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Abstract: TH-OR38

Calcium Isotope Ratios in Serum: A Novel Biomarker of Bone and Vessel Calcium Balance in Patients on Dialysis

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Shroff, Rukshana, UCL Great Ormond Street Hospital and Institute of Child Health, London, United Kingdom
  • Eisenhauer, Anton, Geomar Helmholtz Centre for Ocean Research, Kiel, Kiel, Germany
  • Heuser, Alexander, Geomar Helmholtz Centre for Ocean Research, Kiel, Kiel, Germany
  • Kolevica, Ana, Geomar Helmholtz Centre for Ocean Research, Kiel, Kiel, Germany
  • Mueller, Michael, University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany
  • D'Haese, Patrick, Universiteit Antwerpen, Antwerpen, Belgium
  • Evenepoel, Pieter, KU Leuven, Department of Immunology and Microbiology, Laboratory of Nephrology, Leuven, Belgium
Background

Dysregulated mineral homeostasis in CKD can cause bone demineralization and vascular calcification. We have shown that non-radioactive calcium (Ca) isotopes, 42Ca and 44Ca, that are naturally present in our diet can be measured in serum, and their ratio (δ44/42Caserum) quantitatively determines changes in bone Ca balance (BCaB). Isotopically light 42Ca is preferentially incorporated into bone, so δ44/42Caserum increases when bone formation exceeds resorption and vice versa.
We studied bone and arterial biopsies to determine the sensitivity of δ44/42Caserum in estimating BCaB and vascular calcification.

Methods

44Ca and 42Ca were measured by inductively coupled plasma mass-spectrometry in the serum, bone and arterial biopsies of 19 chronic dialysis patients. Data were compared with adults with osteoporosis.

Results

δ44/42Caserum and δ44/42Cabone were significantly lower in dialysis patients (median age 59.8 years, time on dialysis 3.3 years) compared to adults with osteoporosis, implying lower BCaB in dialysis patients.(Fig 1). δ44/42Caserum showed a strong positive correlation with δ44/42Cabone and δ44/42Cavessel.
δ44/42Ca serum and bone correlated positively with the BAP/TRAP5-b ratio and osteoblastic markers P1NP and inversely with osteoclastic markers PTH and RANKL. Although δ44/42Caserum indicated low BCaB in 89%, only 31% manifested DXA confirmed osteoporosis (T-scores <-2.5). On histology δ44/42Cabone inversely correlated with osteoid area and positively with absolute mineralized area and trabecular thickness. Significant and independent predictors of δ44/42Caserum were δ44/42Cabone (p=0.01, 95%CI -1.35 to -0.26), BAP/TRAP5-b ratio (p=0.04, 95%CI 0.04 to 0.26) and osteoid area (p=0.03, 95%CI -1.11 to – 0.09), together predicting 79% of the variability in δ44/42Caserum.

Conclusion

δ44/42Caserum is a significant and independent maker of BCaB, correlating with bone histology, and may provide a more sensitive and non-invasive measure of BCaB than bone biomarkers or DXA.

Funding

  • Government Support – Non-U.S.