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A multicenter study to evaluate harmonization of assays for N-terminal propeptide of type I procollagen (PINP): a report from the IFCC-IOF Joint Committee for Bone Metabolism

Etienne Cavalier EMAIL logo , Richard Eastell , Niklas Rye Jørgensen , Konstantinos Makris , Symeon Tournis , Samuel Vasikaran , John A. Kanis , Cyrus Cooper , Hans Pottel , Howard A. Morris and on behalf of the IFCC-IOF Joint Committee for Bone Metabolism (C-BM)

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.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.

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Received: 2019-02-13
Accepted: 2019-04-08
Published Online: 2019-05-14
Published in Print: 2019-09-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

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