Effect of 2 Years of Monthly Calcifediol Administration in Postmenopausal Women with Vitamin D Insufficiency.

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.

Nutrition, Vitamin D, and Calcium in Elderly Patients before and after a Hip Fracture and Their Impact on the Musculoskeletal System: A Narrative Review.

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.

The Women's Health Initiative Randomized Trials and Clinical Practice: A Review.

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.

Effect of vitamin D, calcium, or combined supplementation on fall prevention: a systematic review and updated network meta-analysis.

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 I2 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 (I2 = 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.

Calcium supplementation for people with overweight or obesity.

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, I2 = 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/m2,95% CI -0.22 to -0.13; P < 0.001, I2 = 0%; 9 studies, 731 participants) and waist circumference (MD -0.51 cm, 95% CI -0.72 to -0.29; P < 0.001, I2 = 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, I2 = 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.

Mineral supplementation for very preterm infants fed fortified human milk.

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.

Safety and Feasibility of Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy With Calcium-Containing Solutions: A Randomized Controlled Trial.

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.

Relación del consumo de calcio con el síndrome metabólico en adultos de la Amazonía Ecuatoriana / Relationship of calcium consumption with metabolic syndrome in adults from the Ecuadorian Amazon

Introducción. El Síndrome Metabólico (SM) comprende un conjunto de factores de riesgo cardiometabólico representado por obesidad central, dislipidemia, hipertensión arterial y glucosa alterada, se ha evidenciado que el consumo adecuado de calcio representa una disminución del riesgo para este síndrome. Objetivo. Analizar la relación entre el consumo de calcio total, de origen animal y vegetal con el SM y sus indicadores. Materiales y métodos. Estudio transversal de eje correlacional, con una muestra de 100 adultos de la región amazónica ecuatoriana, durante el último trimestre del 2020. La ingesta dietética de calcio se determinó mediante un recordatorio de 24 horas y el SM según los criterios de Adult Treatment Panel-IV (ATP-IV). Resultados. La población estuvo conformada por adultos maduros (40 a 60 años) que evidenciaron una ingesta de calcio deficiente (182,50 mg y 228,60 mg en mujeres y hombres respectivamente). Se evidenció, además, una relación directamente proporcional entre la circunferencia abdominal (r=0,391 ­ p=0,000), presión arterial sistólica (r=0,290 ­ p=0,000) y glucosa en ayuno (r=0,326 ­ p=0,000) con la edad. La ingesta de calcio total se relacionó positivamente con los triglicéridos, (r=0,221 ­ p=0,027). Conclusiones. La ingesta dietética de calcio en ambos sexos no alcanza el requerimiento diario y se relaciona positivamente con los triglicéridos(AU)

Introduction. The Metabolic Syndrome (MS) comprises a set of cardiometabolic risk factors represented by central obesity, dyslipidemia, high blood pressure and altered glucose, it has been shown that adequate calcium intake represents a decreased risk for this syndrome. Objective. To analyze the relationship between the consumption of total calcium, animal and vegetable origin, with MS and its indicators. Materials and methods. Cross-sectional study of correlational axis, with a sample of 100 adults from the Ecuadorian Amazon region, during the last quarter of 2020. Dietary calcium intake was determined through a 24-hour recall and the diagnosis of MS according to the Adult Treatment Panel- IV (ATP-IV) criteria. Results. The population consisted of mature adults (40 to 60 years) who showed a deficient calcium intake in both sexes (182.50 mg and 228.60 mg in women and men respectively). There is also evidence of a directly proportional relationship between abdominal circumference (r=0.391 - p=0.000), systolic blood pressure (r=0.290 - p=0.000) and fasting glucose (r=0.326 - p=0.000) with age. Total calcium intake was positively related to triglycerides (r=0.221 ­ p=0.027). Conclusions. Calcium dietary intake in both sexes does not reach the daily requirement and is positively related to triglycerides(AU)

Metabolomics in liver injury induced by dietary cadmium exposure and protective effect of calcium supplementation.

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.

Effect of calcium and magnesium on inflammatory cytokines in accidentally multiple fracture adults: A short-term follow-up.

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)-1ß, 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-1ß, 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.

Nutritional Approaches as a Treatment for Impaired Bone Growth and Quality Following the Consumption of Ultra-Processed Food.

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.

Neuroleptic Malignant Syndrome: A Potential Etiology of Multisystem Organ Failure in a Burn Patient.

Neuroleptic malignant syndrome (NMS) is described in the medical literature but rarely seen among acutely ill trauma patients. A 44-year-old man with burns to the hands and back after a chemical explosion was transported to an outside facility where he received treatment for presumed acute coronary syndrome after developing ventricular tachycardia and elevated serum troponins after the exposure. His cardiac catheterization was unremarkable, but an echocardiogram revealed severe cardiomyopathy, and he was also in multisystem organ failure. He was transferred to our facility after hospital day 2 for treatment of his multisystem organ failure and 2% total body surface area burns. His laboratory results were remarkable for a creatine kinase of >100 000 units/L, and he required 14 g of intravenous calcium. Upon further investigation, the patient reported taking ziprasidone for his bipolar disorder, and he had a core temperature of 103.5 °F on his initial presentation to the outside facility. As he convalesced, the unifying diagnosis was NMS. NMS is a side effect of antipsychotic therapy and is manifested by hyperpyrexia, rigidity, autonomic instability, and altered consciousness. An elevated creatine kinase >100 000 units/L is almost pathognomonic for NMS. Patients can also present with leukocytosis, organ failure, and electrolyte disturbances including hypocalcemia. We hypothesized that dehydration, the warm environmental conditions at our patient's job, and immense stress resulting in a catecholamine surge following his trauma were inciting triggers to this event. This case highlights the importance of considering alternate diagnoses in patients whose clinical presentation does not fit the most "obvious cause."

The effect of vitamin D and calcium supplementation on inflammatory biomarkers, estradiol levels and severity of symptoms in women with postpartum depression: a randomized double-blind clinical trial.

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.

PaTH Forward: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of TransCon PTH in Adult Hypoparathyroidism.

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.

Vitamin D Supplementation Improves Fasting Insulin Levels and HDL Cholesterol in Infertile Men.

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.

Vitamin D repletion in primary hyperparathyroid patients undergoing parathyroidectomy leads to reduced symptomatic hypocalcaemia and reduced length of stay: a retrospective cohort study.

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.