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Dysregulated calcium homeostasis is common in chronic kidney disease and causally associated with disorders of bone mineralization. However, radiological measures and biomarkers do not allow accurate evaluation of bone calcium balance. Non-radioactive calcium isotopes, 42Ca and 44Ca, are present in our diet and sequestered into body compartments following principles of kinetic isotope fractionation. Isotopically light 42Ca is preferentially incorporated into bone, while heavier 44Ca is excreted. The ratio (44/42Caserum) increases when bone formation exceeds resorption and vice versa, reflecting bone calcium balance. We measured these calcium isotopes by inductively coupled plasma mass-spectrometry in blood, urine and feces of 42 children with chronic kidney disease and 92 receiving dialysis therapy. We compared the isotope ratios with bone biomarkers and determined total bone mineral content by dual-energy x-ray absorptiometry and peripheral quantitative CT expressed as age-adjusted z-scores. The 44/42Caserum ratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The 44/42Caserum ratio positively correlated with age-adjusted z-scores of tibial trabecular bone mineral density and total bone mineral content measured by peripheral quantitative CT, and hip bone mineral density measured by dual-energy X-ray absorptiometry. Significant and independent predictors of total bone mineral content, measured by, were the 44/42Caserum ratio and parathyroid hormone. The 44/42Caserum ratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the 44/42Caserum ratio in patients receiving dialysis was 157% lower than that of age-matched children and 29% lower than levels in elderly women with osteoporosis, implying significantly lower bone mineral content. Thus, calcium isotope ratios may provide a novel, sensitive and non-invasive method of assessing bone calcium balance in chronic kidney disease.

The effect of the dialysate calcium concentration (D[Ca]) on mineral and bone metabolism in patients on peritoneal dialysis (PD) is overlooked. D[Ca] of 1.75 mmol/L is still prescribed to many patients on PD around the world. Previous studies on the effects of reducing D[Ca] have been carried out before the incorporation of calcimimetics in clinical practice. We hypothesized that a reduction in D[Ca] is safe and without the risk of a rise in serum parathyroid hormone (PTH).In this non-randomized clinical trial, the D[Ca] was reduced from 1.75 mmol/L to 1.25 mmol/L for one year in prevalent patients on PD. Demographic, clinical, and CKD-MBD-related biomarkers were evaluated at baseline, 3, 6, and 12 months of follow-up.20 patients completed 1-year follow-up (56 ± 16 years, 50 % male, 25 % diabetic, 55 % with baseline parathyroid hormone - PTH300 pg/mL). Over time, there was no significant change in calcium, phosphate, total alkaline phosphatase, 25(OH)-vitamin D or PTH, although adjustments in calcitriol and sevelamer prescription were required. After 1 year, absolute and percentual change in PTH levels were 36 (-58, 139) pg/mL, and 20 % (-28, 45) respectively. The proportion of patients with PTH 300 pg/mL did not change during the follow-up (p = 0.173).Knowing the risk of a positive calcium balance in patients on PD, reducing the D[Ca] concentration is a safe and valuable option, although medication adjustments are needed to detain PTH rising.

Calcium supplements for prevention and treatment of mineral and bone disorders in chronic kidney disease (CKD) have been alternately praised and damned. Clinical evidence in favor of either attitude has been lacking. The calcium balance study by Spiegel and Brady in patients with late stage 3 and stage 4 CKD suggests that CKD subjects ingesting 2000mg of elemental calcium per day are in marked positive balance. Methodological limitations such as unproven steady state warrant caution and confirmatory studies.

The effect of dietary lentils on calcium balance was evaluated in nine healthy male subjects. The Control and Experimental (+ 130 g dry lentils) diets were each fed for three weeks in a cross-over design. Study diets were matched to subjects' usual calcium and energy intakes, and balanced for protein and phytate. Complete fecal collections were made for all weeks and 24-hour urine collections were made in Week 3 of each period. Calcium balance was maintained during both the Control (0.4 ± 0.8 mmol/day, mean ± SEM) and Experimental periods (− 0.6 ± 0.9 mmol/day); fecal calcium remained unchanged (28.5 ± 1.7 mmol/day, 29.7 ± 1.5 mmol/day, respectively). Urinary excretion, however, varied from Control to Experimental periods for the following: calcium decreased from 5.43 ± 0.44 to 4.53 ± 0.41 mmol/day (P

Calcium is an important nutrient but also contributes to the texture, taste and functionality of most dairy products. The balance between micellar and free calcium in curd and serum phase during direct acidification of bovine milk was studied by changing organic acid type, pH and acidification temperature. Concentration of free calcium increased with decreasing pH and increasing temperature. Citric acid was more efficient than lactic acid at lowering free calcium concentration, while temperature effect was larger for acidification with lactic acid. These findings are rationalized by the stronger binding of calcium to citrate compared to lactate with an almost athermal binding for citrate and an endothermal binding for lactate. Curd yield decreased by decreasing pH as solubilization of colloidal calcium phosphate causes loss of minerals into the serum phase decreasing the concentration of both calcium and phosphate left in the curd, while acidification temperature had little effect on curd yield. These results are important to improve yield and tailor the properties and functionality of dairy products, such as for example Mozzarella cheese.

Calcium balances performed on 519 individuals from birth to 30 years of age, derived from 34 published reports, were pooled by age group and the relationship between intake and balance for each group was compared at both extremes of the intake range. At all ages, from infancy through the young adult years, balance values tended to flatten and become constant at higher intakes, while at lower intakes balance was invariably highly correlated with intake. Threshold intakes and balances were estimated by fitting the data to a two-component, split, linear-regression model. The threshold values at which balance no longer rose with intake exceeded the US recommended dietary allowances for calcium for all the age groups concerned.

Calcium flux and mode of uptake were investigated in an underground dwelling mole-rat, Cryptomys damarensis, fed diets of varying Ca content. The amount of dietary Ca positively influenced the amounts ingested, absorbed and retained. The linear relationship between ingested and absorbed Ca was significantly (P less than 0.001) correlated, implying that this process is nonsaturable. When mole-rats were fed a diet low in Ca, apparent fractional absorption of Ca was high (85.88%). This increased still further when the diet was changed to a food of greater Ca content (96.13%, carrots; 96.97%, gemsbok cucumber). Mineral homeostasis is regulated at the intestinal level in most mammals. Regardless of dietary Ca content, uptake of 45Ca (examined via the everted gut sac technique) was passive, confirming that absorption is via a nonsaturable process. Plasma Ca concentrations were not tightly regulated, yet when fed the diet with the highest Ca content, mole-rats were not hypercalcemic. Regardless of diets, Ca apparent fractional retention was positive, and approached physiological maxima (greater than 97%). Cryptomys damarensis, in using highly efficient modes of mineral uptake and retention, is therefore capable of fully exploiting the limited food resources of their arid ecotope.

Calcium balance in chronic kidney disease is poorly understood as calcium deficiency is a stimulus for secondary hyperparathyroidism and consequent bone loss while calcium excess promotes extraosseous calcifications. To help resolve this, we evaluated calcium balance in normal individuals and in patients with chronic kidney disease (CKD) on daily diets containing 800 and 2000 mg elemental calcium. Both normal individuals and patients with late stage 3 and stage 4 CKD were in slightly negative to neutral calcium balance on the 800-mg calcium diet. Normal individuals were in modest positive calcium balance on the 2000-mg diet, while patients with CKD on the same diet were in marked positive calcium balance at least over the 9 days of study; and significantly greater than the normal individuals. Increased calcium intake significantly decreased 1,25-dihydroxy-vitamin D and intact parathyroid hormone levels but did not alter the serum calcium concentration. Thus, our findings have important implications for both preventing calcium deficiency and loading in individuals with late stage 3 and stage 4 CKD.

Few calcium balance data are available from young children on which to base dietary recommendations.The objective of the study was to evaluate the relation between calcium intake and balance in healthy children aged 1-4 y consuming typical American diets.Subjects were assigned to a diet with nutrient intakes similar to those of their usual diet. Calcium absorption was assessed by using a dual-tracer stable-isotope technique. Endogenous fecal excretion was measured in a subset of children, and net calcium balance was calculated.Mean calcium intake was 551 mg/d (range: 124-983 mg/d), and mean (+/-SEM) calcium retention was 161 +/- 17 mg/d. Both linear and nonlinear modeling of balance data showed that a calcium intake of approximately 470 mg/d led to calcium retention of 140 mg/d, which is the amount that meets expected bone growth needs in children of this age. No evidence was found that calcium intakes of 800 to 900 mg/d reached the threshold intake beyond which no additional increase in calcium retention would occur.Bone growth needs in 1-4-y-old children following American diets are met by a daily calcium intake of approximately 470 mg/d, which suggests that the current Adequate Intake of 500 mg/d is close to the actual Estimated Average Requirement. The benefits and risks of higher calcium intakes consistent with threshold values should be evaluated in a controlled trial before those intakes could be used as a basis for dietary recommendations.

Objective Bone mineral density is compromised in individuals with cystic fibrosis (CF); calcium is the major bone mineral. This study examined the impact of endogenous fecal calcium (V endo ) losses on calcium balance in girls with CF. Study design V endo was measured in 12 girls with CF (aged 7-18 years): 7 younger, premenarcheal girls with compromised nutritional status; and 5 older, postmenarcheal girls with adequate nutritional status. V endo was measured as the amount of intravenously administered 42 Ca, a calcium stable isotope, in stool relative to urine over 6 days. V endo was compared between pre- and postmenarcheal girls by Student's t test. Actual calcium balance [absorbed calcium−(urinary calcium (V u )+V endo )] was compared with estimated balance (assuming V endo =1.6 mg/kg/day calcium) by paired t test. Results V endo was 99.3±42.3 mg/day. By body weight, V endo was highest among premenarcheal girls (3.37±1.09 mg/kg/day), resulting in excess losses (>1.6 mg/kg/day) of 55.0±45.7 mg/day. Over 1 year, this represents 20.1±16.7 g of unattained bone calcium or 6.7±4.2% of the bone calcium content of these girls. Conclusions V endo is a significant source of calcium loss in individuals with CF and may limit calcium availability for bone mineral deposition.

Chinese dietary reference intakes (DRIs) for calcium were developed mainly from studies conducted amongst Caucasians, yet a recent review showed that reference calcium intakes for Asians are likely to be different from those of Caucasians (Lee and Jiang, 2008). In order to develop calcium DRIs for Chinese adolescents, it is necessary to explore the characteristics and potential influencing factors of calcium metabolic balance in Chinese adolescents. A total of 80 students (15.1+/-0.8 years) were recruited stratified by gender from a 1-year calcium supplementation study. Subjects were randomly designed to four groups and supplemented with calcium carbonate tablets providing elemental calcium at 63, 354, 660, and 966 mg/day, respectively. Subjects consumed food from a 3-day cycle menu prepared by staff for 10 days. Elemental calcium in samples of foods, feces, and urine was determined in duplicates by inductively coupled plasma atomic emission spectrometry. The total calcium intake ranged from 352 to 1323 mg/day. The calcium apparent absorption efficiency and retention in boys were significantly higher than that in girls (68.7% vs. 46.4%, 480 mg/day vs. 204 mg/day, P

Vitamin K2 (menatetrenone) has been used for the treatment of osteoporosis in Japan. We investigated the effects of ovariectomy (OVX) and vitamin K2 on the calcium (Ca) balance in 20-week-old female Fischer rats. Vitamin K2 (31 mg/kg per day) was given to animals as a dietary supplement. At weeks 4 and 8 after OVX, a Ca balance study was performed for 5 days. The intestinal Ca transport was determined using the everted gut-sac technique at week 9. The Ca balance was poorer in the OVX-control group than in the sham-control group at weeks 4 and 8 after OVX. The Ca balance improved significantly in the vitamin K2 groups as compared with the sham- and OVX-control groups. The intestinal Ca transport decreased due to OVX and was higher in the vitamin K2 administration groups than in the sham- and OVX-control groups, but not to a significant extent. The bone mineral density in the femoral metaphysis as well as the cortical area and cortical thickness in the femoral diaphysis in the OVX-control group were lower than in the sham-control group. The administration of vitamin K2 significantly inhibited an OVX-induced decrease in cortical area and cortical thickness in the femur. These findings suggest that the poor Ca balance observed in ovariectomized rats may be improved by vitamin K2; vitamin K2 may be involved in preventing bone loss in vivo.

Prostaglandins (PGs) are known to have various effects on bone metabolism. The supplementation of essential fatty acids (EFAs), the precursors of PGs, leads to increased intestinal calcium absorption and calcium balance. It is, however, not known whether increased calcium absorption and calcium balance will enhance the calcium content in bone. Male Sprague-Dawley rats (n = 40) aged 5-12 weeks were supplemented with EFAs. The main dietary EFAs, linoleic acid (LA) and alpha-linolenic acid (ALA) were administered in a ratio of 3:1 as a control group. The conversion of LA to ALA to the PG precursors is slow, with the first step, delta-6-desaturation being rate limiting. Fatty acids beyond this rate-limiting step, gamma-linolenic acid (GLA, n-6) and eicoapentaenioc acid (EPA, n-3), were administered to different groups in the ratios 3:1, 1:1 and 1:3 to explore the impact of different ratios of n-6 and n-3 EFAs. Intestinal calcium absorption (mg/24 h) increased by 41.5% in the 3:1 supplemented group, compared with the control group. The decrease in urinary calcium (mg/24 h) correlated with the increase in n-3 level. The calcium balance (mg/24 h) and bone calcium (mg/g bone ash) increased significantly in the 3:1 (41.5% and 24.7%) group, compared with the control. The increase in bone calcium might be attributed to an EFA-induced increase in circulating PGs. An increased synthesis of PGs acting on target bone cells, as well as changes in membrane fluidity, may underlie these observations.

Sprague Dawley rats were supplemented with either fish oil, evening primrose oil or sunflower oil (control) for 12 weeks. Calcium balance and fatty acid analyses of plasma and intestinal membranes were performed at week 12. Fish oil decreased faecal calcium excretion significantly leading to an increased calcium balance (p < 0.05). Increased unsaturation of the intestinal membranes in the fish oil group may facilitate calcium absorption.

Calcium signaling has been implicated in plant graviperception. In order to investigate the role of intracellular calcium in the process, I used lithium ions (LiCl), which suppress inositol 1,4,5-trisphosphate (IP 3 ) cycling and signaling by inhibiting inositol-1-phosphatase. After 4 h of gravistimulation, no curvature was observed in 81% of the roots of 5-day Pisum sativum seedlings pretreated with 5 mM LiCl. Structural features of statocyte ultrastructure in these roots were the following: loss of a cellular polarity, appearance of amyloplast clusters, condensed mitochondria, local dilations in a perinuclear space, increases in a relative volume of vacuoles. The intensity of a cytochemical reaction (pyroantimonate staining which detected Ca 2+ ions) was moderate: the Ca 2+ pyroantimonate deposits were observed in all organelles. There were few granules of this precipitate in a hyaloplasm of the statocytes. Mitochondria and vacuoles were found to contain more granules of the precipitate compared with the controls. Additionally, Ca 2+ -ATPase activity in the statocytes of pea roots pretreated with LiCl was approximately the same as in control roots. Data obtained by using inhibitor of inositol signaling suggest that the observed effects of LiCl on root gravicurvature and ultrastructure of root statocytes were due to effects on Ca 2+ homeostasis, particularly on IP 3 -mediated release of intracellular Ca 2+ which can be inhibited by inositol depletion. The work demonstrates the key role played by second messengers (Ca 2+ and IP 3 ) in a gravity perception and response.

The effect of an acid or alkali diet was investigated in 14 mature dairy cows during the last 28 days of pregnancy. The acid diet reduced the incidence of parturient hypocalcaemia compared with the alkali diet and was associated with higher blood ionised calcium and plasma chloride concentrations and lower blood pH and acid-base excess before parturition. Plasma 1,25-dihydroxyvitamin D concentrations before parturition were increased by the acid diet but the concentrations of parathyroid hormone and intact 1–86 parathyroid-hormone-related peptide were unaffected. The estimated fractional calcium absorption and calcium mobilisation rate during an ethylenediamine tetraacetic acid infusion were increased by the acid diet 14 days before parturition. Cortical bone remodelling occurred in all the animals during late pregnancy but was particularly evident in the cows given the acid diet. The data suggest that an acid diet ameliorates parturient hypocalcaemia by enhancing calcium mobilisation before parturition by increasing calcium absorption and bone resorption, these increases possibly being mediated by increases in the plasma concentration of 1,25-dihydroxyvitamin D.

Summary The ‘meal effect’ on mineral bioavailability is evaluated in short-term studies on humans whereas feeding experiments on pigs lasting several weeks allow both mineral balance studies and measurements of bone ash contents or breaking strength. Three groups of 7 pigs were given 3 dietary treatments, differing essentially in the mode of Ca and P distribution, for 7 weeks. Group 1 received Ca and P within the meals, Group 2 was fed Ca separate from meals, and Group 3 was given both Ca and P separate from meals. Ca and P absorption were evaluated by a 10-day balance trial, then several bones were collected to determine mineral contents and breaking strength. Ca was much better absorbed and retained by giving CaC03 within meals. Simultaneous administration of Ca and P did not influence Ca absorption, but tended to improve Ca and P retention. The best bone scores were obtained when CaC03 and NaH2PO4 were given simultaneously in meals. The Ca and P balance values and bone parameters were strongly correlated. Thus meal incorporation and simultaneous intake of Ca and P are both required for the best mineral retention, evaluated by balance or bone scores.

One serious difficulty with calcium balance studies is the unpredictable fecal excretion of calcium which follows ir-regular bowel habits. The calcium balance is often impossible to evaluate because of the error introduced by inadequate demarcation of feces. The significance of the demarcation error can be evaluated in the course of a balance study by a simple, continuous registration of the cumulative calcium balance expressed in mg./day. A calcium balance study should not be discontinued before the cumulative balance has attained a plateau for at least 3–4 periods. The length of the study will thus be dependent on the bowel habits of the subject studied. At a large calcium intake the plateau is generally obtained later than at a low one.

Methods for the measurement of calcium in the diet, urine and faeces for the performance of a calcium balance study are described, along with experiments on analytical procedures including recovery values. A means of calculating the inherent “technical error” in such a balance is given, and a method for determining the significance of any change in a patient's balance is described. These are illustrated by worked examples of data from a patient suffering from Paget's disease and one with osteoporosis before and after treatment with calcitonin.

Calcium balance performance was evaluated in 130 normal perimenopausal women ages 35 to 50, studied on their usual, self-selected dietary calcium intakes. Two distinct balance methods were used, one based on customary intake and output measurements, and the other based on absorption and clearance of two simultaneously administered calcium isotopes. Both methods yielded essentially identical results. Under study conditions as closely approximating normal living as possible, these women averaged -24 and -31 mg Ca/day by the two balance methods (exclusive of unmeasured dermal losses). More significantly, there was a positive correlation between intake and balance, with women on higher self-selected intakes exhibiting more positive balance than women selecting lower intakes. The calcium intake predicted from our data which would be required to produce an average balance of zero was 1.241 g/day. This is significantly in excess of the current recommended dietary allowance for calcium. The implications and significance of this discrepancy are explored in detail.