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Purpose of Review The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent Findings Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Summary Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients’ dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

Although the implications of long-term high Ca intakes have been well documented in growing dogs, the health consequences of Ca excess in adult dogs remain to be established. To evaluate the impact of feeding a diet containing 7·1 g/4184 kJ (1000 kcal) Ca for 40 weeks on Ca balance and health parameters in adult dogs, eighteen neutered adult Labrador Retrievers, (nine males and nine females) aged 2·5–7·4 years were randomised to one of two customised diets for 40 weeks. The diets were manufactured according to similar nutritional specifications, with the exception of Ca and P levels. The diets provided 1·7 and 7·1 g/4184 kJ (1000 kcal) (200(SD26) and 881(SD145) mg/kg body weight0·75 per d, respectively) Ca, respectively, with a Ca:P ratio of 1·6. Clinical examinations, ultrasound scans, radiographs, health parameters, metabolic effects and mineral balance were recorded at baseline and at 8-week intervals throughout the study. Dogs in both groups were healthy throughout the trial without evidence of urinary, renal or orthopaedic disease. In addition, there were no clinically relevant changes in any of the measures made in either group (all P>0·05). The high-Ca diet resulted in a 3·3-fold increase in faecal Ca excretion (PP>0·05). Ca intakes of up to 7·1 g/4184 kJ (1000 kcal) are well tolerated over a period of 40 weeks, with no adverse effects that could be attributed to the diet or to a high mineral intake.

Agnieszka Makowka, Michal Nowicki Department of Nephrology, Hypertension and Kidney Transplantation, Medical University of Lodz, Lodz, PolandCorrespondence: Michal NowickiDepartment of Nephrology, Hypertension and Kidney Transplantation, Medical University of Lodz, Central University Hospital, Pomorska Str 251, Lodz, 92-213, PolandTel +48 42 2014400Fax +48 42 2014401Email nefro@wp.plObjective: Opposite to lanthanum carbonate (LC), sevelamer hydrochloride (SH) may increase intestinal calcium absorption. The study compared the effects of LC and SH on serum and urine phosphate and calcium, and on hormones regulating mineral-bone metabolism.Patients and Methods: A prospective randomized crossover study included 34 patients with eGFR < 60 mL/min. A single oral dose of LC (1,000 mg) or SH (2,400 mg) was administered in random order 15 minutes after a standardized meal fortified with 5 g calcium carbonate. Serum calcium, phosphate, and parathormone were measured before and 3, 6, 12, and 24 hours after each medication. Bone alkaline phosphatase (BAP), sclerostin, calcitriol, and FGF-23 were measured at baseline and after 12 and 24 hours. A 24-hour calcium and phosphate excretion was measured after each drug.Results: Serum calcium increased 3 and 6 hours after SH then returned to baseline. After LC calcium was unchanged for up to 3 hours then transiently increased and eventually returned to baseline. The area under curve (AUC) of serum calcium for 12 hours after SH was larger than after LC (p=0.04). Serum phosphate decreased after each drug with a nadir 3 hours post-SH and 6 hours post-LC. AUC of serum phosphate was similar after both medications. PTH decreased transiently after both drugs. BAP did not change. FGF-23 was constant for the first 12 hours but later decreased after each drug.Conclusion: A 2,400 mg SH and 1,000 mg LC are similarly effective in lowering serum phosphate in CKD, but LC induce in less intestinal calcium absorption after a meal. The trial was registered on February 23, 2018 in the clinicaltrial.gov database – NCT03451019.Keywords: calcium, chronic kidney disease – mineral bone disorder, hyperphosphatemia, phosphate-binders, PTH

The purpose of this study was to investigate the antihypertensive mecha-nisms of piperitenone oxide in spontaneously hypertensive rat (SHR). Compared to control SHR, piperitenone oxide reduced the systolic blood pressure and serum endothelium-1 (ET-1). The nitric oxide (NO) production and ET-1 secretion were significantly inhibited in the noradrenaline-exposed bovine aortic endothelial cells. Piperitenone oxide showed endothelium-independent but concentration-dependent relaxation of the artery rings. The responsible mechanisms appear to be related to the modulation of ET-1 and NO levels. The vasorelaxant effect of piperitenone oxide is independent of endothelium-derived mediators, which is associated with interfering intracellular calcium homeostasis by blocking Ca2+ influx, as well as intracellular Ca2+ release. Video Clip of Methodology: 2 min 58 sec: Full Screen Alternate

Calcium regulation in sturgeon is of special interest because they are a representative of the ancient fishes possessing mainly cartilaginous skeletons and a supposedly low calcium demand. The present study aimed to characterize the effect of a chronic absence of dietary calcium and the effect of parathyroid hormone-related protein (PTHrPA) (1-34) ( 7 ) on calcium balance in juvenile sturgeon ( Acipenser naccarii). At rest, sturgeon juveniles are in net positive calcium balance, since whole body calcium uptake is significantly higher than efflux and calcium accumulates in the body. To study the importance of dietary calcium, the sturgeon were kept on a calcium-free diet for 8 wk. This manipulation impaired growth as measured by failure to gain weight or increase in length and indicates that dietary calcium is important for growth in sturgeon. An increased whole body calcium uptake partially compensated dietary calcium deficiency and was associated with increased gill chloride cell number in lamellae and filaments in parallel with increased gill Na+K+-ATPase activity. In addition, a single injection of piscine PTHrP(1-34) significantly increased whole body calcium uptake and decreased whole body calcium efflux. Administration of PTHrP significantly increased circulating plasma calcium 4–24 h postinjection. The increase in net calcium transport and increased plasma levels of calcium is consistent with the actions of a hypercalcemic factor. It would appear that the sturgeon rely on calcium for growth and tightly regulate calcium transport. The action in calcium balance is consistent with PTHrP acting as a hypercalcemic factor in sturgeon.

The aim of this study was to evaluate the effect of Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herbal medicine, on the biochemical markers of bone turnover, calcium metabolism and balance in osteoporotic rat model developed by ovariectomy. Four weeks after surgical operation, animals were randomly assigned to one of the four treatments for 14 weeks: sham-operated control treated with vehicle (sham, n=8), ovariectomized group treated with vehicle (OVX, n=8), OVX group treated with 17beta-estradiol (E(2), n=10, 2 microg/kg/d) and OVX group treated with FLL extracts (FLL, n=10, 550 mg/kg/d). Serum osteocalcin and urinary deoxypyridinoline levels were upregulated in rats in response to OVX, suggesting that the bone turnover rate was accelerated in these animals. Treatment of OVX rats with FLL extract could prevent OVX-induced increase in bone turnover by suppression of both serum osteocalcin (p0.05, vs. OVX) and urinary deoxypyridinoline (p0.05, vs. OVX) levels. In addition, FLL extract could prevent OVX-induced loss of calcium in rats by increasing the intestinal calcium absorption rate (p0.01, vs. OVX), suppressing urinary Ca excretion (p0.05, vs. OVX) as well as increasing bone calcium content (p0.05, vs. OVX). Our study is the first to report that FLL can modulate bone turnover and calcium balance in OVX rats and it might be a potential candidate for prevention and treatment of postmenopausal osteoporosis.

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.

Prior to the advent of calcitriol therapy, haemodialysis (HD) patients were often in negative calcium (Ca) balance between dialyses because of severely impaired Ca absorption [1] that led to the recommendation of dialysate inlet Ca concentration (CdiCa++) 3.0–3.5 mEq/L, higher than plasma concentration [2]. Over the past 25 years since the advent of calcitriol, virtually all haemodialysis patients absorbed a substantial portion of dietary and phosphate binder calcium ingested between dialyses and yet CdiCa++ 3.0 mEq/L has continued to be widely used. The total Ca absorbed between dialyses (CaAbsT) must be removed by the dialyser (JdCaT) to achieve net zero Ca mass balance over the dialysis cycle and prevent chronic Ca overload that likely contributes to the high rate of vascular calcification in haemodialysis patients [3–5]. From this perspective, it follows that the CdiCa++ prescribed should result in neutral Ca mass balance and thus total Ca removed during dialysis (JdCa++), the sum of diffusive (JDiffCa++) and convective Ca++ (JConvCa++) removal, should equal CaAbs in accordance with

Item does not contain fulltext BACKGROUND: Identification of the underlying causes of secondary hyperparathyroidism (SHPT) in individual patients on hemodialysis (HD) is hampered by the lack of clinically reliable information on calcium balance. The aim of this study was to assess calcium balance during HD sessions with a method that is applicable in day-to-day practice. METHODS: Plasma ionized calcium (pCa2+) and parathyroid hormone (PTH) were measured at the beginning and end of HD to evaluate calcium fluxes in 23 patients on a dialysate calcium (DCa) concentration of 1.25 mmol/L. RESULTS: HD with a DCa of 1.25 mmol/L caused a decrease in pCa2+ from 1.15 +/- 0.01 mmol/L to 1.09 +/- 0.01 mmol/L (p1.06 mmol/L had a calcium efflux, whereas those with a predialysis pCa2+

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 +/- 18.5 kg; age: 47.0 +/- 18.5 y (range: 20-75 y); men: n = 82; weight: 76.6 +/- 12.5 kg; age: 28.2 +/- 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 99 th 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(-1) d(-1) [95% PI: 6.4, 12.9; Y = 1.44 + 0.85C], or 0.28 mg kcal(-1) d(-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(-1) d(-1). CONCLUSION The findings suggest that the calcium requirement for men and women is lower than previously estimated.

Contains fulltext : 35554.pdf ( ) (Open Access) Juvenile gilthead sea bream were exposed to diluted seawater (2.5 per thousand salinity; DSW) for 3 h or, in a second experiment, acclimated to DSW and fed a control or calcium-deficient diet for 30 days. Branchial Ca(2+) influx, drinking rate and plasma calcium levels were assessed. Sea bream plasma parathyroid hormone related protein (sPTHrP) was measured, and mRNAs of pthrp, its main receptor, pth1r, and the calcium-sensing receptor (casr) were quantified in osmoregulatory tissues and the pituitary gland. When calcium is limited in water or diet, sea bream maintain calcium balance; however, both plasma Ca(2+) and plasma sPTHrP concentrations were lower when calcium was restricted in both water and diet. Positive correlations between plasma sPTHrP and plasma Ca(2+) (R(2)=0.30, N=39, P

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) 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) 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.

The dietary acid load created by the typical Western diet may adversely impact the skeleton by disrupting calcium metabolism. Whether neutralizing dietary acid with alkaline potassium salts results in sustained improvements in calcium balance remains controversial. In this randomized, double-blind, placebo-controlled study, 52 men and women (mean age 65.2 ± 6.2 years) were randomly assigned to potassium citrate 60 mmol/d, 90 mmol/d, or placebo daily with measurements of bone turnover markers, net acid excretion, and calcium metabolism, including intestinal fractional calcium absorption and calcium balance, obtained at baseline and at 6 months. At 6 months, net acid excretion was significantly lower in both treatment groups compared to placebo and it was negative, meaning subjects' dietary acid was completely neutralized (-11.3 mmol/d on 60 mmol/d; -29.5 mmol/d on 90 mmol/d, p < 0.001 compared to placebo). At 6 months, 24-hour urine calcium was significantly reduced in persons taking potassium citrate 60 mmol/d (-46 ± 15.9 mg/d) and 90 mmol/d (-59 ± 31.6 mg/d) compared with placebo (p < 0.01). Fractional calcium absorption was not changed by potassium citrate supplementation. Net calcium balance was significantly improved in participants taking potassium citrate 90 mmol/d compared to placebo (142 ± 80 mg/d on 90 mmol/d versus -80 ± 54 mg/d on placebo; p = 0.02). Calcium balance was also improved on potassium citrate 60 mmol/d, but this did not reach statistical significance (p = 0.18). Serum C-telopeptide decreased significantly in both potassium citrate groups compared to placebo (-34.6 ± 39.1 ng/L on 90 mmol/d, p = 0.05; -71.6 ± 40.7 ng/L on 60 mmol/d, p = 0.02) whereas bone-specific alkaline phosphatase did not change. Intact parathyroid hormone was significantly decreased in the 90 mmol/d group (p = 0.01). Readily available, safe, and easily administered in an oral form, potassium citrate has the potential to improve skeletal health. Longer-term trials with definitive outcomes such as bone density and fracture are needed.

Osteoblast function was investigated in 27 patients with idiopathic osteoporosis. Transiliac bone biopsy specimens were taken after double labelling with tetracycline, and metabolic calcium balance was studied almost simultaneously. Many of the patients showed poor double labelling of their otherwise unremarkable trabecular osteoid, suggesting impaired formation of bone at many of these surfaces. This phenomenon was not accompanied by increased width of osteoid seams (as seen in osteomalacia), indicating that formation of the matrix and its mineralisation were in equilibrium. For the first time, highly significant positive correlations (p less than 0.01) were found between indices of bone formation, determined by labelling with tetracycline, and calcium balance. Thus some patients with osteoporosis who are rapidly losing bone have low rates of formation of trabecular bone both by individual osteoblasts and in relation to available bone surfaces. As histological indices of bone resorption also independently correlated strongly and inversely (p less than 0.01) with calcium balance the rate of initiation of new basic multicellular units by osteoclastic resorption of trabecular surfaces (or the depth of resorption at these surfaces) also appears to be an important determinant of mineral balance. The mechanisms that regulate the effective life span of mature osteoblasts require further investigation, particularly as some promising treatments that can increase trabecular bone volume in osteoporosis, such as parathyroid peptide hPTH (1-34) and sodium fluoride, must work through a reversal of osteoblastic depression.

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.

The acid-ash hypothesis posits that protein and grain foods, with a low potassium intake, produce a diet acid load, net acid excretion (NAE), increased urine calcium, and release of calcium from the skeleton, leading to osteoporosis. The objectives of this meta-analysis were to assess the effect of changes in NAE, by manipulation of healthy adult subjects' acid-base intakes, on urine calcium, calcium balance, and a marker of bone metabolism, N-telopeptides. This meta-analysis was limited to studies that used superior methodological quality for the study of calcium metabolism. We systematically searched the literature and included studies if subjects were randomized to the interventions and followed the recommendations of the Institute of Medicine's Panel on Calcium and Related Nutrients for calcium studies. Five of 16 studies met the inclusion criteria. The studies altered the amount and/or type of protein. Despite a significant linear relationship between an increase in NAE and urinary calcium (p < 0.0001), there was no relationship between a change of NAE and a change of calcium balance (p = 0.38; power = 94%). There was no relationship between a change of NAE and a change in the marker of bone metabolism, N-telopeptides (p = 0.95). In conclusion, this meta-analysis does not support the concept that the calciuria associated with higher NAE reflects a net loss of whole body calcium. There is no evidence from superior quality balance studies that increasing the diet acid load promotes skeletal bone mineral loss or osteoporosis. Changes of urine calcium do not accurately represent calcium balance. Promotion of the "alkaline diet" to prevent calcium loss is not justified.

The debate on the most adequate dialysate calcium concentration for intermittent haemodialysis therapy is ongoing. There is probably no one optimal concentration. In general, one would like to maintain a neutral calcium balance in adult haemodialysis patients. However, a slightly negative balance may be preferable to avoid soft-tissue calcium accumulation in face of net calcium loss from the bone with ageing. The problem with measurements of calcium balance is that they are generally imprecise, as are estimations of total body calcium and its distribution in various compartments, unless done with labour-intensive methods and great care. The choice of the dialysate calcium will depend on several factors, including parathyroid and vitamin D status, type and severity of concomitant bone disease, presence or absence of arterial calcification, dietary habits, drug treatment and dialysis modality. Ideally the dialysate calcium would be adapted to each patient's needs. This is not feasible, however, in most dialysis settings and neither is it cost-effective. From a practical point of view, a relatively high dialysate calcium concentration in the range of of 1.50-1.75 mmol/L (3.0-3.5 mEq/L) should probably be preferred in haemodialysis patients with high serum PTH levels who are not prescribed calcium-based phosphate binders or high doses of active vitamin D sterols, and in those who are receiving a calcimimetic. In those who are treated with high doses of calcium-based binders and/or active vitamin D derivatives or who have a very low serum PTH level, the optimal dialysate calcium concentration is probably lower, in the range of 1.25-1.50 mmol/L (2.50-3.0 mEq/L). In the present pro/con debate about the optimal dialysate calcium concentration used for the haemodialysis session, we have accepted to defend the viewpoint that a low calcium concentration may do more harm than benefit in many patients. This viewpoint is opposite to that taken by Gotch [1]. He argues that since calcitriol and other active vitamin D derivatives have become available virtually all haemodialysis patients are in positive calcium balance. We would like to take issue with this statement and warn against the indiscriminate use of a low calcium dialysate in all patients receiving haemodialysis therapy.

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.

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.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.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.Thirty-eight adults (19 D2 and 19 D3) ≥18 years of age with baseline 25D levels30 ng/mL were recruited from an academic ambulatory osteoporosis clinic.Serum measures were total 25D, free 25D (directly measured), 1,25-dihydroxyvitamin D, calcium, and iPTH. Urine measure was fasting calcium:creatinine ratio.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.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.

We examined the effect of vitamin K and vitamin D supplementation on calcium balance in young rats fed a normal or low calcium diet. Eighty female Sprague-Dawley rats, 6 wk of age, were randomized by the stratified weight method into eight groups with 10 rats in each group: 0.5% (normal) or 0.1% (low) calcium diet, 0.5% or 0.1% calcium diet+vitamin K (vitamin K2, menatetrenone, 30 mg/100 g, food intake), 0.5% or 0.1% calcium diet+vitamin D (25 microg/100 g, food intake), and 0.5% or 0.1% calcium diet+vitamin K+vitamin D. The duration of the study was 10 wk. Vitamin K supplementation promoted the reduction in urinary calcium excretion and retarded the abnormal elevation of serum PTH level in rats fed a low calcium diet, and stimulated intestinal calcium absorption in rats fed a normal calcium diet. Vitamin D supplementation stimulated intestinal calcium absorption with prevention of the abnormal elevation of serum PTH levels and prevented hypocalcemia in rats fed a low calcium diet, and stimulated intestinal calcium absorption in rats fed a normal calcium diet. The stimulation of intestinal calcium absorption was associated with increased serum 1,25-dihydroxyvitamin D levels. An additive effect of vitamin K and vitamin D on intestinal calcium absorption was found only in rats fed a normal calcium diet. This study shows the differential effects of vitamin K and vitamin D supplementation on calcium balance in young rats fed a normal or low calcium diet.

This study was conducted to evaluate the effect of Sigma Anti-bonding Molecule Calcium Carbonate (SAC) as therapy for ovariectomy-induced osteoporosis in rats. Three weeks after surgery, fifteen ovariectomized Sprague-Dawley rats were divided randomly into 3 groups: sham-operated group (sham), ovariectomized group (OVX) and SAC-treatment group (OVX+SAC). The OVX+SAC group was given drinking water containing 0.0012% SAC for 12 weeks. Bone breaking force and mineralization as well as blood parameters related to the bone metabolism were analyzed. In OVX animals, blood concentration of 17β-estradiol decreased significantly, while osteocalcin and type I collagen C-terminal telopeptides (CTx) increased. Breaking force, bone mineral density (BMD), calcium and phosphorus in femurs, as well as uterine and vaginal weights, decreased significantly following OVX. However, SAC treatment (0.0012% in drinking water) not only remarkably restored the decreased 17β-estradiol and increased osteocalcin and CTx concentrations, but also recovered decreased femoral breaking force, BMD, calcium and phosphorus, although it did not reversed reproductive organ weights. It is suggested that SAC effectively improve bone density by preventing bone turnover mediated osteocalcin, CTx and minerals, and that it could be a potential candidate for therapy or prevention of postmenopausal osteoporosis.

Fructus Ligustri Lucidi(FLL) is a commonly prescribed herb in many kidney-tonifying Traditional Chinese Medicinal formulae for the treatment of osteoporosis. The present study aimed to identify the active fractions in FLL and to characterise its effects on Ca balance, calciotropic hormone levels as well as bone properties in mature female rats fed diets containing different levels of Ca. In the present study, 4-month-old Sprague–Dawley female rats were treated with either FLL ethanol extract (EE), ethyl acetate-soluble fraction of EE (EAF), water-soluble fraction of EE (WF) or their vehicle for 12 weeks on a medium-Ca diet (MCD, 0·6 % Ca, 0·65 % P). Then, the Sprague–Dawley female rats treated with WF or its vehicle for 12 weeks were fed diets containing different levels of dietary Ca (low-Ca diet (LCD), 0·1 % Ca, 0·65 % P; MCD; high-Ca diet (HCD), 1·2 % Ca, 0·65 % P). The results demonstrated that WF from EE but not EAF exerted a prominent effect on Ca balance by inhibiting urinary and faecal Ca excretion. WF significantly increased Ca balance in rats fed MCD or HCD with an associated increase in serum parathyroid hormone (PTH) levels. WF did not alter bone mineral density or bone mineral content of the tibia in all the rats fed with different levels of dietary Ca. In conclusion, WF was responsible for the positive actions of FLL on Ca absorption and balance. The regulation of Ca balance by WF might involve its action in stimulating PTH production in the mature female rats.

The amount of phosphorus contained in food as food additives is currently increasing and a high intake of phosphorus can cause various diseases. To determine the effects of a prolonged high phosphorus diet, here we investigated the phosphorus and calcium balance and expression of type IIa sodium-dependent phosphate transporter (Npt IIa) in mature rats. Wistar male rats (8-weeks old) were divided into five groups and fed diets containing 0.6% calcium plus 0.3, 0.6, 0.9, 1.2 or 1.5% phosphorus for 4 weeks. Urinary and fecal phosphorus excretions were significantly increased by the high phosphorus diets (from 0.6 to 1.5%), dependent on the amount of dietary phosphorus. The net absorption of intestinal phosphorus was also significantly increased by high phosphorus diets. As a result, a negative phosphorus balance was observed in rats given the 1.2% or 1.5% phosphorus diets. Serum parathyroid hormone and 1,25-dihydroxyvitamin D(3) concentrations were increased by high phosphorus diets. In addition, high phosphorus diets decreased the expression of Npt IIa mRNA and protein in the renal brush border membrane. Taken together, these results suggest that diets containing 1.2 or 1.5% phosphorus plus 0.6% calcium have potentially adverse effects on phosphorus homeostasis in mature rat.

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.

Regional citrate hemodialysis anticoagulation is used when heparin is contraindicated, but most protocols require large infusions of calcium and frequent intradialytic plasma ionized calcium measurements.The objective of this study was to determine the safety, efficacy, and effect on calcium balance of regional citrate anticoagulation using sparse plasma ionized calcium sampling.The design of this study was observational.The setting of this study was the hospital hemodialysis center.The subjects of this study were the hospital hemodialysis patients.Dialysate calcium concentration by atomic absorption spectroscopy and total dialysate weight were used as measurements.Regional citrate anticoagulation was introduced using zero calcium dialysate, pre-dialyzer citrate infusion, and post-dialyzer calcium infusion. Infusions were adjusted based on pre- and post-dialyzer calcium measurements obtained at least twice during a 4-h dialysis. The protocol was simplified after the first 357 sessions to dispense with post-dialyzer calcium measurements. Heparin-anticoagulated sessions were performed using acetate-acidified 1.25 mmol/L calcium or citrate-acidified 1.5 mmol/L calcium dialysate. Calcium balance assessment was by complete dialysate recovery. Safety and efficacy were assessed prospectively using a point-of-care database to record ionized calcium and clinical events. Groups were compared using t test, ANOVA, Wilcoxon rank sum, or Kruskal-Wallis as appropriate.Seventy-five patients received regional citrate-anticoagulated dialysis over 1051 dialysis sessions. Of these, 357 dialysis sessions were performed using the original citrate anticoagulation protocol and 694 using the simplified protocol. Dialysis was effective and safe. Only 3 dialyzers clotted; 1 patient suffered symptomatic hypercalcemia and none suffered symptomatic hypocalcemia. Calcium balance was assessed in 15 regional citrate-anticoagulated dialysis sessions and 30 heparin-anticoagulated sessions. The median calcium loss was 0.8 mmol/h dialyzed in both groups (p = 0.43), and end of treatment ionized calcium was the same in both groups (1.07 ± 0.04 mmol/L).Our findings for calcium balance, efficacy, and safety are valid only for the protocol studied, which excluded patient with severe liver dysfunction.Regional citrate dialysis can be performed safely and effectively using a sparse plasma calcium sampling protocol. The calcium balance induced by this protocol is not different to that seen in standard heparin-anticoagulated dialysis, but in the absence of prospective studies, it is unknown whether this is optimal for patient care.On recommande l’utilisation de l’anticoagulation régionale au citrate (ARC) d’un circuit de dialyse lorsque l’héparine est contre-indiquée. Toutefois la plupart des protocoles requièrent alors une perfusion de calcium et de fréquentes mesures intradialytiques du taux de calcium ionisé plasmatique.L’étude visait à déterminer l’innocuité l’efficacité et les effets sur l’équilibre calcique de l’ARC à l’aide d’un protocole de prélèvements épars du calcium ionisé plasmatique.Il s’agit d’une étude observationnelle menée sur les patients de centres d’hémodialyse en milieu hospitalier.L’anticoagulation régionale au citrate implique l’utilisation de trois différentes solutions : un dialysat sans calcium une perfusion de calcium pré-dialyseur ou une perfusion de calcium post-dialyseur. Les perfusions avaient été ajustées selon les taux de calcium mesurés au minimum deux fois pré-dialyseur et post-dialyseur, au cours d’une hémodialyse de quatre heures. Après 357 séances, la mesure du taux de calcium post-dialyseur a été éliminée pour simplifier le protocole. Les séances où l’héparine agissait à titre d’anticoagulant ont été effectuées au moyen de deux différents dialysats : une solution à 1,25 mmol/L de calcium acidifiée à l’acétate et une solution à 1,5 mmol/L de calcium acidifiée au citrate. Le bilan calcique s’est fait en récupérant la totalité du dialysat. L’innocuité et l’efficacité ont été évaluées de façon prospective en consignant les taux de calcium ionisé et les événements cliniques à l’aide des bases de données du lieu de soins. Les groupes de patients ont été comparés en utilisant le test T, l’ANOVA, le test signé des rangs de Wilcoxon ou le test de Kruskal-Wallis selon le cas.Au cours de l’étude 75 patients ont reçu des traitements d’hémodialyse sous anticoagulation régionale au citrate, pour un total de 1051 séances analysées. De celles-ci, 357 séances ont été effectuées en suivant le protocole original d’anticoagulation au citrate, alors que 694 l’ont été en suivant le protocole simplifié. La dialyse s’est avérée sécuritaire et efficace : seuls trois dialyseurs ont coagulé, un seul patient a souffert d’hypercalcémie symptomatique et aucun cas d’hypocalcémie symptomatique n’a été rapporté. Le bilan calcique a été évalué lors de 15 séances d’hémodialyse sous anticoagulation par citrate et de 30 séances utilisant l’héparine. La médiane de perte de calcium se situait à 0,8 mmol/heure de dialyse pour chacun des deux groupes (Ces observations de bilan calcique d’efficacité et d’innocuité ne sont valables que pour le protocole utilisé, excluant ainsi les cas de patients souffrant de dysfonction hépatique grave.L’anticoagulation régionale au citrate lors de séances d’hémodialyse peut être effectuée à l’aide d’un protocole d’échantillonnage épars du calcium plasmatique. Le bilan calcique établi par ce protocole n’est pas différent de celui observé lors d’une hémodialyse anticoagulée par l’héparine. Toutefois en absence d’études prospectives, nous ignorons si ce protocole est optimal pour prodiguer des soins aux patients.

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.

This study investigated changes in Ca balance and BMD during pregnancy in female rats. During pregnancy, the intestinal Ca absorption increased significantly, and Ca accumulation was also markedly elevated. However, BMD values for the lumbar spine decreased significantly during pregnancy. Twenty female SD rats, 10 weeks of age (Japan SLC Co., Shizuoka, Japan) were acclimated for 2 weeks. Then, the rats were divided into two groups; the control (no pregnancy) group (n=10) and the pregnant group (n=10). The rats in the pregnant group were kept in a cage with a male rat for 5 days at 12 weeks of age, and all 10 were successfully impregnated. During the pregnancy period, the values for intestinal Ca absorption and the rate of the intestinal Ca absorption in the pregnant group were significantly greater than those of the control group. In addition, in spite of the significant increase in urinary Ca excretion in the pregnant group, the Ca accumulation was markedly elevated during the latter half of pregnancy. On the other hand, the BMD value in the lumbar spine for the pregnant group significantly decreased during pregnancy. These findings suggest that pregnancy accelerated intestinal Ca absorption and Ca accumulation in female rats, while the lumbar spine BMD decreased during pregnancy.

International audience; High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet. European Journal of Clinical Nutrition (2012) 66, 281-295; doi: 10.1038/ejcn.2011.196; published online 30 November 2011

Furosemide, a potent natriuretic agent, is well known to increase urinary calcium excretion. We study the effects of long term administration of furosemide on the calcium balance, renal function and histopathological changes of the kidneys and the parathyroid glands in the rat. Furosemide (20 mg/kg) was administered 3-4 times per week for 62 weeks intraperitoneally in 10 male rats. The same volume of normal saline was administered intraperitoneally in 9 male rats as control. All were given with standard diet (CE-2) and deionized water. While urinary calcium and creatinine were measured every 1-4 weeks, serum calcium and creatinine were measured in the first week and at the end of examination. 24 hours urinary excretion of calcium was elevated to two to three folds (a significant increase over the control: p less than 0.01) after the furosemide loading, though serum calcium and creatinine levels remained as in control. Despite a marked hypercalciuria in the furosemide loaded rats, there was no evidence of stone formation in the kidney or in the urinary tract. On histopathological examination renal parenchyma showed some pyelonephritic changes but without evidence of crystal formation, while no significant change was noted in the parathyroid glands. Based on these data we concluded that in our model, 1) there was a significant calcium loss in the absence of any change in the serum calcium, but 2) this hypercalciuria alone was not lithogenic, and 3) parathyroid glands showed no discernible secondary morphological changes.(ABSTRACT TRUNCATED AT 250 WORDS)

In all teleost fishes vitellogenesis is triggered and maintained by oestradiol-17beta (E2) and is accompanied by an increase of blood plasma calcium and phosphate. The action of this hormone on calcium metabolism was investigated by treating fast-growing immature juvenile sea bream (Sparus aurata) with coconut butter implants alone (control) or implants containing 10 microg/g E2. Treatment with E2 induced the production of circulating vitellogenin, a 2.5-fold increase in plasma ionic Ca2+ and a 10-fold increase in plasma total calcium, largely bound to protein. In contrast to freshwater species, which obtain most of their calcium from the environment directly through the gills, the intestinal component of calcium uptake of the salt water-living sea bream represented up to 60-70% of the total uptake. The whole body calcium uptake, expressed as the sum of calcium obtained via intestinal and extra-intestinal (likely branchial) routes increased significantly in response to E2. Combined influx and unchanged efflux rates resulted in a significant 31% increase in net calcium uptake. There was no evidence for an effect of E2 on the calcium and phosphate content of the scales or the tartrate-resistant acid phosphatase activity (an index for bone/scale osteoclast activity). While most freshwater fish appear to rely on internal stores of calcium, i.e. bone and/or scales to increase calcium availability, the marine sea bream accommodates calcium-transporting mechanisms to obtain calcium from the environment and preserve internal stores. These observations suggest that a fundamental difference may exist in the E2-dependent calcium regulation between freshwater and marine teleosts.

The 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 less than 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 less than 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 less than 0.001). The cumulative calcium balance in the control group exceeded by 7% that of the furosemide-treated animals [2696.3 +/- 20.8 mg versus 2518.6 +/- 20.1 mg (P less than .001]. The findings indicate that distal nephron compensatory mechanisms effecting sodium conservation following furosemide do not result in similar conservation of calcium. Calcium balance may be deleteriously affected.

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.

The impact of estrogen deficiency on bone has been extensively studied in the female; however, the effects of androgen deficiency on calcium fluxes in males have been less well characterized. We investigated the effect of short-term, severe androgen deficiency on measures of calcium absorption and kinetics as well as on markers of bone turnover in males. To accomplish this, 11 healthy male volunteers were recruited (mean age 23.3 +/- 0.5 years [SEM], body mass index 25.3 +/- 0.8 kg/m2). They consumed a weight maintenance diet for at least 3 days prior to admission to our Research Unit, with a calcium intake of approximately 1200 mg/day. At baseline (D1), subjects received 42Ca intravenously as well as 44Ca PO mixed with milk or juice. A 29-h urine collection was begun and blood samples collected at frequent intervals for the measurement of the isotopic enrichment of 42Ca and 44Ca using thermal ionization mass spectrometry. Twice daily urine samples were collected for 5 days after the administration of the isotopes. A gonadotropin-releasing hormone agonist (Lupron) was given after D1, again 3 weeks later, and studies repeated identically 4 weeks (D2, n = 6) and 10 weeks from baseline (D3, n = 7) (two subjects completed three studies). Testosterone concentrations were markedly suppressed on both D2 and D3 (-95%, p < 0.006), whereas there were no detectable changes in growth hormone and insulin-like growth factor-1 concentrations. Urinary calcium excretion increased significantly after 4 weeks (43%, p = 0.0007) and 10 weeks (73%, p = 0.003) of sustained hypogonadism. Using a multicompartmental kinetic model, the contribution of oral calcium to the urinary losses was decreased by D3 (-41%, p = 0.01), yet the contribution of bone calcium to urine losses increased by 10 weeks (+11%, p = 0.01). There was a 21% decrease in bone calcium deposition (Vo+) by D3 (p < 0.05) with no significant change in bone resorption rates (Vo-). There was a significant correlation between the decrease in testosterone concentration and the increase in urinary calcium excretion, especially at 10 weeks (R2 = 0.84, p = 0.004). These kinetic changes were accompanied by a decrease in osteocalcin concentrations on D2, with improvements by D3. Urinary N telopeptide, a measure of bone resorption, also increased during the studies. In summary, profound hypogonadism in young males is associated with marked increases in urinary calcium losses, with a greater contribution of bone calcium to those losses and decreased kinetic markers of bone calcium deposition. We conclude that even short-term, severe deficiency in gonadal steroids can have profound negative effects on calcium and bone metabolism in males.

Department of Human Biology, University of Limburg, Maastricht, The Netherlands.The present study was conducted to investigate the effect of dietary protein on urinary Ca excretion, apparent Ca absorption and Ca balance in young and elderly subjects. Young adults (n 29) and elderly persons (n 26) consumed diets containing 12% (diet A) and 21% (diet B) of total energy as protein for 3 weeks according to a randomized crossover design. Results showed no differences between the two age groups with respect to the interaction between protein intake and Ca excretion (both in urine and in faeces), apparent Ca absorption and Ca balance. Therefore analyses were done for both age groups separately and also for the whole group. In elderly persons and in the whole group the Ca excretion in faeces (as a percentage of Ca intake) was lower during the higher protein intake (elderly: diet A, 106 (SEM 7)%; diet B, 86 (SEM 7)%; P = 0.018; whole group: diet A, 99 (SEM 4)%; diet B, 84 (SEM 4)%; P = 0.003). In young adults faecal Ca excretion tended to be lower when they consumed diet B (diet A: 94 (SEM 5)%; diet B: 83 (SEM 6)%; P = 0.093). Relative urinary Ca excretion was greater during the higher protein intake in young adults and in the whole group while relative urinary Ca excretion was not different in the elderly (diet A: 15 (SEM 1)%, 14 (SEM 1)%, 15 (SEM 1)%; diet B: 16 (SEM 1)%, 16 (SEM 1)%, 17 (SEM 2)% for the whole group, the young and elderly subjects respectively, P = 0.019; P = 0.016; P = 0.243). The resulting Ca balance was not influenced by the amount of protein in the diet in young adults. Values for the elderly and for the whole group showed that the Ca balance during diet A was significantly more negative compared with Ca balance during diet B, despite the higher urinary Ca excretion during diet B. It can be concluded that increasing the protein intake from 12 to 21% of total energy intake had no negative effect on Ca balance.Publication Types: Clinical Trial Randomized Controlled Trial

Changes in Ca(2+) content and flux, and the development of skin chloride cells in embryos and larvae of tilapia, Oreochromis mossambicus, were studied. Tilapia embryos hatched within 96h at an ambient temperature of 26-28°C. Total body Ca(2+) content was maintained at a constant level, about 4-8 nmol per individual, during embryonic development. However, a rapid increase in body Ca(2+) level was observed after hatching, 12.8 to 575.3 nmol per individual from day 1 to day 10 after hatching. A significant influx and efflux of Ca(2+) occurred during development, with the average influx rate for Ca(2+) increasing from 5.9 pmol mg(-1) h(-1) at 48h postfertilization to 47.8 pmol mg(-1) h(-1) at 1 day posthatching. The skin was proposed as the main site for Ca(2+) influx before the development of gills, and the increased Ca(2+) influx may be ascribed to gradual differentiation of skin surface and chloride cells during embryonic development. Ca(2+) efflux was 16-56 pmol mg(-1) h(-1) in 1-day-old larvae. The resulting net influx of Ca(2+), 10-12 pmol mg(-1) h(-1), accounted for the increased Ca(2+) content after hatching. When comparing the measured and estimated ratios of efflux and influx, active transport was suggested to be involved in the uptake of Ca(2+). Chloride cells, which may be responsible for the active uptake of Ca(2+), started to differentiate in the skin of embryos 48h after fertilization, and the density of chloride cells increased following the development. A possibility of active transport for Ca(2+) in early developmental stages of tilapia is suggested.

Dietary calcium and serum 1,25-(OH) 2 -vitamin D concentrations as determinants of calcium balance in healthy men. We previously reported that experimental elevations of serum 1,25-(OH) 2 -vitamin D [1,25-(OH) 2 -D] concentrations produced by the chronic oral administration of calcitriol, 0.75 µg every 6 hr, to healthy human males eating diets providing only 4 mmoles Ca/day stimulate net bone resorption as evidenced by more negative Ca balances and higher rates of urinary hydroxyproline excretion. To determine whether increased dietary Ca intake modifies this response we have compared serum 1,25-(OH) 2 -D and iPTH concentrations, Ca and PO 4 balances, and urinary hydroxyproline excretion in three healthy human males adapted to diets providing 22.3 ± 1.3 mmoles Ca/day and three healthy human males adapted to diets providing 9.3 ± 0.7 mmoles Ca/day before and during the continuous oral administration of calcitriol 0,5 µg every 6hr. For all six subjects, serum 1,25-(OH) 2 -D levels averaged 89 ± 25 pM during control and 143 ± 26 pM during calcitriol. Net intestinal Ca absorption and urinary Ca excretion rose during calcitriol but Ca balances did not change, averaging +2.2 ± 2.2 mmoles/day during control and +4.3 ± 2,2 mmoles/day during calcitriol for the subjects fed 22 mmoles Ca/day and - 1.6 ± 1.5 mmoles Ca/day during control and - 1.7 ± 2.0 mmoles Ca/day during calcitriol for the subjects fed 9 mmoles Ca/day. Urinary hydroxyproline excretion also did not change. Thus, when serum 1,25-(OH) 2 -D levels are elevated, the availability of dietary Ca appears to prevent more negative Ca balances and increased urinary hydroxyproline excretion suggesting that net bone resorption is not stimulated. Le calcium alimentaire et les concentrations seriques de 1,25-(OH) 2 -vitamine D determinants de la balance calcique chez des hommes sains. Nous avons prealablement rapporte que des elevations experimentales des concentrations seriques de 1,25-(OH) 2 -D par administration chronique orale de calcitriol, 0,75 µg toutes les 6 heures a des hommes sains ingerant des regimes n'apportant que 4 mmoles Ca/jour stimulent la resorption osseuse nette, ce qui est mis en evidence par des balances Ca plus negatives et par des debits d'excretion urinaire d'hydroxyproline plus eleves. Afin de determiner si une augmentation de l'apport en Ca alimentaire modifie cette reponse, nous avons compare les concentrations seriques de 1,25-(OH) 2 -D et d'iPTH, les balances Ca et PO 4 et l'excretion urinaire d'hydroxyproline chez trois hommes sains adaptes a des regimes apportant 22,3 ± 1,3 mmoles Ca/jour et chez trois hommes sains adaptes a des regimes apportant 9,3 ± 0,7 mmoles Ca/jour avant et pendant l'administration orale continue de calcitriol, 0,5 µg toutes les 6 heures. Pour les six sujets, les niveaux seriques de 1,25-(OH) 2 -D etaient en moyenne de 89 ± 25 pM pendant le controle et de 143 ± 26 pM pendant le calcitriol. L'absorption intestinale nette de Ca et l'excretion urinaire de Ca se sont elevees pendant le calcitriol, mais les balances Ca n'ont pas change, etant en moyenne de +2,2 ± 2,2 mmoles/jour pendant le controle et de 4,3 ± 2,2 mmoles/jour pendant le calcitriol chez les sujets ingerant 22 mmoles Ca/jour et de - 1,6 ± 1,5 mmoles Ca/jour pendant le controle et de 1,7 ± 2,0 mmoles Ca/jour pendant le calcitriol chez les sujets ingerant 9 mmoles Ca/jour. L'hydroxyproline urinaire aussi ne s'est pas modifiee. Ainsi, lorsque les niveaux seriques de 1,25-(OH) 2 -D sont eleves, la disponibilite du calcium alimentaire parait prevenir des balances Ca plus negatives et une excretion urinaire d'hydroxyproline elevee, suggerant que la resorption osseuse nette n'est pas stimulee.

Potassium bicarbonate, but not sodium bicarbonate, reduces urinary calcium excretion and improves calcium balance in healthy men. Previous studies demonstrated that the administration of NaHCO3 or sodium citrate had either only a small effect to reduce urinary Ca excretion or no effect, but that potassium citrate significantly reduced urinary Ca excretion. In order to further evaluate and compare the effects of NaHCO3 and of KHCO3, we performed ten metabolic balances in healthy men during 18 control days, 12 days of NaHCO3, 60 mmol/day and 12 days of KHCO3, 60 mmol/day. Six subjects were fed a low Ca diet (5.2 ± 0.7 SD mmol/day) and three of these were also given calcitriol (0.5 µg 6-hourly). Four subjects ate a normal Ca diet (19.5 ± 1.3 mmol/day). For all 10 subjects, KHCO3 administration reduced urinary Ca excretion from control by -0.9 ± 0.7 mmol/day, P < 0.001. Net intestinal Ca absorption did not change detectably so that Ca balances became less negative by a +0.9 ± 0.9 mmol/day; P = 0.01. KHCO3 administration was also accompanied by more positive PO4 and Mg balances. NaHCO3 administration had no significant effect on urinary Ca excretion or Ca balance. NaHCO3 and KHCO3 administration were accompanied by equivalently more positive Na or K balances, respectively and equivalently more negative acid balances (HCO3 retention). Neither NaHCO3 or KHCO3 altered fasting serum HCO3 concentrations, blood pH, serum 1,25-(OH)2-D or PTH concentrations. We conclude that KHCO3 promotes more positive Ca balances by either enhancing renal Ca retention or skeletal Ca retention or both.

Young adult male and laying female quail, fed with a diet containing 2.64% Ca and 0.70% P, were used to study nutritive utilization, corporal calcium retention and endogenous excretion, calcemia, laying and properties of the egg (including the shell structure), mineralization of the femur bone, as well as the influence of diethylstilbestrol upon these parameters. The coefficient of nutritive utilization (C.N.U.) in the female was high and logically superior to that of the male, while the corporal retention was quite similar for both sexes. Most of the Ca absorbed (81.8%) and not excreted in urine, went to the egg and only 18.2% remained in the body. The diethylstilbestrol caused a big reduction of the C.N.U. in the female, but not in the male, parallel to an inhibition of laying, and an increase of corporal retention of used calcium. In both sexes the calcemia surprisingly increased, and the calcium level of the femur bone was higher, and even though the cortical osseous zone was slightly wider, the effect of treatment was noticeable, particularly in the medular tissue, which incremented in the female and appeared in the male. When quail were fed a calcium-restricted diet, the endogenous excretion of this mineral was small in the case of the female and significantly smaller in the male. This situation suppressed egg laying and resulted in a clearly decreased bone mineralization. The ingestion of diethylstilbestrol before feeding a diet poor in calcium provoked an increase of the endogenous excretion of calcium in both female and male quail.

Myocardial function is tuned by dynamic changes in length and load via mechano-calcium feedback. This regulation may be significantly affected by heart rhythm. We evaluated the mechano-induced modulation of contractility and Ca-transient (CaT) in the rat myocardium subjected to twitch-by-twitch shortening–re-lengthening (↓–↑) trains of different lengths (N = 1 … 720 cycles) at low (1 Hz) and near-physiological (3.5 Hz) pacing rates. Force/CaT characteristics were evaluated in the first post-train isometric twitch (immediate effect) and during slow changes (delayed maximal elevation/decrease) and compared with those of the pre-train twitch. The immediate inotropic effect was positive for N = 30 … 720 and negative for N = 1 … 20, while the delayed effect was always positive. The immediate and delayed inotropic effects were significantly higher at 3.5-Hz vs 1-Hz (P < 0.05). The prominent inotropism was accompanied by much smaller changes in the CaT diastolic level/amplitude. The shortening–re-lengthening train induced oscillations of the slow change in force at 3.5-Hz (always) and at 1-Hz (∼50% of muscles), which were dependent of the train length and independent of the pacing rate. We suggest that twitch-by-twitch shortening–re-lengthening of cardiac muscle decreases Ca2+ buffering by troponin C and elevates Ca2+ loading of the sarcoplasmic reticulum (SR); the latter cumulatively depends on the train length. A high pacing rate intensifies the cumulative transient shift in the SR Ca2+ loading, augmenting the post-train inotropic response and prolonging its recovery to the pre-train level. The pacing-dependent mechano-induced inotropic effects remain to be elucidated in the myocardium with impaired Ca handling. © 2020 Elsevier Ltd The study was supported by RFBR grant # 18-04-00572 and by RF Government Act #211 of March 16, 2013 (agreement 02.A03.21.0006 ), and was carried out within the framework of the IIF UrB RAS theme No АААА-А18-118020590031-8 .

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.

Glucocorticoids are known to affect calcium balance but are not thought to cause clinically significant hypocalcemia. This case adds to a list of isolated reports noting significant hypocalcemia developing post administration of glucocorticoids in a patient with known hypoparathyroidism, postulating PTH deficiency as a risk factor of decompensated calcium homeostasis.\ud