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Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability

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Abstract

Summary

The National Bone Health Alliance (NBHA) recommends standardized sample handling and patient preparation for C-terminal telopeptide of type I collagen (CTX-I) and N-terminal propeptide of type I procollagen (PINP) measurements to reduce pre-analytical variability. Controllable and uncontrollable patient-related factors are reviewed to facilitate interpretation and minimize pre-analytical variability.

Introduction

The IOF and the International Federation of Clinical Chemistry (IFCC) Bone Marker Standards Working Group have identified PINP and CTX-I in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA Bone Turnover Marker Project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation.

Methods

Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection.

Results

Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation.

Conclusion

Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.

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Acknowledgements

The NBHA would like to acknowledge the efforts of the IFCC and IOF in BTM standardization. We fully support further joint initiatives toward achieving this common goal and believe that, ideally, the relevant commercial parties should be involved as well.

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  1. N. R. Hoyle

    Present address: , Murnau, Germany

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  1. INSERM UMR 1033, Hôpital Edouard Herriot, University of Lyon, Pavillon F, Place d’Arsonval, 69437, Lyon, France

    P. Szulc

  2. Academic Unit of Bone Metabolism and Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK

    K. Naylor & R. Eastell

  3. ETL Consulting, Seattle, WA, 98177, USA

    E. T. Leary

  4. Pacific Biomarkers, Seattle, WA, 98119, USA

    E. T. Leary

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R.E. received grants and consultancy payments from both Roche Diagnostics and Immunodiagnostic Systems. NRH was previously an employee of Roche and received routine remunerations.

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Szulc, P., Naylor, K., Hoyle, N.R. et al. Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability. Osteoporos Int 28, 2541–2556 (2017). https://doi.org/10.1007/s00198-017-4082-4

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