Are Twin Pregnancies at Higher Risk for Iron and Calcium Deficiency than Singleton Pregnancies?

The aim of this study was to compare the iron and calcium status in singleton and twin pregnancies and to assess whether there is an increased risk for iron and calcium deficiency in twin gestation. The study included 105 singleton and 9 twin pregnancies at or above 35 weeks of gestation. Information on prenatal supplementation with iron or calcium was acquired, and adverse perinatal outcomes were recorded. Biosamples from all 114 mothers and 73 newborns (61 singleton and 12 twin newborns) were finally analyzed. Total iron and calcium concentrations in serum were measured through total reflection X-ray fluorescence analysis. The results indicated no significant differences in maternal serum iron and calcium concentrations between singleton and twin pregnancies. Similarly, iron and calcium concentrations in newborn umbilical cord serum samples were not different between singleton and twin pregnancies. The comparison of total iron and calcium between mothers and umbilical cord serum indicated significantly lower concentrations in the mothers, with the differences being not homogenous but rather pair-specific. A significant positive correlation between maternal serum and umbilical cord serum calcium concentration was noticed. Prenatal iron supplementation was associated with higher iron concentrations in both mothers and newborns, supporting the efficiency of supplementation and the quality of the study methods. Collectively, the data indicate no significant differences in serum iron and calcium concentrations with regard to singleton or twin pregnancies and the efficiency of iron supplementation during pregnancy for increasing iron status.

Prevalence of Vitamin D and Calcium Deficiency and Insufficiency in Women of Childbearing Age and Associated Risk Factors: A Systematic Review and Meta-Analysis.

Vitamin D deficiency and insufficiency as well as low serum calcium levels can trigger negative health outcomes in women of childbearing age. Therefore, we aimed to estimate the prevalence of serum vitamin D and calcium deficiencies and insufficiencies and associated risk factors in Brazilian women of childbearing age and to assess whether there are differences in prevalence according to regions of the country and the presence or absence of pregnancy. The systematic literature review was performed using the following databases: PubMed, LILACS, Embase, Scopus, and Web of Science. Cross-sectional, cohort, and intervention studies were included. Among pregnant women, the prevalence of vitamin D deficiency ranged from 0% to 27% and of vitamin D insufficiency from 33.9% to 70.4%. Among non-pregnant women, the prevalence of vitamin D deficiency ranged from 0% to 41.7% and of vitamin D insufficiency from 38.5% to 69.3%. We found a high prevalence of vitamin D deficiency and insufficiency in women of childbearing age, with insufficiency affecting more than half of these women. The highest prevalence of vitamin D deficiency and insufficiency was observed in the South region. It was not possible to assess the prevalence and factors associated with calcium deficiency.

Applications of Metabolomics in Calcium Metabolism Disorders in Humans.

The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, the present review highlights the potential of metabolomics in identifying the biomarkers of some of the most common endocrine disorders, such as primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), calcium deficiency, osteoporosis and vitamin D supplementation. Metabolites related to above-mentioned diseorders were grouped into specific classes and mapped into metabolic pathways. Furthermore, disturbed metabolic pathways can open up new directions for the in-depth exploration of the basic mechanisms of these diseases at the molecular level.

Evaluation of an Ionic Calcium Fiber Supplement and Its Impact on Bone Health Preservation in a Dietary Calcium Deficiency Mice Model.

Ionic calcium can help in the prevention of the process of osseous decalcification. This study aimed to evaluate the physicochemical properties and toxic effects of ionic calcium-fiber supplement (ICa+) and its impact on bone health preservation in mice C57/BL6 fed a calcium-deficient diet. Physicochemical properties include FTIR, apparent calcium solubility estimated by the calcium ratio obtained by ionization chromatography and atomic absorption. In vitro genotoxicity and cytotoxicity of the ICa+ were assessed. Twenty-five 7-week-old C57/BL6 mice were fed calcium-free diet (CFD) or CFD plus CaCO3 (1.33 mg Ca) or CFD plus ICa+ (1.33-6.66 mg Ca) for six weeks. After that, bone mass and microstructure parameters were assessed. Histological staining was performed to determine calcium deposits. ICa+ (100%) exhibited an apparent calcium solubility higher than CaCO3 (12.3%). ICa+ showed no cytotoxic and genotoxic in vitro activities. Histomorphometry analysis showed that the ICa+ treated group displayed a higher trabecular number than the trabecular space. Also, the ratio BV/TV was increased compared with all treatments. Ionic calcium-fiber supplementation prevents bone deterioration compared to mice fed a calcium-deficient diet.

The Molecular Basis of Calcium and Phosphorus Inherited Metabolic Disorders.

Calcium (Ca) and Phosphorus (P) hold a leading part in many skeletal and extra-skeletal biological processes. Their tight normal range in serum mirrors their critical role in human well-being. The signalling "voyage" starts at Calcium Sensing Receptor (CaSR) localized on the surface of the parathyroid glands, which captures the "oscillations" of extracellular ionized Ca and transfers the signal downstream. Parathyroid hormone (PTH), Vitamin D, Fibroblast Growth Factor (FGF23) and other receptors or ion-transporters, work synergistically and establish a highly regulated signalling circuit between the bone, kidneys, and intestine to ensure the maintenance of Ca and P homeostasis. Any deviation from this well-orchestrated scheme may result in mild or severe pathologies expressed by biochemical and/or clinical features. Inherited disorders of Ca and P metabolism are rare. However, delayed diagnosis or misdiagnosis may cost patient's quality of life or even life expectancy. Unravelling the thread of the molecular pathways involving Ca and P signaling, we can better understand the link between genetic alterations and biochemical and/or clinical phenotypes and help in diagnosis and early therapeutic intervention.

Modern India and Dietary Calcium Deficiency-Half a Century Nutrition Data-Retrospect-Introspect and the Road Ahead.

Calcium and vitamin D are inseparable nutrients required for bone health. In the past half a century, the dietary calcium intake of rural, tribal, and urban India has declined. Though India is the largest producer of milk and cereals, the major source of calcium in India is through non-dairy products. The highest intake of cereals and lowest intake of milk & milk products was observed in rural and tribal subjects whereas, the intake of cereals, milk & milk products were similar in both urban and metropolitan subjects. One of the reasons for lower calcium intake was the proportion of calcium derived from dairy sources. Over the past half a century, the average 30-day consumption of cereals in the rural and urban population has declined by 30%. The Per Capita Cereal Consumption (PCCC)has declined despite sustained raise in Monthly Per capita Consumption Expenditure (MPCE) in both rural and urban households. The cereal consumption was the highest in the lowest income group, despite spending smaller portion of their income, as cereals were supplied through public distribution system (PDS). About 85% of the Indian population are vitamin D deficient despite abundant sunlight. Dietary calcium deficiency can cause secondary vitamin D deficiency. Though India as a nation is the largest producer of milk, there is profound shortage of calcium intake in the diet with all negative consequences on bone health. There is a decline in dietary calcium in the background of upward revision of RDI/RDA. There is a gap in the production-consumption-supply chain with respect to dietary calcium. To achieve a strong bone health across India, it is imperative to have population based strategies addressing different segments including supplementing dietary/supplemental calcium in ICDS, mid-day-meals scheme, public distribution system, educational strategies. Other measures like mass food fortification, biofortification, bioaddition, leveraging digital technologies, investments from corporate sector are some measures which can address this problem. India is a vast country with diverse social, cultural and dietary habits. No single measure can address this problem and requires a multi-pronged strategic approach to tackle the dietary calcium deficiency to achieve strong bone health while solving the problem of nutritional deficiency.

The Medical Benefits of Vitamin K2 on Calcium-Related Disorders.

BACKGROUND: Due to the potentially crucial role of vitamin K2 in calcium metabolism, a deficit can disrupt many mechanisms, resulting in an array of different issues, such as broken bones, stiff arteries and poor fertility. Although there has been existing research, the potential of vitamin K2 as a treatment for conditions including cerebral palsy, parathyroid disease, heart disease and gastrointestinal disease is unknown. This review discusses the biochemistry of vitamin K and the metabolism of calcium, followed by an analysis of the current literature available on vitamin K2 and its prospects. METHODS: Using public libraries including PubMed and Wiley, we searched for existing research on the metabolism and use of vitamin K2 that has been conducted in the preceding two decades. RESULTS: Data indicated that vitamin K2 had a positive impact on osteoporosis, cardiovascular disease, parathyroid disorders, cerebral palsy and sperm motility. CONCLUSION: Due to the existence of confounding variables and limitations in the quality and volume of research conducted, further investigation must be done to see whether the beneficial effects seen are reproducible and must assess the viability of vitamin K2 as treatment in isolation for these conditions.

Rare diseases of phosphate and calcium metabolism: Crossing glances between nephrology and endocrinology.

Rare diseases of phosphate/calcium metabolism correspond to a wide and heterogeneous spectrum of diseases. Recent knowledge in physiology and genetics has made it possible to better characterize them and to propose attractive therapeutic approaches based on the underlying pathophysiology. These diseases are often at the interface between nephrology and endocrinology. In this spirit of a multidisciplinary care, each specialty can bring its own critical point of view and its own specificities to improve patient care. The objective of this manuscript is to "read" with a nephrologist's point of view the main frameworks of diseases of phosphate/calcium metabolism, to illustrate the three crucial messages of nephro-protection sent to endocrinologists. First, calciuria must be interpreted both in absolute value (concentration hypercalciuria) and in ratio (flow hypercalciuria). Second, renal monitoring of therapies inducing hypercalciuria on kidneys with normal renal function (e.g. active vitamin D analogs or teriparatide) should be systematic. Last, hyperphosphatemia, often latent in hypoparathyroidism and pseudo-hypoparathyroidism, should be detected and at least benefit from dietary measures, in the context of Western diets rich in phosphate hidden in food additives.

Normocalcaemic hyperparathyroidism and primary hyperparathyroidism: least significant change for adjusted serum calcium.

INTRODUCTION: The least significant change (LSC) is a term used in individuals in order to evaluate whether one measurement has changed significantly from the previous one. It is widely used when assessing bone mineral density (BMD) scans. To the best of our knowledge, there no such estimate available in the literature for patients with disorders of calcium metabolism. Our aim was to provide an estimate of the least significant change for albumin-adjusted calcium in patients with normocalcaemic hyperparathyroidism (NPHPT) and primary hyperparathyroidism (PHPT). METHODS: We used the within-subject standard deviatio calculated in a population of NPHPT and PHPT patients and multiplied it by 2.77. RESULTS: The LSC for NPHPT and PHPT were found to be 0.25 and 0.24 mmol/L, respectively (1.00 and 0.96 mg/dL). In clinical practice, the value of 0.25 mmol/L could be used. DISCUSSION: The least significant change given, could be used in two ways in these patients. First, it gives a range to which values are expected. This can provide some reassurance for the patient and the physician in cases of intermittent hypercalcaemia. Moreover, it can be a marker of whether an individual has an actual significant change of his calcium after parathyroid surgery.

Evaluation of a New Automated Routine Measurement for Serum Adjusted Ionized Calcium (at pH 7.4) in Patients Suspected of Calcium Metabolic Disease.

BACKGROUND: Total calcium is a less accurate test in predicting ionized calcium (Ca2+) in patients suspected of calcium metabolic disease. Nevertheless, total calcium continues to be used as routine measurement instead of adjusted Ca2+ (at pH 7.4). In the current study we evaluate a new multichannel instrument, the ISE Module E1200 for adjusted Ca2+ (at pH 7.4), containing three different ion-selective electrode (ISE) units. METHODS: Serum from 1350 patients was compared to the ABL835 flex and KoneLab. Total calcium was also evaluated on the Dimension Vista 1500 system. Correlations between instruments were assessed by Deming regression and degree of agreement by Cohen's kappa (κ). RESULTS: Analytical imprecisions for the three ISE units for adjusted Ca2+ (at pH 7.4) was between 0.36% and 2.52%, and for pH between 0.32% and 3.24%. Results were comparable for each ISE unit (r = 0.797-0.917; all P < 0.0001) and in high-throughput settings (r = 0.871; P < 0.0001). The degree of agreement between instruments was moderate to good (κ = 0.52-0.77). In contrast, there was a very poor agreement (κ = -0.14) for total calcium with discrepancy in 53.4% of the samples. CONCLUSIONS: The new ISE Module E1200 is comparable with the ABL835 flex and KoneLab 30i and therefore may be used for routine analysis of serum adjusted Ca2+ (at pH 7.4). The measured adjusted Ca2+ (at pH 7.4) was less comparable with very poor agreement to total calcium measured on the Dimension Vista 1500 system.

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of calcium metabolic disorders and osteoporosis.

Endocrinologists have had to make rapid changes to services so that resources can be focused on the COVID-19 response to help prevent spread of the virus. Herein we provide pragmatic advice on the management of commonly encountered calcium metabolic problems and osteoporosis. Non-urgent elective appointments should be postponed, and remote consultations and digital health solutions promoted. Patients should be empowered to self-manage their conditions safely. Patients, their caregivers and healthcare providers should be directed to assured national or international online resources and specific patient groups. For patients in acute hospital settings, existing emergency guidance on the management of hyper- and hypo-calcaemia should be followed. An approach to osteoporosis management is outlined. IV zoledronic acid infusions can be delayed for 6-9 months during the pandemic. Patients established on denosumab, teriparatide and abaloparatide should continue planned therapy. In the event of supply issues with teriparatide or abaloparatide, pausing this treatment in the short term is likely to be relatively harmless, whereas delaying denosumab may cause an immediate increased risk of fracture. The challenge of this pandemic will act as a catalyst to innovate within our management of metabolic bone and mineral disorders to ensure best use of resources and resilience of healthcare systems in its aftermath.

A case of tophaceous pseudogout of the temporomandibular joint extending into the cranium.

A case of tophaceous pseudogout (i.e., calcium pyrophosphate dihydrate crystal deposition disease) in the temporomandibular joint (TMJ) extending into the cranium is reported. A 59-year-old woman was referred to hospital with swelling and pain in the left cheek, and with trismus. Computed tomography imaging revealed a large, granular, calcified mass surrounding the left condylar head, partly destroying the cortex of the condylar head, and extending into the cranium by destroying the glenoid fossa. Magnetic resonance imaging revealed that the soft-tissue mass was of low-signal intensity on T1- and T2-weighted images, and was enhanced after intravenous injection of gadolinium. The mass was clinically and radiographically suspected to be a neoplastic lesion or a synovial osteochodromatosis. However, histological analysis demonstrated that the mass contained granulomatous lesion due to multiple nodular deposits of numerous rod-shaped and rhomboid crystals, which verified the diagnosis of tophaceous pseudogout. The lesion was excised surgically using a preauricular approach. Neither radiographic nor clinical examination demonstrated any signs of mass recurrence in the long-term 8- and 14-year postoperative recall examinations. Tophaceous pseudogout is a rare benign arthropathy that presents with clinical and radiographic features mimicking neoplastic conditions of the TMJ. Therefore, it is recommended that tophaceous pseudogout is considered in the differential diagnosis when a calcified mass lesion of the TMJ is encountered.

[Update - Calcium Metabolism]. / Update ­ Kalziumstoffwechsel.

A finely balanced control system keeps the extracellular calcium concentration within narrow limits. Disorders of calcium metabolism are often based on altered parathormone levels. Symptoms are not always clear, sometimes they are even missing: the more it is important to know possible associated diseases. The author presents basics, current diagnostics and concrete therapy options. Central hormone for the regulation of the calcium balance is the parathyroid hormone. With decreasing calcium, PTH leads to an increase in extracellular free calcium concentration in three ways. The classic symptoms of pHPT (polyuria, polydipsia, "stone, leg, and stomach pain") are rare now, as the condition is diagnosed much earlier. Treatment of choice in all symptomatic patients with pHPT is surgery. FHH and pHPT are both characterized by hypercalcaemia and increased parathyroid hormone. The differential diagnosis of urinary calcium excretion, which is usually lower in FHH but normal or elevated in pHPT, is crucial. In primary hypoparathyroidism, parathyroid failure interferes with calcium homeostasis at a central location. Consequences are hypocalcaemia, hyperphosphatemia and lack of active vitamin D. Due to increased urinary calcium excretion, patients with ADH are at high risk for kidney stones, nephrocalcinosis and the development of renal insufficiency. Recently, rhPTH 1-84 has been available for the treatment of hypoparathyroidism. However, long-term data is still lacking to provide a safe indication, considering potential effects and side effects.

Calcium Metabolic Disorders in Pregnancy: Primary Hyperparathyroidism, Pregnancy-Induced Osteoporosis, and Vitamin D Deficiency in Pregnancy.

Physiologic changes during pregnancy include calcium, phosphate, and calciotropic hormone status. Calcium metabolic disorders are rare in pregnancy and management with close calcium and vitamin D control and supplementation. Primary hyperparathyroidism is mostly asymptomatic and does not affect conception or pregnancy. It requires control of plasma calcium levels. Surgical intervention may be indicated. Data on severe cases are missing. Osteoporosis in or before pregnancy is rare but usually diagnosed from fractures. Medical treatment other than supplementation is contraindicated. Vitamin D deficiency is common and may affect conception and increase complications. Current evidence does not prove vitamin D supplements effective in improving outcomes.

Alzheimer's Disease Presenilin-1 Mutation Sensitizes Neurons to Impaired Autophagy Flux and Propofol Neurotoxicity: Role of Calcium Dysregulation.

BACKGROUND: Disruption of intracellular Ca2+ homeostasis and associated autophagy dysfunction contribute to neuropathology in Alzheimer's disease (AD). OBJECTIVE: To study the effects of propofol on cell viability via its effects on intracellular Ca2+ homeostasis, and the impact of autophagy, in a neuronal model of presenilin-mutated familial AD (FAD). METHODS: We treated PC12 cells, stably transfected with either mutated presenilin-1 (L286V) or wild type (WT) controls, with propofol at different doses and durations, in the presence or absence of extracellular Ca2+, antagonists of inositol trisphosphate receptors (InsP3R, xestospongin C) and/or ryanodine receptors (RYR, dantrolene), or an inhibitor of autophagy flux (Bafilomycin). We determined cell viability, cytosolic Ca2+ concentrations ([Ca2+]c), vATPase protein expression, and lysosomal acidification. RESULTS: The propofol dose- and time-dependently decreased cell viability significantly more in L286V than WT cells, especially at the pharmacological dose (>50µM), and together with bafilomycin (40 nM). Clinically used concentrations of propofol (<20µM) tended to increase cell viability. Propofol significantly increased [Ca2+]c more in L286V than in WT cells, which was associated with decrease of vATPase expression and localization to the lysosome. Both toxicity and increased Ca2+ levels were ameliorated by inhibiting InsP3R/RYR. However, the combined inhibition of both receptors paradoxically increased [Ca2+]c, by inducing Ca2+ influx from the extracellular space, causing greater cytotoxicity. CONCLUSION: Impairment in autophagy function acts to deteriorate cell death induced by propofol in FAD neuronal cells. Cell death is ameliorated by either RYR or InsP3R antagonists on their own, but not when both are co-administered.

Association of klotho gene polymorphism and the regulation of calcium-phosphate metabolism disorders in patients with end-stage renal disease.

BACKGROUND: Klotho G-395-A gene polymorphism is associated with several diseases; however, its association with calcium-phosphate metabolism disorders in end-stage renal disease (ESRD) is unknown. METHODS: A total of 137 patients with ESRD and 80 healthy adults (control) were enrolled in the study. Patients with ESRD were divided into three subgroups: haemodialysis (A1, n = 52), peritoneal dialysis (A2, n = 30), and non-dialysis (A3, n = 55). The klotho G-395-A genotype was detected by TaqMan PCR assay, and ELISA was used to detect the soluble klotho protein (sKL) and fibroblast growth factor (FGF23). Intact parathyroid hormone (iPTH) and other related clinical biochemical parameters were also analyzed for all subjects. RESULTS: (i) Three genotypes (GG, GA and AA) of KL G-395A were detected, and a significant difference between the ESRD and control groups was observed, (ii) sKL was inversely associated with FGF23 in each subgroup and phosphate and positively associated with calcium in A1 and A3. FGF23 was positively associated with phosphate and inversely associated with calcium in each subgroup, (iii) a statistical difference in levels of sKL and FGF23 was observed between GG and AA, as well as between GA and AA. The expression of sKL was lowest and the level of FGF23 was highest in AA and (iv). GA + AA genotypes and FGF23 were risk factors and sKL might be protective factor of calcium-phosphate metabolism disorders. CONCLUSION: Soluble klotho protein and FGF23 were associated with the regulation of calcium and phosphate metabolism, and the A allele of the G-395A klotho gene polymorphism could be a risk factor on calcium-phosphate metabolism disorders in patients with ESRD.

Impacts of parathyroidectomy on calcium and phosphorus metabolism disorder, arterial calcification and arterial stiffness in haemodialysis patients.

BACKGROUND: Secondary hyperparathyroidism (SHPT) and calcium and phosphorus metabolism disorder are important complications in haemodialysis patients. Parathyroidectomy (PTX) may prevent or delay the progress of vascular calcification in haemodialysis patients. OBJECTIVE: To investigate the impacts of PTX on calcium and phosphorus metabolism, arterial calcification and arterial stiffness in haemodialysis patients with SHPT. METHODS: Twenty-one SHPT-haemodialysis patients were selected for PTX. The preoperative and postoperative 1-year scores of coronary artery calcification were measured via multislice spiral CT, along with the brachial-ankle pulse wave velocity (baPWV), and preoperative and postoperative 1-year indexes such as calcium, phosphorus, calcium-phosphorus product concentration and parathyroid hormone (PTH) level were compared. RESULTS: Compared with the preoperative score, the postoperative 1-year coronary artery calcification score was significantly reduced; the mean baPWVs of the bilateral limbs were reduced; and the levels of serum calcium, phosphorus, calcium-phosphorus product concentration and PTH were all reduced; all differences were statistically significant (P < 0.05). CONCLUSIONS: PTX can be used to correct calcium and phosphorus metabolism disorder, reduce arterial calcification, and improve arterial stiffness.

The association between periodontal conditions, inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis patients.

OBJECTIVES: To analyze the association between periodontal conditions and inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis (HD) patients. MATERIAL AND METHODS: We analyzed 128 HD patients divided into two groups: dentate (n = 103) and edentulous (n=25). The following items were assessed: baseline characteristics, age at the start and duration of HD, biochemical data: C-reactive protein (CRP), serum albumin, calcium, phosphorus, alkaline phosphatase, parathormone. A single dentist performed a complete dental/periodontal examination, including parameters of oral hygiene and gingival bleeding. RESULTS: One person had healthy periodontium, 62.14% of the patients had gingivitis, and 36.9% had moderate or severe periodontitis. The age at HD onset had a positive impact on periodontal status and negatively correlated with the number of teeth. A positive correlation between age and CRP level and negative correlations between age and serum albumin and phosphorus were found. Pocket depth (PD) was negatively correlated with serum albumin. The number of teeth was negatively correlated with serum CRP. CONCLUSIONS: High prevalence and severity of periodontal disease are observed in hemodialysis patients. There is a high probability that periodontal disease may be present at the early stages of chronic kidney disease (CKD) before the hemodialysis onset.