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Introduction: Although vascular calcification is a recognised complication for haemodialysis patients, peritoneal dialysis (PD) patients are also at risk. As such we wished to review peritoneal and urinary calcium balance and the effect of calcium containing phosphate binders (CCPBs). Methods: Twenty-four-hour peritoneal calcium balance and urinary calcium were reviewed in PD patients undergoing their first assessment of peritoneal membrane function. Results: Results from 183 patients, 56.3% male, 30.1% diabetic, mean age 59.4 ± 16.4 years, median 2.0 (2–6) months of PD, 29% treated by automated PD (APD), 26.8% continuous ambulatory (CAPD) and 44.2% APD with a day-time exchange (CCPD) were reviewed. Peritoneal calcium balance was positive in 42.6%, and remained positive in 21.3% after including urinary calcium losses. PD calcium balance was negatively associated with ultrafiltration (odds ratio 0.99 (95% confidence limits 0.98–0.99), p= 0.005. PD calcium balance was lowest with APD (APD − 0.45 (− 0.78 to 0.05) vs CAPD − 0.14 (− 1.18 to 0.59) vs CCPD − 0.03) − 0.48 to 0.5) mmol/day), p< 0.05, with 82.1% of patients with a positive balance prescribed icodextrin, when combining peritoneal and urinary losses. When considering CCPB prescription, then 97.8% of subjects prescribed CCPD had an over-all positive calcium balance. Discussion: Over 40% of PD patients had a positive peritoneal calcium balance. Elemental calcium intake from CCPB had a major effect on calcium balance, as median combined peritoneal and urinary calcium losses were < 0.7 mmol/day (26 mg), so caution is required to prevent excessive CCPB prescribing, increasing the exchangeable calcium pool and thus potentially increasing vascular calcification, particularly for anuric patients. Graphical abstract:

Tomato fruits of high quality and yield are of interest to greenhouse growers. As potassium (K) and calcium (Ca) have been associated with fruit quality, we studied the effect of the balance between such cations and the electrical conductivity (EC) on fruit yield and quality. Plants were fertigated with K (Kext) and Ca (Caext) balances in the nutrient solution varying from 0.54–1.22 and 0.69–1.44 at ECs of 2.3 ± 0.1 dS m−1and 2.7 ± 0.1 dS m−1, respectively. Optimum balance for fruit yield was 0.82–0.85, and it was associated with high fruit K internal (Kint) concentration (~ 200 mmol kg−1). Higher EC increased firmness when the balance was ≤ 1.00, with the optimum at 0.85; firmness was correlated with Caintwhen EC was 2.3 dS m−1; however, at 2.7 dS m−1, increasing Kextincreased firmness and intensified the effect of Caext. Increasing a* values were associated with high lycopene and uniform maturation when that balance was 0.82 and 1.00 at low and high EC, respectively. Highest a* values were observed when Kintin the fruit was ~ 200 mmol kg−1, while 91 to 130 mmol kg−1were associated with lower a* values. Fruits contained higher starch (+ 20%), total (+ 12%), and reducing sugars (+ 29%) at high EC. The optimum K and Ca balance, 0.82–0.85, is independent of their concentration and was associated with high yield and firmness, improved fruit color, and increased lycopene and sugar concentrations.

Background: Supplementation of calcium during continuous venovenous hemofiltration (CVVH) with citrate anticoagulation is usually titrated using a target blood ionized calcium concentration. Plasma calcium concentrations may be normal despite substantial calcium loss, by mobilization of calcium from the skeleton. Aim of our study is to develop an equation to calculate CVVH calcium and to retrospectively calculate CVVH calcium balance in a cohort of ICU-patients. Methods: This is a single-center retrospective observational cohort study. In a subcohort of patients, all calcium excretion measurements in patients treated with citrate CVVH were randomly divided into a development set (n= 324 in 42 patients) and a validation set (n= 441 in 42 different patients). Using mixed linear models, we developed an equation to calculate calcium excretion from routinely available parameters. We retrospectively calculated calcium balance in 788 patients treated with citrate CVVH between 2014 and 2021. Results: Calcium excretion (mmol/24 h) was − 1.2877 + 0.646*[Ca]blood,total* ultrafiltrate (l/24 h) + 0.107*blood flow (ml/h). The mean error of the estimation was − 1.0 ± 6.7 mmol/24 h, the mean absolute error was 4.8 ± 4.8 mmol/24 h. Calculated calcium excretion was 105.8 ± 19.3 mmol/24 h. Mean daily CVVH calcium balance was − 12.0 ± 20.0 mmol/24 h. Mean cumulative calcium balance ranged from − 3687 to 448 mmol. Conclusion: During citrate CVVH, calcium balance was negative in most patients, despite supplementation of calcium based on plasma ionized calcium levels. This may contribute to demineralization of the skeleton. We propose that calcium supplementation should be based on both plasma ionized calcium and a simple calculation of calcium excretion by CVVH. Graphical abstract:

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Background: Low intakes of calcium are associated with an increased risk of both osteoporosis and cardiovascular disease. Objective: To provide new estimates of the average calcium requirement for men and women, we determined the dietary calcium intake required to maintain neutral calcium balance. Design: Calcium balance data [calcium intake--(fecal calcium + urinary calcium)] were collected from 155 subjects [women: n = 73; weight: 77.1 [+ or -] 18.5 kg; age: 47.0 [+ or -] 18.5 y (range: 20-75 y); men: n = 82; weight: 76.6 [+ or -] 12.5 kg; age: 28.2 [+ or -] 7.7 y (range: 19-64 y)] who participated in 19 feeding studies conducted in a metabolic unit. Balance data from the final 6-12 d of each dietary period (minimum length: 18 d) of each study (1-9 observations per subject) were analyzed. Data were excluded if individual intakes of magnesium, copper, iron, phosphorus, or zinc fell below the estimated average requirements or exceeded the 99th percentile of usual intakes from the 1994 Continuing Survey of Food Intakes by Individuals (for iron, above the upper limit). Daily intakes of calcium ranged between 415 and 1740 mg. The relation between intake and output was examined by fitting random coefficient models. Coefficients were included to test for sex and age differences. Results: The models predicted a neutral calcium balance [defined as calcium output (Y) equal to calcium intake (C)] at intakes of 741 mg/d [95% prediction interval (PI): 507, 1035; Y = 148.29 + 0.80C], 9.4 mg * kg body [wt.sup.-1] * [d.sup.-1] [95% PI: 6.4, 12.9; Y = 1.44 + 0.85C], or 0.28 mg * [kcal.sup.-1] * [d.sup.-1] [95% PI:0.19,0.38; Y = 0.051 + 0.816C]. Neither age nor sex affected the estimates when calcium intakes were expressed as mg/d or as mg * kg body [wt.sup.-1] * [d.sup.-1]. Conclusion: The findings suggest that the calcium requirement for men and women is lower than previously estimated. KEY WORDS Calcium intake, calcium excretion, calcium balance, calcium requirement

Background: Few calcium balance data are available from young children on which to base dietary recommendations. Objective: 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. Design: 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. Results: Mean calcium intake was 551 mg/d (range: 124-983 mg/ d), and mean ([+ or -] SEM) calcium retention was 161 [+ or -] 17 mg/d. Both linear and nonlinear modeling of balance data showed that a calcium intake of [approximately or equal to] 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. Conclusions: Bone growth needs in l-4-y-old children following American diets are met by a daily calcium intake of [approximately or equal to] 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. Am J Clin Nutr 2007;85: 750-4. KEY WORDS Calcium absorption, stable isotopes, bioavailability, nutrient requirements

Background: Additional calcium is required during lactation, and several calcium regulatory factors are involved in calcium balance. In lactating rural women who have marginal nutrition and consume a high-fiber diet, negative calcium balance may be expected. Objective: We evaluated calcium balance and its association with potential calcium regulatory factors in lactating, rural Mexican women who had marginal nutrition and consumed a high-fiber diet. Design: This cross-sectional study included women at 1, 3, 6, and 12 mo of lactation (L1, L3, L6, and L12 groups) and women who had weaned their infants (W group). Age-matched, nonlactating women (NL group) were also included. Calcium balance and concentrations of calcium regulatory factors were determined. Correlation analysis was performed by using data from all of the lactating women. Results: Calcium balance in the L1, L3, and L6 groups was negative and was significantly different (P < 0.05) from that in the W .and NL groups. Serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D 1,25-[(OH).sub.2]D] concentrations were significantly higher (P < 0.05) in the W group than in the L and NL groups. Calcium balance was positively associated with serum estradiol concentrations (r = 0.58, P < 0.05) and negatively associated with serum 1,25-[(OH).sub.2]D concentrations (r = -0.52, P < 0.05). Breast-milk calcium concentrations correlated positively with serum PTH-related peptide (PTHrP) concentrations (r = 0.51, P < 0.05) and negatively with serum estradiol concentrations (r = -0.57, P < 0.05). Conclusions: Negative calcium balance was observed during lactation in rural Mexican women who consumed a high-fiber diet. Furthermore, the data suggest that the hormones estradiol and PTHrP are involved in the regulation of calcium balance and of the calcium content of milk during lactation. KEY WORDS Calcium balance, calciotrophic hormones, parathyroid hormone--related peptide, PTHrP, insulin-like growth factor I, IGF-I, lactation, rural Mexican women

Nine healthy, young men consumed constant diets to determine selected large-bowel, serum cholesterol and triacylglycerol, and calcium balance responses to 3 amounts of fiber provided by a mixture of fruit, vegetables, and grains. The diets, each consumed for 1 mo, contained 16, 30, and 42 g total fiber/d, of which 2.9, 4.8, and 7.7 g, respectively, was soluble. Mean daily wet and dry stool weights increased with each fiber addition. The first fiber addition increased defecation frequency and decreased fecal pH, bile acid concentration, and neutral steroid concentration; the second addition had no further effect. Mean weight of each defecation and stool moisture did not increase and serum cholesterol and triacylglycerol concentrations, calcium balance, and gastrointestinal transit time did not decrease as fiber intake increased. We conclude that 1) fiber provided by a mixed-food diet increases stool weight as effectively as does wheat or oat bran; 2) even high amounts of dietary fiber do not change transit time or defecation frequency if they are already [approximately equals] 1 and 2-3 d, respectively; 3) food patterns consistent with the food pyramid and incorporating legumes and whole grains are necessary to achieve recommended fiber intakes of 20-35 g/d, even if energy intake is [is greater than] 12.55 MJ (3000 kcal); 4) soluble fiber provided by a mixture of whole foods has no effect on serum cholesterol concentrations or output of fecal bile acids; and 5) mixed-food fiber has little effect on calcium balance when calcium intakes are high ([is greater than or equal to] 1.5 g/d). Am J Clin Nutr 1998:68:615-22.

Osteoporosis is a decrease in bone density which can lead to fractures and is a serious health problem, particularly among postmenopausal white women. Many factors are thought to be related to development of osteoporosis, including extent of skeletal mass acquisition during adolescence, familial factors, and hormonal factors, which influence the rate of bone loss after menopause. Most treatments of established osteoporosis are rather ineffective, so prevention of osteoporosis has become a more important treatment goal. Achievement of a maximum bone mass at the time of skeletal maturation is thought to be the most important factor in preventing later bone loss, but little is known about the mechanisms by which peak bone density can be achieved. It is possible that nutrition, specifically calcium intake, as well as age, sex, and genetically determined factors, may influence peak bone mass. Calcium balance, bone density, and the effect of two years of calcium supplementation were studied in 31 adolescent females, and the bone densities of their biological parents were evaluated as well. Calcium balance, the amount of calcium retained in the body, was determined by calcium ingestion, since the level of urinary calcium did not increase with increased intake. At the start of the study, 29 percent of subjects were consuming less than the RDA (recommended dietary allowance) of calcium. The group given calcium supplements for two years had about twice the calcium intake of the unsupplemented group. Bone mass and density increased over two years in both groups. The supplemented group had greater increases, but these were not significant, possibly because of studying too few subjects. Bone size, mass, and density correlated well between daughters and their parents. The bone mass of daughters at age 14 was 80 to 85 percent of that of their mothers, and this increased to 90 to 97 percent by age 16. The results suggest that calcium intake may exert a significant influence on peak bone mass and thus on later development of osteoporosis. Calcium supplementation should be considered for adolescent women. (Consumer Summary produced by Reliance Medical Information, Inc.)

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.

The word is out. One out of every two women and one in eight men will suffer from a debilitating bone fracture caused by osteoporosis. These staggering statistics have made [...]

The physiology of calcium balance and the associated implications are discussed. The physiological principles are vital to ensure that the patients' calcium balance is maintained.

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).

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Context:Controversy persists over: 1) how best to restore low serum 25-hydroxyvitamin D (25D) levels (vitamin D2 [D2] vs vitamin D3 [D3]); 2) how best to define vitamin D status (total [protein-bound + free] vs free 25D); and 3) how best to assess the bioactivity of free 25D.Objective:To assess: 1) the effects of D2 vs D3 on serum total and free 25D; and 2) whether change in intact PTH (iPTH) is more strongly associated with change in total vs free 25D.Design:Participants previously enrolled in a D2 vs D3 trial were matched for age, body mass index, and race/ethnicity. Participants received 50 000 IU of D2 or D3 twice weekly for 5 weeks, followed by a 5-week equilibration period. Biochemical assessment was performed at baseline and at 10 weeks.Setting and Participants:Thirty-eight adults (19 D2 and 19 D3) ≥18 years of age with baseline 25D levels <30 ng/mL were recruited from an academic ambulatory osteoporosis clinic.Outcome Measures:Serum measures were total 25D, free 25D (directly measured), 1,25-dihydroxyvitamin D, calcium, and iPTH. Urine measure was fasting calcium:creatinine ratio.Results:Baseline total (22.2 ± 3.3 vs 23.3 ± 7.2 ng/mL; P= .5) and free (5.4 ± 0.8 vs 5.3 ± 1.7 pg/mL; P= .8) 25D levels were similar between D2 and D3 groups. Increases in total (+27.6 vs +12.2 ng/mL; P= .001) and free (+3.6 vs +6.2 pg/mL; P= .02) 25D levels were greater with D3 vs D2. Percentage change in iPTH was significantly associated with change in free (but not total) 25D, without and with adjustment for supplementation regimen, change in 1,25-dihydroxyvitamin D, and change in calcium.Conclusions:D3 increased total and free 25D levels to a greater extent than D2. Free 25D may be superior to total 25D as a marker of vitamin D bioactivity.

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 44/42Caserumratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The 44/42Caserumratio 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 44/42Caserumratio and parathyroid hormone. The 44/42Caserumratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the 44/42Caserumratio 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.

Fructus ligustri lucidi (FLL) is a widely used herb in China that is classically included in antiaging formulas for the treatment of age-related symptoms. Our laboratory previously showed that FLL could regulate calcium balance in young ovariectomized (OVX) rats. In the present study, we aimed to determine whether FLL could regulate calcium balance in aged OVX rats and to study the potential mechanisms that mediate its action in vivo.

Background Calcium balance in chronic kidney disease patients on peritoneal dialysis (PD) has not been well studied. This issue is particularly important, given the careful attention now being paid to vascular calcification, the increasing use of cinacalcet therapy (with accompanying reductions in serum Ca levels), the increasing use of vitamin D and its analogs (which increase Ca), and the increasing use of Ca-containing phosphate binders. The present study was conducted to examine the factors influencing transperitoneal calcium balance during continuous cycling peritoneal dialysis (CCPD) therapy, with particular attention to net ultrafiltration (UF) and serum ionized Ca (iCa).Patients and Methods This open, prospective cohort study included 40 medically stable patients maintained on CCPD for at least 3 months. Most patients used low-Ca (2.5 mEq/L) PD fluid; the Ca content of PD fluid for patients on icodextrin-based solutions was 3.5 mEq/L. Patients were instructed to record the quantity of dialysate instilled in a 24-hour period and net UF, and to bring a well-mixed aliquot of PD drainage to the dialysis unit. Concentrations of iCa and dialysate Ca were measured. Total Ca instilled into and drained from the PD fluid was calculated, and then the transperitoneal calcium balance was determined.Results Significant correlations were noted between transperitoneal calcium balance and both serum iCa (r= –0.360) and the UF rate (r= –0.708). Of the patients whose iCa was over 5 mg/dL, 71% were in negative calcium balance; of those with iCa levels below 5 mg/dL, 62% were in positive calcium balance. Of patients with UF below 1000 mL daily, 58% were in positive calcium balance; of those with 1000 mL UF or more, net Ca gain was noted in only 38%.Conclusions The present study demonstrates the importance of UF and iCa in determining transperitoneal Ca transport. These findings are of particular importance given the widening use of calcimimetic agents, vitamin D analogs, and Ca-based phosphate binders (all of which alter iCa) and the potential association between UF rate and outcome in PD patients.

AbstractObjective: The purpose of this study was to examine the effects of vitamin K2 administration on calcium balance and bone mass in young rats fed a normal or low calcium diet. Methods: Forty female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into four groups with 10 rats in each group: 0.5% (normal) calcium diet, 0.1% (low) calcium diet, 0.5% calcium diet + vitamin K2 (menatetrenone, 30 mg/100 g chow diet), and 0.1% calcium diet + vitamin K2. After 10 weeks of feeding, serum calcium and calciotropic hormone levels were measured, and intestinal calcium absorption and renal calcium reabsorption were evaluated. Bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Results: Feeding a low calcium diet induced hypocalcemia, increased serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels with decreased serum 25-hydrovyvitamin D [25(OH)D] level, stimulated intestinal calcium absorption and renal calcium reabsorption, and reduced cortical bone mass as a result of decreased periosteal bone gain and enlarged marrow cavity, but did not significantly influence cancellous bone mass. Vitamin K2 administration in rats fed a low calcium diet stimulated renal calcium reabsorption, retarded the abnormal elevation of serum PTH level, increased cancellous bone mass, and retarded cortical bone loss, while vitamin K2 administration in rats fed a normal calcium diet stimulated intestinal calcium absorption by increasing serum 1,25(OH)2D level, and increased cortical bone mass. Conclusion: This study clearly shows the differential response of calcium balance and bone mass to vitamin K2 administration in rats fed a normal or low calcium diet.Copyright © 2005 S. Karger AG, Basel

Abstract.:  For people in Western countries, the vegan diet has the advantage of low energy intake, but the calcium status of this strictly plant-based diet is still unclear. The aim of this study was to determine the calcium balance of individuals on a vegan diet in comparison with a lactovegetarian diet in a short-term investigation. Seven women and one man, ranging in age from 19 to 24 years, received during the first 10 days a vegan diet based on plant foods and calcium-rich mineral water and a lactovegetarian diet during the following 10 days. Portion size was adapted to the subjects' individual energy requirements. Calcium status was assessed by means of calcium intake in food and calcium output in feces and urine as measured by flame atomic absorption spectrophotometry. In addition, deoxypyridinoline was measured in urine as a marker of bone resorption. The results show a significantly smaller daily calcium intake with an average of 843 ± 140 mg in the vegan versus 1322 ± 303 mg in the lactovegetarian diet. Apparent calcium absorption rates were calculated as 26% ± 15% in the vegan and 24% ± 8% in the lactovegetarian group (NS). The calcium balance was positive both in the vegan diet (119 ± 113 mg/day) and in the lactovegetarian diet (211 ± 136 mg/day) (NS). Deoxypyridinoline excretion showed no significant difference between the two diets (105 ± 31 and 98 ± 23 nmol/day). The present results indicate that calcium balance and a marker of bone turnover are not affected significantly when calcium is provided either solely by plant foods or by a diet including dairy products, despite the significantly different calcium intake levels in the diets. We conclude that a well-selected vegan diet maintains calcium status, at least for a short-term period.

Cardiovascular complications caused by an accelerated atherosclerotic disease represent the largest single cause of mortality in chronic renal failure patients. The rapidly developing atherosclerosis of the uremic syndrome appears to be caused by a synergism of different mechanisms, such as malnutrition, oxidative stress and genetic factors. Recent studies provide evidence that chronic inflammation plays an important role in the pathogenesis of cardiovascular diseases. Hyperphosphatemia and an increased calcium-phosphate ion product have also been associated with an increased risk of death. Cardiovascular calcifications secondary to increases in phosphate and calcium load in dialysis patients might exert an important contribution to the excess cardiovascular mortality and morbidity in dialysis patients.Elevated serum levels of plasma C-reactive protein (CRP) are associated with the extent and severity of the atherosclerotic processes as well as with an increased risk of experiencing myocardial infarction and sudden cardiac death in apparently healthy subjects.In patients affected by pre-dialytic renal failure increased levels of CRP and IL-6 were recorded in 25% of our population; CRP and IL-6 were inversely related with renal function. These data suggest the activation - even in the predialytic phase of renal failure - of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.In recent years we have investigated the hypothesis that the chronic inflammatory state of the uremic patient could be at least in part due to the dialytic technique. We have shown that the increase of CRP in stable dialysis patients may be due to the stimulation of monocyte/macrophage by backfiltration of dialysate contaminants. During conventional dialysis, a positive calcium balance and a concomitant inflammatory state may act as cofactors in the development of cardiovascular calcifications. We suggest that this hypothesis should be verified by clinical studies. A reevaluation of the ideal calcium levels in the dialysate is warranted: a neutral intradialytic calcium balance is probably more appropriate, although not easily attainable.

Like hemodialysis patients, peritoneal dialysis (PD) patients are facing an excessively increased burden of vascular and valvular calcification. According to some surveys, more than 80% of prevalent PD patients are complicated with vascular calcification, and more than one third have heart valve calcification.Dysregulated phosphate metabolism is well recognized to play an important role in inducing vascular calcification, but increasing evidence is suggesting that dysregulated calcium metabolism also promotes vascular calcification and might in fact be more potent than phosphate in inducing that calcification. Growing evidence from randomized controlled trials shows more progression of vascular calcification and higher mortality among chronic kidney disease (CKD) patients receiving calcium-based phosphate binders than among those receiving non-calcium-containing phosphate binders. Those results raise important safety concern about the use of high-dose calcium-based phosphate binders in the CKD population, including both non-dialysis and dialysis patients (especially anuric dialysis patients), who have markedly reduced urinary calcium excretion. To prevent calcium overload, this review recommends restricting the dose of calcium-based phosphate binders in CKD patients, especially those who are elderly, who have increased cardiovascular risk, who already have baseline vascular or valvular calcification, or who have low intact parathyroid hormone and adynamic bone disease.

Abstract.: The role of estrogen in the regulation of calcium balance is still poorly understood. A calcium balance study was performed to examine the effects of estrogen status in relation to fecal calcium loss as a component of bone loss after oophorectomy (OOX) in the mature rat. The components of the classic calcium balance were compared with calcium balance estimates obtained from whole body bone density. Six month or older Sprague Dawley rats were allocated to either a sham-operated or OOX group and fed a 0.1% calcium diet. The bone mineral density (BMD) and bone mineral content (BMC) were measured at baseline, 6 weeks, and 9 weeks. A calcium balance was done for 6 days before and 6 weeks post OOX. The fall in BMD from baseline to 9 weeks in the OOX group was significantly greater than in the sham-operated group. The calcium balance was more negative at baseline than at 6 weeks in both groups of animals because they had not adapted to the low calcium diet. However, the increase in calcium balance was significantly less in the OOX animals than in the sham-operated animals. The greater the rise in calcium balance from the baseline to the 6 weeks balance the less the fall in the calcium content of the whole body (Spearman correlation: r = 0.604 P = 0.008). The fall in fecal calcium, but not urine calcium or calcium consumed, was negatively correlated with the change in whole body BMC (Spearman correlation: fecal calcium r =−0.763 P = 0.001). Thus, the primary effect of estrogen deficiency on calcium balance in the mature rat appears to be calcium flux in the bowel, rather than renal calcium handling.

Hypercalcemia frequently occurs in continuous ambulatory peritoneal dialysis (CAPD) patients treated with calcium carbonate and vitamin D metabolites. To reduce the incidence of this complication, it has been proposed to use dialysate solutions with a low calcium concentration. However, there is concern that these solutions may lead to a negative calcium balance. We measured calcium balance in 13 CAPD patients with secondary hyperparathyroidism who were treated with calcium carbonate and alfacalcidol, 2 μg twice weekly, while using 1.0- (1.0 group) and 1.25-mmol/L (1.25 group) dialysate calcium solutions. Calcium absorption was measured after the administration of Ca47. Results for the 1.0 (n = 6) and 1.25 (n = 7) groups included fractional calcium absorptions of 0.14 (range, 0.09 to 0.27) and 0.08 (range, 0.03 to 0.40; P= not significant [NS]) and calcium absorptions of 380 ± 92 and 331 ± 83 mg/d (P= NS). Dialysate calcium losses were 93 ± 20 and 91 ± 26 mg/d, and total calcium losses (dialysate and urine) were 106 ± 16 and 108 ± 40 mg/d (P= NS). Calcium balance was positive in all patients (274 ± 92 and 223 ± 65 mg/d; P= NS). These data suggest that the use of 1.0- and 1.25-mmol/L calcium solutions in conjunction with calcium carbonate and pulse alfacalcidol therapy is associated with a positive calcium balance in CAPD patients.

Bone resorption inhibitors, such as bisphosphonates, are potentially useful in treatments aimed at increasing bone mass. Among bisphosphonates, tiludronate has proven efficacious in preventing bone loss in postmenopausal women. However, it is not clearly established whether bisphosphonates are more potent when given intermittently or continuously. We investigated the effects of tiludronate on (1) retinoid‐stimulated bone resorption in thyroparathyroidectomized rats, (2) calcium balance in intact rats, and (3) bone mineral density (BMD) as measured by dual‐energy x‐ray absorptiometry at the levels of the lumbar spine, tail, and tibia in 6‐month‐old rats made osteoporotic by ovariectomy (OVX), in which an intermittent cyclic schedule of treatment was compared to continuous administration. Tiludronate induced a dose‐dependent decrease in retinoid‐stimulated bone resorption. It increased the intestinal absorption and body retention of calcium. In OVX rats it caused a time‐ and dose‐dependent increase in BMD at the level of the three investigated sites, the effects being maintained for at least 8 weeks after the end of therapy. Continuous and intermittent cyclic regimens appeared to induce similar increases in BMD. These results indicate that tiludronate is efficacious in decreasing bone resorption and increasing calcium balance and bone mineral density in rats.

1. Chromium sesquioxide (Cr2O3; 1·5 g/day) and [51Cr]chromic chloride [31CrCl3 (0·3 μCi/day)] were compared as continuously administered non-absorbed markers for the correction of faecal recoveries in 14 calcium balance studies each lasting at least 18 days. 2. The mean recoveries of each, 98·4% for Cr2O3 and 101·9% for 51CrCl3, were not significantly different from 100. 3. The two markers reduced the uncertainty in a typical 3 × 6 day calcium balance study to a similar extent (sd = 1·4 mmol/day for Cr2O3 and sd = 1·5 mmol/day for 51CrCl3). 4. 5lCrCl3 is a convenient and satisfactory alternative to Cr2O3 when the laboratory hazards associated with estimating the latter cannot easily be eliminated.

This study was designed to determine the calciuretic effect of furosemide and its impact upon calcium balance during chronic (25 days) furosemide administration to growing rats. Experiments were performed on 18 six-wk-old rats. Nine animals received furosemide, and 9 served as controls. The administration of furosemide in a dose of 40 mg resulted in a significant increase in calcium excretion in the treated group; urinary calcium excretion almost doubled that of the controls during the first 24-hr collection (3.74 ± 0.44 mg in the treated animals compared with 1.90 ± 0.15 mg in the controls; P < 0.05). The average daily urinary calcium excretion during each of four subsequent 6-day periods remained approximately three-fold higher in animals which received furosemide compared with controls (P < 0.001 for each 6-day period). The furosemide-induced increase in urinary calcium excretion did not diminish with time. Sodium excretion did not significantly increase either acutely or chronically in response to furosemide. Daily urinary volume increased approximately 40 to 60 in the furosemide-treated group compared with that of the controls (P< 0.001). The cumulative calcium balance in the control group exceeded by 7 that of the furosemide-treated animals (2696.3 ± 20.8 mg versus2518.6 ± 20.1 mg (P±.001).

1. The effect of a high calcium intake (1 mmol day−1 kg−1) alone or with the concomitant administration of oestradiol and testosterone derivatives was monitored by serial calcium balances in 48 patients with osteoporosis of various types. 2. On high calcium alone there was an increase (P < 0.001) in both total calcium balance and net calcium absorption as compared with values on a simulated home intake. This effect was sustained for periods up to 10 years (mean 3.5 years) by the addition of the hormones. 3. Discontinuation of the hormones (only) produced a significant decrease in both calcium balance and nett absorption but both were still increased when compared with the initial values under simulated home calcium intake. 4. No significant change in the urinary calcium output was observed under any of the regimens.

Net absorption of calcium, calcium balance and bone mineral content were studied in 83 patients with small-bowel resections of various lengths, mainly owing to CIBD, while they were receiving a standardized diet supplying 70 g fat and 800 mg calcium. Median duration of disease was 9 years (range, 5 months to 53 years) and median length of time from resection 3 years (range, 2 months to 18 years). In the whole case material net absorption of calcium ranged from 573 to −268 mg/day; median, 65 mg/day (56 to −26 of dietary calcium; median, 6). A weak inverse correlation was found between net absorption of calcium and length of resected small bowel, both in patients with ileostomy (no. 32, r −0.43, p < 0.01) and in patients with part of or the whole colon in function (no. 51, r−0.34, p < 0.01). Net absorption of calcium and urinary calcium correlated only weakly (no. 78, r 0.39, p < 0.001). In all patients studied the median calcium balance was −49 mg/day (range. 447 to −339 mg/day). No difference in net absorption of calcium or calcium balance could be demonstrated between patients with ileostomy and patients with colon in function. Nor did serum ionized calcium correlate with net absorption of calcium or calcium balance. Eleven per cent of 64 patients studied had significantly decreased bone mineral content, and more than half had bone mineral content below the mean value for 191 normal controls. No correlation was observed between bone mineral content and net absorption of calcium, calcium balance, duration of disease. or length of time from resection. On the basis of this cross-sectional study of the incidence and severity of negative calcium balance and skeletal demineralization, prospective, longitudinal studies should be carried out to find the most suitable form of treatment for disturbances in bone mineral metabolism after small-bowel resection owing to CIBD.

1. Mean linear attenuation coefficients for trabecular bone (T) in the distal radius and total absorption coefficients (TA) in the radial mid-shafts of 22 patients with crush fracture osteoporosis were measured serially for a year by using computed tomography. After approximately 6 months, each patient was admitted to a metabolic ward for an 18-day calcium balance study. 2. The rate of change (trend) in trabecular bone (T) in the distal radius was a better predictor of calcium balance than the trend in mid-shaft cortical bone (TA). 3. The scatter in the regressions of the trends of T and TA on calcium balance could be accounted for by known methodological uncertainties.

An acute effect of a single dose of 0.02 mg prolactin/100 g body weight administered intraperitoneally on distribution of absorbed calcium and the effect of daily subcutaneous injections of 0.25 mg prolactin/100 g body weight for 13 days on calcium balance were assessed in weaned, young, and mature female rats. The acute administration of prolactin failed to affect distribution of absorbed calcium at 2 h after instillation of test solution. In contrast, the daily injection of a lower dose of prolactin over 13 days significantly decreased fecal and urinary excretion of 45Ca, an index of absorbed calcium, in mature rats, while having no effect on muscle and tibial 45Ca contents. In young rats, in addition to a reduction in the urinary 45Ca excretion, prolactin decreased the gastrocnemius muscle total calcium content from 7.28 ± 0.37 to 5.58 ± 0.37 μmol/g dry weight (p < 0.01) while increasing tibial calcium content from 6.65 ± 0.18 to 7.35 ± 0.15 mmol/g dry weight (p < 0.01). Bone formation (represented by serum alkaline phosphatase) in weaned rats was significantly elevated by prolactin, but bone resorption (represented by urinary hydroxyproline) was not altered. It could be concluded that prolonged administration of prolactin decreased calcium excretion in mature rats and increased bone formation and tibial calcium content in growing rats.Key words: bone formation, bone resorption, calcium, calcium balance, prolactin.

Eight young adult males were subjects in a 51-day metabolic study conducted to examine the effects of level of protein and of phosphorus intake on urinary calcium and calcium balance. Two levels of protein (50–150 g) were given at each of two levels of phosphorus intake (1,010 and 2,525 mg). Dietary calcium and magnesium were maintained at 500 and 350 mg, respectively. Raising the protein intake from 50 to 150 g caused a calciuresis at both phosphorus intakes, but the actual increase in urinary calcium was 71 mg/day greater at the low than at the high phosphorus intake and calcium balance was changed from 24 to -116 mg/day at the low phosphorus intake and from 8 to -25 mg/day at the high. When the phosphorus intake was raised, urinary calcium decreased from 156 to 93 mg/day at the low protein intake and from 334 to 200 mg/day at the high protein intake and the markedly negative calcium balance found at the high protein intake was greatly improved. Simultaneous increases in protein and phosphorus intakes caused a 28% increase in urinary calcium whereas the increase in protein intake alone caused a 115% increase.

The short-term effects of dietary sodium chloride supplementation on calcium balance were examined in an animal model of corticosteroid-mediated osteoporosis. Changes in calcium and phosphate balance, parathyroid function and bone resorption elicited by salt supplements alone (8 g/100 g diet), prednisolone alone (2.2 mg/kg body wt per day) and both salt and prednisolone in combination were measured in rats consuming a low calcium diet (0.1% calcium) for 10 d. Parathyroid function was monitored by measuring urinary cyclic AMP excretion. Bone resorption was monitored by measuring urinary hydroxyproline excretion. Salt alone raised urinary calcium, cyclic AMP and hydroxyproline; prednisolone alone depressed net calcium absorption and urinary hydroxyproline but had no effect on urinary calcium. Salt and prednisolone each depressed calcium retention independently and together produced an additive adverse effect on calcium balance. Thus high dietary salt intakes augment urinary calcium loss, raise parathyroid activity, increase bone resorption and adversely affect calcium balance in prednisolone-treated growing rats with a restricted dietary calcium intake. These findings support the view that high salt intakes may exaggerate bone loss during chronic glucocorticoid therapy. Because people also develop osteoporosis during glucocorticoid therapy and respond to dietary salt supplements by increasing urinary calcium excretion and parathyroid hormone, high salt intakes may accelerate bone loss in patients receiving chronic glucocorticoid therapy. The beneficial effects of dietary salt restriction on the conservation of bone mass warrant investigation in these patients.

The effect of level of protein intake on urinary and fecal calcium and calcium balance of nine young adult human males was investigated. Calcium intake was 500 mg daily and protein intake was varied from 47 to 95 to 142 g daily. When the protein intake was 47 g daily, the mean calcium retention of the subjects was 31 mg, with only two subjects showing a slight negative balance. When the protein intake was 95 and 142 g, respectively, the mean calcium balance was -58 and -120 mg, and no subject was in calcium balance. Increasing the intake of fruits and vegetables by 50% had no beneficial effect on calcium balance. The urinary calcium increased significantly with each increase in protein intake, the mean value being 168, 240, 301 and 278 mg, respectively, when the low, the medium and the high protein and the high protein-high fruit and vegetable diet was given. Fecal calcium was not significantly affected by protein intake.

In bicarbonate-based hemodialysis, dialysate total calcium (tCa) concentration may have effects on mineral metabolism.

The effects of dietary sodium chloride supplements (8 g/100 g diet) on parathyroid function, serum 1,25-dihydroxyvitamin D [1,25-(OH)2D], calcium balance, bone metabolism, and bone composition were studied in rats treated with prednisolone (2 mg/kg w·day) for 12 weeks. Animals on a low calcium diet (0.1% Ca) received the following treatments: group 1, control; group 2, NaCl; group 3, prednisolone; group 4, NaCl plus prednisolone. Parathyroid function was assessed indirectly from urinary cAMP excretion: bone resorption was estimated by studying urinary hydroxyproline excretion and mobilization of 45Ca from bone. Dietary salt loading increased the urinary excretion of calcium, 45Ca, cAMP, and hydroxyproline and raised serum 1,25-(OH)2D and net calcium absorption, but lowered calcium retention, femoral calcium, and total body calcium. Prednisolone slowed body growth and lowered net calcium absorption, calcium retention, femoral calcium, and total body calcium. Urinary calcium excretion was higher in rats receiving salt and prednisolone in combination than in animals taking salt without prednisolone, but other responses to salt and prednisolone were independent. Thus, salt and prednisolone each elicit osteopenia, and salt causes bone loss in rats receiving prednisolone. The osteopenic effect of salt is attributed to primary augmentation of urinary calcium excretion and secondary increases in PTH-medicated bone resorption. Although salttreated rats have higher blood levels of 1,25-(OH)2D, bone loss occurs because alimentary calcium absorption is not elevated sufficiently to offset urinary calcium losses. Prednisolone lowers bone formation and net calcium absorption without lowering serum 1,25-(OH)2D values. The parathyroid-vitamin D axis remains intact in prednisolone-treated rats, as they show increases in PTH and 1,25-(OH)2D after salt treatment. (Endocrinology119:2148–2154, 1986)

Glucocorticoid induced osteoporosis has been associated with high doses and it has been partially attributed to decreased absorption and to increased calcium excretion. The present study examined the effect of low but effective doses of methylprednisolone (MP) on calcium balance and on skeleton in rats. Total duration of the experiment 29 days. Thirty-one male Wistar rats (MP group) were injected with 4mg/kg body weight MP sc at the 1st, 11th and 20th day of the experiment and 28 rats (C group) were used as matched controls. The 1st, 11th and 20th day of the experiment rats were placed in individual metabolic cages for three days. Food and water consumption were measured at the 2nd and 3rd days after each injection; urine and faeces were collected at the same days for calcium estimation. Calcium intake and excretion after each injection was significantly lower in the MP group as compared to controls. A statistically significant positive correlation between calcium consumption and calcium excretion was found in both groups resulting in a negative final balance. Rats were killed the 29th day. Adrenal weight was statistically significant lower in MP group (p<0.001). Morphometric properties were evaluated for the right femur. No significant difference was found between the two groups. Mineral and calcium content was slightly increased in the MP group. According to these results, it seems that methylprednisolone while effective on HPA axis did not have any effect on calcium absorption and on bone calcium deposition in rats.

1. We have examined the relation between the rate of cortical bone loss and other measured variables in 108 women, untreated and on various therapies, observed for nearly 300 patient years. The majority of the subjects were post-menopausal women with various degrees of simple osteoporosis, but a few cases of hyperparathyroidism and other calcium disorders were included. 2. Calcium balance, bone resorption rate, urinary hydroxyproline and plasma alkaline phosphatase were shown to be related to the rate of bone loss; patients with the more negative balance or the higher values of the other variables had significantly higher rates of loss. The rate of bone loss was independent of the rate of bone formation.

A 35-day experimental study consisting of 28-day growth and 7-day calcium (Ca) balance periods was conducted to assess the effects of fibre and N ratios on growth and Ca balance of rats. Growth and Ca balance of rats (45–80 g) fed mixtures of cooked (CS) and uncooked (RS) sorghum and dehulled (DB) and undehulled (UB) bean were studied. The diets contained 10% protein. Casein served as the control protein. The control group ate more food except for the group fed the CS:DU (60:40) diets (P<0.05) had higher values for all parameters tested than the test groups. There were increases in food and Ca intakes, fecal Ca, weight gain, protein efficiency ration (PER), liver weight and composition except for the low moisture value for the CS:DS (60:40) group when N ratios were changed from 80:20 to 60:40. These results appear to indicate that fiber and N ratio had significant effects on growth liver composition and calcium balance of the rats.

The utility of Ca efflux studies to examine lens calcium balance is limited because of the dominant contribution of efflux from the extracellular space of the lens. On the other hand, examination of lens "Ca uptake characteristics can generate valuable information regarding the mechanism by which calcium is largely restricted from the intracellular compartment. Such studies have enabled us to demonstrate that the access of calcium to the intracellular compartment is dependent to some extent upon the concentration of calcium in the extracellular environment. Additionally, experimental evidence speaks against extracellular binding of calcium. Finally, lens membrane permeability to calcium appears to be independent of membrane voltage.

The effect of low protein intake from plant sources on calcium excretions and calcium balance of seven young adults was investigated. The diets (four combinations of egg, groundnut and soyabean nitrogen) furnished 43 g protein (0.58 g protein/kg) and 550 mg calcium daily.

Experiments to evaluate the effect of in‐season calcium (Ca) sprays on late‐season peach (Prunus persicaL. Batsch cv. Calrico) were carried out for a 2‐year period. Calcium formulations (0.5% and 1.0% in 2008 and only 0.5% tested in 2009) supplied either as CaCl2or Ca propionate in combination with two or three adjuvants (0.05% of the nonionic surfactants Tween 20 and Break Thru, and 0.5% carboxymethylcellulose, CMC) were sprayed four to five times over the growing season. Peach mesocarp and endocarp Ca concentrations were determined on a 15‐day basis from the beginning of May until the end of June. Further tissue analyses were performed at harvest. A decreasing trend in fruit Ca concentrations over the growing season was always observed regardless of the Ca treatments. Both in 2008 and 2009, significant tissue Ca increments associated with the application of Ca‐containing sprays in combination with adjuvants were only observed in June, which may be coincident with the period of pit hardening. In 2008, both at harvest and after cold storage, the total soluble‐solids concentration (° Brix) of fruits supplied with Ca propionate (0.5% and 1.0% Ca) was always lower as compared to the rest of treatments. The application of multiple Ca‐containing sprays increased firmness at harvest and after cold storage, especially when CaCl2was the active ingredient used. Supplying the adjuvants Tween 20 and CMC increased fruit acidity both at harvest and after cold storage. Evaluation of the development of physiological disorders after cold storage (2 weeks at 0°C) indicated a lower susceptibility of Ca‐treated fruits to internal browning. Fruits treated with multiple CaCl2‐, CMC‐, and Break Thru®‐containing sprays during the growing season were significantly less prone to the development of chilling injuries as compared to untreated peaches.