-
1.
Effectiveness and safety of routine calcium supplementation in postmenopausal women. A narrative review.
Heidari, B, Hajian-Tilaki, K, Babaei, M
Diabetes & metabolic syndrome. 2020;(4):435-442
Abstract
BACKGROUND To determine whether routine administration of calcium supplementation is useful in postmenopausal women, while it is associated with an increased risk of cardiovascular complications. METHODS A literature search was performed using Medline/PubMed, Scopus and Google Scholar by using relevant keywords. RESULTS Calcium supplement exerts a small protective effect against bone loss which disappears after cessation. Antifracture effect of supplemental calcium is limited to older frail women or community-dwelling residents who are vitamin D deficient and have inadequate dietary calcium intake. The results of studies on the association between calcium supplementation and cardiovascular complications are contradictory and do not lead to a decisive conclusion CONCLUSION Current data do not support routine calcium supplementation to all postmenopausal women for prevention of bone loss or bone fracture.
-
2.
Calcium mishandling in absence of primary mitochondrial dysfunction drives cellular pathology in Wolfram Syndrome.
La Morgia, C, Maresca, A, Amore, G, Gramegna, LL, Carbonelli, M, Scimonelli, E, Danese, A, Patergnani, S, Caporali, L, Tagliavini, F, et al
Scientific reports. 2020;(1):4785
Abstract
Wolfram syndrome (WS) is a recessive multisystem disorder defined by the association of diabetes mellitus and optic atrophy, reminiscent of mitochondrial diseases. The role played by mitochondria remains elusive, with contradictory results on the occurrence of mitochondrial dysfunction. We evaluated 13 recessive WS patients by deep clinical phenotyping, including optical coherence tomography (OCT), serum lactic acid at rest and after standardized exercise, brain Magnetic Resonance Imaging, and brain and muscle Magnetic Resonance Spectroscopy (MRS). Finally, we investigated mitochondrial bioenergetics, network morphology, and calcium handling in patient-derived fibroblasts. Our results do not support a primary mitochondrial dysfunction in WS patients, as suggested by MRS studies, OCT pattern of retinal nerve fiber layer loss, and, in fibroblasts, by mitochondrial bioenergetics and network morphology results. However, we clearly found calcium mishandling between endoplasmic reticulum (ER) and mitochondria, which, under specific metabolic conditions of increased energy requirements and in selected tissue or cell types, may turn into a secondary mitochondrial dysfunction. Critically, we showed that Wolframin (WFS1) protein is enriched at mitochondrial-associated ER membranes and that in patient-derived fibroblasts WFS1 protein is completely absent. These findings support a loss-of-function pathogenic mechanism for missense mutations in WFS1, ultimately leading to defective calcium influx within mitochondria.
-
3.
The Association between Excess Body Mass and Disturbances in Somatic Mineral Levels.
Banach, W, Nitschke, K, Krajewska, N, Mongiałło, W, Matuszak, O, Muszyński, J, Skrypnik, D
International journal of molecular sciences. 2020;(19)
Abstract
BACKGROUND Obesity and excess body weight are significant epidemiological issues, not only because they are costly to treat, but also because they are among the leading causes of death worldwide. In 2016, an estimated 40% of the global population was overweight, reflecting the importance of the issue. Obesity is linked to metabolism malfunction and concomitantly with altered mineral levels in the body. In this paper, we review alterations in somatic levels of iron, calcium, magnesium, copper, iodine, chromium, selenium, and zinc in relation to excess body mass. METHODOLOGY An electronic literature search was performed using PubMed. Our search covered original English research articles published over the past five years, culminating in 63 papers included for study. RESULTS The reviewed papers presented correlation between obesity and hypomagnesemia and hypozincemia. They also indicated that patients with excess body mass present increased body copper levels. Studies have similarly indicated that obesity appears to be associated with lower selenium levels in both blood and urine, which may be correlated with the decline and weakening of defenses against oxidative stress. It has been found that decreased level of chromium is connected with metabolic syndrome. Chromium supplementation influences body mass, but the effect of the supplementation depends on the chemical form of the chromium. It is hypothesized that obesity poses a risk of iodine deficiency and iodine absorption may be disrupted by increased fat intake in obese women. A range of studies have suggested that obesity is correlated with iron deficiency. On the other hand, some reports have indicated that excess body mass may coexist with iron excess. The relation between obesity and body iron level requires further investigation. Calcium signaling seems to be disturbed in obesity, due to the increased production of reactive oxygen species and low level of fast troponin isoform responsible for mediating calcium sensitivity of muscle relaxation. Correlation between excess body mass and calcium levels needs further research. CONCLUSIONS Excess body mass is associated with alterations in mineral levels in the body, in particular hypomagnesemia and decreased selenium (Se) and zinc (Zn) levels. Chromium (Cr) deficiency is associated with metabolic syndrome. Obese patients are at risk of iodine deficiency. Excess body mass is associated with elevated levels of copper (Cu). Data on the association between obesity and iron (Fe) levels are contradictory. Obesity coexists with disturbed calcium (Ca) signaling pathways. The association between obesity and body Ca levels has not been investigated in detail.
-
4.
Risk factors and evolution of calcium and parathyroid hormone levels in hungry bone syndrome after parthyroidectomy for primary hyperparathyroidism.
Guillén Martínez, AJ, Smilg Nicolás, C, Moraleda Deleito, J, Guillén Martínez, S, García-Purriños García, F
Endocrinologia, diabetes y nutricion. 2020;(5):310-316
Abstract
INTRODUCTION Hungry bone syndrome (HBS) is a complication occurring after parathyroid surgery that can cause severe and prolonged hypocalcemia. The study objective was to know the risk factors for HBS after surgery for primary hyperparathyroidism and its relationship with serum calcium and parathyroid hormone levels. MATERIAL AND METHODS A case-control, observational, analytical study was conducted in patients who had undergone surgery for primary hyperparathyroidism in the past 10 years (2007-2016). Changes over time in serum calcium and PTH levels and the general characteristics of patients were analyzed. RESULTS The incidence rate of HBS in our series was 12.2%. HBS was found to be significantly associated to thyroid surgery during the surgical procedure itself (adjusted odds ratio [aOR]=17.241), to age older than 68 years (aOR=6.666), and to lesions greater than 1.7cm (aOR=7.165). A statistically significant relationship was seen between presence of HBS and corrected serum calcium levels higher than the mean the day after surgery and one week and 3 months later, and also with PTH levels higher than the mean before, during, and one day after surgery. CONCLUSION In our series, independent risk factors for development of HBS included patient age, lesion size, and whether or not the procedure was accompanied by thyroid surgery, which requires closer monitoring of mineral metabolism during the perioperative period.
-
5.
Reliability of calcium-phosphorus (Ca/P) ratio as a new, accurate and inexpensive tool in the diagnosis of some Ca-P disorders.
Madeo, B, De Vincentis, S, Kara, E, Vescini, F, Trenti, T, Guaraldi, G, Rochira, V
Journal of endocrinological investigation. 2019;(9):1041-1049
Abstract
PURPOSE The serum calcium/phosphorus (Ca/P) ratio is an accurate tool to differentiate patients with primary hyperparathyroidism (PHPT) from healthy subjects. However, other disorders of the Ca-P metabolism might impair the Ca/P ratio, such as hypophosphatemia (HypoP) not PHPT related. The aim of this study is to examine the diagnostic value of Ca/P ratio in the diagnosis of PHPT and HypoP not PHPT related. METHODS Single-center, retrospective, case-control study, including 150 patients with PHPT and 306 patients with HypoP, compared with 150 controls. HypoP patients were enrolled among HIV-infected patients by selecting those with Fanconi-like syndrome due to antiretroviral treatment. Parameters which were measured were serum Ca, P, parathyroid hormone (PTH), 25-OH vitamin D, albumin and creatinine). RESULTS The Ca/P ratio was significantly higher in PHPT and HypoP patients, compared to controls (p < 0.0001). At receiver operator characteristic (ROC) curve analysis, the cut-off of 3.56 (2.75 SI) for Ca/P ratio was able to identify patients with PHPT and HypoP (sensitivity 95%; specificity 93%). Among patients with Ca/P ratio above 3.56, the thresholds of 10.3 mg/dL (2.6 mmol/L) for serum Ca (sensitivity 93%; specificity 98%) and 80.5 pg/mL for PTH (sensitivity 91%; specificity 91%) were defined for the specific diagnosis of PHPT. CONCLUSIONS The Ca/P ratio above 3.56 (2.75 SI) is a highly accurate tool to identify PHPT and HypoP not PHPT-related patients. Thanks to its simplicity, this index can be proposed as a screening and first-line examination in the diagnostic work-up when a disorder of Ca-P metabolism is suspected or should be ruled out.
-
6.
Functional properties and mode of regulation of the mitochondrial Na+/Ca2+ exchanger, NCLX.
Kostic, M, Sekler, I
Seminars in cell & developmental biology. 2019;:59-65
Abstract
Mitochondrial Ca2+ transient is the earliest discovered organellar Ca2+ signaling pathway. It consist of a Ca2+ influx, mediated by mitochondrial Ca2+ uniporter (MCU), and mitochondrial Ca2+ efflux mediated by a Na+/Ca2+ exchanger (NCLX). Mitochondrial Ca2+ signaling machinery plays a fundamental role in linking metabolic activity to cellular Ca2+ signaling, and in controlling local Ca2+ concertation in distinct cellular compartments. Impaired balance between mitochondrial Ca2+ influx and efflux leads to mitochondrial Ca2+ overload, an early and key event in ischemic or neurodegenerative syndromes. Molecular identification of NCLX and MCU happened only recently. Surprisingly, MCU knockout yielded a relatively mild phenotype while conditional knockout of NCLX led to a rapid fatal heart failure. Here we will focus on recent functional and molecular studies on NCLX structure and its mode of regulation. We will describe the unique crosstalk of this exchanger with Na+ and Ca2+ signaling pathways in the cell membrane and the endoplasmic reticulum, and with protein kinases that posttranslationally modulate NCLX activity. We will critically compare selectivity of pharmacological blockers versus molecular control of NCLX expression and activity. Finally we will discuss why this exchanger is essential for survival and can serve as an attractive therapeutic target.
-
7.
Bacteria, Bones, and Stones: Managing Complications of Short Bowel Syndrome.
Johnson, E, Vu, L, Matarese, LE
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2018;(4):454-466
Abstract
Short bowel syndrome (SBS) occurs in patients who have had extensive resection. The primary physiologic consequence is malabsorption, resulting in fluid and electrolyte abnormalities and malnutrition. Nutrient digestion, absorption, and assimilation may also be diminished by disturbances in the production of bile acids and digestive enzymes. Small bowel dilation, dysmotility, loss of ileocecal valve, and anatomical changes combined with acid suppression and antimotility drugs increase the risk of small intestinal bacterial overgrowth, further contributing to malabsorption. Metabolic changes that occur in SBS due to loss of colonic regulation of gastric and small bowel function can also lead to depletion of calcium, magnesium, and vitamin D, resulting in demineralization of bone and the eventual development of bone disease. Persistent inflammation, steroid use, parenteral nutrition, chronic metabolic acidosis, and renal insufficiency may exacerbate the problem and contribute to the development of osteoporosis. Multiple factors increase the risk of nephrolithiasis in SBS. In the setting of fat malabsorption, increased free fatty acids are available to bind to calcium, resulting in an increased concentration of unbound oxalate, which is readily absorbed across the colonic mucosa where it travels to the kidney. In addition, there is an increase in colonic permeability to oxalate stemming from the effects of unabsorbed bile salts. The risk of nephrolithiasis is compounded by volume depletion, metabolic acidosis, and hypomagnesemia, resulting in a decrease in renal perfusion, urine output, pH, and citrate excretion. This review examines the causes and treatments of small intestinal bacterial overgrowth, bone demineralization, and nephrolithiasis in SBS.
-
8.
Metabolic Syndrome in Parathyroid Diseases.
Corbetta, S, Mantovani, G, Spada, A
Frontiers of hormone research. 2018;:67-84
Abstract
Parathyroid glands are the main regulator of body mineral metabolism through parathormone (PTH) actions on bone and kidney. Experimental evidence suggests that PTH may have non-classical target organs such as adipose tissue, arterial vascular wall, cardiac muscle cells, and adrenal cortex cells, where it may play a role in controlling body energy, blood pressure, and metabolism. Cardiometabolic features have been investigated in the wide spectrum of clinical parathyroid disorders, from hyperparathyroidism to pseudohypoparathyroidism and hypoparathyroidism. Indeed, in parathyroid disorders, besides altered PTH secretion, impaired serum calcium levels and vitamin D status occur. Both calcium and vitamin D have been shown to regulate metabolism and to be associated with cardiovascular diseases. However, despite the complexity of parathyroid disorders, features of metabolic syndrome, such as obesity, insulin resistance, and glucose intolerance, arterial blood hypertension, and dyslipidemia, are frequently diagnosed in primary and secondary hyperparathyroidism as well as in pseudohyperparathyroidism. Here, we reviewed the most consistent data highlighting challenges and providing clinical remarks.
-
9.
Glutathione depleting drugs, antioxidants and intestinal calcium absorption.
Moine, L, Rivoira, M, Díaz de Barboza, G, Pérez, A, Tolosa de Talamoni, N
World journal of gastroenterology. 2018;(44):4979-4988
Abstract
Glutathione (GSH) is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2+ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2+ absorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxidative/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca2+ transport or the paracellular Ca2+ route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2+ pathway are decreased. The flavonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2+ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2+ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2+ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety, pharmacokinetics and pharmacodynamics of them.
-
10.
[Altered urinary calcium excretion in prostate cancer patients subjected to androgen deprivation. Preliminary pilot study results.].
Díaz-Convalía, EJ, Arrabal-Martín, M, Arrabal-Polo, MÁ, Miján-Ortiz, JL, Cózar-Olmo, JM
Archivos espanoles de urologia. 2018;(7):569-574
Abstract
OBJECTIVES Androgen deprivation therapy (ADT) in prostate cancer is associated with the appearance of different adverse effects. Among these effects, notable ones that may affect metabolism are osteoporosis and metabolic syndrome. The aim of this study is to analyse lithogenic risk markers three months after initiating treatment with LHRH analogue. METHODS Pilot study encompassing 15 prostate cancer patients who were candidates for ADT, which they received in the form of quarterly doses of goserelin 10.8 mg. A blood and urine analyses for lithogenic risk, bone and metabolic markers were carried out, as was a study of metabolic syndrome criteria. Statistical analysis was performed with SPSS 17.0, taking P≤.05 to be statistically significant. RESULTS Patients included in the study had a mean age of 72.46 ± 6.61 years. We observed a significant increase in the percentage of metabolic syndrome (20% versus 46.7%; P<.05) and insulin resistance index (1.87 versus 2.96; P=.01) at 3 months treatment. There was a notable increase in bone remodelling markers and significant increases in 24 h urinary calcium values (9.46 versus 14.57 mg/dl; P=.008), 24 h urinary calcium excretion index (0.10 versus 0.13 mg/dl GF [glomerular filtration]; P=.01) and the fasting calcium/ creatinine ratio (0.107 versus 0.195; P=.007), without any changes to other lithogenous risk markers. CONCLUSIONS Androgen deprivation therapy can lead to the short-term appearance, primarily when fasting, of hypercalciuria in prostate cancer patients, possibly in association with bone metabolism.