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Background: Maternal nutrition during pregnancy is known to have an effect on fetal growth and development. It is recommended that women increase their calcium intake during pregnancy and lactation, although the recommended dosage varies among professionals. Currently, there is no consensus on the role of routine calcium supplementation for pregnant women other than for preventing or treating hypertension., Objectives: To determine the effect of calcium supplementation on maternal, fetal and neonatal outcomes, excluding women with multiple gestation (other than for preventing or treating hypertension), including the occurrence of adverse effects., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (which includes results of comprehensive searches of CENTRAL, MEDLINE, Embase, CINAHL, two trials registers and relevant conference proceedings) on 3 December 2022. We also searched the reference lists of retrieved studies., Selection Criteria: We considered all published, unpublished and ongoing randomised controlled trials (RCTs) comparing maternal, fetal and neonatal outcomes in pregnant women who received calcium supplementation versus placebo or no treatment. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion., Data Collection and Analysis: Two review authors independently assessed trials for inclusion. At least one review author assessed trials meeting the inclusion criteria for trustworthiness, consulting another review author in cases that were not immediately clear. Two review authors independently assessed the studies for risk of bias, extracted data, and checked trials for accuracy. We assessed the certainty of the evidence using GRADE., Main Results: Twenty-one studies met the inclusion criteria, but only 19 studies contributed data to the review. These 19 trials recruited 17,370 women, with 16,625 women included in the final analyses. The trials were generally at low risk of bias for randomisation and allocation concealment. We chose three outcomes for GRADE assessment: preterm birth less than 37 weeks, preterm birth less than 34 weeks and low birthweight (less than 2500 g). All trials compared calcium supplementation with placebo or no treatment with 17 trials comparing high-dose calcium (greater than 1000 mg/day). Calcium supplementation probably slightly reduces the risk of preterm birth less than 37 weeks (average risk ratio (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99; 11 trials, 15,379 women; moderate-certainty evidence), but probably has little effect on the risk of preterm birth less than 34 weeks (average RR 1.03, 95% CI 0.79 to 1.35; 3 trials, 5569 women; moderate-certainty evidence), and may have little or no effect on low birthweight (less than 2500 g) (average RR 0.93, 95% CI 0.81 to 1.07; 6 trials, 14,162 women; low-certainty evidence; 1 study reported low birthweight (less than 2500 g) but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 5 studies rather than 6). We downgraded the evidence for imprecision (wide CIs crossing the line of no effect) and inconsistency (high levels of heterogeneity between the studies). There was no evidence that calcium supplementation had any effect on maternal weight gain during pregnancy; increasing bone mineral density in pregnant women; rate of intrauterine growth restriction; perinatal mortality; stillbirth or fetal death rate; increase birth length or fetal head circumference; and adverse effects such as postpartum haemorrhage, gall stones, gastrointestinal symptoms, headache, urinary stones, urinary tract infection or impaired renal function., Authors' Conclusions: This review indicates that calcium supplementation probably reduces preterm birth before 37 weeks. There are no clear additional benefits to calcium supplementation in preterm birth before 34 weeks or prevention of low birthweight. Large multicentre trials to detect the effect of calcium supplementation on fetal birthweight and preterm birth before 34 weeks as the primary outcomes are needed. Further research into the short- and long-term effects of calcium supplementation would also be beneficial., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives: To determine if bolus administration of calcium increases pulmonary artery pressures after unifocalization procedures or pulmonary artery reconstruction surgery., Design: Retrospective cohort study using Stanford University's data warehouse., Setting: A large pediatric heart center within an academic quaternary care facility., Participants: All patients undergoing pulmonary artery reconstruction or unifocalization procedures identifiable in the data warehouse., Interventions: Data were collected from Stanford University's data repository and formatted and analyzed using RStudio (v 2023.06.1+524)., Measurements and Main Results: The primary outcome was the change in pulmonary artery systolic pressure (PASP) after a bolus administration of calcium. Secondary endpoints include changes in pulmonary arterial-to-systemic arterial pressure ratio, mean arterial pressure, right-sided filling pressure, and left atrial pressure. The Friedman test was used to assess differences and the Durbin-Conover rank-sum for pairwise comparisons. A difference in PASP after a bolus dose of calcium was found (Friedman X 2 = 13.67, p = 0.003), with a higher PASP 5 minutes after calcium administration compared with 2 minutes before administration (35 mmHg v 33 mmHg, p = 0.01), and a higher PASP 10 minutes after calcium administration compared with2 minutes before administration (35 mmHg v 33 mmHg, p = 0.008)., Conclusions: Calcium bolus administration led to an increase in pulmonary arterial pressure in patients after pulmonary artery reconstruction or unifocalization surgeries. It may be prudent to avoid bolus administration in this patient population immediately after repair or in patients with right ventricular dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

An Italian multidisciplinary working group discussed the current Italian scenario of osteoporosis management during a meeting and highlighted the essential role of calcium and vitamin D supplementation in the prevention of fragility fractures., Purpose: This paper aims to review and discuss data on calcium and vitamin D requirements and the role of combined calcium and vitamin D supplementation in the treatment of patients with osteoporosis., Methods: The discussion of the experts covered literature data on calcium and vitamin D supplementation, gaps in the diagnosis and treatment of osteoporosis, and the role of the primary care physician in identifying and treating patients with osteoporosis. Articles for consideration were identified through PubMed searches using different combinations of pertinent keywords., Results: The discussion highlighted that insufficient calcium or vitamin D intake increases the risk of fragility fractures. The experts also drew attention to the essential role of calcium and vitamin D supplementation in achieving an anti-fracture effect and supporting the efficacy of anti-osteoporotic agents without increasing nephrolithiasis and cardiovascular risks. In addition, the discussion underlined the role of the primary care physician in the initial clinical approach to patients with osteoporosis., Conclusions: The experts believe that efficient treatment for patients with osteoporosis should include calcium and vitamin D supplementation to achieve adequate levels that are able to inhibit the parathyroid hormone and bone resorption., (© 2024. The Author(s).)

Aim: To conduct the first-ever systematic review and meta-analysis evaluating calcium infusion versus cabergoline in preventing ovarian hyperstimulation syndrome (OHSS) among high-risk women undergoing assisted reproductive technology., Methods: Six databases were screened from inception until April 1, 2024. The included randomized and non-randomized controlled studies were assessed for quality. The endpoints included the severity of OHSS and selected pregnancy-related outcomes. Endpoints were summarized as risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model., Results: Six studies were analyzed, including 1687 patients (828 in the calcium group and 859 in the cabergoline group). The quality of the studies varied and reflected low risk and high risk of bias in two and four studies, respectively, according to the revised Cochrane risk of bias tool. No significant differences were noted between both groups regarding the rates of overall (n = 5, RR = 0.65, 95 % CI [0.39, 1.07], p = 0.09), mild (n = 4, RR = 1.05, 95 % CI [0.59, 1.89], p = 0.86), moderate (n = 5, RR = 0.41, 95 % CI [0.15, 1.08], p = 0.07), and severe (n = 6, RR = 0.36, 95 % CI [0.11, 1.22], p = 0.1) cases of OHSS. Leave-one-out sensitivity analysis of an outlier study revealed that calcium significantly reduced the occurrence of severe OHSS compared with cabergoline (n = 5, RR = 0.16, 95 % CI [0.09, 0.43], p < 0.001, Higgins I 2  = 0 %). No significant differences were observed between both groups regarding the rates of clinical pregnancy (n = 4, RR = 0.97, 95 % CI [0.88, 1.07], p = 0.57), ongoing pregnancy, live birth, and spontaneous abortion (Higgins I 2  < 50 % for all)., Conclusion: Both agents yielded similar pregnancy-related outcomes. However, calcium infusion could potentially be more effective than cabergoline in reducing the rate of severe OHSS. Additional high-quality and well-controlled trials are essential to draw firm conclusions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aim: Although vitamin D (VD) supplementation or calcium supplementation during pregnancy has become publicly accepted and part of health care behavior, the effect of co-supplementation on preterm birth remains unclear., Objective: To explore whether the supplementation with vitamin D and calcium during pregnancy is associated with preterm birth., Methods: The study was the baseline survey from the birth cohort in Jinan, which was built at one month after the baby birth. Preterm birth and monthly VD and calcium supplementation during pregnancy were obtained by the questionnaire. The logistic model was conducted to exam the association. The distributed lag nonlinear model was applied to explore the critical window for the supplements., Results: Preterm birth occurred in 4.4 % (285/6501) of the study subjects with single live births and the rates were 39.7% and 82.6% for single VD supplementation or calcium supplementation in pregnancy. The adjusted OR (95% CI) for preterm birth was 1.428 (1.115-1.829) related to VD and 0.883 (0.652-1.216) related to calcium. It is interesting to note that the increased risk of preterm birth with VD supplementation during pregnancy was only seen in pregnant women who supplemented with calcium (OR was 1.600) and had a significant increase in preterm birth weight (P = 0.040). Besides, supplementation VD with calcium during pregnancy from the 3rd to 6th month during pregnancy was associated with preterm birth (OR 3rd  = 1.216, 95% CI: 1.119-1.320; OR 4th  = 1.275, 95% CI: 1.152-1.411; OR 5th  = 1.279, 95% CI: 1.130-1.446; OR 6th  = 1.208, 95% CI: 1.076-1.356). Moreover, birth weight mediated 10.8% of the total effect of supplementation on preterm birth., Conclusion: Women who supplemented with VD among taking calcium during pregnancy were more likely to experience preterm birth, and birth weight partly mediates the effect. The critical window for association between supplements and preterm birth may be from the 3 rd to 6 th weeks of pregnancy., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the validity of the conclusion from Cochrane reviews and meta-analyses that treatment with calcium supplementation during pregnancy reduces the risk for pre-eclampsia by 55%, which has been influential in international guidelines and future research., Design: Sensitivity analysis of data from Cochrane reviews of trials evaluating high-dose calcium supplementation (of at least 1 g/day) for reduction of pre-eclampsia risk., Setting: Systematic review and meta-analysis., Population: The Cochrane reviews and meta-analyses included 13 trials enrolling a total of 15 730 women. Random-effects meta-analysis of these studies resulted in a mean risk ratio (RR, calcium/placebo) of 0.45 (95% confidence interval [CI] 0.31-0.65; p < 0.0001)., Methods: We carried out a sensitivity analysis of evidence from the relevant Cochrane review, to examine the impact of study size., Main Outcome Measures: pre-eclampsia., Results: In the three largest studies, accounting for 13 815 (88%) of total recruitment, mean RR was 0.92 (95% CI 0.80-1.06) and there was no evidence of heterogeneity between studies (I 2  = 0). With inclusion of the smaller studies, mean RR decreased to 0.45 and I 2 increased to 70%., Conclusions: In assessment of the effect of calcium supplementation on pre-eclampsia risk, the naive focus on the mean of the random-effects meta-analysis in the presence of substantial heterogeneity is highly misleading., (© 2024 John Wiley & Sons Ltd.)

Introduction: After total thyroidectomy (TT), postoperative hypoparathyroidism (PH) is the most frequent complication. Yet, management strategies for PH remain disputed. The aim of this study was to evaluate outcomes of a reactive supplementation in case of symptomatic PH. Additionally, risk factors for symptomatic PH and readmission due to PH were analyzed., Materials and Methods: All consecutive patients who underwent TT or completion from 2017 to 2022 were considered for inclusion. During this period, a reactive to symptom vitamin-calcium supplementation was used. The primary outcome was the occurrence of severe PH after discharge resulting in readmission., Results: Overall, 307 patients were included, of which 98 patients (31.9%) developed symptomatic PH including 43 patients before discharge. Independent risk factors for developing symptomatic PH were age (p = 0.010) and postoperative day 1 (POD1) PTH level (p < 0.001). Overall, 264 patients (86%) did not present PH before discharge and were discharged home. Among them, 55 patients (20.8%) experienced symptomatic PH, requiring readmission in 18 patients. The overall readmission rate owing to symptomatic PH requiring intravenous supplementation despite oral vitamin-calcium supplementation was 6.8% (n = 18). Independent risk factors for symptomatic PH-related readmission were age (p = 0.007) and POD1 PTH level (p < 0.001). Adequate cut-off values for predicting readmission were POD1 albumin-adjusted calcium = 2.1 mmol/l (Sensibility = 0.95, Specificity = 0.30) and POD1 PTH = 11.5 pg/ml (Sensibility = 0.90, Specificity = 0.71)., Conclusion: Supplementing only symptomatic patients was safe and efficient. This attitude does not alter on morbidity, mortality or readmission rate which is in line with current literature., (© 2024. The Author(s).)

Objective: Prompted by an alarmingly low screening rate for metabolic bone disease of prematurity (MBDP), we aimed to increase MBDP screening with serum calcium, phosphorous, and alkaline phosphatase at four to six weeks of life in infants born at <1500 g and <32 gestational weeks from a baseline of 27.37% to 90% within one year., Study Design: We used the Institute for Healthcare Improvement's Model for Improvement as a framework. A key driver diagram informed the interventions which were carried out through four Plan-Do-Study-Act cycles., Results: There were 129 and 130 neonates in the pre-intervention baseline group and post-intervention MBDP bundle group, respectively. MBDP bundled primary screening rates increased from 27.37% to 95.56% (p < 0.001). Furthermore, 20% of infants had an individualized change in their enteral mineral supplementation after the initiative., Conclusions: An interdisciplinary team-based quality improvement approach was effective in altering clinical practice to improve screening and subsequent treatment for MBDP., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: The use of vitamin D-calcium supplementation for treating gestational diabetes remains unclear. This meta-analysis aims to evaluate the efficacy of vitamin D-calcium supplementation in the treatment of gestational diabetes., Methods: Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systemically searched from inception to August 2023, and we included the randomized controlled trials (RCTs) assessing the effect of vitamin D-calcium supplementation on the metabolic profile of gestational diabetes., Results: We included five eligible RCTs and 306 pregnant women in this meta-analysis. Compared with control group in pregnant women with gestational diabetes, vitamin D-calcium supplementation was associated with remarkably decreased fasting plasma glucose (SMD=-0.67; 95% CI=-0.93 to -0.41; p  <0.00001), serum insulin (SMD=-1.09; 95% CI=-1.89 to -0.29; p  = .007) and LDL (SMD=-0.35; 95% CI=-0.63 to -0.06; p  = .02), but demonstrated no impact on total cholesterol (SMD=-0.05; 95% CI=-0.81 to 0.71; p  = .90) or triglycerides (SMD=-0.14; 95% CI=-0.86 to 0.58; p  = .70)., Conclusions: Vitamin D-calcium supplementation is effective to improve metabolic profile for the treatment of gestational diabetes.

Purpose of Review: This narrative review summarizes the evidence for the most commonly used intra-cardiac arrest adjunctive medications and routes of administration and discusses promising new therapies from preclinical animal models., Recent Findings: Large trials on the administration of calcium as well as the combination of vasopressin and glucocorticoids during cardiac arrest have been published. Calcium administration during cardiopulmonary resuscitation does not improve outcomes and might cause harm. Vasopressin and glucocorticoid administration during cardiopulmonary resuscitation improve the chance of return of spontaneous circulation but has uncertain effects on survival. We identified a total of seven ongoing clinical trials investigating the potential role of bicarbonate, of vasopressin and glucocorticoids, and of intravenous versus intraosseous vascular access. Several medications such as levosimendan and inhaled nitric oxide show promise in preclinical studies, and clinical trials are either planned or actively recruiting., Summary: Large trials on intra-cardiac arrest administration of calcium and vasopressin with glucocorticoids have been performed. Several trials are ongoing that will provide valuable insights into the potential benefit of other intra-cardiac arrest medications such as bicarbonate as well as the potential benefit of intravenous or intraosseous vascular access., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Hypocalcemia is associated with increased mortality in trauma patients with hemorrhagic shock who require massive transfusion protocols (MTPs). Despite known risks of potentiating hypocalcemia with blood product administration, there is little research discussing appropriate calcium replacement. The purpose of this study was to evaluate the ability of a standardized calcium replacement protocol to reduce the incidence of hypocalcemia in trauma patients undergoing MTP., Methods: This retrospective, single-center, pre-post study evaluated the use of a calcium replacement protocol during MTP. Adult trauma patients with MTP orders who received at least one "round" of product transfusion were included. Patients were excluded if their ionized calcium (iCa) levels were unavailable or they were transferred to a higher level of care within 4 hours of presentation. The primary outcome was incidence of hypocalcemia (iCa of <1.1 mg/dL) within 24 hours of MTP initiation. Secondary endpoints included the incidence of severe hypocalcemia (iCa of <0.9 mg/dL), time to first calcium dose, total calcium dose administered (mEq), resolution of hypocalcemia within 24 hours, hypercalcemia, adherence to the calcium replacement protocol, and mortality., Results: The incidence of hypocalcemia within 24 hours was significantly lower in the postprotocol group (63% vs 95.2%; P = 0.006). There was not a significant difference in the incidence of severe hypocalcemia between the groups (39.1% vs 69.1%; P = 0.083). Time to first calcium dose was significantly shorter in postprotocol patients compared to preprotocol patients (median [interquartile range], 5.5 [0-21] minutes vs 43 [22.8-73] minutes; P < 0.0001), and postprotocol patients were administered more calcium during MTP (40.8 [27.2-54.4] mEq vs 27.2 [14-32.2] mEq; P = 0.005). Adherence to the protocol was seen in only 37% of patients in the postprotocol group. There was no difference in the rate of adverse events or overall mortality., Conclusion: Trauma patients who received massive transfusion of blood products had a significantly lower incidence of hypocalcemia after a calcium replacement protocol was implemented., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The aim of this study was to explore maternity care providers' knowledge, attitudes, and perceptions about the use of calcium supplements during pregnancy for the prevention of preeclampsia in three hospitals from Metropolitan Buenos Aires, Argentina. We conducted semi-structured interviews and followed a thematic analysis framework. Maternity care providers' knowledge, attitudes, and practices regarding calcium supplementation during pregnancy are linked to barriers to the potential implementation of calcium supplementation. Free provision of calcium supplements by the government, coupled with training that reinforces the scientific evidence supporting their use to prevent preeclampsia, along with documented recommendations from credible sources, would be crucial to ensure that health providers adopt the use of calcium supplements in antenatal care. Future studies should assess pregnant women and policymakers' perceptions about calcium supplementation during pregnancy, as well as local infrastructure to provide access to free-of-charge calcium supplements in antenatal care settings. Economic evaluation with local information could inform policymakers and advocate for the implementation of strategies to reduce preeclampsia.

In lactating mothers, the high calcium (Ca 2+ ) demand for milk production triggers significant bone loss 1 . Although oestrogen normally counteracts excessive bone resorption by promoting bone formation, this sex steroid drops precipitously during this postpartum period. Here we report that brain-derived cellular communication network factor 3 (CCN3) secreted from KISS1 neurons of the arcuate nucleus (ARC KISS1 ) fills this void and functions as a potent osteoanabolic factor to build bone in lactating females. We began by showing that our previously reported female-specific, dense bone phenotype 2 originates from a humoral factor that promotes bone mass and acts on skeletal stem cells to increase their frequency and osteochondrogenic potential. This circulatory factor was then identified as CCN3, a brain-derived hormone from ARC KISS1 neurons that is able to stimulate mouse and human skeletal stem cell activity, increase bone remodelling and accelerate fracture repair in young and old mice of both sexes. The role of CCN3 in normal female physiology was revealed after detecting a burst of CCN3 expression in ARC KISS1 neurons coincident with lactation. After reducing CCN3 in ARC KISS1 neurons, lactating mothers lost bone and failed to sustain their progeny when challenged with a low-calcium diet. Our findings establish CCN3 as a potentially new therapeutic osteoanabolic hormone for both sexes and define a new maternal brain hormone for ensuring species survival in mammals., (© 2024. The Author(s).)

Background : Potential calcium-related adverse events of vitamin D supplement use have not been addressed in large-scale, real-world data so far. Methods: Leveraging data from the UK Biobank, encompassing 445,493 individuals aged 40-69, we examined associations of high 25-hydroxyvitamin (25(OH)D) levels ≥ 100 nmol/L and vitamin D supplementation with hypercalcemia (serum calcium > 2.6 mmol/L), kidney stones, and atherosclerosis assessments (pulse wave arterial stiffness index and carotid intima-medial thickness). Regression models were comprehensively adjusted for 49 covariates. Results: Approximately 1.5% of the participants had high 25(OH)D levels, 4.3% regularly used vitamin D supplements, and 20.4% reported regular multivitamin use. At baseline, the hypercalcemia prevalence was 1.6%, and 1.1% was diagnosed with kidney stones during follow-up. High 25(OH)D levels were neither associated with calcium-related adverse events nor atherosclerosis assessments. Vitamin D and multivitamin supplementation were associated with an increased prevalence of hypercalcemia (odds ratios and 95% confidence intervals: 1.46 [1.32-1.62] and 1.11 [1.04-1.18], respectively) but were neither associated with atherosclerosis nor future kidney stones. Conclusions: High 25(OH)D levels observable in routine care were not associated with any adverse outcome. Vitamin D users have a slightly higher prevalence of hypercalcemia, possibly due to co-supplementation with calcium, but without a higher atherosclerosis prevalence or risk of kidney stones.

Hip fractures are a major health issue considerably impacting patients' quality of life and well-being. This is particularly evident in elderly subjects, in which the decline in bone and muscle mass coexists and predisposes individuals to fall and fracture. Among interventions to be implemented in hip fractured patients, the assessment and management of nutritional status is pivotal, particularly in subjects older than 65. Nutrition plays a central role in both primary and secondary preventions of fracture. An adequate protein intake improves muscle mass and strength and the intestinal absorption of calcium. Other nutrients with recognized beneficial effects on bone health are calcium, vitamins D, K, and C, potassium, magnesium, folate, and carotenoids. With reference to calcium, results from longitudinal studies showed that the consumption of dairy foods has a protective role against fractures. Moreover, the most recent systematic reviews and meta-analyses and one umbrella review demonstrated that the combination of calcium and vitamin D supplementation significantly reduces hip fracture risk, with presumed higher efficacy in older and institutionalized subjects. Owing to these reasons, the adequate intake of calcium, vitamin D, protein, and other macro and micronutrients has been successfully implemented in the Fracture Liaison Services (FLSs) that represent the most reliable model of management for hip fracture patients. In this narrative review, papers (randomized controlled trials, prospective and intervention studies, and systematic reviews) retrieved by records from three different databases (PubMed, Embase, and Medline) have been analyzed, and the available information on the screening, assessment, and management of nutritional and vitamin D status and calcium intake in patients with hip fractures is presented along with specific prevention and treatment measures.

Background: We assessed the long-term (24 months) efficacy and safety of monthly calcifediol (0.266 mg) in the correction and maintenance of total 25(OH)D levels in postmenopausal women with basal values <30 ng/mL., Methods: We initially enrolled 45 consecutive patients during the period September 2019-September 2020. After an initial visit, patients were instructed to return at 3, 6, 9, 12 and 24 months for measuring serum total 25(OH)D, ionised calcium, creatinine and isoenzyme of alkaline phosphatase (bALP). Here, we report only the per-protocol analysis, because the COVID-19 pandemic precluded adherence to the scheduled visits for some patients., Results: The patients' mean age was 62.4 ± 9.0 years. Mean basal 25(OH)D levels were 20.5 ± 5.3 ng/mL. There was a continuous increase of mean 25(OH)D values ( p for trend < 0.001). However, mean values at month 24 (36.7 ± 15.9) were not significantly different in respect to values at month 12 (41.2 ± 11.18). At 24 months, only 1 out 19 patients had a value <20 ng/mL. There was a significant decrease with time of mean values of bALP ( p < 0.0216), with no significant changes between 12 and 24 months. No significant changes were observed as far as ionised calcium or creatinine were concerned., Conclusions: The long-term administration of calcifediol maintains stable and sustained 25(OH)D concentrations, with no safety concerns.

Background: In vitro studies have shown that genistein inhibits the CYP240 enzyme, which is involved in the degradation of 1,25-dihydroxycholecalciferol and its precursor 25-hydroxycholecalciferol, and increases their plasma levels. However, no clinical studies have primarily assessed the synergistic effect of isoflavones on vitamin D levels. The aim of this study was to evaluate the possible additive effect of genistein supplementation on vitamin D levels, calcium metabolism and bone remodeling markers in healthy postmenopausal women during the spring-summer months. Patients and methods: We made a prospective, double-blind study with 150 healthy postmenopausal women that were randomized to three groups. One received placebo, another received calcium (1000 mg/day) and vitamin D (cholecalciferol, 800 U/day) and the third received calcium (1000 mg/day), vitamin D (cholecalciferol, 800 U/day) and genistein (90 mg/day). The study period was from May to September (spring-summer). Vitamin D, PTH, CTX and P1NP were determined by electrochemiluminescence at baseline and after 12 weeks. Results: Vitamin D levels increased in all groups: placebo (23±9 ng/ml vs. 29±10 ng/ml, p<0.05), calcium+vitamin D (26±10 ng/ml vs. 33±8 ng/ml, p<0.05) and calcium+vitamin D+genistein (24±9 ng/ml vs. 31±8 ng/l, p<0.05) without between-group differences. At study end, the percentage of women with vitamin D <20 ng/ml (11%) and <30 ng/ml (39%) had fallen without between-group differences. The effects on calcium metabolism and bone remodeling markers were similar between groups: rises in vitamin D were significantly linked to reductions in PTH, CTX and P1NP. Conclusion: Adding genistein to supplementation with calcium and vitamin D provided not additional changes in vitamin D levels, calcium metabolism or bone remodeling markers in healthy Spanish postmenopausal women during the spring-summer months.

Background: Attention deficit hyperactivity disorder (ADHD) is one of the common neurodevelopmental diseases that are accompanied with EEG pattern changes and Low levels of 25-hydroxyvitamin D [25(OH)D]. Neurofeedback provides a feedback signal to alleviate brain wave abnormalities and offers an alternative therapy for ADHD. This study aimed to investigate the concomitant effects of Vitamin D3 supplementation and Neurofeedback on children with ADHD., Method: This study was implemented on children with an established diagnosis of ADHD who received multisession Neurofeedback therapy. The intervention and control groups received 50000 IU vitamin D3 capsules and placebo respectively once a week for 2 months. The background rhythm was measured using quantitative EEG both before and at the end duration of the therapy., Results: All of the vitamin D3 treated children showed a significant increase in the 25(OH)D (46 ± 18, 28 ± 10 (ng/ml), p  = 0.001) and serum calcium level (9.5 ± 0.5, 9.8 ± 0.3 (mg/dl), p  = 0.003) compared to the baseline. There were a statistically significant decrease in the treatment group about theta relative power, theta/beta, and theta/alpha power ratios within two eyes conditions ( p  = 0.004). All the changes were significant within eye open state in the treatment group (2.4 ± 1.2, 1.7 ± 0.5, p  = 0.01). There is a significant relationship between Connors scores and some brain waves improvement (in relative theta (r = 0.998) and theta-to-beta power difference score (r = 0.56) ( p  < 0.001)., Conclusion: Concomitant use of vitamin D3 supplementation and neurofeedback, increases the serum level of this vitamin and reveal favorable electrophysiological results in children with ADHD. Trial registration: Iranian Registry of Clinical Trials identifier: IRCT20200922048802N1..

Objectives: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry., Methods: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk., Results: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively)., Conclusions: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years., Observations: The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up., Conclusions and Relevance: For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.

Background: Obesity is a major health problem worldwide as it can lead to high blood pressure, heart disease, stroke, diabetes, and insulin resistance. The prevalence of overweight and obesity is increasing worldwide across different age groups. There is evidence of an inverse relationship between calcium intake and body weight. The clinical relevance of a small reduction in body weight has been questioned. However, at a population level, a small effect could mitigate the observed global trends., Objectives: To assess the effects of calcium supplementation on weight loss in individuals living with overweight or obesity., Search Methods: We searched CENTRAL, MEDLINE, Embase, LILACS (Latin American and Caribbean Health Science Information database), and two clinical trials registries. The date of the last search of all databases (except Embase) was 10 May 2023. No language restrictions were applied., Selection Criteria: We included randomised controlled trials evaluating the effect of calcium in participants with overweight or obesity of any age or gender. We excluded studies in participants with absorption problems. We included studies of any dose with a minimum duration of two months. We included the following comparisons: calcium supplementation versus placebo, calcium-fortified food or beverage versus placebo, or calcium-fortified food or beverage versus non-calcium-fortified food or beverage. We excluded studies that evaluated the effect of calcium and vitamin D or mixed minerals compared to placebo., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Our primary outcomes were body weight, health-related quality of life, and adverse events. Our secondary outcomes were anthropometric measures other than body weight, all-cause mortality, and morbidity., Main Results: We found 18 studies that evaluated the effect of calcium compared to placebo or control, with a total of 1873 randomised participants (950 participants in the calcium supplementation groups and 923 in the control groups). All included studies gave oral calcium supplementation as the intervention. We did not find any studies evaluating calcium-fortified foods. We excluded 38 studies, identified four ongoing studies, and listed one study as 'awaiting classification'. Sixteen studies compared calcium supplementation to placebo; two studies compared different doses of calcium supplementation. Doses ranged from very low (0.162 g of calcium/day) to high (1.5 g of calcium/day). Most studies were performed in the USA and Iran, lasted less than six months, and included only women. Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in little to no difference in body weight (mean difference (MD) -0.15 kg, 95% confidence interval (CI) -0.55 to 0.24; P = 0.45, I 2 = 46%; 17 studies, 1317 participants; low-certainty evidence). We downgraded the certainty of the evidence by two levels for risk of bias and heterogeneity. None of the included studies reported health-related quality of life, all-cause mortality, or morbidity/complications as outcomes. Only five studies assessed or reported adverse events. Low-certainty evidence suggests a low frequency of adverse events, with no clear difference between intervention and control groups. Moderate-certainty evidence shows that calcium supplementation compared to placebo or control probably results in a small reduction in body mass index (BMI) (MD -0.18 kg/m 2 ,95% CI -0.22 to -0.13; P < 0.001, I 2 = 0%; 9 studies, 731 participants) and waist circumference (MD -0.51 cm, 95% CI -0.72 to -0.29; P < 0.001, I 2 = 0%; 6 studies, 273 participants). Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in a small reduction in body fat mass (MD -0.34 kg, 95% CI -0.73 to 0.05; P < 0.001, I 2 = 97%; 12 studies, 812 participants)., Authors' Conclusions: Calcium supplementation for eight weeks to 24 months may result in little to no difference in body weight in people with overweight or obesity. The current evidence is of low certainty, due to concerns regarding risk of bias and statistical heterogeneity. We found that the degree of heterogeneity might be partly explained by calcium dosage, the presence or absence of a co-intervention, and whether an intention-to-treat analysis was pursued. While our analyses suggest that calcium supplementation may result in a small reduction in BMI, waist circumference, and fat mass, this evidence is of low to moderate certainty. Future studies could investigate the effect of calcium supplementation on lean body mass to explore if there is a change in body composition., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The association between vitamin D supplementation and the risk of falls in older adults has been controversial. This systematic review and network meta-analysis aims to assess the efficacy of vitamin D, calcium, and combined supplementation in the prevention of falls., Methods: Randomized controlled trials (RCTs) on the efficacy of vitamin D in fall prevention were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science from inception to May 9, 2023. The network meta-analysis was performed using a random effects model in R4.1.3 and Stata15.0. Heterogeneity was evaluated by the I 2 statistic, and publication bias was assessed using funnel plots, Begg's test, and Egger's tests. Data were pooled and expressed as relative risk (RR) and 95% confidence interval (CI)., Results: A total of 35 RCTs involving 58,937 participants were included in this study, among which 11 RCTs (31.4%) applied calcium combined with vitamin D. There was low heterogeneity (I 2  = 11%) among the included studies. Vitamin D supplementation at 800-1000 International Unit (IU)/d resulted in a lower risk of falls than placebo or no treatment (RR = 0.85, 95%CI: 0.74-0.95). In addition, 800-1000 IU/d of vitamin D with or without calcium were more effective in preventing falls than calcium alone. High-dose vitamin D (> 1000 IU/day) increased the risk of falls compared with 800-1000 IU/d of vitamin D. According to the subgroup analysis, daily administration of 800-1000 IU/d vitamin D was associated with a 22% reduction in the risk of falls (RR = 0.78, 95%CI:0.64-0.92), whereas intermittent vitamin D administration had no preventive effect. Furthermore, 800-1000 IU/d of vitamin D also significantly decreased the risk of falls in old adults with ≤ 50 nmol/L 25-hydroxyvitamin D [25(OH)D] (RR = 0.69, 95%CI:0.52-0.86) but not in individuals with > 50 nmol/L 25(OH)D., Conclusion: Vitamin D supplementation at 800-1000 IU/d is associated with a lower risk of falls among older adults. 800-1000IU/d of vitamin D has a benefit on prevention of falls in population received daily dose regimens and in population with vitamin D deficiency., (© 2024. The Author(s).)

Background: Calcium-free (Ca-free) solutions are theoretically the most ideal for regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT). However, the majority of medical centers in China had to make a compromise of using commercially available calcium-containing (Ca-containing) solutions instead of Ca-free ones due to their scarcity. This study was designed to probe into the potential of Ca-containing solution as a secure and efficient substitution for Ca-free solutions., Methods: In this prospective, randomized single-center trial, 99 patients scheduled for CRRT were randomly assigned in a 1:1:1 ratio to one of three treatment groups: continuous veno-venous hemodialysis Ca-free dialysate (CVVHD Ca-free) group, continuous veno-venous hemodiafiltration calcium-free dialysate (CVVHDF Ca-free) group, and continuous veno-venous hemodiafiltration Ca-containing dialysate (CVVHDF Ca-containing) group at cardiac intensive care unit (CICU). The primary endpoint was the incidence of metabolic complications. The secondary endpoints included premature termination of treatment, thrombus of filter, and bubble trap after the process., Results: The incidence of citrate accumulation (18.2% vs. 12.1% vs. 21.2%) and metabolic alkalosis (12.1% vs. 0% vs. 9.1%) did not significantly differ among three groups (p > 0.05 for both). The incidence of premature termination was comparable among the groups (18.2% vs. 9.1% vs. 9.1%, p = 0.582). The thrombus level of the filter and bubble trap was similar in the three groups (p > 0.05 for all)., Conclusions: In RCA-CRRT for CICU population, RCA-CVVHDF with Ca-containing solutions and traditional RCA with Ca-free solutions had a comparable safety and feasibility., Trial Registration: ChiCTR2100048238 in the Chinese Clinical Trial Registry., (© 2024 The Authors. Seminars in Dialysis published by Wiley Periodicals LLC.)

A major complication of chronic kidney disease is the derangement of mineral metabolism, leading to increased risk of fractures and cardiovascular mortality. Current therapeutic regimens are focused on reducing parathyroid hormone levels caused by secondary hyperparathyroidism, and the active vitamin D metabolite l,25(OH) 2 D, with limited success. It may be a more effective approach, however, if we could target the delayed response of parathyroid hormone in the early retention of phosphate following loss of renal function.We propose intermittent administration (even in stage 2 chronic kidney disease) of parathyroid hormone, known for its bone anabolic effects compared to the catabolic effects of the continuously elevated parathyroid hormone associated with the hyperparathyroid state, to mitigate the retention of phosphate. This approach may prevent the compensatory responses of the other two major calcium- and phosphate-regulating hormones (FGF-23 and l,25(OH) 2 D) that lead to further worsening of the derangement of mineral metabolism.In addition to its strong theoretical basis, there are data supporting the need for further research focused on the use of intermittent parathyroid hormone in the management of chronic kidney disease-mineral bone disorder., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

This study investigated the impact of calcium (Ca) and vitamin D supplements on bone metabolism, bone measurement, lameness, and selection rate in gilts fed 5 dietary treatments. Two Ca levels (6.85/6.42 [adequate; ACa] or 8.99/8.56 [high; HCa] g/kg) were combined with either 856 IU/kg vitamin D3 (Danish feeding standards; adequate; AD3) or 50 μg/kg 25-hydroxyvitamin D3 (high; HHyD) to create ACaAD3, HCaAD3, ACaHHyD, and HCaHHyD diets. The values 6.85/6.42 and 8.99/8.56 g/kg correspond to adequate and high Ca supply for gilts weighing 32 to 100 and 100 to 180 kg body weight (BW), respectively. The fifth diet was a combination of HCa and 2,000 IU/kg vitamin D3 (high; HD3) to create HCaHD3. Two hundred gilts were phase fed the dietary treatments from 32 to 100 and 100 to 180 kg BW until they were slaughtered, either at 100 or 180 kg BW. The gilts were weighed fortnightly, and plasma and urine samples were collected at 100 and 180 kg BW. At slaughter, the 2nd and 3rd metacarpal bones were collected for bone parameters measurements. Lameness and selection rate were assessed within the last 7 d at 100 and 180 kg BW. Dietary treatments did not affect gilts' growth performance and plasma concentration of Ca, but the urinary concentration of Ca was greater in HCa-supplemented gilts at both 100 (P = 0.003) and 180 (P = 0.05) kg BW. Plasma concentration of vitamin D3 (P < 0.001) and 25-hydroxyvitamin D3 (P < 0.001) showed dose-dependent responses at both 100 and 180 kg BW. Bone-specific alkaline phosphatase was greater (P = 0.02) in the plasma sample collected at 180 kg BW in gilts fed the HCaHD3 diet and tended to be greater in gilts fed the ACaAD3 diet (P = 0.06). The bone ash content (P = 0.02) was greater in gilts fed the HCaAD3 diet and slaughtered at 100 kg BW compared with gilts fed the ACaAD3 and ACaHHyD diets. However, bone weight, length, thickness, dry matter, and mineral content did not differ among the dietary treatments at both 100 and 180 kg BW (P > 0.05). Neither lameness nor selection rate was affected by the dietary treatments. The average daily gain of gilts weighing 32 to 100 and 100 to 180 kg BW showed a positive correlation with bone strength (r = 0.37; P < 0.001) and bone ash content (r = 0.24; P = 0.02), respectively. In conclusion, higher Ca and vitamin D3 supplementation slightly increased bone ash content but had no effect on the lameness or selection rate of the gilts compared to those fed according to the Danish nutrient standards., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Surgery is the main treatment for insulinoma, and precise preoperative localization is important to determine the extent of resection and to rule out multiple lesions. The selective arterial calcium injection (SACI) test is instrumental in the localization of insulinoma. Here we report a patient in whom the exact location of pancreatic insulinoma could not be determined by the conventional SACI test, and thus surgery was replaced with oral diazoxide. The hyperselective SACI test subsequently localized the lesion accurately, allowing surgical resection of the pancreatic body and tail while preserving the pancreatic head. We recommend the use of the hyperselective SACI test when the conventional SACI test fails to accurately determine the location of insulinoma lesions within the pancreas.

Calcium Supplementation in Pregnancy Trial This Patient Platform recalls the experience of four pregnant women who were enrolled in a clinical trial in Argentina 35 years ago, as described to narrator and translator, Dr. José M. Belizán. None had enrolled in a clinical trial before, but all four women found it rewarding. The trial examined the role of calcium supplementation in pregnancy in the incidence of hypertensive events in the pregnancy.

The purpose of the study was to explore the effect of calcium (Ca) supplementation on liver injury induced by cadmium (Cd) in rats and its potential metabolic mechanisms through metabolomics analysis. Seventy rats were randomly allotted into 7 groups, including a control group, 3 groups with different levels of Cd exposed (1, 5, and 50 mg Cd/kg diet), and 3 corresponding Ca supplement groups (4 g Ca/kg diet) based on the Cd exposed groups. Dietary intake was simulated by giving Cd or Cd+Ca in the diets of rats. After 13-week feeding, serum biochemical parameters and liver histopathology were examined. Then the metabolic analysis of rat liver tissues was performed by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS). It was demonstrated that Ca supplementation could reverse the abnormal alterations in TG, TC, GSH, MDA induced by Cd exposure, as well as the hepatic pathological changes in rats. Furthermore, the metabolomics analysis of liver samples revealed several distinct regulatory pathways, including energy, amino acid, and lipid metabolic pathways. In conclusion, it showed that Ca supplementation had an ameliorative effect on liver injury induced by Cd exposure in rats, which may be related to the role of Ca in regulating multiple metabolic pathways., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The severe impairment of bone development and quality was recently described as a new target for unbalanced ultra-processed food (UPF). Here, we describe nutritional approaches to repair this skeletal impairment in rats: supplementation with micro-nutrients and a rescue approach and switching the UPF to balanced nutrition during the growth period. The positive effect of supplementation with multi-vitamins and minerals on bone growth and quality was followed by the formation of mineral deposits on the rats' kidneys and modifications in the expression of genes involved in inflammation and vitamin-D metabolism, demonstrating the cost of supplementation. Short and prolonged rescue improved trabecular parameters but incompletely improved the cortical parameters and the mechanical performance of the femur. Cortical porosity and cartilaginous lesions in the growth-plate were still detected one week after rescue and were reduced to normal levels 3 weeks after rescue. These findings highlight bone as a target for the effect of UPF and emphasize the importance of a balanced diet, especially during growth.

Abstract: Calcium (Ca) and magnesium (Mg), which play an important role in several cellular processes, is essential for normal development of the skeleton and maintenance of tissue homeostasis. Deficiency of these elements might delay bone fracture recovery or accelerates bone loss. We aimed to examine whether supplementation of trace element (TE) promotes fracture healing in accidentally fracturing adults by involvement of inflammatory mechanism.A short-term follow-up in clinic was performed. Totally, 117 subjects diagnosed with multiple fractures by traffic accidents were recruited in this study. Serum Ca and Mg levels were measured by inductively coupled plasma atomic emission spectrophotometry. Short-term changes such as serum C-reactive protein, interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha in normal treatment and TE supplement groups were detected by enzyme-linked immunosorbent assay. Student t test and the Spearman correlation were performed to analyze the data.Significantly negative correlations between Ca (r = 0.7032; P < .001) and Mg (r = 0.2719; P < .05) and injury severity score were observed. Serum Ca and Mg were significantly increased at Day 5, 7, and 9 following TE supplements. After treatment, serum C-reactive protein, IL-1β, IL-6, and tumor necrosis factor alpha were significantly reduced whereas cytokine levels of the TE supplement group were found to be lower than that of the normal treatment group after Day 3.These findings suggest that Ca and Mg levels are associated with the injury severity of multiple fractures, and the supplement could reduce the inflammation, which may be beneficial for the bone recovery and disease process., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Context: Hypoparathyroidism is characterized by insufficient levels of parathyroid hormone (PTH). TransCon PTH is an investigational long-acting prodrug of PTH(1-34) for the treatment of hypoparathyroidism., Objective: This work aimed to investigate the safety, tolerability, and efficacy of daily TransCon PTH in adults with hypoparathyroidism., Methods: This phase 2, randomized, double-blind, placebo-controlled 4-week trial with open-label extension enrolled 59 individuals with hypoparathyroidism. Interventions included TransCon PTH 15, 18, or 21 µg PTH(1-34)/day or placebo for 4 weeks, followed by a 22-week extension during which TransCon PTH dose was titrated (6-60 µg PTH[1-34]/day)., Results: By Week 26, 91% of participants treated with TransCon PTH achieved independence from standard of care (SoC, defined as active vitamin D = 0 μg/day and calcium [Ca] ≤ 500 mg/day). Mean 24-hour urine Ca (uCa) decreased from a baseline mean of 415 mg/24h to 178 mg/24h by Week 26 (n = 44) while normal serum Ca (sCa) was maintained and serum phosphate and serum calcium-phosphate product fell within the normal range. By Week 26, mean scores on the generic 36-Item Short Form Health Survey domains increased from below normal at baseline to within the normal range. The Hypoparathyroidism Patient Experience Scale symptom and impact scores improved through 26 weeks. TransCon PTH was well tolerated with no treatment-related serious or severe adverse events., Conclusion: TransCon PTH enabled independence from oral active vitamin D and reduced Ca supplements (≤ 500 mg/day) for most participants, achieving normal sCa, serum phosphate, uCa, serum calcium-phosphate product, and demonstrating improved health-related quality of life. These results support TransCon PTH as a potential hormone replacement therapy for adults with hypoparathyroidism., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Objectives: Postpartum depression (PPD) is a major depressive disorder. Vitamin D deficiency may play a role in PPD pathogenesis. This study was designed to determine the effect of vitamin D and calcium supplementation on the severity of symptoms and some related inflammatory biomarkers in women with PPD. Materials and Methods: Eighty-one women with a PPD score >12 participated in this study. A total of 27 patients were randomly assigned into three groups (1:1:1 ratio) to receive either 50,000 IU vitamin D3 fortnightly + 500 mg calcium carbonate daily; or 50,000 IU vitamin D3 fortnightly + placebo of calcium carbonate daily, or placebo of vitamin D3 fortnightly + placebo of calcium carbonate daily (placebo group) for 8 weeks. At the baseline and end of the study, the severity score of PPD, levels of 25-hydroxy vitamin D, calcium, tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6) and estradiol were measured. Results: The PPD score had more reduction in the vitamin D + calcium and vitamin D + calcium placebo groups than that of the placebo group (-1.7 ± 3.44, -4.16 ± 5.90 and 0.25 ± 2.81, respectively; p  = 0.008). The effect of vitamin D on the PPD score was larger when vitamin D was given alone than given together with calcium ( p  = 0.042 and p  = 0.004, respectively). No significant differences in estradiol, IL6 and TNFα were observed between the three groups. Discussion: Vitamin D may be effective in improving the clinical symptoms of PPD; however, the mechanism of the effect might not entirely operate through inflammatory and/or hormonal changes.

Context: Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator., Objective: This work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men., Methods: A single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300 000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported., Results: Men receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, P = .018) and 19% lower HOMA-IR (2.2 vs 2.7, P = .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, P = .008) compared with the placebo group., Conclusion: High-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Vitamin D deficiency co-exists with and can confuse the diagnosis of primary hyperparathyroidism (PHPT). Vitamin D replete (VDR) status may prevent significant postparathyroidectomy hypocalcaemia; however, reports from previous studies are conflicting. This study aimed to assess differences in early and/or late postoperative hypocalcaemia and length of stay (LOS) postparathyroidectomy between VDR and vitamin D non-replete (VDNR) PHPT patients., Methods: This was a retrospective cohort study of a prospectively maintained single surgeon operative database. All records of patients who underwent parathyroidectomy over a four-year period (July 2014 to December 2018) were extracted. Data were collected on vitamin D and corrected calcium levels pre- and postoperatively as well as postoperative complications and LOS., Results: On presentation, there were 91 (47.9%) VDR and 99 (52.1%) VDNR patients. Following vitamin D therapy there were 148 (77.9%) VDR and 42 (22.1%) VDNR. The multivariate analysis showed that vitamin D status was the only significant factor impacting on the hypocalcaemia symptoms (OR 4.9, 95% CI 1.8-13.7, p  = 0.002) and the most significant factor for the calcium supplementation (OR 6.5, 95% CI 2.1-19.4, p  = 0.001). Bilateral neck exploration was associated with increased likelihood of transient hypocalcaemia ( p  = 0.007) but no other post-op complication. Median LOS was significantly shorter for VDR (1 day) versus VDNR (1.5 days) patients ( p  = 0.001)., Conclusion: There is a statistically significant increased likelihood of postoperative hypocalcaemia symptoms, requirement for calcium supplements and increased LOS in VDNR patients. This study suggests optimising preoperative vitamin D status improves patient experience and could reduce healthcare costs.

Kidney stone disease is a multifactorial condition influenced by both genetic predisposition and environmental factors such as lifestyle and dietary habits. Although different monogenic polymorphisms have been proposed as playing a causal role for calcium nephrolithiasis, the prevalence of these mutations in the general population and their complete pathogenetic pathway is yet to be determined. General dietary advice for kidney stone formers includes elevated fluid intake, dietary restriction of sodium and animal proteins, avoidance of a low calcium diet, maintenance of a normal body mass index, and elevated intake of vegetables and fibers. Thus, balanced calcium consumption protects against the risk for kidney stones by reducing intestinal oxalate availability and its urinary excretion. However, calcium supplementation given between meals might increase urinary calcium excretion without the beneficial effect on oxalate. In kidney stone formers, circulating active vitamin D has been found to be increased, whereas higher plasma 25-hydroxycholecalciferol seems to be present only in hypercalciuric patients. The association between nutritional vitamin D supplements and the risk for stone formation is currently not completely understood. However, taken together, available evidence might suggest that vitamin D administration worsens the risk for stone formation in patients predisposed to hypercalciuria. In this review, we analyzed and discussed available literature on the effect of calcium and vitamin D supplementation on the risk for kidney stone formation.

Since medullary thyroid carcinoma is an aggressive cancer, it is important to have an early detection based on stimulated calcitonin (CT), especially when basal-CT is slightly elevated. The objective of this work was to set specific thresholds for basal-CT- and calcium-stimulated calcitonin for prediction of thyroid malignancy in female population. The study included 2 groups: group A-women with elevated basal-CT (>9.82 pg/ml) and group B-women with normal basal-CT (control group). After calcium stimulation test precise protocol, histopathological reports of those that required surgery were correlated with both basal and stimulated calcitonin. The best basal and stimulated calcitonin cut-offs for distinguishing female patients with medullary thyroid carcinoma or C-Cell-hyperplasia from other pathologies or normal cases were: 12.9 pg/ml, respectively 285.25 pg/ml. For basal-CT above 30 pg/ml, malignancy was diagnosed in 9/9 patients (100%): 9 MTC. For stimulated calcitonin above 300 pg/ml, malignancy was diagnosed in 17/21 patients (80.95%): 12 MTC and 5 papillary thyroid carcinomas. The smallest nodule that proved to be medullary thyroid carcinoma had only 0.56/0.34/0.44 cm on ultrasound, with no other sonographic suspicious criteria. In conclusion, we have identified in Romanian female population basal and stimulated calcitonin thresholds to discriminate medullary thyroid carcinoma or C-Cell-hyperplasia from other cases. We recommend thyroid surgery in all women with stimulated calcitonin above 285 pg/ml. Further studies on larger groups are necessary to establish and confirm male and female cut-offs for early diagnosis of medullary thyroid carcinoma, and interestingly, maybe for macro-papillary thyroid carcinomas alike. The calcium administration has minimum side-effects, but continuous cardiac monitoring is required., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objectives: We aimed to evaluate total serum calcium (TSC) and ionized serum calcium (ISC) levels and their effects on clinical outcomes in neonates underwent exchange transfusion (ET)., Method: In this study, the data of newborn infants who underwent ET due to hyperbilirubinemia in a third level neonatal intensive care unit (NICU) were retrospectively analyzed. The patients were monitored by electrocardiogram during ET. Cardiac and respiratory rates, peripheral oxygen saturation, blood pressure values ​​and clinical findings as convulsion, tremor, hypertonia, laryngospasm, cyanosis and apnea were recorded in ET observation forms. The infants with no symptoms of hypocalcemia during the procedure were not routinely given IV calcium gluconate. TSC and ISC measured at the beginning, at the end and 24 h after the end of ET were evaluated retrospectively., Results: Data of 36 newborn patients were evaluated. Median gestational age was 39 (35-40) weeks, mean birthweight was 2840 ± 841 (mean ± SD) grams. During the ET, desaturation was observed in five patients(13.9 %), sinus bradycardia in six(16.7 %), tachypnea in two(5.5 %), sinus tachycardia in one(2.8 %), and rare ventricular extrasystoles in one(2.8 %). Hypocalcaemia was not detected in any of the patients at the beginning of ET. Hypocalcemia was observed in two cases (5.5 %) at the end of ET. There was no statistically significant difference between the TSC and ISC levels at the beginning of ET, at the end and at the end of 24 h., Conclusion: As a result, routine intravenous (IV) calcium administration seems to be unnecessary provided that vital signs and neurological status are closely monitored during ET., (Copyright © 2021. Published by Elsevier Ltd.)

Background and Objectives: Therapeutic plasma exchange (TPE) is a blood purification treatment capable of removing large molecular weight substances from plasma. It is commonly used for the removal of circulating pathogenic immunoglobulins presumed to be the cause of many autoimmune diseases. TPE can be performed with a membrane-based system (mTPE) or a centrifugal-based system (cTPE). When plasma separation is performed with a membrane, filter clotting can lead to longer treatment time, higher cost and can negatively impact patient satisfaction. In this study, we examine the operational characteristics that might influence filter life., Design, Setting, Participants, & Measures: We report on 24 patients, with a total of 135 mTPE treatments in a single tertiary care academic center using the NxStage machine. The study focuses on treatment specific parameters that may lead to procedure failure. The main parameters of interest were transmembrane pressure (TMP) and the filtration fraction as displayed on the machine (FFd) compared to the calculated filtration fraction (FFc). Primary outcome was to measure whether TMP, FFc, and FFd influenced filter survival. Secondary outcomes included factors that might have indirectly resulted in filter failure, including hematocrit (Hct), platelet count, heparin use, and intra-treatment calcium administration., Results: In this study, we demonstrated that machine displayed filtration fractions (FFd) were lower than FFc and this difference was significantly larger in TPE sessions that experienced a clotting event (7.58 vs 6.22, P = .031). TPE sessions that clotted had a higher mean TMP (57.48 mmHg vs 44.43 mmHg, P = .001) and clotting events tended to have a lower mean blood flow rate (175.83 mL/min vs 189.55 mL/min, P = .002). In TPE sessions that received prefilter calcium administration, a higher mean dose of calcium gluconate was found in the sessions that experienced clotting (3.27 g vs 2.70 g, P = .013). Patients who experienced at least one clotting event were noted to be heavier than those patients without any clotting events (91.52 kg vs 72.15 kg, P = .040). Prefilter heparin administration was not associated with a lower incidence of filter clotting. We did not find a statistically significant difference in clotting events based upon type of intravenous access, pretreatment hematocrit, or pretreatment platelet counts., Conclusion: Among patients undergoing mTPE, machine FFd on the NxStage system are consistently lower than FFc. Treatments where there was a greater difference between displayed and FFc had a greater likelihood of filter clotting. Treatments with higher TMP were associated with failed treatments. Prefilter calcium administration during treatment was associated with increased filter clotting. Lower blood flow rates and higher patient weight were also associated with increased filter clotting. Prefilter heparin administration did not reduce the incidence of filter clotting., (© 2021 Wiley Periodicals LLC.)

Optimising nutrition intake is a key component for supporting athletic performance and supporting adaption to training. Athletes often use micronutrient supplements in order to correct vitamin and mineral deficiencies, improve immune function, enhance recovery and or to optimise their performance. The aim of this review was to investigate the recent literature regarding micronutrients (specifically iron, vitamin C, vitamin E, vitamin D, calcium) and their effects on physical performance. Over the past ten years, several studies have investigated the impacts of these micronutrients on aspects of athletic performance, and several reviews have aimed to provide an overview of current use and effectiveness. Currently the balance of the literature suggests that micronutrient supplementation in well-nourished athletes does not enhance physical performance. Excessive intake of dietary supplements may impair the body's physiological responses to exercise that supports adaptation to training stress. In some cases, micronutrient supplementation is warranted, for example, with a diagnosed deficiency, when energy intake is compromised, or when training and competing at altitude, however these micronutrients should be prescribed by a medical professional. Athletes are encouraged to obtain adequate micronutrients from a wellbalanced and varied dietary intake., (Copyright © 2021. Published by Elsevier Ltd.)

Background: The transient acute hypocalcemia (HypoCa) is the most prevalent complication after total thyroidectomy, detected primarily by subnormal intact parathyroid hormone (iPTH) and calcium levels. However, the need for calcium supplementation is ambiguous in patients who exhibit low iPTH with normal calcium levels. The aim of this study was to evaluate complementary predictors of HypoCa in this scenario., Methods: A retrospective cohort study with of 1597 consecutive patients undergoing total thyroidectomy, with or without neck dissection, from January 2014 to December 2018 at a single institution. Patients with an iPTH <12 pg/mL and a total calcium level ≥8 mg/dL in the first 8 h after surgery were included., Results: 1597 patients identified with low postoperative iPTH without overt calcium deficiency was diagnosed. The transient HypoCa in that specific subgroup was 509 (31.9%). Multivariate analysis indicated that HYPOCA was associated with bilateral level VI neck dissection and pre- to postoperative calcium reduction >38 pg/mL. To better illustrate the model, we plotted a nomogram with the variables selected for the final model., Conclusion: Total thyroidectomy patients who exhibit low postoperative iPTH levels without overt calcium deficiency should be considered for calcium replacement therapy when they a marked drop in iPTH postoperatively and underwent bilateral level VI neck dissection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The treatment of osteochondral (OC) defects remains challenging because of the lack of economical and feasible therapeutic strategies for OC repair and reconstruction. In this study, we report an integrated bilayer hydrogel with robust interface binding force (40 kPa) by facilitating the diffusion of calcium ions to the secondary crosslink of the bilayer hydrogel, in which gellan gum and sodium alginate acted as the chondral layer, gellan gum and hydroxyapatite acted as subchondral layer. This integrated construct has high cytocompatibility, and can seed with mesenchymal stem cells (MSCs) related to different functional protein expression for cartilage and bone formation, respectively. Furthermore, in the rabbit critical-sized osteochondral defect model (4.0 mm in diameter and 8.0 mm in depth), the calcium enriched hydrogel act as a calcium reservoir, promote neovascularization at week 4, and repair the critical defect at week 8, demonstrating the feasible preparation of an acellular hydrogel for OC repair., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Regional citrate anticoagulation (RCA) is the preferred anticoagulation method for continuous kidney replacement therapy (CKRT) recommended by KDIGO. Limited availability of calcium-free solutions often imposes challenges to the implementation of RCA for CKRT (RCA-CKRT). The principal purpose of this study was to characterize the outcomes of RCA-CKRT using calcium-containing solutions., Study Design: Retrospective cohort study., Setting & Participants: We evaluated the safety and efficacy of RCA-CKRT with calcium-containing dialysate and replacement fluid used for 128 patients. A total of 571 filters and 1,227 days of CKRT were analyzed., Exposures: Liver disease, sepsis in the absence of liver disease, and sepsis with liver disease., Outcomes: Filter life and metabolic complications per 100 CKRT days., Analytical Approach: Linear mixed-effects model and generalized linear mixed-effects models., Results: The majority of patients were male (91; 71.1%), 32 (25%) had liver disease, and 29 (22.7%) had sepsis without liver disease. Median filter life was 50.0 (interquartile range, 22.0-118.0) hours, with a maximum of 322 hours, and was significantly lower (33.5 [interquartile range, 17.5-60.5] h) in patients with liver disease. Calcium-containing replacement solutions were used in 41.6% of all CKRT hours and reduced intravenous calcium requirements by 31.7%. Hypocalcemia (ionized calcium<0.85mmol/L) and hypercalcemia (total calcium>10.6mg/dL) were observed in 6.0 and 6.7 per 100 CKRT days, respectively. Citrate accumulation was observed in 13.3% of all patients and was associated with metabolic acidosis in 3.9%, which was not significantly different in patients with liver disease (9.3%; P = 0.2)., Limitations: Lack of control groups that used calcium-free dialysate and replacement solutions with RCA-CKRT. Possible overestimation of filter life from incomplete data on cause of filter failure., Conclusions: Our study suggests that RCA-CKRT with calcium-containing solutions is feasible and safe in critically ill patients, including those with sepsis and liver disease., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

In this study, irreversible electroporation (IRE), electrochemotherapy (ECT), and calcium electroporation (CaEP) techniques were investigated as new strategies for human pancreatic cancer. Qualification of the patients, best "therapeutic moment" for each patient, safety, and complications after procedures were examined. In this pilot study were included 13 patients in this study, which were operated on in different pancreatic cancer stages. Patients underwent IRE or ECT with intravenous admission of cisplatin or electroporation with calcium intratumoral administration. The IRE procedure was safe for the patients. Medium overall survival for IRE, IRE + CTH, and IRE + CaCl 2 was respectively: 16, 29.5, and 19 months comparing to 10 months in control chemotherapy (CTH) group. Thus, IRE, ECT, and CaEP can be effective strategies for pancreatic cancer treatment., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Concerns regarding the adequacy of vegetarian diets with respect to fracture risk continue., Objectives: We aimed to explore the influence of 5 previously defined dietary patterns on hip fracture risk and whether this association is modified by concomitant calcium and vitamin D supplementation., Methods: The Adventist Health Study 2 is a prospective cohort study in which participants were enrolled during 2002-2007; proportional hazards regression analyses were used to estimate fracture risk. Participants reside throughout the United States and Canada. A total of 34,542 non-Hispanic white peri- and postmenopausal women and men 45 y and older responded to the biennial hospital history form and were followed for a median of 8.4 y., Results: The study identified 679 incident hip fractures during 249,186 person-years of follow-up. Fracture risk varied according to dietary pattern, with a clear effect modification by concurrent supplementation with both vitamin D and calcium. In multivariable models, including adjustment for calcium and vitamin D supplementation, female vegans had 55% higher risk of hip fracture (HR: 1.55; 95% CI: 1.06, 2.26) than nonvegetarians (NVEGs), whereas there was no association between diet pattern and hip fracture risk in men. When further stratifying females on supplement use with both vitamin D and calcium, vegans taking both supplements were at no greater risk of hip fracture than the subjects with other dietary patterns including the NVEGs., Conclusions: Without combined supplementation of both vitamin D and calcium, female vegans are at high risk of hip fracture. However, with supplementation the excessive risk associated with vegans disappeared. Further research is needed to confirm the adequacy of a vegan diet supplemented with calcium and vitamin D with respect to risk of fracture., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes., Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status., Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models., Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d)., Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)