The principle objective of this study is to elucidate the kinetics of calcium metabolism in normal children and to evaluate disease related changes in calcium metabolism in both children and adults. Stable isotopes make such studies possible in children and in women of childbearing age, for whom the risk of radioactive calcium tracers prevent such studies; stable tracers also permit repeated measurements. Thermal ionization isotope ratio mass spectrometry with a quadrupole mass filter are used to measure tracer enrichments in serum, urine, feces and food. Isotope ratio measurements are analyzed by using a multi-compartmental mathematical model from which mineral mixing kinetics and metabolic fluxes are determined. The clinical protocol employed for these studies uses two stable isotopic tracers, one given i.v., the other orally. This use of two tracers allows direct measurement of several important parameters of calcium metabolism, principally the fraction absorbed and the endogenous fecal excretion. The acquisition of a new instrument has permitted the measurement of isotope ratios with greatly expanded accuracy and precision. We are now able to detect a 2-2.5% change in the natural ratio of 42Ca/48Ca with a relative standard deviation of 0.5%. The protocol has been expanded to include pregnancy and lactation as areas for study, and the first participant in this part of the program has been studied. Population statistics for a group of normal children have been obtained for the mean residence time of Ca in plasma (ll.l + 2.5 hrs) and fraction of Ca absorbed from diet (0.45 + .2) using a non-compartmental model.
