Search

Huntington's disease (HD) is a neurodegenerative, dominantly inherited genetic disease caused by expansion of the polyglutamine tract in the huntingtin gene. At the cellular level, HD is characterized by the accumulation of mutant huntingtin protein in brain cells, resulting in the development of the HD phenotype, which includes mental disorders, decreased cognitive abilities, and progressive motor impairments in the form of chorea. Despite numerous studies, no unambigous connection between the accumulation of mutant protein and selective death of striatal neurons has yet been established. Recent studies have shown impairments in the calcium homeostasis in striatal neurons in HD. These cells are extremely sensitive to changes in the cytoplasmic concentration of calcium and its excessive increase leads to their death. One of the possible ways to normalize the balance of calcium in striatal neurons is through the sigma 1 receptor (S1R), which act as a calcium sensor that also exhibits modulating chaperone activity upon the cell stress observed during the development of many neurodegenerative diseases. The fact that S1R is a ligand-operated protein makes it a new promising molecular target for the development of drug therapy of HD based on the agonists of this receptor. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We studied the role of calcium-regulating structures of slow- ( m. soleus, SOL) and fast-twitch ( m. extensor digitorum longus, EDL) skeletal muscles of rats during adaptation to exhausting physical activity and the possibility of modulating this adaptation with decaffeinated green tea extract. It was established that EDL adaptation is mainly aimed at Са elimination from the sarcoplasm by Са-ATPase and its retention in the reticulum by calsequestrin. Administration of green tea extract increased endurance due to involvement of slow-twitch muscles whose adaptation is associated with enhanced expression of all the studied genes responsible for the regulation of Ca balance. [ABSTRACT FROM AUTHOR]

Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use. [ABSTRACT FROM AUTHOR]

Copyright of Der Nephrologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The rare, long-lived radiotracer, Ca, measured by accelerator mass spectrometry in the urine or serum following incorporation into the bone provides an ultra-sensitive tool to assess changes in bone calcium balance in response to an intervention. Changes in bone balance can be followed for years with one small dose that is both radiologically and biologically non-invasive. Sequential interventions can be compared, with greater precision than they can with biochemical markers of bone turnover and with greater power than with bone densitometry. This method is especially useful to screen interventions over a period of weeks. The development and validation of this tool and its applications are reviewed. Mini abstract: Use of Ca measured in the urine or blood by accelerator mass spectrometry to assess bone balance provides a tool to compare the relative efficacy of multiple interventions. This perspective provides insights in the use of this novel method and comparisons with more traditional methods for evaluating the efficacy of interventions. [ABSTRACT FROM AUTHOR]

The kidney plays a pivotal role in regulating calcium levels within the body. Approximately 98% of the filtered calcium is reabsorbed in the nephron, and this process is tightly controlled to maintain calcium homeostasis, which is required to facilitate optimal bone mineralization, preserve serum calcium levels within a narrow range, and support intracellular signalling mechanisms. The maintenance of these functions is attributed to a delicate balance achieved by various calcium channels, transporters, and calcium-binding proteins in renal cells. Perturbation of this balance due to deficiency or dysfunction of calcium channels and calcium-binding proteins can lead to severe complications. For example, polycystic kidney disease is linked to aberrant calcium transport and signalling. Furthermore, dysregulation of calcium levels can promote the formation of kidney stones. This Review provides an updated description of the key aspects of calcium handling in the kidney, focusing on the function of various calcium channels and the physiological stimuli that control these channels or are communicated through them. A discussion of the role of calcium as an intracellular second messenger and the pathophysiology of renal calcium dysregulation, as well as a summary of gaps in knowledge and future prospects, are also included. Calcium reabsorption along the nephron is essential for calcium homeostasis and whole-body electrolyte balance. Here, Staruschenko et al. highlight signalling pathways and molecules involved in renal calcium handling in health and disease, and discuss progress in the integration of systems-level and molecular understanding of calcium transport and regulation. Key points: The kidney has an essential role in the maintenance of serum calcium levels owing to its careful regulation of reabsorption along the nephron, which contributes to whole-body calcium balance. Physiologically relevant mechanisms that control calcium channels in the kidney include endocrine and paracrine signals and physical factors such as fluid flow. Tight control of calcium influx and intracellular calcium levels maintains intracellular calcium concentrations within the physiological range, despite acute and chronic variation in calcium intake. Failure to reabsorb calcium from renal tubules results in hypercalciuria and an increased risk of kidney stones. Aberrant calcium signalling in particular renal cell types is a hallmark of renal diseases such as polycystic kidney disease and focal segmental glomerulosclerosis. [ABSTRACT FROM AUTHOR]

Excessive activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propoinic acid (AMPA) receptors instigates excitotoxicity via enhanced calcium influx in the neurons thus inciting deleterious consequences. Additionally, Endoplasmic Reticulum (ER) is pivotal in maintaining the intracellular calcium balance. Considering this, studying the aftermath of enhanced calcium uptake by neurons and its effect on ER environment can assist in delineating the pathophysiological events incurred by excitotoxicty. The current study was premeditated to decipher the role of ER pertaining to calcium homeostasis in AMPA-induced excitotoxicity. The findings showed, increased intracellular calcium levels (measured by flowcytometry and spectroflourimeter using Fura 2AM) in AMPA excitotoxic animals (male Sprague dawely rats) (intra-hippocampal injection of 10 mM AMPA). Further, ER resident proteins like calnexin, PDI and ERp72 were found to be upregulated, which further modulated the functioning of ER membrane calcium channels viz. IP3R, RyR, and SERCA pump. Altered calcium homeostasis further led to ER stress and deranged the protein folding capacity of ER post AMPA toxicity, which was ascertained by unfolded protein response (UPR) pathway markers such as IRE1α, eIF2α, and ATF6α. Chemical chaperone, 4-phenybutric acid (4-PBA), ameliorated the protein folding capacity and subsequent UPR markers. In addition, modulation of calcium channels and calcium regulating machinery of ER post 4-PBA administration restored the calcium homeostasis. Therefore the study reinforces the significance of ER stress, a debilitating outcome of impaired calcium homeostasis, under AMPA-induced excitotoxicity. Also, employing chaperone-based therapeutic approach to curb ER stress can restore the calcium imbalance in the neuropathological diseases. [ABSTRACT FROM AUTHOR]

The sodium-calcium exchanger (NCX) is essential in maintaining the intracellular calcium balance in neurons and is a regulator of glutamatergic synaptic transmission. NCX dysfunction is implicated in various neurodegenerative and mental illnesses, while pharmacological agents modulating NCX (specific antagonists, allosteric modulators, lithium ions, etc.) are considered potential drugs. However, the effects of the exchanger selective blockers or lithium ions on the electrogenic transport of NCX in neurons have not been previously studied. In this work, using a patch-clamp recording of transmembrane currents in neocortical neurons in primary culture and HEK293 cells, we investigated the effects of the selective NCX antagonists KB-R7943 and SN6 on the current–voltage characterisrics (I–V) of the cell membranes. Also, we examined the influence of lithium ions, a non-transportable NCX substrate, on the NCX transport currents. We show that in cortical neurons, transport current generated by NCX contributes to neuronal I–V, which can be detected when NCX is inhibited by KB-R7943 or SN6. When using a Ca2+-free pipette solution ([Ca2+]i < 100 nM), the exchanger transport current can be recorded only in its reverse mode of operation, when neurons are depolarized, but not in the forward mode of operation at resting potential. Pipette solution with high content of free Ca2+ ([Ca2+]i > 1000 nM) creates the conditions that allow forward operation of the NCX at negative membrane potentials mode of NCX at negative membrane potentials. However, in neurons, unlike HEK293, replacing more than 50% Na+ by Li+ in the extracellular solution inhibits NCX and other sodium-dependent electrogenic transport mechanisms, which is accompanied by a drop in the input resistance and considerably complicates the detection of transport currents generated by NCX. Thus, we demonstrate the possibility of a direct study of NCX transport features and pharmacological characteristics in neurons and HEK293 cells. [ABSTRACT FROM AUTHOR]

To maintain calcium homeostasis during physical inactivity, precise coordination is necessary between different organs of the body. There are a number of factors which alter an organism's calcium balance, such as growth, aging, physical inactivity and acquired or inherited disorders which ultimately lead to bone loss. In non-hibernating mammals, physical inactivity causes bone loss which may not be completely recoverable during the lifespan of an individual despite a resumption of activity. Extreme physical inactivity and nutritional deprivation are two other important factors that lead to bone loss in non-hibernating mammals. The mechanism of bone loss is still poorly understood, however, there is some evidence which shows that during hibernation, smaller mammals (ground squirrels, bats, and hamsters) undergo bone loss. While on the other hand, hibernating bears do not show any sign of bone loss and retain their bone structure and strength. This may be due to differences in their hibernation patterns, as smaller mammals may excrete calcium throughout the hibernation period, which ultimately leads to bone loss, whereas bears seem to have a more developed and advanced mechanism to prevent calcium loss and maintain their bone structure. In this review, we summarize calcium homeostasis and its adaptive mechanisms with reference to bone loss in hibernating as compared to non-hibernating mammals. We also review the effect of microgravity and simulated microgravity on bone physiology and subsequent adaptation. [ABSTRACT FROM AUTHOR]

Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: The recent observation that urinary calcium excretion (UCE) drops considerably with CKD and that this effect may occur beyond compensation for reduced intestinal calcium absorption suggests that CKD per se is a state of sustained positive calcium balance, a mechanism likely to contribute to vascular calcification and CVD in CKD. However, the determinants of UCE reduction in CKD are not well understood and there is a lack of clinical studies, particularly in the CKD population. Therefore, in this study, we aimed to evaluate variables associated with UCE in a CKD cohort. Methods: Baseline data on 356 participants of the Progredir Study, Sao Paulo, Brazil, essentially composed of CKD G3a–G4, were analyzed according to UCE (24 h urine collection). Results: Median 24 h UCE was 38 mg/day (IQR 21–68 mg/day) and 0.48 mg/kg/day (IQR 0.28–0.82 mg/kg/day). In univariate analysis, UCE was inversely related to age, phosphorus, 1-84 PTH, FGF-23 and sclerostin, and positively associated with eGFR, DBP, 1,25(OH)2-vitamin D, calcium, bicarbonate, total calorie intake and spironolactone use. After adjustments for age, sex and eGFR, only 1,25(OH)2-vitamin D, calcium, FGF-23, bicarbonate and total calorie intake remained associated with it, but not PTH nor sclerostin. Lastly, in a multivariable model, eGFR, serum 1,25(OH)2-vitamin D, calcium, and FGF-23 remained associated with UCE. Similar results were observed when calcium fractional excretion was used instead of UCE, with eGFR, 1-25-vitamin D and FGF-23 remaining as independent associations. Conclusion: Our results showed that CKD is associated with very low levels of UCE and that 1,25(OH)2-vitamin D, serum calcium and FGF-23 were independently associated with UCE in this population, raising the question whether these factors are modulators of the tubular handling of calcium in CKD. [ABSTRACT FROM AUTHOR]

Copyright of Calcified Tissue Research is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Hyponatremia is associated with bone demineralization. We hypothesized that, during hyponatremia, calciuria and calcium balance depend on volemic status. We evaluated calciuria in patients with hyponatremia, secondary to SIAD or hypovolemia. Patients with SIAD exhibited a volemic expansion that was associated with hypercalciuria. Calciuria was proportional to markers of volemia. Introduction: Chronic mild hyponatremia has been associated with bone demineralization of unknown mechanisms. During chronic hyponatremia, arginine-vasopressin secretion can result from hypovolemia or from syndrome of inappropriate anti-diuresis (SIAD) that leads to a slightly volemic expansion. Since volemia determines renal calcium excretion and balance, we evaluated calcium homeostasis in patients with chronic hyponatremia, related to SIAD or to hypovolemia. Methods: We retrospectively included all patients referred to our Department between May 2006 and May 2014 for hyponatremia, resulting from SIAD or chronic hypovolemia. None had edema, cirrhosis, cardiac, or renal insufficiency. Exploration included estimation of volemia, extracellular fluid volume (ECFV) measurement with inulin, and calcium homeostasis. Results: In total, the SIAD and hypovolemic groups included 22 and 7 patients, respectively. The SIAD group exhibited signs of increased volemia: higher glomerular filtration rate, higher fractional excretion of uric acid, and lower plasma renin. ECFV exceeded that of the hypovolemic group and was above usual values. There was no difference between the two groups regarding plasma calcium, PTH, and vitamin D. However, in the SIAD group, calciuria was higher than in the hypovolemic group, reaching levels of hypercalciuria. Furthermore, there was a positive correlation between calciuria and markers of volemia. Conclusions: Our results show that SIAD results in a volemic expansion tendency that is associated with a decrease in renal calcium reabsorption and thus hypercalciuria, whereas in the hypovolemic group, calciuria was not increased. Therefore, renal loss of calcium and bone demineralization in SIAD patients could be partly induced by volemic expansion. [ABSTRACT FROM AUTHOR]

The expression of genes responsible for the synthesis of essential proteins regulating the calcium-ion balance and ultrastructural characteristics of fast-twitch (m. extensor digitorum longus, EDL) and slow-twitch (m. soleus, SOL) skeletal muscles under prolonged exercise were studied in an experimental model of forced-swimming rats. A day after the end of the exercise, no significant changes in any of the five investigated genes were revealed in the SOL. A few triad elements (T-tubules and cisternae of sarcoplasmic reticulum) were revealed. A small number of excitation-contraction coupling (ECC) structures in the control and a slight increase in their amount after exercises were noticed. Polymorphism and mitochondrial defects within SOL muscles indicate the importance of these structures in the regulation of calcium balance. In EDL muscles, adaptation mechanisms are aimed mainly at pumping Ca ions to the sarcoplasmic reticulum, where the main calcium buffer is calsequestrin. Expression of SERCA1 gene increased by an order of magnitude, and that of CASQ1 increased by three times. Electron microscopy showed a major role of triads in the maintenance of calcium homeostasis in the EDL muscles, as well as a greater destruction of these muscles compared to SOL after exhausting exercise. The high level of triads and a possible activation of the CICR (calcium-induced calcium release) mechanism in fast-twitch muscles can cause damage to them during exhausting exercise. Adaptation of SOL muscles is associated with structural rearrangements of the mitochondrial apparatus, while adaptation of the EDL muscles is caused by calcium removal from the sarcoplasm with Ca-ATPase and its retention in the sarcoplasmic reticulum by calsequestrin. [ABSTRACT FROM AUTHOR]

The oophorectomized (OOX) rat has been proposed as a good model of postmenopausal osteoporosis in women. The aim of this study was to compare the effect of OOX in 6-month-old rats to the effects of menopause in women with respect to bone mass, the renal handling of calcium and phosphorus, and calcitropic hormones. To more closely replicate the human situation the rats were pair fed a 0.1% calcium diet. Thirty four, 6-month-old rats were randomized to sham operation or OOX. Whole body and regional bone density was performed at baseline and 6 weeks postoperation. Blood and 24-hour urine samples were obtained at baseline, 1, 3, and 6 weeks and assayed for various biochemical variables, parathyroid hormone (PTH), and calcitriol. The OOX rats lost significantly more bone than the sham-operated rats (change in global bone mineral density, sham -1.7 +/- 2.0%, OOX -3.9 +/- 2.6%, P < 0.001). In the OOX animals, an increase in the 24-hour urine calcium was observed at 1 and 3 weeks, which had returned to sham-operated levels by 6 weeks. In the whole group, the increase in urine calcium at 1 week was negatively correlated with the change in bone mass at 6 weeks (r = -0.39, P = 0. 029). OOX resulted in an increased filtered load of calcium and phosphorus. There was an increase in the maximal renal tubular reabsorption of phosphorus (TmP-GFR) but no clear change in renal calcium handling. Neither calcitriol nor parathyroid hormone showed a significant change as a result of OOX. As in postmenopausal women, following oophorectomy in the rat, there was significant generalized bone loss and a negative calcium balance. This was associated with an initial rise in urine calcium due to a rise in the filtered calcium load; plasma phosphorus and TmP-GFR also rose. The rat model may differ from postmenopausal bone loss in that the initial rise in urine calcium was not present at later time points as occurs in natural menopause in women. Calcitropic hormone levels did not change. This study has shown that the 6-month-old OOX rat fed a 0.1% calcium diet has many similarities of calcium and phosphorus homeostasis to that seen at menopause in women. [ABSTRACT FROM AUTHOR]

Balance studies were conducted on 4 normal elderly subjects, 2 males and 2 females, ranging in age between 66 and 86 years in order to compare the bioavailability of oyster shell electrolysate with that of calcium carbonate and calcium lactate, in a crossover design. In each subject, 600 mg oyster shell electrolysate was more effective than calcium carbonate or calcium lactate containing the same 600 mg calcium to restore the negative calcium balance found on 600 mg/day calcium intake, suggesting a better bioavailability of oyster shell electrolysate than the two kinds of calcium salts. [ABSTRACT FROM AUTHOR]

Summary: We assessed the prevalence of hypocalcemia after denosumab injections in a real-world cohort routinely monitored for calcium during up to 7.5 years of treatment. Among 1096 injections in 242 patients, 6.3% resulted in hypocalcemia, and was independent of the injection number. Severe hypocalcemia was rare (1%). Purpose: To assess the prevalence of and risk factors for hypocalcemia after administration of denosumab in a patient cohort routinely monitored for ionized calcium after each dose. Methods: In this retrospective observational study, we analyzed denosumab-induced hypocalcemia in a real-world cohort who were routinely followed up with ionized calcium pre- and post-injection (within 31 days after injection) during the period 2011 to 2020. Results: In total, we included data from 1096 denosumab injections in 242 individuals (1–15 injections per patient). The mean age for the first injection was 74 ± 10 years, and 88% were female. Post-injection hypocalcemia occurred after 6.3% of all injections (4.6% mild, 0.6% moderate, and 1.1% severe) and was independent of the number of injections (rate of hypocalcemia varied from 3–8%). Risk factors for hypocalcemia were male sex, severe renal failure, pre-injection hypocalcemia, hypomagnesemia, hypophosphatemia, and vitamin D insufficiency. Furthermore, older age was not associated with an increased hypocalcemia risk. Conclusions: Denosumab-induced hypocalcemia is a prevalent adverse event, which occurs independently of the number of injections. However, severe hypocalcemia is a rare occurrence, and severe renal failure and nutritional status appear to be important predictive factors. Magnesium and phosphate might add value in the pre-injection risk assessment; however, this observation needs to be confirmed in larger cohorts. [ABSTRACT FROM AUTHOR]

Purpose: Calcium L-threonate is a novel drug that was developed for the treatment of osteoporosis and as a calcium supplement. However, calcium bioavailability of this drug is unknown due to lack of effective evaluation methods. In this study, we sought to measure the bioavailability of calcium L-threonate with a double-label stable isotope method. Methods: Fourteen healthy Chinese subjects were enrolled in the clinical study and were given 300 mg calcium L-threonate tablets containing 40 mg Ca after an intravenous injection of 4 mg Ca solution (as calcium chloride). Fractional urine samples were collected at the following time intervals: 0-3, 3-6, 6-9, 9-13, 13-24, 24-36 and 36-48 h. The abundance ratios of Ca/Ca and Ca/Ca in the urine were determined with thermal-ionization mass spectrometry (TI-MS). The calcium bioavailability was estimated by calculating the true fractional calcium absorption (TFCA) using the abundance ratios of Ca/Ca and Ca/Ca. Results: The bioavailability of calcium L-threonate in 14 healthy Chinese subjects was 26.49 ± 9.39 %. There was good agreement between TFCA from the 24 to 36 h and the 36 to 48 h urine pool, indicating that calcium balance was achieved at 24 h after dosing. The TFCA of the subjects did not statistically correlate with total urinary calcium excretion (0-48 h). There were no serious adverse events in this study. Conclusions: The bioavailability of calcium L-threonate in humans was successfully determined by estimating TFCA with the double-label stable isotope method, thus providing a useful approach for the evaluation of bioavailability of calcium formulations. [ABSTRACT FROM AUTHOR]

Calcium homeostasis plays vital roles in the management of bone health. Traditional herbal formula Gushukang (GSK) was clinically applied to treat primary osteoporosis. This study aimed to explore the osteoprotective effects of GSK and its roles in maintaining calcium homeostasis in ovariectomized (OVX) mice. The OVX mice were orally treated with low (0.38 g/kg), middle (0.76 g/kg) and high (1.52 g/kg) dose of GSK for 8 weeks. GSK treatment dramatically increased serum calcium level and decreased urinary calcium excretion as well as enhanced calcium content in bone of OVX mice. Serum level of 25-hydroxyvitamin D was significantly increased in OVX mice with exposure to GSK. Treatment with GSK improved bone mass and micro-structure of trabecular bone at distal metaphysis of femur and proximal metaphysis of tibia in OVX mice shown by safranin O staining and micro-CT measurement. GSK treatment at all doses up-regulated mRNA expression of calcium-binding protein-28k and vitamin D receptor in kidney of OVX mice, and dose-dependently decreased mRNA expression of claudin-14 and elevated mRNA expression of claudin-16 in duodenum of OVX mice. Taken together, GSK exerted beneficial effects on trabecular bone of OVX mice by improving calcium homeostasis via regulating paracellular calcium absorption in duodenum and transcellular calcium reabsorption in kidney. [ABSTRACT FROM AUTHOR]

The purpose of this article is to provide recommendations on the choice of peritoneal dialysis (PD) fluids in children by the European Pediatric Dialysis Working Group. The literature on experimental and clinical studies with PD solutions in children and adults was analyzed together with consensus discussions within the group. A grading was performed based on the international KDIGO nomenclature and methods. The lowest glucose concentration possible should be used. Icodextrin may be applied once daily during the long dwell, in particular in children with insufficient ultrafiltration. Infants on PD are at risk of ultrafiltration-associated sodium depletion, while anuric adolescents may have water and salt overload. Hence, the sodium chloride balance needs to be closely monitored. In growing children, the calcium balance should be positive and dialysate calcium adapted according to individual needs. Limited clinical experience with amino acid-based PD fluids in children suggests good tolerability. The anabolic effect, however, is small; adequate enteral nutrition is preferred. CPD fluids with reduced glucose degradation products (GDP) content reduce local and systemic toxicity and should be preferred whenever possible. Correction of metabolic acidosis is superior with pH neutral bicarbonate-based fluids compared with single-chamber, acidic, lactate-based solutions. Prospective comparisons of low GDP solutions with different buffer compositions are still few, and firm recommendations cannot yet be given, except when hepatic lactate metabolism is severely compromised. [ABSTRACT FROM AUTHOR]

Plasma phosphate levels are important in the evolution of hyperparathyroidism and ectopic calcification in chronic kidney disease (CKD). Although dietary management may be adequate to control plasma phosphate in its early stages, most patients develop hyperphosphataemia by CKD stages 3−4 and require the addition of a phosphate binder. Calcium-containing phosphate binders are the most used and cheapest binders but have fallen out of favour because of the potential for positive calcium balance and calcium toxicity. This problem may be attenuated by newer phosphate binders such as sevelamer hydrochloride and lanthanum carbonate. In this review, the role of phosphate as a uraemic toxin and the advantages and disadvantages of the currently available phosphate binders are discussed. [ABSTRACT FROM AUTHOR]

The traditional view of calcium homeostasis is that it is maintained by two essential reactions. First, changes in extracellular Ca2+ are sensed in several distinct cell types, stimulating the secretion of parathyroid hormone (PTH), 1,25(OH)2 D and calcitonin in response to the body’s requirement. Second, these calcitropic hormones then act on the calcium-translocating cells of the kidney, bone, and intestine to restore calcium balance. Recent progress indicates that α-Klotho and fibroblast growth factor (FGF) 23 are key players that integrate the multi-step regulatory system of calcium homeostasis that rapidly adjusts the extracellular calcium concentration and continuously maintains its concentration within a narrow physiological range. α-Klotho and FGF23 are also found to be major players in the regulatory system of phosphate homeostasis. Here, the demonstration of the molecular functions of α-Klotho and FGF23 has recently given new insight into the field of calcium and phosphate homeostasis. [ABSTRACT FROM AUTHOR]

Abstract  Many epidemiological studies have reported that the severity of arterial diseases such as arterial calcification and stiffness is inversely related to bone loss, i.e., osteoporosis. However, the nature of this relationship is unclear. The purpose of the present study was to examine the influences of estrogen deficiency and/or low-calcium diet (0.1% Ca) on bone metabolism and calcium balance, as well as aortic wall composition and stiffness in young female rats. Twenty-eight 6-week-old female rats were randomized into four groups: OVX-Low calcium (OL) and OVX-Normal calcium groups (ON) were ovariectomized, and Sham-Low calcium (SL) and Sham-Normal calcium groups (SN) were sham-operated. After 12 weeks, the bone mineral density of the lumbar spine and tibial proximal metaphysis were significantly lower in ON than in SN, and also significantly lower in OL than in ON. Additionally, OL rats had significant higher (vs. SN and SL) urinary deoxypyridinoline, but not urinary calcium, excretion at 4 weeks after ovariectomy. However, at 12 weeks after ovariectomy, urinary calcium excretion was significantly higher in OL than in SL, with corresponding increases in two bone turnover markers, bone-type alkaline phosphatase and tartrate-resistant acid phosphatase. Neither estrogen deficiency nor low-calcium diet affected aortic stiffness or elastin degeneration and calcium deposition over the course of the present study, although changes of bone metabolism occurred rapidly. Taken together, these results show that bone loss and arterial stiffness did not progress simultaneously in the present experimental protocol. [ABSTRACT FROM AUTHOR]

This study aimed to demonstrate and delineate the mechanism of action of Fructus Ligustri Lucidi (FLL) involved in improving Ca balance in aged female rats. FLL could enhance the apparent Ca absorption rate and reduce Ca excretion, via its actions on modulating the levels of calciotropic hormones and CaBPs expression. Fructus Ligustri Lucidi (FLL) is a herb classically used for the treatment of age-related symptoms in China. The present study aimed to determine if FLL could improve calcium balance in aged female rats and delineate its mechanism of action in vivo. Aged Sprague-Dawley rats (11 months of age) were orally administered with ethanol extract of FLL or its vehicle and fed with diets containing different levels of Ca (low Ca diet, LCD, 0.1% Ca; medium Ca diet, MCD, 0.6% Ca; high Ca diet, HCD, 1.2% Ca) for 12 weeks. Serum, urine and feces were collected for biochemical markers and Ca balance determination. mRNA expressions of calcium binding proteins (CaBPs) were determined by real time RT-PCR. The effects of diets and herb were analyzed by both one-way and two-way ANOVA. FLL significantly reduced fecal Ca excretion and induced apparent Ca absorption rate in rats fed with MCD and HCD. FLL increased serum 1,25(OH)2D3 level and duodenal CaBP-9k mRNA expressions in all rats. Renal CaBP-28k mRNA expressions were induced in rats fed with MCD and HCD upon FLL treatment. Our study demonstrated that FLL improved Ca balance in aged female rats by increasing serum 1,25 (OH)2D3 level and vitamin D-dependent CaBPs expression. [ABSTRACT FROM AUTHOR]

Bed rest studies of the past 20 years are reviewed. Head-down bed rest (HDBR) has proved its usefulness as a reliable simulation model for the most physiological effects of spaceflight. As well as continuing to search for better understanding of the physiological changes induced, these studies focused mostly on identifying effective countermeasures with encouraging but limited success. HDBR is characterised by immobilization, inactivity, confinement and elimination of Gz gravitational stimuli, such as posture change and direction, which affect body sensors and responses. These induce upward fluid shift, unloading the body’s upright weight, absence of work against gravity, reduced energy requirements and reduction in overall sensory stimulation. The upward fluid shift by acting on central volume receptors induces a 10–15% reduction in plasma volume which leads to a now well-documented set of cardiovascular changes including changes in cardiac performance and baroreflex sensitivity that are identical to those in space. Calcium excretion is increased from the beginning of bed rest leading to a sustained negative calcium balance. Calcium absorption is reduced. Body weight, muscle mass, muscle strength is reduced, as is the resistance of muscle to insulin. Bone density, stiffness of bones of the lower limbs and spinal cord and bone architecture are altered. Circadian rhythms may shift and are dampened. Ways to improve the process of evaluating countermeasures—exercise (aerobic, resistive, vibration), nutritional and pharmacological—are proposed. Artificial gravity requires systematic evaluation. This review points to clinical applications of BR research revealing the crucial role of gravity to health. [ABSTRACT FROM AUTHOR]

Studies in adults show superior serum phosphate and parathyroid hormone (PTH) control on slow nocturnal haemodialysis (NHD) compared with conventional haemodialysis. We studied the progress of four children aged 12, 13, 14 and 16 years after they had been initiated on NHD. The follow-up period ranged from 6 months to 20 months. Biochemical indices of bone metabolism were collected prospectively. All four children were initially dialysed against a 1.5 mmol/l calcium bath. In two patients, owing to biochemical hypocalcaemic episodes, the dialysate calcium concentration was increased to 1.75 mmol/l. One patient became hypercalcaemic and received calcitonin for bone pain secondary to osteoporosis and was dialysed against a 1.0 mmol/l calcium bath. Including an evaluation of dietary intake, all four patients had a net positive calcium balance, ranging from 5.1 mmol/m2 body surface area (BSA) per day to 24.3 mmol/m2 BSA per day. A significant reduction in the pre-dialysis phosphate level was observed in all four patients, such that none required dietary restrictions or phosphate binders, and dialysate phosphate supplements of 0.8–2.03 mmol/l were employed to prevent hypophosphataemia. The (Ca×PO4) dropped below 4.4 mmol2 l−2 in all four patients. Concurrently, significant reductions in intact PTH levels were seen in all four patients, but the level dropped to below normal range in two. In our cohort of patients, NHD rapidly lowered plasma phosphate and PTH levels, and additional dialysate phosphate and possibly calcium may be necessary to prevent bone demineralisation due to chronic losses and to prevent oversuppression of PTH. [ABSTRACT FROM AUTHOR]

BACKGROUND:: Sodium intake increases urinary calcium excretion and may thus lead to negative calcium balance and bone loss. OBJECTIVE:: We hypothesised that reducing sodium intake would reduce urinary calcium excretion and have a beneficial influence in bone metabolism. DESIGN:: A total of 29 subjects, 14 males and 15 females, were divided into two study groups. One group (low-sodium group (LS)) reduced sodium intake for 7 weeks by substituting low- salt alternatives for the most important dietary sources of sodium. The other group, serving as a control group (C), was given the same food items in the form of normally salted alternatives. Fasting serum samples as well as 24-h urine samples were obtained in the beginning and at the end of the study. Urinary sodium, urinary calcium, urinary creatinine, serum calcium, serum phosphate, serum creatinine, serum parathyroid hormone (s-PTH), serum C-terminal telopeptides of Type-I collagen and serum bone alkaline phosphatase (s-B-ALP) were analysed. RESULTS:: The LS group showed a significant decline (P=0.001) in urinary sodium/creatinine ratio without a significant effect on urinary calcium/creatinine ratio. In the LS group, s-PTH increased (P=0.03). The C group showed an increase in s-PTH (P=0.05) and in s-B-ALP, but no differences were observed between the study groups in the changes of serum markers of calcium and bone metabolism. CONCLUSIONS:: We have shown that reducing the sodium intake of young, healthy people with adequate calcium intake over a 7-week period does not affect the markers of bone metabolism. SPONSORSHIP:: The study was supported by Tekes-National Technology Agency of Finland.European Journal of Clinical Nutrition (2005) 59, 311-317. doi:10.1038/sj.ejcn.1602074 Published online 26 January 2005 [ABSTRACT FROM AUTHOR]

Objective: To study the calcium homeostasis in healthy, calcium and vitamin D replete early postmenopausal women during oral supplementation with calcium and vitamin D3. Design: A prospective, placebo-controlled, randomised, double-single-blind, 3-week study. Setting: Outpatient clinic at Copenhagen University Hospital, Denmark. Subjects: In all, 17 started, one was excluded. Totally, 16 healthy women, 45–61 y of age (mean 57.3 y) who were at least 4 y after menopause (mean 6.7 y) completed. Interventions: All underwent three consecutive 7-day study periods. Each began with 4 days of normal diet followed by 3 days treatment of either C: one tablet of 1.250mg calcium carbonate (ie 500mg Ca2+ per tablet) twice daily (breakfast and dinner), or CD3: as in C but plus 400 IU vitamin D3 b.i.d., or P (only) placebo tablets b.i.d. Results: At baseline plasma 25-hydroxycholecalciferol was normal (66±22 nmol/l) and the calcium intake without supplements 850 mg/day. In group C, the 24-h urinary calcium increased by 35% (6.9±2.0 mmol), vs the placebo group P (5.171.6 mmol) (P<0.05). Addition of 800 IU vitamin D3 daily (CD3) did not increase calcium excretion further (6.6±2.1 mmol) but decreased plasma 1,25-(OH)2-vitamin D3 by 21% (P<0.05). Conclusions: In this carefully controlled study calcium plus vitamin D3 supplements only had minor influences of uncertain significance on the calcium balance in healthy, calcium and vitamin D sufficient early postmenopausal women. Sponsorship: Copenhagen University, Karolinska Institutet and Nycomed A/S. [ABSTRACT FROM AUTHOR]

In mammals, neonatal positive calcium balance is required for adequate growth. Parathyroid hormone (PTH) plays a central role in this process mainly through its action on the distal nephron. We studied the effect of PTH on cytosolic calcium in distal segments from neonatal rat kidney. PTH elicited a concentration-dependent increase in cytosolic calcium in neonatal distal nephron (EC50=0.5 nM) but not in proximal tubules. At similar PTH concentrations the response was higher in the neonatal than in the adult tubules. The response was associated with protein kinase C (PKC), since phorbol myristate acetate (100 nM) increased [Ca2+]i, and staurosporin, an inhibitor of PKC, decreased (10 nM) or suppressed (100 nM) the PTH effect. cAMP analogues did not change [Ca2+]i. The response was diminished in low external calcium (0.1 mM) and absent at zero calcium, indicating dependency on external calcium. Resting calcium decreased from 80±10.8 to 28.6±2.6 nM at zero [Ca2+]e. PTH and nifedipine increased cytosolic calcium in an additive fashion. We show for the first time that PTH increased cytosolic calcium in the distal nephron of neonatal kidney, in a concentration-dependent pattern and in association with PKC activation. Higher sensitivity of the neonatal tubule might facilitate absorption of this cation during the neonatal period, when growth requires a positive balance of calcium. [ABSTRACT FROM AUTHOR]

In recent years several new peritoneal dialysis solutions have come onto the market. These solutions differ from the conventional ones with respect to osmotic agent, buffer, and/or calcium concentration. Icodextrin-containing solutions are characterized by slow, but sustained ultrafiltration. Experience in both adults and children has been favorable for the long dwell period, giving rise to both increased ultrafiltration and clearances. The use of icodextrin during the daytime seems ideal in patients on nightly intermittent peritoneal dialysis with a low peritoneal ultrafiltration rate. However, long-term experience still has to be obtained, particularly in children. The application of pH-neutral solutions, containing bicarbonate, lactate, or a bicarbonate/lactate mixture as a buffer, has shown better preservation of peritoneal cells and better tolerance. The standard calcium concentration of 1.75 mmol/l of the dialysis solution is too high in many situations. Individual strategies for an adequate calcium balance are required depending on age, clinical situation, and oral intake of calcium and vitamin D metabolites. [ABSTRACT FROM AUTHOR]

Osteoporosis is a well-defined health risk in cystic fibrosis (CF) patients due to many factors. Vitamin D insufficiency, despite routine cholecalciferol supplementation in CF patients, may contribute to a relative secondary hyperparathyroidism and possibly deficient bone mineralization. An alternate form of vitamin D, calcitriol, was studied to determine short-term effects on fractional calcium absorption and other calciotropic markers in 10 adult CF subjects and in 10 age-, sex- and body mass index (BMI)-matched controls. Serum fractional absorption of 45Ca was determined after a calcium-containing meal prior to calcitriol intervention. Other measurements included serum parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D) and urinary calcium:creatinine and N-telopeptide (NTx) concentrations. Both groups were then given calcitriol (0.5 µg p.o. b.i.d. for 14 days) and restudied following the same protocol. Both groups increased their fractional absorption of 45Ca after calcitriol (p=0.015 CF subjects, p=0.001 controls), although calcitriol tended to be less effective in the CF group compared with the controls (p=0.055). Post-prandial serum PTH concentrations were suppressed compared with baseline in both groups (p=0.03 CF subjects, p=0.006 controls). Urinary NTx concentrations, a marker for bone resorption, decreased significantly in CF subjects after calcitriol (96.0±16.0 vs 63.9±12.7 nmol BCE/mmol Cr, p=0.01) and remained unchanged in the control group. The controls had an increase in serum 1,25(OH)2D concentrations (69.9±4.2 vs 90.7±9.6 pmol/l, p=0.02) while there was no significant change in the CF group. Oral calcitriol administration appears to improve markers of calcium balance in adults with CF by increasing fractional absorption of 45Ca and lowering PTH concentrations, similar to its known effects in healthy subjects, while also suppressing urinary NTx, a marker of bone turnover. [ABSTRACT FROM AUTHOR]

A high sucrose diet reduces dentin apposition of growing rats. The mechanisms of reduction are unclear, but disturbances in calcium balance or in mineralization of predentin may explain them. In this experiment, 29 Sprague-Dawley rats, 21 days old, were weaned and randomized into calcium-deficient, high-sucrose or standard-diet groups for 3 weeks. They were given food and water ad libitum. During the experiment, animals were individually housed in metabolic cages where urine samples were collected. At ages of 21 and 40 days mineralizing dentin was marked using I.P. injections of oxytetracycline hydrochloride. At 42 days of age, the animals were anesthetized and their blood was collected by cardiac puncture. Right hemimandibles were sectioned sagittally and left hemimandibles were fixed, decalcified, and cut into histological sections. Dentin appositions were measured planimetrically, predentin width, from histological sections. Ca, K, and Na levels of serum and urine were measured flame photimetrically and P levels were measured by the UV method. Statistical analyses were done using one-way analysis of variation (ANOVA) Tuckey's HSD t test. In the calcium-deficient group, hypocalcemia, reduced dentin apposition, and increased predentin width were noticed when compared with the control group (P<0.05). Also, the increase in predentin width, caused by calcium deficiency, was significant compared with sucrose-fed animals (P<0.05). Sucrose diet reduced dentinogenesis, increased Ca excretion to urine, but also reduced urinary levels of P, K, and Na, and the differences were significant for the controls (P<0.05). In conclusion, despite the same kind of reduced dentinogenesis in calcium-deficient and high-sucrose groups, calcium imbalance or reduced mineralization of predentin does not explain reduced dentinogenesis in sucrose-fed animals. [ABSTRACT FROM AUTHOR]

The stable calcium (Ca) isotopes offer a minimally invasive method for assessing Ca balance in the body, providing a new avenue for research and clinical applications. In this study, we measured the Ca isotopic composition of soft tissues (brain, muscle, liver, and kidney), mineralized tissue (bone), and blood (plasma) from 10 mice (5 females and 5 males) with three different genetic backgrounds and same age (3 months old). The results reveal a distinctive Ca isotopic composition in different body compartments of mice, primally controlled by each compartment's unique Ca metabolism and genetic background, independent of sex. The bones are enriched in the lighter Ca isotopes (δ44/40Cabone = − 0.10 ± 0.55 ‰) compared to blood and other soft tissues, reflecting the preferential incorporation of lighter Ca isotopes through bone formation, while heavier Ca isotopes remain preferentially in blood. The brain and muscle are enriched in lighter Ca isotopes (δ44/40Cabrain = − 0.10 ± 0.53 ‰; δ44/40Camuscle = 0.19 ± 0.41 ‰) relative to blood and other soft tissues, making the brain the isotopically lightest soft tissues of the mouse body. In contrast, the kidney is enriched in heavier isotopes (δ44/40Cakidney = 0.86 ± 0.31 ‰) reflecting filtration and reabsorption by the kidney. This study provides important insight into the Ca isotopic composition of various body compartments and fluids. [ABSTRACT FROM AUTHOR]

Background: Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. Methods: PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2–5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. Results: We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). Conclusion: As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. [ABSTRACT FROM AUTHOR]

Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility. Substantial femoral bone loss continues throughout old age, with a continuous and exponential increase in the risk of hip fracture; thus any reduction or arrest of this loss will induce an important reduction in the incidence of hip fracture. Preventive measures may be achieved during childhood by increasing peak bone mass with calcium and exercise, by using long-term estrogen replacement therapy after menopause, but also by using vitamin D and calcium supplements for late prevention in the elderly. Vitamin D insufficiency and a deficit in calcium intake are very common in the elderly living either in institutions or at home and the cumulative response to these deficits is a negative calcium balance which stimulates parathyroid hormone secretion. This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements. We have shown in a 3-year controlled prospective study that the daily use of supplements (1.2 g calcium and 800 IU vitamin D) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced the number of hip fractures by 23% (intention-to-treat analysis). In parallel, serum parathyroid hormone concentrations were reduced by 28% and low baseline serum 25-hydroxy vitamin D concentration returned to normal values. After 18 months of treatment the bone density of the total proximal femoral region had increased by 2.7% in the vitamin D-calcium group and decreased by 4.6% in the placebo group (p<0.001). This prevention is safe and can be recommended for people living in institutions. It could also be useful in other elderly subjects at particular risk due to a low calcium intake, an absence of solar exposure, a low femoral bone density, a high serum parathyroid hormone concentration, a low serum 25-hydroxyvitamin D concentration and a previous history of falls. Prospective studies are needed for further evaluation of these risk factors. [ABSTRACT FROM AUTHOR]

Vitamin D3 is generated in skin by UV irradiation of 7-dehydrocholesterol (7-DEHC). Whether the 7-DEHC amount in skin affects vitamin D3 formation, and thereby the plasma level of 25-hydroxyvitamin D3 (25[OH]D3) is not known. In the present work we report on the influence on vitamin D and Ca metabolism of a new hypocholesterolemic agent, HCG-917 (0-2-[hydroxy-3-]N′-(2-chlorophenyl)-N-piperazinyl-1-[propyl]-4-chloro-benz-aldoxim-hydrochloride) which inhibits 7-DEHC reductase and thereby increases skin 7-DEHC. Rats were treated with HCG 917 (0.3 and 5.0 mg/kg, orally) for 13 days. HCG 917 caused a dose-dependent decrease in cholesterol and concomitant accumulation of 7-DEHC in plasma and skin. In skin, 7-DEHC was: control: 1.05±0.20; HCG 917, 0.3 mg/kg: 1.41±0.22; HCG 917, 5.0 mg/kg: 2.35±0.35 mg/g. At a dose of 0.3 mg/kg, HCG 917 had no significant influence on the plasma level of neither 25(OH)D3 nor 1,25(OH)2D3. However, at a dose of 5.0 mg/kg, HCG 917 induced a significant increase in plasma 25(OH)D3 (control: 36.2±2.2; HCG 917 5.0 mg/kg: 57.6±6.5 nmol/l) and a slight but not significant rise in 1,25(OH)2D3. Calcium balance studies indicated that HCG 917 did not influence intestinal Ca absorption nor urinary Ca excretion. At a dose of 5.0 mg/kg HCG 917 slightly induced a decrease in total plasma Ca. In conclusion, HCG 917 treatment can induce a significant rise in skin 7-DEHC with an increase in plasma 25(OH)D3. These results suggest that variation in the skin level of 7-DEHC can directly influence the cutaneous production of vitamin D3 and thereby the vitamin D status of the organism. [ABSTRACT FROM AUTHOR]

Tilapia larvae were exposed to 0 (control), 50 (50-Cd) or 100 (100-Cd) µg l-1 cadmium for 4 days and then transferred to cadmium-free fresh water for 3 days of detoxification. Total length and weight, calcium influx and total body calcium and cadmium content were examined at various times during detoxification. All the groups grew normally with regards to total length and body weight. Within the first 12h of detoxification the 50- and 100-Cd exposed groups released cadmium at the similar rate of about 24 ng mg-1 h-1 (or 140 ng larva-1 h-1). Later, however, this rate declined to only 4–16% of the initial level. Calcium influx in the control group showed a 10–26% increase during the detoxification period. Calcium influx in the 50-Cd group increased by about 280% and reached it peak at 12h. Calcium influx in the 100-Cd group increased by 440% and did not peak until 24h after transfer. After peaking, the influxes in both 50- and 100-Cd groups declined to the level of control at the end of the experiment. Calcium contents in 50- and 100-Cd groups increased more rapidly than that in control group within first 24h of the detoxification period. However the rate of increase in calcium content in three groups was the same after 24h. The changes in calcium influx appeared to be correlated with those in calcium content, and these suggested that tilapia larvae regulate the mechanism of calcium balance to compensate for the reduced calcium level in the body. [ABSTRACT FROM AUTHOR]

Microgravity-induced bone loss increases urinary calcium excretion which increases kidney stone formation risk. Not all individuals show the same degree of increase in urinary calcium and some pre-flight characteristics may help identify individuals who may benefit from in-flight monitoring. In weightlessness the bone is unloaded, and the effect of this unloading may be greater for those who weigh more. We studied whether pre-flight body weight was associated with increased in-flight urinary calcium excretion using data from Skylab and the International Space Station (ISS). The study was reviewed and approved by the National Aeronautics and Space Administration (NASA) electronic Institutional Review Board (eIRB) and data were sourced from the Longitudinal Study of Astronaut Health (LSAH) database. The combined Skylab and ISS data included 45 participants (9 Skylab, 36 ISS). Both weight and day in flight were positively related to urinary calcium excretion. There was also an interaction between weight and day in flight with higher weight associated with higher calcium excretion earlier in the mission. This study shows that pre-flight weight is also a factor and could be included in the risk assessments for bone loss and kidney stone formation in space. [ABSTRACT FROM AUTHOR]

Inadequate calcium intake during childhood and adolescence is detrimental to bone metabolism. Here, we postulated that calcium supplement prepared from tuna bone with tuna head oil should benefit for skeletal development than CaCO3. Forty female 4-week-old rats were divided into calcium-replete diet (0.55% w/w, S1, n = 8) and low-calcium groups (0.15% w/w for 2 weeks; L; n = 32). Then L were subdivided into 4 groups (8/group), i.e., remained on L, L + tuna bone (S2), S2 + tuna head oil + 25(OH)D3 and S2 + 25(OH)D3. Bone specimens were collected at week 9. We found that 2 weeks on low calcium diet led to low bone mineral density (BMD), reduced mineral content, and impaired mechanical properties in young growing rats. Intestinal fractional calcium absorption also increased, presumably resulting from higher plasma 1,25(OH)2D3 (1.712 ± 0.158 in L vs. 1.214 ± 0.105 nM in S1, P < 0.05). Four-week calcium supplementation from tuna bone further increased calcium absorption efficacy, which later returned to the basal level by week 9. Calcium supplementation successfully restored BMD, bone strength and microstructure. However, 25(OH)D3 + tuna head oil + tuna bone showed no additive effect. Voluntary running also effectively prevented bone defects. In conclusion, both tuna bone calcium supplementation and exercise are effective interventions for mitigating calcium-deficient bone loss. [ABSTRACT FROM AUTHOR]

Calcium (Ca) and magnesium (Mg) in drinking water and the relevant health effects have been ignored for too long. This study aims to reveal the concentrations, spatial distributions, origins and contributions to the daily estimated average requirements of Ca and Mg in public drinking water. Using hydrochemical data of collected samples of public drinking water in 314 cities across China, the contributions of Ca and Mg intakes from public drinking water to their daily estimated average requirements (EARs) were assessed. And the significance of Ca/Mg ratio and total hardness (TH) was evaluated as well. The Ca and Mg concentrations of the samples were in the range of 2.5–155.1 mg/L and 0.2–81.9 mg/L, with an average of 40.4 mg/L and 12.4 mg/L, respectively. There exist obvious differences in Ca and Mg concentrations in different regions, under the impact of climate conditions and water–rock interactions. The intake of Ca via the consumption of public drinking water for adults may be twice as much as that for other age groups. In cities with high Ca levels in public drinking water, the Ca contributions to EAR could reach up to 51.59% for adults. By contrast, Mg in drinking water is an important and even the main pathway to ingest Mg for infants and children. Therefore, public drinking water is critical for Ca and Mg intake among urban residents of China. Besides, attention should be paid to the health effects of high Ca/Mg ratio and low TH in public drinking water, especially in southern China. This research is the first systematic and comprehensive national scale study of Ca and Mg in public drinking water and can provide an important reference to improve healthy public drinking water standards around the world. [ABSTRACT FROM AUTHOR]

Summary: The impact of urine calcium on kidney, bone, and cardiovascular systems in osteoporosis is not well-known. In this 7-year-follow-up study, high urine calcium did not affect kidney function but increased risk of kidney stones, while low urine calcium increased cardiovascular diseases. Maintaining normal urine calcium is beneficial for bone health. Purpose: Hypercalciuria is common in patients with osteoporosis. However, the long-term effect of urinary calcium excretion (UCaE) on patients' health is not well-examined. The current study aims to assess the impact of UCaE on kidney, bone, and cardiovascular outcomes in patients with bone biopsy proven osteoporosis. Methods: Longitudinal study of all patients with osteoporosis who underwent bone biopsy and 24-h urine collection between 2008 and 2015 in the University of Kentucky. DXA scans, serum markers, kidney function, and cardiovascular events were recorded until last clinic visit in 2021. Exclusion criteria were secondary osteoporosis or conditions that might substantially impact UCaE. The significant results in univariate analysis were confirmed in multi-variable regression models involving clinically important covariates that might impact patients' outcomes. Results: Study included 230 patients with mean follow-up of 7.2 ± 2.9 years. The mean age was 61 years, and the mean eGFR at baseline was 85 ± 19 ml/min/1.73 m2. Low bone turnover (LBT) was present in 57% and high bone turnover (HBT) in 43% of patients. Hypercalciuria was found in one-third of patients with no difference between LTB and HTB. UCaE correlated positively with eGFR but did not affect the rate of eGFR decline over time. Higher UCaE predicted kidney stones development. We observed U-shaped effect of UCaE on bone health. Hypercalciuria predicted loss of BMD at all sites, but also hypocalciuria was associated with higher loss in total hip BMD. Upper limb fractures were the most observed fractures, and their incidence was higher in patients with hyper- or hypo-calciuria. Lower UCaE independently predicted development of major adverse cardiac events (MACE) and cardiovascular disease (CVD). Conclusion: UCaE correlated with eGFR but it did not affect the change of eGFR over time. Patients with normal UCaE had lower incidence of upper limb fractures and less reduction in BMD. Low UCaE predicted MACE and CVD. [ABSTRACT FROM AUTHOR]

Background: Idiopathic infantile hypercalcemia (IIH) etiologies include pathogenic variants in CYP24A1, leading to increased 1,25(OH)2 D, hypercalciuria and suppressed parathyroid hormone (PTH), and in SLC34A1 and SLC34A3, leading to the same metabolic profile via increased phosphaturia. IIH has not been previously described in CKD due to kidney hypodysplasia (KHD). Methods: Retrospective study of children with bilateral KHD and simultaneously tested PTH and 1,25(OH)2D, followed in a tertiary care center between 2015 and 2021. Results: Of 295 screened patients, 139 had KHD, of them 16 (11.5%) had IIH (study group), 26 with normal PTH and any 1,25(OH)2D were controls. There were no differences between groups' gender, obstructive uropathy rate and baseline eGFR. Study patients were younger [median (IQR) age: 5.2 (3.2–11.3) vs. 61 (13.9–158.3) months, p < 0.001], had higher 1,25(OH)2D (259.1 ± 91.7 vs. 156.5 ± 46.4 pmol/l, p < 0.001), total calcium (11.1 ± 0.4 vs. 10.7 ± 0.3 mg/dl, p < 0.001), and lower phosphate standard deviation score (P-SDS) [median (IQR): − 1.4 (− 1.9, − 0.4) vs. − 0.3 (− 0.8, − 0.1), p = 0.03]. During 12 months of follow-up, PTH increased among the study group (8.8 ± 2.8 to 22.7 ± 12.4 pg/ml, p < 0.001), calcium decreased (11 ± 0.5 to 10.3 ± 0.6 mg/dl, p = 0.004), 1,25(OH)2D decreased (259.5 ± 91.7 to 188.2 ± 42.6 pmol/l, p = 0.1), P-SDS increased [median (IQR): − 1.4 (− 1.9, − 0.4) vs. − 0.3 (− 0.9, 0.4), p = 0.04], while eGFR increased. Five of 9 study group patients with available urine calcium had hypercalciuria. Five patients had nephrocalcinosis/lithiasis. Genetic analysis for pathogenic variants in CYP24A1, SLC34A1 and SLC34A3 had not been performed. Conclusions: Transient IIH was observed in infants with KHD, in association with hypophosphatemia, resembling SLC34A1 and SLC34A3 pathogenic variants' metabolic profile. [ABSTRACT FROM AUTHOR]

Objectives: Few prospective cohort studies have evaluated the relationship between dairy product intake frequency and risk of osteoporotic fractures in Asians. This study aimed to investigate the association between habitual dairy product intake and risk of osteoporotic fractures. Design: Secondary analysis of prospective cohort study. Setting: Five municipalities of Japan. Participants: This study included 1,429 postmenopausal Japanese women (age ≥45 years at baseline). Measurements: Baseline milk-intake frequency was obtained using nurse-administered questionnaires. Intakes of yogurt and cheese, and estimated calcium intake, were assessed using a validated food frequency questionnaire. Osteoporotic fracture was defined as a clinical fracture diagnosed using radiography. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Results: Over a median follow-up period of 15.1 years (interquartile range [IQR], 10.1–15.4 years; total, 18,118 person-years), 172 women sustained at least one osteoporotic fracture. The proportions of participants with milk intakes <1, 1, and ≥2 cups/d were 34.4%, 48.0%, and 17.6%, respectively. After adjustment for age, frequency of yogurt intake, frequency of cheese intake, body mass index, history of osteoporotic fractures, and frequency of natto intake, the HRs compared with that for milk intake <1 cup/d were 0.71 (95% CI: 0.51–0.98) and 0.57 (95% CI: 0.35–0.92) for 1 cup/d and ≥2 cups/d, respectively. After adjustment for bone mineral density, HR significance for milk intakes ≥2 cups/d remained significant. Yogurt and cheese intakes were not related to the risk of osteoporotic fractures. Conclusion: High habitual milk intake, but not a habitual yogurt or cheese intake is associated with a decreased risk of osteoporotic fractures, independent of bone mineral density, in postmenopausal Japanese women. [ABSTRACT FROM AUTHOR]

The most common presentation of nephrolithiasis is idiopathic calcium stones in patients without systemic disease. Most stones are primarily composed of calcium oxalate and form on a base of interstitial apatite deposits, known as Randall's plaque. By contrast some stones are composed largely of calcium phosphate, as either hydroxyapatite or brushite (calcium monohydrogen phosphate), and are usually accompanied by deposits of calcium phosphate in the Bellini ducts. These deposits result in local tissue damage and might serve as a site of mineral overgrowth. Stone formation is driven by supersaturation of urine with calcium oxalate and brushite. The level of supersaturation is related to fluid intake as well as to the levels of urinary citrate and calcium. Risk of stone formation is increased when urine citrate excretion is <400 mg per day, and treatment with potassium citrate has been used to prevent stones. Urine calcium levels >200 mg per day also increase stone risk and often result in negative calcium balance. Reduced renal calcium reabsorption has a role in idiopathic hypercalciuria. Low sodium diets and thiazide-type diuretics lower urine calcium levels and potentially reduce the risk of stone recurrence and bone disease. [ABSTRACT FROM AUTHOR]

Extracellular fluid calcium concentration must be maintained within a narrow range in order to sustain many biological functions, encompassing muscle contraction, blood coagulation, and bone and tooth mineralization. Blood calcium value is critically dependent on the ability of the renal tubule to reabsorb the adequate amount of filtered calcium. Tubular calcium reabsorption is carried out by various and complex mechanisms in 3 distinct segments: the proximal tubule, the cortical thick ascending limb of the loop of Henle, and the late distal convoluted/connecting tubule. In addition, calcium reabsorption is tightly controlled by many endocrine, paracrine, and autocrine factors, as well as by non-hormonal factors, in order to adapt the tubular handling of calcium to the metabolic requirements. The present review summarizes the current knowledge of the mechanisms and factors involved in calcium handling by the kidney and, ultimately, in extracellular calcium homeostasis. The review also highlights some of our gaps in understanding that need to be addressed in the future. [ABSTRACT FROM AUTHOR]

Mitochondrial-associated endoplasmic reticulum (ER) membranes (MAMs) play a key role in several physiological functions, including calcium ion (Ca2+) transfer and autophagy; however, the molecular mechanism controlling this interaction in cadmium (Cd)-induced neurotoxicity is unknown. This study shows that Cd induces alterations in MAMs and mitochondrial Ca2+ levels in PC12 cells and primary neurons. Ablation or silencing of mitofusin 2 (Mfn2) in PC12 cells or primary neurons blocks the colocalization of ER and mitochondria while reducing the efficiency of mitochondrial Ca2+ uptake. Moreover, Mfn2 defects reduce interactions or colocalization between GRP75 and VDAC1. Interestingly, the enhancement of autophagic protein levels, colocalization of LC3 and Lamp2, and GFP-LC3 puncta induced by Cd decreased in Mfn2−/− or Grp75−/− PC12 cells and Mfn2- or Grp75-silenced primary neurons. Notably, the specific Ca2+ uniporter inhibitor RuR blocked both mitochondrial Ca2+ uptake and autophagy induced by Cd. Finally, this study proves that the mechanism by which IP3R-Grp75-VDAC1 tethers in MAMs is associated with the regulation of autophagy by Mfn2 and involves their role in mediating mitochondrial Ca2+ uptake from ER stores. These results give new evidence into the organelle metabolic process by demonstrating that Ca2+ transport between ER-mitochondria is important in autophagosome formation in Cd-induced neurodegeneration. [ABSTRACT FROM AUTHOR]