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Acute and 3-month effects of calcium carbonate on the calcification propensity of serum and regulators of vascular calcification: secondary analysis of a randomized controlled trial

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Abstract

Summary

Calcium supplements have been associated with increased cardiovascular risk, but the mechanism is unknown. We investigated the effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50). Changes in serum calcium were related to changes in T50.

Introduction

Calcium supplements have been associated with increased cardiovascular risk; however, it is unknown whether this is related to an increase in vascular calcification.

Methods

We investigated the acute and 3-month effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50), and on three possible regulators of calcification: fetuin-A, pyrophosphate and fibroblast growth factor-23 (FGF23). We randomized 41 postmenopausal women to 1 g/day of calcium as carbonate, or to a placebo containing no calcium. Measurements were performed at baseline and then 4 and 8 h after their first dose, and after 3 months of supplementation. Fetuin-A, pyrophosphate and FGF23 were measured in the first 10 participants allocated to calcium carbonate and placebo who completed the study.

Results

T50 declined in both groups, the changes tending to be greater in the calcium group. Pyrophosphate declined from baseline in the placebo group at 4 h and was different from the calcium group at this time point (p = 0.04). There were no other significant between-groups differences. The changes in serum total calcium from baseline were significantly related to changes in T50 at 4 h (r = −0.32, p = 0.05) and 8 h (r = −0.39, p = 0.01), to fetuin-A at 3 months (r = 0.57, p = 0.01) and to pyrophosphate at 4 h (r = 0.61, p = 0.02).

Conclusions

These correlative findings suggest that serum calcium concentrations modulate the propensity of serum to calcify (T50), and possibly produce counter-regulatory changes in pyrophosphate and fetuin-A. This provides a possible mechanism by which calcium supplements might influence vascular calcification.

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Author information

Authors and Affiliations

  1. University of Auckland, Auckland, New Zealand

    S. M. Bristow, G. D. Gamble, A. Stewart, A. M. Horne & I. R. Reid

  2. Department of Clinical Chemistry, University Hospital Bern, Inselspital, Bern, Switzerland

    A. Pasch

  3. Renal Division, School of Medicine, Emory University, Atlanta, GA, USA

    W. C. O’Neill

  4. Department of Endocrinology, Auckland District Health Board, Auckland, New Zealand

    I. R. Reid

  5. Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand

    I. R. Reid

Authors
  1. S. M. Bristow
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  2. G. D. Gamble
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  3. A. Pasch
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  4. W. C. O’Neill
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  5. A. Stewart
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  6. A. M. Horne
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  7. I. R. Reid
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Corresponding author

Correspondence to I. R. Reid.

Ethics declarations

The study was approved by a government ethics committee and all participants gave informed consent.

Conflicts of interest

Andreas Pasch is a co-founder of Calciscon AG, Bern, Switzerland. Sarah Bristow, Greg Gamble, W. Charles O’Neill, Angela Stewart, Anne Horne and Ian Reid have no disclosures to declare.

Additional information

This paper was supported by the Health Research Council of New Zealand.

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Bristow, S.M., Gamble, G.D., Pasch, A. et al. Acute and 3-month effects of calcium carbonate on the calcification propensity of serum and regulators of vascular calcification: secondary analysis of a randomized controlled trial. Osteoporos Int 27, 1209–1216 (2016). https://doi.org/10.1007/s00198-015-3372-y

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  • DOI: https://doi.org/10.1007/s00198-015-3372-y

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