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Front. Physiol. | doi: 10.3389/fphys.2019.00012

Calcium isotopes in human urine as a diagnostic tool for bone loss: additional evidence for time delays in bone response to experimental bed rest

 Alexander Heuser1, Petra Frings-Meuthen2,  Jörn Rittweger2, 3 and  Stephen J. Galer4*
  • 1GEOMAR Helmholtz Center for Ocean Research Kiel, Germany
  • 2German Aerospace Center, Helmholtz Association of German Research Centers (HZ), Germany
  • 3Universität zu Köln, Germany
  • 4Max Planck Institute for Chemistry, Germany

The calcium (Ca) isotopic composition in urine during bed rest has been demonstrated to be systematically light, indicating a negative bone mineral balance (i.e. bone loss). Here we present new Ca isotope data on urine during the “nutritional countermeasures”(NUC) bed rest study. We analysed the Ca isotopic composition of 24h pooled urine samples from seven healthy male subjects during baseline data collection, head-down-tilt bed rest and recovery. Additionally, we analysed urine from two follow-up examinations after the regeneration phase. We observed a change in Ca isotopic composition during the bed rest phase, indicative of bone loss with a time delay of 10 to 21 days. We also observe that the Ca isotopic composition of urine is strongly dependent on the individual Ca metabolism and varies between subjects. We relate this individuality in Ca metabolism to differences in the amounts of Ca being recycled in the kidneys. Previous studies have shown that the more Ca is reabsorbed in the kidneys the more enriched the urine becomes in heavy isotopes of calcium. The Ca isotopic composition of urine is thus modified by more than one process and cannot be used in a straightforward manner to monitor net bone mineral balance. To overcome this problem, we propose a new baseline approach for using Ca isotopes, which effectively cancels out the effects of individual renal Ca reabsorption. This allows us to detect bone loss in patients without ambiguity by combining measurements of the Ca isotopic composition of urine and daily Ca excretion rate and comparing these to data collected on healthy individuals with a normal steady-state bone balance.

Keywords: Calcium Isotopes, Urine, renal Ca reabsorption, Ca metabolism, bone loss, Bed Rest

Received: 23 Oct 2018; Accepted: 08 Jan 2019.

Edited by:

Costantino Balestra, Haute École Bruxelles-Brabant (HE2B), Belgium

Reviewed by:

Rahul Goel, Baylor College of Medicine, United States
Sergey Ponomarev, Institute of Biomedical Problems (RAS), Russia  

Copyright: © 2019 Heuser, Frings-Meuthen, Rittweger and Galer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Stephen J. Galer, Max Planck Institute for Chemistry, Mainz, 55128, Rhineland-Palatinate, Germany,