Retention Of 47Ca Research Articles

Determination of the retention of 47Ca by whole-body counting

Retention of intravenously or orally administered 47Ca in the human body are described by a two-parameter function. It is then sufficient to make only a few whole-body measurements to determine the retention function, avoiding faeces sampling and stool markers. Seven days after intake the non-absorbed calcium was excreted and the model agreed with the measured relative retention. Absorption of calcium could then, in some cases (e.g. comparative studies), be described by relative retention at the 7th day after intake.

59Fe Is Retained from an Elemental 59Fe Powder Supplement without Effects on 65Zinc, 47Calcium and 67Copper in Young Pigs1–4

In vivo counting with the use of a germanium detector evaluated the retention of an elemental 59Fe powder supplement while measuring potential interactions with zinc, calcium and copper. Effects of dietary iron and zinc on in vivo retentions of 59Fe, 65Zn, 67Cu and 47Ca were studied in young pigs. In Experiment 1, 4-d-old piglets fed a cereal-based diet were randomly assigned to one of four treatment groups (2 × 2 factorial arrangement, n = 5 per group). Variables were dietary iron source (either elemental iron or FeSO4, each at 100 mg iron/kg diet) and the dosage form of radioactive iron (either elemental 59Fe powder or 59FeSO4). Experiment 2 (2 × 3 factorial arrangement) was performed using two levels of iron (100 and 200 mg/kg, as elemental iron) and three levels of zinc (25, 50 and 100 mg/kg). Piglets were also dosed with 47Ca, 65Zn and 67Cu; all radioisotopes were measured for 8 d. Apparent absorption of elemental 59Fe powder was 13 ± 1%, whereas 59Fe sulfate was significantly (P < 0.05) higher at 26 ± 1%. The FeSO4 diet decreased 65Zn retention in Experiment 1, in contrast to the elemental iron diet, which did not have this effect in either experiment. Apparent 65Zn absorption averaged 44 ± 2, 35 ± 1 and 27 ± 2% for the three levels of zinc (25, 50 and 100 mg/kg), respectively. Retention of 47Ca was not affected by dietary iron or zinc; retention of 67Cu was not affected by dietary iron. The data demonstrate good bioavailability of elemental iron without effects on zinc, copper and calcium.

Bone changes and mineral metabolism disorders in rats with experimental liver cirrhosis.

To investigate the pathogenesis of hepatic osteodystrophy (HOD) in parenchymal liver disease, we developed a laboratory model in animals using carbon tetrachloride (CCl4) and thioacetamide. Biochemical and histological parameters in the model were measured. In rats with both chronic non-cirrhotic liver injury and CCl4-induced cirrhosis, tibial bone volume was significantly lower than in controls. In CCl4-treated cirrhotic rats, the osteoid volume decreased while the urinary calcium/creatinine ratio increased. In all CCl4-treated rats, bone volume was significantly correlated with both the serum albumin concentration and the number of goblet cells reflecting intestinal villous atrophy. The serum concentration of vitamin D metabolites was not correlated with bone volume. Whole body retention of 47Ca was significantly lower in CCl4-treated cirrhotic rats than in controls. Furthermore, the bone volume in thioacetamide-treated cirrhotic rats was significantly lower than in controls. These data demonstrate that chronic parenchymal liver injury itself causes osteoporosis (i.e. HOD) due to a combination of low bone formation rates and high resorption rates, that HOD begins at the stage of chronic non-cirrhotic liver injury, that bone volume in HOD parallels liver damage and that the principal pathogenesis of HOD seems to be intestinal Ca malabsorption due to lower serum albumin and villous atrophy, while serum levels of vitamin D metabolites have little influence on the pathogenesis of HOD.

Calcium absorption from apple and orange juice fortified with calcium citrate malate (CCM).

Determine calcium (Ca) absorption from Ca fortified orange and apple juice. Absorbability was assessed by measuring 45Ca absorption in healthy women (mean age 57 years, n = 57/group) and whole body 47Ca retention in adult female beagle dogs (n = 6/group) and young adult male rats (n = 6/group). Women received 6.24 mmol (250 mg) Ca as calcium citrate malate fortified orange juice (CCM-OJ) or apple juice (CCM-AJ). Dogs received 3.12 mmol (125 mg) Ca as CCM-OJ or CCM-AJ. Rats were administered 0.15 mmol (6 mg) Ca as either milk, CCM-OJ, or CCM-AJ. Additional 47Ca whole body retention experiments in rats measured the effects of differences in the carbohydrate and organic acid contents of the juices on Ca absorption. Mean +/- SEM percent Ca fractional absorption was greater (p < 0.003) in women who consumed CCM-AJ (42 +/- 2%) than those who consumed CCM-OJ (36 +/- 1%). Ca retention in dogs was 15 +/- 1% for CCM-OJ and 29 +/- 2% for CCM-AJ (p < 0.001). Ca retention was significantly different (p < 0.05) in rats administered milk (42 +/- 2%), CCM-OJ (52 +/- 2%), or CCM-AJ (61 +/- 2%). By manipulating the carbohydrate and organic acid concentrations of test solutions to mimic the composition of Ca fortified juices, we found that the greater fructose and lower organic acid content of apple juice accounted for its greater Ca absorbability. CCM fortified versions of orange and apple juice have high Ca absorbability and are potentially important vehicles for increasing dietary Ca intake. The greater Ca absorption from CCM-AJ compared with CCM-OJ is accounted for by differences in the carbohydrate and organic acid content of the juices. These data suggest that by modifying common beverage ingredients, products with even greater Ca absorbability could be formulated.

Effect of age, calcium source, and radiolabeling method on whole body 47Ca retention in the rat

In a longitudinal study we determined the effect of animal age as well as Ca source and radiolabeling method on Ca bioavailability by measuring whole body 47Ca retention (WBR) in male Sprague-Dawley rats. The WBR assay was performed without surgery or anesthesia, and the same groups of animals were studied at 8, 16, 20, and 32 wk of age. Rats were administered a 6-mg radiolabeled oral dose of Ca as Ca citrate malate (CCM) or intrinsically or extrinsically labeled CaCO3 or hydroxyapatite (HAP). Fractional Ca retention was measured from the 72-h postdose WBR divided by WBR at time 0. WBR was significantly affected by Ca source with CCM > CaCO3 > HAP at all ages (P < 0.001). The rank order and relative bioavailabilities of these Ca salts in the rat model agreed well with literature values for Ca absorption in adult humans. Although percent WBR decreased significantly with advancing age (P < 0.001), the mean rate of decline (-3.4%/wk) was not affected by Ca source. Extrinsic radiolabeling overestimated (approximately 20%) Ca bioavailability when the rats were young. However, the magnitude of this effect diminished with advancing animal age and was not significant across all ages (repeated measures analysis of variance P = 0.10).

Intraduodenal delivery of intrinsically and extrinsically labelled CaCO3 in the rat: effect of solubilization on calcium bioavailability.

The dissolution of CaCO3 before intraduodenal administration was found to be an important factor determining calcium (Ca) bioavailability. Extrinsically and intrinsically labelled 47CaCO3 preparations were sequentially dissolved by serial additions of HCl. Aliquots of these preparations were collected before (no HCl added) and during the solubilization process and administered intraduodenally to rats. Whole body 47Ca retention 72 h post-dose was used as a measure of Ca bioavailability. Although dissolution of CaCO3 significantly increased Ca bioavailability (P < 0.001), Ca from both intrinsically and extrinsically labelled CaCO3 was absorbed and retained to some extent without prior acid dissolution. Due to a disproportionately high concentration of 47Ca on the particle surface, extrinsically labelled 47CaCO3 overestimated bioavailability when unsolubilized or partially solubilized CaCO3 preparations were used (P < 0.05). These data indicate that dissolution is a determining factor for Ca bioavailability from CaCO3. Incomplete dissolution will significantly limit but not completely prevent Ca bioavailability. The disintegration and dissolution characteristics of commercial CaCO3 preparations, which vary widely, may produce important differences in Ca absorption.

98083411 Relation of fractional 47Ca retention to season and rates of bone loss in healthy postmenopausal women

98083411 Relation of fractional 47Ca retention to season and rates of bone loss in healthy postmenopausal women

Relation of fractional 47Ca retention to season and rates of bone loss in healthy postmenopausal women

Fractional whole-body retention of 47Ca (retention fraction) in 58 healthy postmenopausal women participating in a calcium supplementation trial was examined for seasonal variation and for relationships to rates of bone loss and plasma vitamin D levels. Retention fraction was measured after 18 months in the trial. Bone mineral densities of the radius, femoral neck, and lumbar spine were measured at baseline, 12 months, and 24 months in the trial, and plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] and 25-hydroxyvitamin D (25-OHD) at 12, 18, and 24 months. The adjusted retention (retention fraction adjusted for total calcium intake, smoking status, and log years since menopause) was significantly higher in women evaluated in the months of August through October (mean +/- SD, 19.8 +/- 4.1%, n = 13) than in March through May (mean +/- SD, 17.0 +/- 4.7%, n = 18, p = 0.05). Plasma 25-OHD was associated with retention fraction only in women with low calcium intakes (partial r = 0.69 controlling for total calcium intake and log body mass index, n = 14, p = 0.01). Plasma 1,25-(OH)2D was not related to retention fraction. Adjusted retention, independent of total calcium intake, log years since menopause, smoking status, and season, explained 8% of the variability in the annual change in radius density (partial r = 0.29, p less than 0.05). No significant associations were seen at the spine and femur.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactose, Calcium Source and Age Affect Calcium Bioavailability in Rats

Calcium bioavailability was defined as either retention of 45Ca in tibias (Experiment 1) or retention of 47Ca in carcasses (Experiment 2). In Experiment 1, rats (age 21, 40 or 100 d) were fed purified meals extrinsically labeled with 45Ca. The meals contained either 0.5% Ca (control) or 1% Ca [control supplemented with CaCO3, calcium citrate-malate (CCM), milk or cheese] and either no lactose or 20% lactose. Lactose increased Ca bioavailability (P less than 0.05) from the control and milk meals in all age groups. Increases from CCM and CaCO3 were significantly only in the 21-d-old group. Lactose did not affect bioavailability from cheese. In Experiment 2, suckling rats (age 7, 12 or 17 d) were gavaged with 47Ca-labeled milk (fluid skim or lactose-hydrolyzed fluid skim) or an aqueous CaCl2-casein mixture (containing either no sugar, glucose + galactose, or lactose). Bioavailability from milk was higher than from lactose-hydrolyzed milk in all age groups. Lactose and glucose + galactose increased bioavailability over the sugar-free CaCl2-casein mixture in all age groups. Data from these experiments show that lactose enhances Ca bioavailability at several stages of development and the effect is not markedly diminished by high Ca diets. Lactose increases Ca bioavailability from a variety of sources but the magnitude of the effect may vary among sources.

Smoking and bone loss among postmenopausal women

We examined the effect of smoking on bone mineral density (BMD), rates of bone loss, and fractional whole-body retention of 47Ca in healthy postmenopausal women enrolled in a 2-year calcium supplementation trial. Bone density was measured by single- and dual-photon absorptiometry. BMD of the radius at the study baseline was inversely related to pack-years of exposure when controlled for body mass index and years since menopause (partial r = -0.18, p = 0.05, n = 125). The adjusted mean (+/- SD) annualized rate of bone change from the radius was greater among smokers than nonsmokers (-0.914 +/- 2.624%/year, n = 34, versus 0.004 +/- 2.568%/year, n = 278, respectively; p = 0.05). Similar trends were observed at the femoral neck, os calcis, and spine. Rates were were adjusted for caffeine intake, alcohol use, supplement type, and, at the spine only, menopausal status. At entry into the trial higher serum levels of alkaline phosphatase and lower levels of total and ionized calcium were found in smokers compared to nonsmokers. These differences did not persist with supplementation. In 44 women studied fractional 47Ca retention was lower in the 8 smokers than the 36 nonsmokers (16.6 versus 19.1%, respectively; p = 0.03). These results demonstrate an increased rate of bone loss at the radius after menopause and suggest that smoking is associated with decreased calcium absorption.

Measurement of47calcium retention with a whole-body counter

A method for measuring the retention of orally administered 47Ca using a whole-body counter (WBC) is described. One microcurie 47Ca in 90 ml of lowfat milk was given along with 5 microCi 51Cr as a stool marker. The retention of 47Ca was determined at 7 days if less than 2% of the administered 51Cr was present in the body. Correlation between calcium retention by the whole-body-counting and the excreta-recovery methods was highly significant (r = 0.835, P less than 0.0001; N = 17). In 5 subjects, each studied twice while on constant self-selected diets, calcium retention was measured by the WBC method with a precision (standard deviation) of +/- 2.6% of the administered dose or +/- 13.9% of the mean retained fraction. Whole-body measurement of 47Ca retention has the advantages over other techniques that no collections of blood or stool are needed, no residency on a metabolic ward is required, and the radiation exposure (13 mrem) is so low that multiple studies may be performed in the same subject.

Clinical and biological effects of low doses of (3 amino-1 hydroxypropylidene)-1,1-bisphosphonate (APD) in Paget's disease of bone.

Abstract. At doses varying between 500 and 1500 mg/day, the disodium salt of (3 amino‐1 hydroxypro‐pylidene)‐1,1‐bisphosphonate (APD) has been shown to induce rapid and complete biochemical responses in Paget's disease of bone, but a short‐lived and self‐limited fever has been observed in 30–40% of patients. The present study is an open and unrandomized trial, performed to explore the use of lower doses of APD (250 and 50 mg/day) given for 6 months to fourteen patients suffering from Paget's disease of bone. Subjective clinical improvement and complete biochemical remission (as assessed by normalization of urinary hydroxyproline excretion and plasma alkaline phosphatase concentration) was observed in ten out of eleven patients given 250 mg/day, but fever did not occur. Thus, a significant decrease in urinary hydroxyproline excretion was noted as early as 15 days after the beginning of the treatment (from 4.5 to 1.3 μmol/l GF; P &gt; 0.05) whereas plasma alkaline phosphatase concentration fell significantly only 1 month later (from 330 to 195 IU/ml; P &gt; 0.05). Both mean (± SEM) urinary hydroxyproline excretion (0.98 ± 0.08 μmol/l GF) and plasma alkaline phosphatase concentration (70 ± 8 IU/ml) were in the normal range after 6 months of treatment. Plasma calcium and phosphorus concentration, urinary calcium excretion and TmP/GFR decreased whereas plasma immunoreactive parathyroid hormone concentration increased. These changes were statistically significant (P &lt; 0.05) only transiently and disappeared at the time when bone formation (assessed by plasma alkaline phosphatase) returned to normal. An increase in total body retention of 47Ca during the second month of treatment was documented in five patients (P &lt; 0.05), compatible with a positive calcium balance. Plasma immunoreactive calcitonin did not change (P &gt; 0.05). After 6 months of treatment at 50 mg/day, APD also induced significant decreases in urinary hydroxyproline excretion (from 4.23 to 1.73 μmol/l GF; P &lt; 0.05) and plasma alkaline phosphatase concentration (from 360 to 162 IU/ml; P &lt; 0.05) but biochemical remissions were not complete and these two variables were significantly higher than the corresponding values in the group of patients receiving 250 mg APD/day. Less marked changes were also noted in all the other variables measured. Biological and clinical tolerance was good in all the patients. It is concluded that 250 mg/day of APD is an effective dose schedule, capable of reducing to normal levels the indirect indices of bone turn‐over, but in contrast with higher doses, without inducing fever.

47Ca turnover in endemic fluorosis and endemic genu valgum

1. Calcium turnover was determined after intravenous injection of radioactive 47Ca in patients with fluorosis and endemic genu valgum and in age-matched controls. Total Ca turnover in the body, loss of Ca from the body in urine, faeces and sweat (external turnover) and bone mineralization rate were calculated from whole-body retention of 47Ca and specific activity of 47Ca in serum. 2. Total Ca turnover was significantly higher in younger subjects than in older subjects. 3. Total Ca turnover was significantly higher in patients with fluorosis and in those with endemic genu valgum than in age-matched controls, but the external turnover of Ca was lower in both groups of patients than in controls. 4. Bone mineralization rate was significantly higher in patients with fluorosis and in those with genu valgum as compared to age-matched controls. 5. Total body Ca turnover and bone mineralization rates were significantly higher in patients with endemic genu valgum than in those with fluorosis. The differences persited even after adjusting for differences in age between patients with fluorosis and those with genu valgum.

A model-independent comparison of the rates of uptake and short term retention of 47Ca and 85Sr by the skeleton.

1. A method has been devised for comparing the impulse response functions of the skeleton for two or more boneseeking tracers, and for estimating the contribution made by measurement errors to the differences between any pair of impulse response functions. 2. Comparisons were made between the calculated impulse response functions for 47Ca and 85Sr obtained in simultaneous double tracer studies in sixteen subjects. Collectively the differences between the 47Ca and 85Sr functions could be accounted for entirely by measurement errors. 3. Because the calculation of an impulse response function requires fewer a priori assumptions than other forms of mathematical analysis, and automatically corrects for differences induced by recycling of tracer and non-identical rates of excretory plasma clearance of tracer, it is concluded that differences shown in previous in vivo studies between the fluxes of Ca and Sr into bone can be fully accounted for by undetermined oversimplifications in the various mathematical models used to analyse the results of those studies. 85Sr is therefore an adequate tracer for bone calcium in most in vivo studies.

A simple whole-body counter for measuring radionuclides in large dogs

The requirement of the apparatus was to measure the retention of 47Ca by greyhounds as part of a wider study of calcium metabolism in human metabolic bone disease, and, in dogs of this size, variation in counting efficiency due to changing distribution of radioactivity presents a considerably greater problem. However, in the studies, up to 50 mu Ci 47Ca had to be administered to permit long term measurements of plasma radioactivity, so it was possible to overcome this problem by using a sensitive large area detector 60 cm from the dog, which was placed in a specially constructed counting chamber.

Effects of 25-hydroxycholecalciferol on calcium metabolism in chronic renal failure.

Abnormalities of vitamin D metabolism, secondary hyperparathyroidism, acidosis and other less well defined factors are postulated to be important factors in the genesis of altered calcium (Ca) metabolism of chronic renal failure (CRF) and renal osteodystrophy. This study quantitatively characterizes a number of parameters of Ca metabolism in patients with CRF before and after oral administration of pharmacologic quantities of 25* hydroxycholecalciferol (25-OHD3). A previously formulated com-partmental model is used to quantitate certain parameters of Ca metabolism. The model consists of a number of compartments of variable size and intercompartmental transfer rates (1). The experimental data required for this analysis were obtained from a 47Ca tracer kinetic study, a Ca balance study, and the retention of 47Ca in the body as measured by whole body counting techniques. Total body (TB) Ca and phosphorus (P) stores were measured by neutron activation analysis (NAA) and compared to values obtained in normal subjects by methods previously described by this laboratory (2).

Total Body Retention of Orally Administered47Calcium in Primary Hyperparathyroidism

Using a whole body radiation detector, we have measured the total body retention of 47-Ca 7 days after oral administration of the isotope to patients with various disorders of calcium metabolism. The percent retention of 47-Ca given with 90 mg of unlabeled (carrier) calcium varied with the calcium metabolic status as follows: normals (n equals 14), 33-43 percent (mean 38); primary hyperparathyroidism (n equals 28), 32-74 percent (mean 52); idiopathic hypercalciuria (n equals 9), 34-49 percent (mean 42); and hypercalcemia of other etiology (n equals 3), 23-26 percent (mean 25). Almost half (13/28) of those with hyperparathyroidism showed a retention above 55 percent, distinguishing them from subjects with idiopathic hypercalciuria. Retention of 47-Ca correlated poorly with clinical measures of severity of hyperparathyroidism. When isotope was diluted with a smaller amount of carrier calcium (20 mg), retention was increaseed in normals (n equals 5) to 46-54 percent (mean 50) and in hyperparathyroidism (n equals 5) to 64-87 percent (mean 73). After surgical cure of hyperparathyroidism retention of isotope returned toward normal in 5 of 7 subjects. Whole body retention of orally administered 47-Ca may prove useful in detecting hyperparathyroidism in subjects with mild hypercalcemia or hypercalciuria.

The retention of americium and calcium by the skeleton of growing and mature female rats.

The retention of47Ca and241Am by 14 parts of the skeleton of growing and mature female rats 7 days after injection has been measured. The various parts of the skeleton possessed widely differing abilities to concentrate both these elements. The bones of the younger rats had a significantly greater ability to concentrate241Am but not47Ca. The implications of these results for the radiation dosimetry of internal contamination by241Am are discussed.

Retention of Oral 47Ca in Patients with Intestinal Malabsorption: Regional Enteritis and Pancreatic Insufficiency

Sjöberg, H. E. & Nilsson, L. H. 1970. Retention of Oral 47Ca in Patients with Intestinal Malabsorption: Regional Enteritis and Pancreatic Insufficiency. Scand. J. Gastroent. 5, 265-272.The retention of a single oral dose of 47Ca was measured in a whole body counter 2 weeks after being administered to 11 patients with regional enteritis and 12 with pancreatic insufficiency. Two μC of 47Ca were given to the fasting patients together with 135 mg of calcium as CaCl2 in water. In all but one of the regional enteritis patients resections of parts of the small intestine had been performed. Three patients with pancreatic insufficiency had undergone operation with exclusion or resection of the upper small intestine. The mean retention of 47Ca was significantly lowered in the group of patients with regional enteritis; 8 retained less than the -2 σ limit for the control group. We have not found any significant decrease of the retention of an oral dose of 47Ca given fasting patients with severely impaired pancreatic function.

47Ca Studies in Adult Coeliac Disease and Other Gastrointestinal Conditions with Particular Reference to Osteomalacia

Harris, O. D., Philip, Helen M., Cooke, W. T. & Pover, W. F. R. 1970. 47Ca Studies in Adult Coeliac Disease and Other Gastrointestinal Conditions with Particular Reference to Osteomalacia. Scand. J. Gastroent. 5, 169-175.Following oral administration of 47Ca the early plasma levels and, using a whole body counter, the 6-day retention of the isotope were studied in 31 patients: 17 with adult coeliac disease and 14 with other gastrointestinal disorders. Osteomalacia was present in 19. Though there was significant correlation between 120-minute plasma levels and 6-day retention of 47Ca, the percentage retention at any given plasma level might range between 40 and 70, which precluded the use of the method as a measure of calcium absorption. No correlation between the percentage retention and the presence or absence of osteomalacia was found.