Abnormal calcium metabolism in adolescent children and postmenopausal women can have devastating consequences. The objectives of this study is to elucidate the kinetics of calcium metabolism in normal children and to evaluate disease related changes in calcium metabolism in children and adults. Stable calcium isotopes were administered to children and women of childbearing age and serial samples were obtained for two to four days. Two stable isotopic tracers were used in these studies; one given orally and one given intravenously. The use of two tracers allows direct measurement of several important parameters of calcium metabolism, principally the fraction of calcium absorbed orally and the endogenous fecal excretion. Thermal ionization isotope ratio mass spectrometry was used to measure tracer enrichments in serum, urine, feces and food. The data was used to develop a multicompartmental model of calcium metabolism that better characterized calcium metabolic fluxes between regions of the body. The results of the initial studies showed the following: comparison of the data from two normal boys with a patient with fibrodysplasia ossificans progressivia (FOP) showed that the metabolic parameters of the normal boys were consistent with each other yet markedly differed from those of the FOP patient. The principal observations are that the fraction of dietary calcium absorbed is about the same for all three children, but that the FOP patient excretes virtually no urinary clacium. The mass of the compartment postulated for the non-skeletial internal calcium is about the same for the two normal boys and about the same size as the most rapidly turning over compartment in the FOP patient; the size of the remaining compartments for the model of the FOP data are 5-6 times greater than normal. Our observations are consistent with clinical observations and will contribute to improvements in the therapeutic treatment of FOP. Additional data is being collected for further testing of the proposed compartmental model. This research is being conducted in collaboration with Dr. A. Yergey of the Laboratory of Theoretical and Physical Biology.
