampp S, Glüer CC, Faulkner KG, Jergas M, Engelke K, et al. Universal standardization for dual X-ray absorptiometry: patient and phantom cross-calibration results. J Bone Miner Res 1994;9:1503–14.10.1002/jbmr.5650091002Search in Google Scholar
15. CLSI. EP15-A3 User Verification of Precision and Estimation of Bias. 2014.Search in Google Scholar
16. Alvarez L, RicOs C, Peris P, GuaNabens N, Monegal A, Pons F, et al. Components of biological variation of biochemical markers of bone turnover in Paget’s bone disease. Bone 2000;26:571–6.10.1016/S8756-3282(00)00279-9Search in Google Scholar
17. Hannon R, Blumsohn A, Naylor K, Eastell R. Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability. J Bone Min Res 1998;13:1124–33.10.1359/jbmr.1998.13.7.1124Search in Google Scholar
18. Clowes JA, Hannon RA, Yap TS, Hoyle NR, Blumsohn A, Eastell R. Effect of feeding on bone turnover markers and its impact on biological variability of measurements. Bone 2002;30:886–90.10.1016/S8756-3282(02)00728-7Search in Google Scholar
19. Rogers A, Glover SJ, Eastell R. A randomised, double-blinded, placebo-controlled, trial to determine the individual response in bone turnover markers to lasofoxifene therapy. Bone 2009;45:1044–52.10.1016/j.bone.2009.07.089Search in Google Scholar PubMed
20. Lin LI. A concordance correlation coefficient to evaluate reproducibility. Biometrics 1989;45:255–68.10.2307/2532051Search in Google Scholar
21. McBride GB. A proposal for strength-of-agreement criteria for Lin’s Concordance Correlation Coefficient. NIWA Client Rep 2005;HAM2005-06:14.Search in Google Scholar
22. Morris HA, Eastell R, Jorgesen NR, Cavalier E, Vasikaran S, Chubb SA, et al. Clinical usefulness of bone turnover marker concentrations in osteoporosis. Clin Chim Acta 2017;467:34–41.10.1016/j.cca.2016.06.036Search in Google Scholar PubMed
23. Redmond J, Fulford AJ, Jarjou L, Zhou B, Prentice A, Schoenmakers I. Diurnal rhythms of bone turnover markers in three ethnic groups. J Clin Endocrinol Metab 2016;101:3222–30.10.1210/jc.2016-1183Search in Google Scholar PubMed PubMed Central
©2019 Walter de Gruyter GmbH, Berlin/Boston
