Interpretation of 41Ca data using compartmental modeling in post-menopausal women.

Calcium-41 (t(1/2) = 10(5) years) can be used after a single dose to follow calcium metabolism over a subject's lifetime. The aims of this study were to expand a (41)Ca kinetic model and estimate bone resorption in women with stable bone loss, compare the rates with those calculated with classical isotope studies, and to use the model to simulate dynamic changes in urinary (41)Ca:Ca ratios and bone balance for the design and interpretation of (41)Ca studies. Forty-two women >5 years post-menopause were given (41)Ca intravenously. Bone mineral content and bone mineral density of total body were measured by dual-energy X-ray absorptiometry at the beginning of the study. Urine collections were made periodically for up to ~5 years while subjects were free living. Urinary (41)Ca:Ca ratios were measured using accelerator mass spectrometry. The isotope data were analyzed by compartmental modeling. Four compartments were necessary to fit the urinary tracer data and total bone calcium. The final model included pathways for absorption, distribution, urinary excretion, and endogenous excretion and was used to calculate rates of bone turnover. Estimates of bone resorption in a subset of the women (n = 13), studied previously in a 3-week balance and full kinetic study with (45)Ca, agreed with those using (41)Ca methodology. Thus, rates of bone resorption can be estimated from (41)Ca urinary data in stable post-menopausal women. The model was used to simulate dynamic changes in urinary (41)Ca:Ca ratios and bone balance, as a result of interventions that perturb calcium metabolism to aid in study design and interpretation.