Changes of calcium, phosphorus, citrate and alkaline phosphatases in metastatic breast cancer.
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PURPOSE: To determine the effect of supplementation with calcium citrate on circulating lipid concentrations in normal older women. SUBJECTS AND METHODS: As part of a study of the effects of calcium supplementation on fractures, we randomly assigned 223 postmenopausal women (mean [+/- SD] age, 72 +/- 4 years), who were not receiving therapy for hyperlipidemia or osteoporosis, to receive calcium (1 g/d, n = 111) or placebo (n = 112) for 1 year. Fasting serum lipid concentrations, including high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol, were obtained at baseline, and at 2, 6, and 12 months. RESULTS: After 12 months, HDL cholesterol levels and the HDL cholesterol to LDL cholesterol ratio had increased more in the calcium group than in the placebo group (mean between-group differences in change from baseline: for HDL cholesterol, 0.09 mmol/L (95% confidence interval [CI]: 0.02 to 0.17; P = 0.01); for HDL/LDL cholesterol ratio, 0.05 (95% CI: 0.02 to 0.08; P = 0.001). This was largely due to a 7% increase in HDL cholesterol levels in the calcium group, with a nonsignificant 6% decline in LDL cholesterol levels. There was no significant treatment effect on triglyceride level (P = 0.48). CONCLUSION: Calcium citrate supplementation causes beneficial changes in circulating lipids in postmenopausal women. This suggests that a reappraisal of the indications for calcium supplementation is necessary, and that its cost effectiveness may have been underestimated.
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BACKGROUND: The aim of this study was to measure the effects of normal (nTHP) and abnormal stone former Tamm-Horsfall protein (SF-THP) on calcium oxalate (CaOx) nucleation and aggregation as well as on crystal morphology, in presence or absence of citrate. METHODS: Nucleation and aggregation of CaOx crystals from a supersaturated, stirred solution (200 mM NaCl, 10 mM Na-acetate, pH 5.70, 5 mM Ca and 0.5 mM Ox) were studied by spectrophotometric time-course measurements of OD at 620 nm (OD(620)). Measured parameters were induction time t(I) (time to induce formation of detectable particles), S(N), (slope of increase of OD(620), mainly due to crystal nucleation), and S(A), (slope of decrease of OD(620) after equilibrium has been reached, due to crystal aggregation). Effects of citrate, nTHP and SF-THP on these parameters were measured, and scanning electron microscopy (SEM) was performed. RESULTS: At 1.5, 2.5 and 3.5 mM, citrate increased t(I) and inhibited crystal nucleation (by 78-87%) as well as aggregation (by 63-70%), and smaller CaOx crystals (length/width ratio 1.7+/-0.1) than under standard conditions (length/width 3.9+/-0.5) were visible (P<0.001). Normal THP at 30 and 40 mg/l inhibited crystal nucleation and, more strongly, aggregation (inhibition 76-81%). SEM revealed a decrease in length/width ratio to 2.6+/-0.4 (P=0.051 vs standard conditions) and less aggregation than without nTHP. At all concentrations tested, SF-THP reduced t(I) (P=0.0001 vs standard conditions) and promoted aggregation (inhibition -48 to -33%); crystals were elongated with a length/width ratio of 4.3+/-0.6 (P<0. 05 vs nTHP). When simultaneously present with nTHP, citrate enhanced the inhibitory effects of nTHP, producing the smallest (length/width 1.5+/-0.1) and least aggregated crystals. Finally, 3.5 mM citrate turned promotory SF-THP into a crystallization inhibitor with abundant small and clustered, but not aggregated crystals. CONCLUSION: Citrate appears to be the main determinant of CaOx crystallization rates and crystal morphology in the presence of nTHP as well as SF-THP. Its effects appear to predominate over those of THP, since even promotory SF-THP is turned into a crystallization inhibitor in the presence of citrate. This re-emphasizes at a morphological level what has been concluded from functional as well from clinical studies, namely that citrate is needed in urine at equimolar concentrations to calcium in order to prevent the formation of large crystal aggregates in presence of abnormal THP.
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OBJECTIVE: to compare the effect of 0.3 and 0.625 mg conjugated equine estrogens on bone mineral density (BMD) in a private practice setting. METHODS: postmenopausal women interested in hormone replacement therapy were prescribed either 0.3 or 0.625 mg conjugated equine estrogens daily with 10 mg medroxyprogesterone acetate days 1-12 of the month. All women were given calcium citrate 1000 mg/day and vitamin D 400 IU/day. DEXA bone mineral density studies of the spine and hip were performed at baseline and 1 year. RESULTS: there was no significant difference in BMD at the spine, the trochanter or the femoral neck compared with baseline in either the 0.625 or 0.3 mg group. The mean percent increase in BMD for the 0.3 versus 0.625 mg group was: spine 2.6 versus 3.8%, femoral neck 1.8 versus 1.5%, and trochanter 0.5 versus 2.6%. CONCLUSION: both the 0.625 mg dose and the 0.3 mg dose of conjugated equine estrogens preserved BMD at the spine and hip over one year in early postmenopausal women who were also given cyclic medroxyprogesterone acetate, calcium citrate and vitamin D.
This study was conducted to compare pharmacokinetic indices of calcium absorption after a single oral (500 mg calcium) load of Citracal (calcium citrate) and Os-Cal (calcium carbonate). In 18 postmenopausal normal women, venous blood samples were obtained for the measurement of calcium before and hourly for 6 hours after an oral ingestion of Citracal, Os-Cal, or placebo with a breakfast meal. The change in area under the curve (delta AUC) in serum calcium from preload was 2.5-fold greater for Citracal than Os-Cal, and the peak-basal variation in serum calcium was 76% higher for Citracal than Os-Cal. The increment in serum calcium from preload after Citracal administration was significantly higher than that obtained after placebo load during most time periods and significantly higher than that of Os-Cal at 1, 4, and 5 hours after load. In contrast, delta AUC and peak basal variation of Os-Cal did not differ significantly from placebo and increment in serum calcium was significantly increased from placebo only at 6 hours. In conclusion, Citracal is much more bioavailable than Os-Cal.
Whether ingested calcium is absorbed more efficiently from freely water-soluble calcium salts than from poorly soluble salts is unclear. It is also unknown whether calcium is absorbed better from dairy products than from calcium salts. Using a method by which the net absorption of calcium can be accurately measured after a single dose, we studied eight healthy fasting subjects after they took a 500-mg dose of calcium from each of five calcium salts with various degrees of water solubility and from milk. The order of administration of the agents given was randomly determined. The mean (+/- SEM) net calcium absorption, in decreasing order of the solubility of the salts, was 32 +/- 4 percent from calcium acetate, 32 +/- 4 percent from calcium lactate, 27 +/- 3 percent from calcium gluconate, 30 +/- 3 percent from calcium citrate, and 39 +/- 3 percent from calcium carbonate. The differences in absorption were not statistically significant according to analysis of variance. On the basis of in vitro solubility experiments in acid mediums, we hypothesize that acid dissolution in the gastrointestinal tract may be responsible for the similar absorption of calcium from salts with widely different water solubilities. Calcium absorption from whole milk (31 +/- 3 percent) was similar to absorption from calcium salts. We conclude that calcium absorption from carbonate, acetate, lactate, gluconate, and citrate salts of calcium, and from whole milk, is similar in fasting healthy young subjects. Further study will be required to determine whether the results would be different in older subjects, with a higher dose of calcium, or if the calcium was ingested with food.
Studies were done to determine the survival of salmonellae in orange juice as affected by fortification with calcium. Four brands of commercially pasteurized orange juice fortified with calcium (350 mg/240-ml serving) and nonfortified juice were inoculated separately with three types of inocula: strains of Salmonella Muenchen (inoculum 1), serotypes of human and animal origin (inoculum 2), and isolates from raw produce- and juice-associated outbreaks (inoculum 3). Juice inoculated with populations of 6.6 to 7.0 log10 CFU of Salmonella per ml was held at 4 degrees C for up to 32 days. The number of cells of inoculum 1 that survived in juice fortified with calcium lactate/tricalcium phosphate (CaL/TCP) was significantly lower (P < or = 0.05) (2.80 log10 CFU/ml) than in nonfortified juice (3.50 log10 CFU/ml) after 32 days' storage. Death of salmonellae in inocula 1 and 2 was less in juice fortified with TCP (3.21 and 3.33 log10 CFU/ml, respectively) than in the nonfortified juice (3.75 and 4.15 log10 CFU/ml, respectively). During the 32-day storage period, populations in inocula 1 and 3 showed significantly less inactivation (2.62 and 3.12 log10 CFU/ml, respectively) in juice fortified with calcium citrate (CC) than in nonfortified juice (3.14 and 3.60 log10 CFU/ml, respectively). There were no significant differences in the survival of Salmonella in juice fortified with calcium citrate malate (CCM) and nonfortified juice. Polymerase chain reaction (PCR) typing of randomly selected Salmonella colonies revealed that Salmonella Heidelberg in inoculum 2 and Salmonella Baildon and Salmonella Poona in inoculum 3 were the most prevalent at the end of the 32-day storage period at 4 degrees C, suggesting that serotypes selected for use in inocula differed in tolerance to acidic environments. This study reveals that the form of calcium used to fortify orange juice may affect the survival of Salmonella.
To better understand how structural and functional bone properties contribute to the changes in bone biomechanical properties revealed by ultrasound critical angle reflectometry (UCR) analysis, we measured both UCR velocities and histomorphometric properties in bone biopsy specimens from 33 osteoporotic patients before and following intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate administration. Mean skeletal fluoride exposure was 17 months, and mean skeletal fluoride content was 0.203 +/- 0.088 SD% bone ash. Intermittent SRNaF and continuous calcium citrate promoted significant increases in trabecular thickness (122 +/- 18 SD microm to 131 +/- 20, p = 0.020), mineral apposition rate (0.79 +/- 0.26 to 1.05 +/- 0.40 microm/day, p = 0.014), and a significant decline in eroded surface (3.9 +/- 1.6 to 2.8 +/- 1.4%, p = 0.002). There were also significant increases in node number (0.193 +/- 0.100 to 0.368 +/- 0.245, p < 0.01) and node-to-node strut length (0.076 +/- 0.087 to 0.191 +/- 0.173, p < 0.01) relative to total cancellous area. Cortical UCR velocity did not change but cancellous velocity significantly increased by 97 m/s following therapy (p = 0.0005). When compared against the significant changes in bone histomorphometry and connectivity, the sum of both cancellous and cortical ultrasound velocities was significantly correlated with node number/area (R2 = 0.305, p < 0.0001) and node-to-node strut length/area (R2 = 0.372, p < 0.0001) and to a lesser extent with mineral apposition rate (R2 = 0.106, p = 0.032). Multiple regression analysis demonstrated that 40% of the variance in the sum of the UCR velocities can be accounted for by the variability in these histomorphometric and connectivity parameters. There were no significant correlations between the sum of cortical and cancellous ultrasound velocities and cancellous bone volume (R2 = 0.014, p = 0533), trabecular thickness (R2 = 0.012, p = 0.47), or bone mineral density (R2 = 0.003, p = 0.80). These observations indicate that velocity measurements with the UCR methodology show an improvement in bone elasticity associated, in part, with an improvement in the rate of bone mineralization and an improvement in bone quality at the structural level as shown by microarchitecture.
BACKGROUND AND OBJECTIVES: Citrate reactions are uncomfortable and potentially dangerous to apheresis donors. Reduction of citrate increases comfort, but may lead to platelet clumping. MATERIALS AND METHODS: We describe a protocol for stepwise reduction of the volume of ACD-A injected during plateletpheresis. This protocol has been carried out in 45 healthy donors with the Cobe 2997 (Cobe) cell separator, and in 35 with the Fenwal-CS 3000 (CS). RESULTS: Using this protocol, during the first hour of platelet collection, ionised calcium decreased on average by 18% for CS and by 18.4% for Cobe. During the second hour, Ca2+ and citrate ion concentration did not change with either Cobe or CS (about 65% of citrate ion load is eliminated). We observed mild signs of neuromuscular hyperexcitability in only 22% and 28% of donors with Cobe and CS, respectively. We also found a significant reduction of phosphate ions (p < 0.0001) at the end of the procedures. CONCLUSIONS: With this stepdown citrate reduction protocol, we obtained a significant reduction of injected citrate without the complication of platelet clumps.
OBJECTIVE: To evaluate the effect of calcium supplementation on bone acquisition in adolescent white girls. DESIGN: A randomized, double-blind, placebo-controlled trial of the effect of 18 months of calcium supplementation on bone density and bone mass. SUBJECTS: Ninety-four girls with a mean age of 11.9 + 0.5 years at study entry. SETTING: University hospital in a small town. INTERVENTIONS: Calcium supplementation, 500 mg/d calcium as calcium citrate malate; controls received placebo pills. MAIN OUTCOME MEASURES: Bone mineral density and bone mineral content of the lumbar spine and total body were measured by dual-energy x-ray absorptiometry and calcium excretion from 24-hour urine specimens. RESULTS: Calcium intake from dietary sources averaged 960 mg/d for the entire study group. The supplemented group received, on average, an additional 354 mg/d of calcium. The supplemented group compared with the placebo group had greater increases of lumbar spine bone density (18.7% vs 15.8%; P = .03), lumbar spine bone mineral content (39.4% vs 34.7%; P = .06), total body bone mineral density (9.6% vs 8.3%; P = .05), and 24-hour urinary calcium excretion (90.4 vs 72.9 mg/d; P = .02), respectively. CONCLUSIONS: Increasing daily calcium intake from 80% of the recommended daily allowance to 110% via supplementation with calcium citrate malate resulted in significant increases in total body and spinal bone density in adolescent girls. The increase of 24 g of bone gain per year among the supplemented group translates to an additional 1.3% skeletal mass per year during adolescent growth, which may provide protection against future osteoporotic fracture.
Recent outbreaks of salmonellosis associated with orange juice have raised interest concerning the survival and growth of Salmonella in juice supplemented with calcium. A study was done to determine the influence of various calcium supplements on the survival of salmonellae in orange juice held at 4 degrees C for up to 32 days. Isolates of Salmonellal Muenchen (inoculum 1), Salmonella isolates from humans and animals (inoculum 2), and Salmonella isolates from produce outbreaks (inoculum 3) were inoculated into pasteurized orange juices with pH values ranging from 3.96 to 4.19 and containing 350 mg of calcium per 240-ml serving (1.46 mg of calcium/ml). Populations of Salmonella declined rapidly in juice containing calcium lactate (CaL), with counts decreasing from 4.86 log10 CFU/ml to < 1 log10 CFU/ml within 16 days, regardless of the Salmonella serotypes present in inoculum. Counts decreased from 4.89 log10 CFU/ml to < 1 log10 CFU/ml in orange juice supplemented with CaL and tricalcium phosphate (TCP) within 30 days. These reductions were significantly (P < or = 0.05) higher than those of the control (no calcium added), in which Salmonella populations decreased 3.19 +/- 0.20 log10 CFU/ml over 32 days. Populations in orange juice containing TCP or calcium citrate (CC) declined 1.34 +/- 0.20 log10 CFU/ml and 1.96 +/- 0.20 log10 CFU/ml, respectively, over 32 days. These counts were significantly higher than respective control counts in juice stored for 32 days. Populations of Salmonella of inoculum 3 inoculated into juice containing calcium citrate malate (CCM) were significantly higher than in the control. Higher numbers of cells in inoculum 3 also survived compared to numbers of cells of inocula 1 or 2 in juice supplemented with CCM. This study reveals that the form of calcium used to supplement orange juice influences the ability of salmonellae to survive.
BACKGROUND: A recent meta-analysis found that cholecalciferol (vitamin D) should reduce falls by more than 20%. However, little is known about whether supplemental cholecalciferol plus calcium citrate malate will lower the long-term risk of falling in men, active older individuals, and older individuals with higher 25-hydroxyvitamin D levels. METHODS: We studied the effect of 3-year supplementation with cholecalciferol-calcium on the risk of falling at least once in 199 men and 246 women 65 years or older and living at home. Individuals received 700 IU of cholecalciferol plus 500 mg of calcium citrate malate per day or placebo in a randomized double-blind manner. Subjects were classified as less physically active if physical activity was below the median level. Low 25-hydroxyvitamin D levels were classified as those below 32 ng/mL (<80 nmol/L). RESULTS: In 3 years, 55% of women and 45% of men reported at least 1 fall. Mean +/- SD baseline 25-hydroxyvitamin D levels were 26.6 +/- 12.7 ng/mL (66.4 +/- 31.7 nmol/L) in women and 33.2 +/- 14.2 ng/mL (82.9 +/- 34.9) in men. Cholecalciferol-calcium significantly reduced the odds of falling in women (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.30-0.97), but not in men (OR, 0.93; 95% CI, 0.50-1.72). Fall reduction was most pronounced in less active women (OR, 0.35; 95% CI, 0.15-0.81). Baseline 25-hydroxyvitamin D level did not modulate the treatment effect. CONCLUSIONS: Long-term dietary cholecalciferol-calcium supplementation reduces the odds of falling in ambulatory older women by 46%, and especially in less active women by 65%. Supplementation had a neutral effect in men independent of their physical activity level.
BACKGROUND: There is currently no consensus on the effect of dietary protein intake on the skeleton, but there is some indication that low calcium intakes adversely influence the effect of dietary protein on fracture risk. OBJECTIVE: The objective of the present study was to determine whether supplemental calcium citrate malate and vitamin D influence any associations between protein intake and change in bone mineral density (BMD). DESIGN: Associations between protein intake and change in BMD were examined in 342 healthy men and women (aged > or = 65 y) who had completed a 3-y, randomized, placebo-controlled trial of calcium and vitamin D supplementation. Protein intake was assessed at the midpoint of the study with the use of a food-frequency questionnaire and BMD was assessed every 6 mo by dual-energy X-ray absorptiometry. RESULTS: The mean (+/-SD) protein intake of all subjects was 79.1 +/- 25.6 g/d and the mean total calcium intakes of the supplemented and placebo groups were 1346 +/- 358 and 871 +/- 413 mg/d, respectively. Higher protein intake was significantly associated with a favorable 3-y change in total-body BMD in the supplemented group (in a model containing terms for age, sex, weight, total energy intake, and dietary calcium intake) but not in the placebo group. The pattern of change in femoral neck BMD with increasing protein intake in the supplemented group was similar to that for the total body. CONCLUSION: Increasing protein intake may have a favorable effect on change in BMD in elderly subjects supplemented with calcium citrate malate and vitamin D.
Two grams of elemental calcium as carbonate or citrate were given after an overnight fast to 14 patients with advanced renal failure (serum creatinine 759 +/- 365 mumol/l, mean +/- SD). The suppressibility of their hyperparathyroidism was confirmed with a calcium infusion test. Both calcium citrate and carbonate increased significantly plasma ionized calcium (6.8 and 4.5%, respectively) and total calcium (9.3 and 6.0%), p less than 0.001. In the majority of the patients, calcium citrate but not carbonate increased plasma calcium sufficiently to induce the suppression of hyperparathyroidism. The decrease of plasma intact parathyroid hormone was 35.9 +/- 24.8% (mean +/- SD); p less than 0.001) after calcium citrate and 9.2 +/- 18.9% (mean +/- SD; NS) after calcium carbonate.
The interaction of citric acid (H(3)Ci) with calcium fluorapatite(Ca(10) F(2)(PO(4))(6)) was explored for two reasons: (i) to determine the role of the acid in the dissolution process and hence in the mechanism of tooth fluoridation and (ii) to determine whether there is any formation of calcium citrate. It was found that the concentration of calcium or fluoride ions is not stoichiometric with respect to that of phosphate ions in the solution and the stoichiometric deficiency of the amount of fluoride ions in the solution is twice that of the calcium ions and this demonstrates that some calcium fluoride is precipitated. The interaction may be represented by the following chemical equation (pH approximately 2.5): where x (presently < 1) is related to the amount of CaF(2) that has precipitated and may be calculated from the experimental ratio of Ca to P in the solution. In order to establish that the interaction occurs generally with all acids, the reaction of hydrochloric acid with fluoroapatite was studied, and exactly analogous behavior was observed. These facts are also in accord with the solubility of fluorapatite and calcium fluoride. When the amounts of Ca and P in solution are corrected for the precipitated CaF(2), the ratio of Ca to P becomes stoichiometric (= 1.67). Preliminary X-ray analysis of the reacted fluorapatite showed that it contained calcium fluoride. The precipitated CaF(2) may act as a reservoir for the subsequent fluoridation of the mineral and may inhibit bacterial action in the mouth. The concentration of citrate ions does not change in solution, and no formation of calcium citrate is observed.