Interpretation of 41Ca data using compartmental modeling in post-menopausal women
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- Lee, WH., Wastney, M.E., Jackson, G.S. et al. Anal Bioanal Chem (2011) 399: 1613. doi:10.1007/s00216-010-4454-5
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Calcium-41 (t1/2 = 105 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 41Ca 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 41Ca:Ca ratios and bone balance for the design and interpretation of 41Ca studies. Forty-two women >5 years post-menopause were given 41Ca 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 41Ca: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 45Ca, agreed with those using 41Ca methodology. Thus, rates of bone resorption can be estimated from 41Ca urinary data in stable post-menopausal women. The model was used to simulate dynamic changes in urinary 41Ca:Ca ratios and bone balance, as a result of interventions that perturb calcium metabolism to aid in study design and interpretation.