The present status of therapy with radioactive isotopes.
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BACKGROUND: An enhancing effect of short-chain fructooligosaccharides (scFOSs) on intestinal calcium absorption has been shown in animals and in some short-term human studies. However, the long-term effect of scFOSs on calcium absorption in humans is still unknown. OBJECTIVE: We investigated the long-term effect of a moderate daily dose (10 g) of scFOSs on intestinal calcium absorption in postmenopausal women. DESIGN: In a randomized, double-blind crossover protocol, 12 healthy, postmenopausal women received scFOSs or placebo for 5 wk. The treatments were separated by a 3-wk washout period. Subjects orally received (44)Ca (stable isotope) and a fecal marker. Feces were collected after the isotope intake for 5-7 d to measure unabsorbed isotope. Calcium-status indexes, calciotropic hormones, and bone turnover were also assessed. RESULTS: Mean (+/-SD) intestinal calcium absorption with scFOS treatment was not significantly different from that with placebo treatment (35.63 +/- 9.40% and 36.55 +/- 8.48%, respectively). However, a tendency for calcium absorption to be higher with scFOS treatment than with placebo treatment was observed in women who had been going through menopause for >6 y. CONCLUSIONS: scFOSs do not modify intestinal calcium absorption in postmenopausal women who do not receive hormonal replacement therapy. The results from a subgroup of women who had been going through menopause for >6 y (n = 6) suggest that scFOSs may influence calcium absorption in the late postmenopausal phase. The small number of subjects and the related P value warrant verification and further investigation with women in late menopause only.
Calcium absorption, as measured by whole-body retention of isotopic (47)calcium, was investigated in 10 controls and 10 patients with primary biliary cirrhosis before and after medium-chain triglyceride therapy. Absorption of calcium was impaired in eight patients with primary biliary cirrhosis, three of whom had normal serum bilirubin. Mean absorption was significantly less in patients with primary biliary cirrhosis than in controls. Impaired calcium absorption correlated well with increased faecal fat excretion and less well with the intensity of jaundice. Osteoporosis was diagnosed radiologically in seven patients with primary biliary cirrhosis, and calcium absorption was restored to normal in seven out of eight patients after medium-chain triglyceride therapy. Decrease of steatorrhoea, weight gain, and relief of bone pain have been noted in most patients with primary biliary cirrhosis after therapy. It is concluded that bone disease occurs early in primary biliary cirrhosis, and early medium-chain triglyceride therapy in these patients is suggested.
Utilizing the recently described reference method for calcium (NBS-AACC) and the recently developed definitive (referee) NBS method for serum calcium measurement by isotopedilution mass spectrometry (IDMS), an evaluation of five recent-model atomic absorption spectrometers was carried out. Under optimal conditions of instrument operation using aqueous standards, significant differences were found during the comparative analyses of three lyophilized pool samples and one liquid serum pool sample. Use of the NBS-AACC serum calcium protocol did not guarantee analytic results within +/- 2% of the IDMS value. In four of eight comparisons, differences from IDMS greater than 2% were observed. Several variables were studied to account for these differences. It was shown that a serum matrix, when present in standards used to bracket the unknown sample, reduced differences between instruments in four of four instances and improved the accuracy of the results from a range of -1.1 to +3.5% to +0.1 to +1.0%. It is concluded that a serum sample with a verified IDMS calcium value is a valuable tool that establishes an accurate and stable reference point for serum calcium measurement. The use of transfer-of-NBS-technology multipliers is suggested. Regional quality control serum pools and clinical chemistry survey sample materials that have been analyzed for calcium concentration by the NBS-IDMS definitive method are examples of these multipliers.
Turner syndrome is characterized by osteopenia and impaired skeletal growth. Neither feature is normalized by current modes of hormone therapy. The purpose of this study was to determine whether GH would increase protein anabolism and provide additional benefit to a regimen of estrogen replacement on calcium metabolism in girls and women with Turner syndrome. Using stable isotopes of calcium and leucine, we determined calcium absorption, urinary calcium loss, calcium retention, deposition into bone, leucine rate of appearance from protein, leucine incorporation into protein, and leucine oxidation in seven girls (10-17 y of age) and four adult females (16-34 y of age) with Turner syndrome, before and after 3 mo of GH treatment. All adults were treated with estrogen (ethinyl estradiol, 50 micrograms/d) and progesterone before and throughout the study. Three girls received no estrogen, and four girls were treated with low-dose estrogen (ethinyl estradiol, 5 micrograms/d) in combination with GH. The addition of estrogen to GH treatment resulted in a significant increase in calcium absorption and deposition in girls. GH did not affect calcium kinetics in adults already receiving estrogen/progesterone replacement therapy, nor did GH alone affect calcium kinetics in girls, and neither GH nor estrogen affected protein metabolism. These data suggest that the addition of low-dose estrogen to a regimen of GH improves bone deposition and calcium metabolism in girls with Turner syndrome and that estrogen is facultative for GH effects on bone.
Four dual-isotopic label methods for determining true fractional absorption of dietary calcium were compared in 23 subjects. The ratio of the integrals of oral label in a 24-h pooled urine to intravenous label in the same urine is called alpha 24h and was taken as the standard against which the others were compared. alpha Spot is the ratio of the fraction of oral label to the fraction of intravenous label in a single urine specimen; alpha Lag is the ratio of the level of oral label in blood 4 h after administration to the level of intravenous label in blood 2 h after administration. alpha Dec is obtained by deconvoluting response to the intravenous label from the response to the oral tracer. Results were as follows: alpha 24h = 0.273 +/- 0.124, alpha Dec = 0.300 +/- 0.101 (n = 14), alpha Spot = 0.359 +/- 0.179, and alpha Lag = 0.271 +/- 0.103. The Bland-Altman approach for comparison of methods was used to show that results for alpha Spot and alpha Lag can be expected, with a 95% confidence limit, to differ from the value of alpha 24h by 60 and 69%, respectively. The results for alpha Dec were shown to be not only indistinguishable from alpha 24h but identical from a theoretical perspective.
Rheumatic fever (RF), a potential sequela of Streptococcus pyogenes pharyngitis, sometimes results in myocarditis and heart failure. Antibodies have been implicated in the pathogenesis of RF and anti-cardiac myosin antibody levels are elevated in RF patients. Since myocarditis is associated with altered cardiomyocyte calcium transients it was of interest to determine the direct effects of RF patient antibodies on calcium transients in cultured myocytes. RF patient polyclonal IgM treatment caused increased calcium retention by neonatal rat heart cells in vitro as determined with isotopically labeled calcium. Therefore, to further characterize this finding, calcium transients were evaluated by real time fluorescence spectroscopy and deconvolution imaging. RF patient polyclonal IgM produced increased calcium retention during the relaxation stage of the contraction cycle leading to a slowing of contraction rate, disorganized calcium transients, and eventual tetany. In contrast, calcium transient studies of cardiomyocytes following treatment with monoclonal anti-myosin antibodies revealed declining intracellular calcium levels, accompanied by disorganized transients and tetany. Treatment with both antibodies led to myocyte dysfunction and these novel findings suggest a role for antibodies in the pathogenesis of the myocarditis associated with rheumatic carditis.
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The extraction of calcium from water, serum, and urine using Bio-Rex 25 mm ion exchange membrane filters was compared with the oxalate precipitation procedure currently used in our laboratory. Total recoveries of a known quantity of calcium loaded onto the membrane filters for water, serum and urine were as follows: (a) cation exchange filter, 85%, 74%, and 66%; (b) Chelex, 65%, 98%, and 20%; and (c) oxalate precipitation, 93%, 100%, and 96%, respectively. Regression analysis for precipitation versus ion exchange isotope ratio measurements of standards prepared using highly enriched calcium-44 showed slopes of unity. An improvement of automated sample analysis was observed for water and urine calcium samples extracted with ion exchange filters.
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PURPOSE OF REVIEW: Calcium metabolism is comprised primarily of absorption, urinary excretion, endogenous secretion and bone turnover. This review evaluates recent findings relating to the role of genetic and environmental factors, especially diet, on perturbing parameters of calcium metabolism. Calcium dynamics are studied with the use of isotopic tracers. We also cover state-of-the-art methods for stable calcium isotope ratio analysis and offer insights on experimental design. RECENT FINDINGS: Some progress has been made identifying genetic and hormonal regulators of calcium absorption. Much progress has been made in understanding the role of diet on influencing calcium retention, especially with regard to dietary protein and salt. Long-held views on dietary factors thought to contribute to bone loss through urinary calcium loss have been shown to have no impact on net calcium retention because of compensatory changes in other aspects of calcium metabolism. SUMMARY: Much more work needs to be done on understanding genetic regulators of calcium metabolism. Despite recent advances in our knowledge of dietary influences on calcium metabolism, more studies are needed on the role of environmental factors, especially physical activity.
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A double-blind controlled Ca supplementation trial was conducted for 6 months in thirty-four 7-year-old Chinese children from Hongkong and Jiangmen, China. The children were randomly allocated to the study group (n 17) or control group (n 17), and a CaCO3 tablet (300 mg Ca) or a placebo tablet was taken daily. True fractional Ca absorption (TFCA) was evaluated before and after the trial using stable isotopes: 8 mg 44Ca mixed in 100 g chocolate milk was given after an intravenous injection of 0.75 mg 42Ca. There was no significant difference in baseline TFCA between the study group (60.6 (SD 11.4)%) and the controls (58.2 (SD 9.0)%; P = 0.55). Serum 25-hydroxycholecalciferol levels were comparable between the two groups (P = 0.71). After 6 months, TFCA of the study group (55.6 (SD 12.7)%) was significantly lower than that of the controls (64.3 (SD 10.7)%; P = 0.015). By comparing the individual changes in TFCA after the trial between the two groups there was a non-significant reduction in TFCA (5.03 (SD 12.4)%; P = 0.11, Wilcoxon signed-rank test) in the study group (60.6-55.6%), whereas a significant increase in TFCA (6.17 (SD 7.7)%; P = 0.004, Wilcoxon signed-rank test) was observed in the controls (58.2-64.3%). The differential in TFCA between the two groups after 6 months was significantly different (P = 0.001), and remained significant after adjustment for baseline dietary intakes, weight and height by multiple-regression analysis (P = 0.003). If the mechanism of TFCA from chocolate milk in response to the treatment effects is similar to that from the total diet, then our results suggest that children with adequate vitamin D status can adapt to a change in Ca intake by adjusting the efficiency of TFCA. In corollary, children on habitually-low Ca diets have a higher TFCA than the counterparts with higher Ca diets.
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