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Variations along the 24-hour cycle of circulating osteoprotegerin and soluble RANKL: a rhythmometric analysis

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Abstract

Summary

The variability of serum osteoprotegerin (OPG) and soluble RANKL (sRANKL) along the 24-h cycle was assessed in 20 healthy women. No rhythmic variations of serum OPG, sRANKL or sRANKL/OPG ratio were detected as a group phenomenon. Timing of sampling is unlikely to influence the results of measurements of circulating OPG and sRANKL.

Introduction

Physiological bone turnover shows diurnal variations. The aim of the study was to assess variability of OPG and sRANKL serum levels along the 24-h cycle.

Methods

Blood was collected from 20 healthy women (median age 31 years, range 25–65 years) at 4-h intervals between 08:00 and 24:00 and at 2-h intervals between 24:00 and 08:00. Serum albumin, cortisol, osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), OPG and total sRANKL were measured. Temporal variations were assessed by the COSINOR model.

Results

Circadian rhythms of cortisol and albumin documented a normal synchronization within the circadian structure. Serum OC and CTX showed rhythmic variations, peaking at night-time. Rhythmic variations of serum OPG, sRANKL and sRANKL/OPG ratio were not detected as a group phenomenon. On an individual basis, rhythmic changes were detected in ten patients for OPG and eight patients for sRANKL, with very small amplitudes and heterogeneous acrophases.

Conclusions

The absence of consistent rhythmic variations of circulating OPG and sRANKL levels may reflect the absence of rhythmic variations of their expression in the bone microenvironment. Were this the case, the nocturnal rise of bone resorption should be accounted for by different, not RANKL/OPG-mediated factors. Since circulating OPG and sRANKL may derive from sources other than bone, rhythmicity could be masked by non-rhythmic or non-synchronized rhythmic expression in these sources. Timing of sampling is unlikely to influence the results of measurements of circulating OPG and sRANKL.

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Acknowledgments

This work was partly supported by grants from the Associazione Patologia Oncologica Mammaria—APOM and Amici dell’Ospedale di Cremona, Cremona, Italy; Consiglio Nazionale Ricerche (CNR), Rome, Italy; Ricerca Sanitaria Finalizzata - Regione Piemonte; Novartis Oncology, Origgio (VA), Italy; AMGEN S.p.A., Milan, Italy. A. Dovio has been awarded one of the 2004 Prizes from the Società Italiana di Medicina Interna.

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Authors and Affiliations

  1. Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

    A. Dovio & A. Angeli

  2. Breast Unit, Azienda Istituti Ospitalieri, Cremona, Italy

    D. Generali, S. Tedoldi, S. Bonardi, G. Allevi, S. Aguggini & A. Bottini

  3. Medical Oncology, Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

    M. Tampellini, A. Berruti, M. Torta, M. Tucci & L. Dogliotti

  4. Medicina Interna I—Dip. Scienze Cliniche e Biologiche, Reg. Gonzole 10, 10043, Orbassano-Torino, Italy

    A. Dovio

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  1. A. Dovio
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  2. D. Generali
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Corresponding author

Correspondence to A. Dovio.

Additional information

Andrea Dovio and Daniele Generali contributed equally to the study.

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Dovio, A., Generali, D., Tampellini, M. et al. Variations along the 24-hour cycle of circulating osteoprotegerin and soluble RANKL: a rhythmometric analysis. Osteoporos Int 19, 113–117 (2008). https://doi.org/10.1007/s00198-007-0423-z

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  • DOI: https://doi.org/10.1007/s00198-007-0423-z

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