Labeling the human skeleton with 41Ca to assess changes in bone calcium metabolism

Denk, E; Hillegonds, D; Vogel, J; Synal, A; Geppert, C; Wendt, K; Fattinger, K; Hennessy, C; Berglund, M; Hurrell, R F; Walczyk, T (2006). Labeling the human skeleton with 41Ca to assess changes in bone calcium metabolism. Analytical and bioanalytical chemistry, 386(6), pp. 1587-602. Heidelberg: Springer 10.1007/s00216-006-0795-5

[img]
Preview
Text
2006_Article_.pdf - Published Version
Available under License Publisher holds Copyright.

Download (385kB) | Preview

Bone research is limited by the methods available for detecting changes in bone metabolism. While dual X-ray absorptiometry is rather insensitive, biochemical markers are subject to significant intra-individual variation. In the study presented here, we evaluated the isotopic labeling of bone using 41Ca, a long-lived radiotracer, as an alternative approach. After successful labeling of the skeleton, changes in the systematics of urinary 41Ca excretion are expected to directly reflect changes in bone Ca metabolism. A minute amount of 41Ca (100 nCi) was administered orally to 22 postmenopausal women. Kinetics of tracer excretion were assessed by monitoring changes in urinary 41Ca/40Ca isotope ratios up to 700 days post-dosing using accelerator mass spectrometry and resonance ionization mass spectrometry. Isotopic labeling of the skeleton was evaluated by two different approaches: (i) urinary 41Ca data were fitted to an established function consisting of an exponential term and a power law term for each individual; (ii) 41Ca data were analyzed by population pharmacokinetic (NONMEM) analysis to identify a compartmental model that describes urinary 41Ca tracer kinetics. A linear three-compartment model with a central compartment and two sequential peripheral compartments was found to best fit the 41Ca data. Fits based on the use of the combined exponential/power law function describing urinary tracer excretion showed substantially higher deviations between predicted and measured values than fits based on the compartmental modeling approach. By establishing the urinary 41Ca excretion pattern using data points up to day 500 and extrapolating these curves up to day 700, it was found that the calculated 41Ca/40Ca isotope ratios in urine were significantly lower than the observed 41Ca/40Ca isotope ratios for both techniques. Compartmental analysis can overcome this limitation. By identifying relative changes in transfer rates between compartments in response to an intervention, inaccuracies in the underlying model cancel out. Changes in tracer distribution between compartments were modeled based on identified kinetic parameters. While changes in bone formation and resorption can, in principle, be assessed by monitoring urinary 41Ca excretion over the first few weeks post-dosing, assessment of an intervention effect is more reliable approximately 150 days post-dosing when excreted tracer originates mainly from bone.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology > Centre of Competence for Psychosomatic Medicine

UniBE Contributor:

Fattinger, Karin

ISSN:

1618-2642

ISBN:

17033771

Publisher:

Springer

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:50

Last Modified:

12 Nov 2020 13:40

Publisher DOI:

10.1007/s00216-006-0795-5

PubMed ID:

17033771

Web of Science ID:

000242144000002

BORIS DOI:

10.7892/boris.21042

URI:

https://boris.unibe.ch/id/eprint/21042 (FactScience: 4919)

Actions (login required)

Edit item Edit item
Provide Feedback