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 41 Ca/Ca in serum after in vivo labeling of calcium pools with 41 Ca. We report the preparation of an intravenous 41 Ca dose suitable for humans, an analytical method for determining 41 Ca/Ca isotope ratios in biological samples, and studies in human volunteers.
Methods:41 Ca was formulated and aliquoted into individual vials, and to the extent possible, the 41 Ca doses were tested according to US Pharmacopeia (USP) guidelines. A 10 nCi dose of 41 Ca 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 cationexchange column, and 41 Ca/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 41 Ca/Ca ratios was linear from 6 ؋ 10 ؊14 to 9.1 ؋ 10 ؊10 . The run-to-run imprecision (as CV) of the method was 4% at 4.6 ؋ 10 ؊11 and 6% at 9.1 ؋ 10 ؊10 . The area under the curve of 41 Ca in the central compartment vs time was