Received on February 14, 2005
Accepted on August 15, 2005

Endocrinology and Metabolism

⁴¹Ca and Accelerator Mass Spectrometry to Monitor Calcium Metabolism in End Stage Renal Disease Patients

¹ VA San Diego Healthcare System, San Diego, CA, and Department of Pathology, University of California, San Diego, CA
² Lawrence Livermore National Laboratories, Livermore, CA
³ VA San Diego Healthcare System, San Diego, CA
⁴ VA San Diego Healthcare System, San Diego, CA, and Department of Medicine, University of California, San Diego, CA
⁵ Lawrence Livermore National Laboratories, Livermore, CA, and Department of Nutrition, University of California, Davis, CA

^* To whom correspondence should be addressed. E-mail: rlfitzgerald{at}vapop.ucsd.edu.

Background: Monitoring bone resorption with measurements of bone density and biochemical markers is indirect. We hypothesized that bone resorption can be studied directly by serial measurements of the ratio ⁴¹Ca/Ca in serum after in vivo labeling of calcium pools with ⁴¹Ca. We report the preparation of an intravenous ⁴¹Ca dose suitable for humans, an analytical method for determining ⁴¹Ca/Ca isotope ratios in biological samples, and studies in human volunteers.

Methods: ⁴¹Ca was formulated and aliquoted into individual vials, and to the extent possible, the ⁴¹Ca doses were tested according to US Pharmacopeia (USP) guidelines. A 10 nCi dose of ⁴¹Ca was administered intravenously to 4 end-stage renal disease (ESRD) patients on hemodialysis and 4 healthy control individuals. Distribution kinetics were determined over 168 days. Calcium was isolated with 3 precipitation steps and a cation-exchange column, and ⁴¹Ca/Ca ratios in serum were then measured by accelerator mass spectrometry.

Results: The dosing solution was chemically and radiologically pure, contained <0.1 endotoxin unit/mL, and passed USP sterility tests. Quantification of ⁴¹Ca/Ca ratios was linear from 6 x 10^-14 to 9.1 x 10-¹⁰. The run-to-run imprecision (as CV) of the method was 4% at 4.6 x 10^-11 and 6% at 9.1 x 10^-10. The area under the curve of ⁴¹Ca in the central compartment vs time was significantly less for ESRD patients than for controls (P <0.005).

Conclusions: Isotope ratios spanning 5 orders of magnitude can be measured by accelerator mass spectrometry with excellent precision in the range observed in samples collected from patients who have received 10 nCi of ⁴¹Ca. The ⁴¹Ca at this dose caused no adverse effects in 8 volunteers. This is the first report of the use of ⁴¹Ca to monitor differences in bone turnover between healthy individuals and ESRD patients.