Natural Calcium Isotopic Composition of Urine as a Marker of Bone Mineral Balance

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Abstract
Background: We investigated whether changes in the natural isotopic composition of calcium in human urine track changes in net bone mineral balance, as predicted by a model of calcium isotopic behavior in vertebrates. If so, isotopic analysis of natural urine or blood calcium could be used to monitor short-term changes in bone mineral balance that cannot be detected with other techniques.Methods: Calcium isotopic compositions are expressed as δ44Ca, or the difference in parts per thousand between the 44Ca/40Ca of a sample and the 44Ca/40Ca of a standard reference material. δ44Ca was measured in urine samples from 10 persons who participated in a study of the effectiveness of countermeasures to bone loss in spaceflight, in which 17 weeks of bed rest was used to induce bone loss. Study participants were assigned to 1 of 3 treatment groups: controls received no treatment, one treatment group received alendronate, and another group performed resistive exercise. Measurements were made on urine samples collected before, at 2 or 3 points during, and after bed rest.Results: Urine δ44Ca values during bed rest were lower in controls than in individuals treated with alendronate (P <0.05, ANOVA) or exercise (P <0.05), and lower than the control group baseline (P <0.05, t-test). Results were consistent with the model and with biochemical and bone mineral density data.Conclusion: Results confirm the predicted relationship between bone mineral balance and calcium isotopes, suggesting that calcium isotopic analysis of urine might be refined into a clinical and research tool.
Funding Information
  • University of Rochester School of Medicine and Dentistry (HIH P30 ES 01247-24)
  • US Geological Survey