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Effects of age and sex on osteocalcin and bone-specific alkaline phosphatase—reference intervals and confounders for two bone formation markers

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Abstract

Summary

Bone formation markers bone-specific alkaline phosphatase and osteocalcin are used in many clinical situations. Therefore, we calculated reference intervals for the two markers and investigated how they are influenced by several factors including sex and age. Furthermore, we established clinically relevant reference intervals for the two markers.

Objective

The bone turnover markers (BTMs), bone-specific alkaline phosphatase (bone ALP), and osteocalcin (OC), are frequently measured formation markers. The purpose of this study was to establish reference intervals (RIs) for the two BTMs in a general adult Danish population.

Methods

Bone ALP and OC were measured on the iSYS (IDS Plc) automatic analyzer in samples from the Danish Health2006 5-year follow-up study on serum from 2308 participants (54% women, age range 24–76). Participants with self-reported diagnosis of osteoporosis or receiving hormonal replacement were excluded from analyses while participants on hormonal contraceptives were included.

Results

The geometric mean and 95%RI for bone ALP were 13.9 μg/L (7.6–25.6) for men and 13.8 μg/L (7.0–27.4) for women, while for OC 16.0 μg/L (7.5–34.4) for men and 18.6 μg/L (8.1–42.9) for women. Levels of bone ALP increased with increasing age (β 1.004, p < 0.001), while female sex had no effect. OC levels decreased with increasing age (β 0.998, p = 0.009) and increased with female sex (β 1.104, p < 0.001). Based on our findings, we propose for bone ALP and OC three clinical RIs for men based on age and three clinical RI for women based on age and menopausal status.

Conclusion

The RI for bone ALP and OC varies with age and sex and the BTMs are influenced differently by the two factors. Consequently, the need for establishing valid RIs is of great importance before the full potential of BTM can be used in clinical practice.

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Disclaimer

The funding organizations(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.

Funding

This work was supported by Immunodiagnostic Systems, plc, Tyne and Wear, UK.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

    Sarah Seberg Diemar, Nadia Quardon & Niklas Rye Jørgensen

  2. Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark

    Line Tang Møllehave, Betina Heinsbæk Thuesen & Allan Linneberg

  3. Department of Clinical Biochemistry, Regional Hospital West Jutland, Herning, Denmark

    Louise Lylloff

  4. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Allan Linneberg

  5. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Niklas Rye Jørgensen

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  1. Sarah Seberg Diemar
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  2. Line Tang Møllehave
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Contributions

All the authors have accepted responsibility for the entire content of this submitted manuscript and approve submission.

Concept and design of the study: AL, NRJ. Conducting experiments: NQ. Set up and validation of analyses: LL, NQ, NRJ. Analyzing and interpreting data: AL, BHT, LTM, NRJ SSD. Writing, critically reviewing, and approving the manuscript: AL, BHT, LL, LTM, NQ, NRJ, SSD.

Corresponding author

Correspondence to Sarah Seberg Diemar.

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Conflict of interest

Niklas Rye Jørgensen and Allan Linneberg declare that they have received the assays for the study as a donation from IDS Plc but have no further conflicts of interest. Sarah Seberg Diemar, Line Tang Møllehave, Nadia Quardon, Louise Lylloff, and Betina Heinsbæk Thuesen declare that they have no conflicts of interest.

Statement of human rights

The study was approved by the Ethical Committee of The Capital Region (approval ‘H-2-2013-080’). All procedures performed were in accordance with the Helsinki Declaration as revised in 1983. Informed written consent was obtained from all participants prior to participation.

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Diemar, S.S., Møllehave, L.T., Quardon, N. et al. Effects of age and sex on osteocalcin and bone-specific alkaline phosphatase—reference intervals and confounders for two bone formation markers. Arch Osteoporos 15, 26 (2020). https://doi.org/10.1007/s11657-020-00715-6

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