Intestinal Calcium Absorption Research Articles

HYPERCALCAEMIA IN PATIENTS WITH SARCOIDOSIS IN THE SOUTH OF IRELAND

TOPIC: Diffuse Lung Disease TYPE: Original Investigations PURPOSE: Sarcoidosis is a multisystem granulomatous disorder whose prevalence is high in the South of Ireland. Hypercalcaemia has been reported in 10-20% of patients with sarcoidosis at presentation. Increased intestinal calcium absorption induced by high serum calcitriol concentrations (1,25-dihydroxyvitamin D, the most active metabolite of vitamin D) is the primary cause and heavy exposure to sunlight is a common precipitant. We sought to determine the prevalence of hypercalcaemia in our patients with sarcoidosis METHODS: We reviewed the data of 317 patients with a tissue-proven diagnosis of sarcoidosis who attended Mercy University Hospital, Cork, Ireland from 2005-2021. RESULTS: Median age was 53y (20-94y) and median serum calcium was 2.41 mmol/L (1.92-3.1 mmol/L). Median serum ACE was 56 IU/L (5-249 IU/L). Hypercalcaemia was present in 6.8% of patients (18/263) at the time of diagnosis, but moderate hypercalcaemia (> 3 mmol/L) was present in only 0.8% of patients (2/263). Higher serum calcium was associated with younger age (p=0.0229), but no correlations with stage of sarcoidosis, serum ACE, lymphocyte count or vitamin D were seen. There were no differences in serum calcium according to month of diagnosis using non-parametric analysis of variance (p=0.2836). CONCLUSIONS: Despite a high background prevalence of sarcoidosis in the South of Ireland, the prevalence of hypercalcaemia at the time of diagnosis was lower than internationally reported. Moderate or clinically significant hypercalcaemia was rare and seasonal variation had no influence on the level of serum calcium. The temperate climate in our region may explain the lack of seasonal variation in serum calcium in patients with sarcoidosis. CLINICAL IMPLICATIONS: Improve our understanding of the prevalence, pathophysiological and environmental factors attributing to hypercalcemia in our patient cohort. DISCLOSURES: No relevant relationships by HISHAM I S IBRAHIM, source=Web Response No relevant relationships by Terence O'Connor, source=Web Response No relevant relationships by Jess O'Sullivan, source=Web Response No relevant relationships by Laura Walsh, source=Web Response

Prevention of hypoparathyroidism with the use of calcium-rich foods in the total thyroidectomy pre-operative period

<p class="abstract"><strong>Background:</strong> Transient hypocalcemia after total thyroidectomy (TT) is a common surgical complication. Authors used calcium supplements in different doses and periods, mainly after TT to try to avoid hypocalcemia. Indistinct use has been challenged due to complications. Currently, the risk of hypocalcemia was assessed by measuring parathormone (PTH) after TT; however, without a consensus on the best time and amount to consider. The objectives of this study were to evaluate the incidence of hypoparathyroidism with the use of calcium-rich foods in the pre-operative period of TT, followed by a measurement of PTH performed 12 hours after such procedure</p><p class="abstract"><strong>Methods:</strong> A preliminary study with 31 patients earmarked for TT. Patients were divided into two groups: (A) without calcium-rich foods intake in the TT pre-operative period; and (B) with the intake of calcium-rich foods, in the TT pre-operative period. These foods composing different menus have been suggested, based on the need for daily calcium intake, according to the age group and nutritional data of the Dietary reference intake (DRI). Beginning of the use of these foods has been standardized as being seven days before surgery, due to the slower calcium intestinal absorption process. </p><p class="abstract"><strong>Results:</strong> Group B, when compared to A, showed a significant difference between PTH values, before and after surgery (p value <0.001).</p><p class="abstract"><strong>Conclusions:</strong> Calcium-rich foods intake in the conditions reported may be associated with lower rates of hypoparathyroidism.</p>

Growth, Dietary Intake, and Vitamin D Receptor (VDR) Promoter Genotype in Indonesian School-Age Children.

Nutrition has been known as a predominant factor associated with stunting. However, some studies have discovered a genetic contribution in calcium absorption that will affect growth, known as the VDR gene. The aim of this study was to assess the association between VDR gene polymorphism and dietary intake towards height-for-age z-score (HAZ) of elementary school children in Malang District, East Java. This study analyzed the baseline of a randomized trial in East Java, Indonesia. School children aged 8–10 years old (n = 142) were included in this study. Energy, protein, calcium, and vitamin D intakes were obtained using 4-day 24-h dietary recalls. Two SNPs located in the promoter region of VDR gene were selected (rs11568820 and rs4516035) and analyzed using Real-Time PCR. The result showed a significant correlation between energy and protein intake with HAZ of the children (p = 0.030 and p = 0.016, respectively). The association between VDR gene and HAZ was not found (p > 0.05). Adjusted by other factors, protein intake was significantly correlated with HAZ (β = 0.034, 95% CI 0.015–0.052, p < 0.001, adj. R2 = 0.089). The children in our study had a favorable VDR gene genotype, however the effect of VDR gene promoter activity might not be revealed due to very low vitamin D and calcium intake to stimulate intestinal calcium absorption which in turn affects HAZ.

ABSORPTION OF CALCIUM IN SMALL INTESTINE OF RATS AFTER IMPACT OF VARIOUS XENOBIOTICS

Relevance. Pathology of the thyroid and parathyroid glands, diseases of the digestive system, blood system, etc, as well as application of medications used for their treatment can result in the condition which is characterised by reduction of bone density – secondary osteoporosis. The aim of the research was to determine absorption of calcium in the small intestine of rats under impact of various xenobiotics. Materials and methods. The research was performed on white rats of herd breeding which, depending on the group obtained during 60 days: 1) cefoperazone (p/o, 180 mg/kg per day) and amoxiclav (p/o, 135 mg/kg per day); 2) mercazolil (p/o, 25 – 40 mg/kg per day); 3) L-thyroxine (p/o, 10 mg/kg per day); 4) hydrazine sulphate (50 mg/kg 2 times per week for 90 days). Calcium absorption was studied in an isolated loop of the small intestine of the animals. The condition of the small intestine mucous membrane was estimated in accordance with inflammation markers (elastate and acid phosphatase activity, index of the degree of opportunistic microbiota (urease activity), index of non-specific antimicrobial protection of mucous membranes (lysozyme activity). Long-term application of antibiotics contributed to reduction of calcium absorption in the small intestine of rats by 25.0 %, of mercazolil – by 29.7 %, of thyroxine – by 11.4 %, of hydrazine sulphate – by 34.5 %. The increase of elastase and acid phosphatase activity in the mucous membrane of the small intestine under the action of xenobiotics, as well as increase of urease activity and reduction of lysozyme activity testify to the change in the small intestine condition. Сonclusions. So, the significant reduction of calcium absorption after long-term application of xenobiotics can be first of all connected with inhibition of antimicrobial protection of the small intestine mucous membrane under the action of antibiotics, mercazolil, thyroxine and hydrazine sulphate. More active multiplication of opportunistic bacteria, presence of dysbiosis, and, after application of antibiotics and hydrazine sulphate, development of inflammation can be the consequence of lysozyme activity reduction.

Proton Pump Inhibitors Inhibit PHOSPHO1 Activity and Matrix Mineralisation In Vitro

Proton pump inhibitors (PPIs) have been associated with an increased risk of fragility fractures in pharmaco-epidemiological studies. The mechanism is unclear, but it has been speculated that by neutralising gastric acid, they may reduce intestinal calcium absorption, causing secondary hyperparathyroidism and bone loss. Here we investigated that hypothesis that the skeletal effects of PPI might be mediated by inhibitory effects on the bone-specific phosphatase PHOSPHO1. We found that the all PPIs tested inhibited the activity of PHOSPHO1 with IC50 ranging between 0.73 µM for esomeprazole to 19.27 µM for pantoprazole. In contrast, these PPIs did not inhibit TNAP activity. We also found that mineralisation of bone matrix in primary osteoblast cultures was inhibited by several PPIs in a concentration dependent manner. In contrast, the histamine-2 receptor antagonists (H2RA) nizatidine, famotidine, cimetidine and ranitidine had no inhibitory effects on PHOSPHO1 activity. Our experiments show for the first time that PPIs inhibit PHOSPHO1 activity and matrix mineralisation in vitro revealing a potential mechanism by which these widely used drugs are associated with the risk of fractures.

Impact of Vitamin D Supplementation on Dry Eye in People with Low Serum Vitamin D

Background: Dry eye is a disease (DED) of the tear film and ocular surface, leading to ocular discomforts and pain. The pathophysiology of DED includes tear film instability and ocular surface inflammation. Vitamin D refers to a group of fat-soluble secosteroids responsible for enhancing intestinal absorption of calcium, iron, magnesium, phosphate, and zinc. It is not strictly a vitamin, and may be considered a hormone as its synthesis and activity occur in different locations. Objective: Thisstudy aimed to investigate tear film function in patients with vitamin D deficiency. Patient and methods: A case-control study included 75 eyes of 39 patients who were referred to the Ophthalmologic Clinic, Menoufia University during the period from March 2020 to December 2020. Patients of dry eye underwent tear break up time, Schirmer I test without anesthesia and special tests as well as measurement of serum vitamin D level were assessed. Results: 25-hydroxy vitamin D level of the studied group ranged from 6-18.50 ng/ml with mean value of 8.22 ± 4.814 ng/ml. Also, majority of studied sample (92.3%) had bilateral affected eyes, followed by Gelinya (30%). Schirmer's test, tear film breakup time (TFBUT) and ocular surface disease index (OSDI) were increased significantly when compared the values at baseline and after treatment to be after 10 weeks (P < 0.001). Conclusion: Vitamin D replacement appears to improve ocular surface health in patients with vitamin D deficiency. However, further clinical trials with a large sample size and control group are warranted to define the role of vitamin D. Vitamin D supplementation is an effective and useful treatment for patients with dry eye syndrome (DES) that is refractory to conventional treatment.

A Cross Sectional Study to Evaluate Adverse Outcomes of Vitamin D Deficiency in Females of Lahore, Pakistan

Vitamin D is a group of fat-soluble sec steroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and multiple other biological effects. The most important compounds in human are vitamin D₃ and vitamin D₂. Vitamin D is essential for strong bones, because it helps the body use calcium from the diet. Vitamin D deficiency has been associated with rickets, a disease in which the bone tissue doesn't properly mineralize, leading to soft bones and skeletal deformities. A cross sectional study was conducted from 30th January 2021 to 30th June 2021 to evaluate adverse outcomes of Vitamin D level among 370 females of aged 20-60 years were recruited through non-probability convenient sampling technique from students and Faculty ofColleges and Universities in Lahore, Pakistan. The data was collected through a Semi-Structured Questionnaire.A total 370 participantswere included age groups of female ranging from 20-60. Comparing age and level of Vitamin D was more common in reproductive age of females with more association in young females of 20 to 30 years. 81.9 % participants had general awareness regarding deficiency of vitamin D. 80% People eat Vitamin D Rich Diet While only 20% use vitamin D supplements and only 41.9 % females drinks a Cup of Cow Milk. 73.8% participants had suffered weakness and general body aches and 82.2% females reported musculoskeletal pain.This studyevaluated thatMost of Educated People are unaware of Vitamin D knowledge and intake. They take insufficient amount of Vitamin D and experience discomfort in Muscoskeletal system.

25 hydroxycholicalciferol levels during Pregnancy in Rural and Urban Population of South India

Maternal 25 dihydroxycholecalciferol is the storage form the vitamin D. It gets activated to 1,25, Dihydroxycholecalciferol (vitamin D3) in the kidneys. Pregnancy increases requirement for the vitamin D3. The 1,25 dihydroxycholecalciferol is produced by the fetal kidneys from maternal sources of 25 dihydroxycholecalciferol. Vitamin D3 is essential for intestinal calcium absorption and bone mineralization in fetus.104 venous blood samples were used to study 25 hydroxycholecalciferol and serum calcium levels. Experimental group involved venous blood samples from 100 ANC between 20-40 years. In the first trimester rural ANC cases had an average 25 hydroxycholecalciferol level of 50.9ng/ml. In Urban participants the average was 31.6nmol/L. Second Trimester ANC in rural sector had an average of 54nmol/L and in urban average was 45nmol/L. In third trimester rural participants had an average of 61nmol/L, urban participants had 28nmol/L. The urban participants in all the three trimesters had 25 hydroxycholecalciferol insufficiency. 25 hydroxycholecalciferol deficiency is higher percentage in first trimester, gradually reduces in second trimester and reaches towards normal limits in third trimester. The placental secretion compensates for the homeostasis and maintenance of normal calcium levels and during third trimester. Active fetal bone mineralization occurs in third trimester.

Calcium as an inhibitor of tripsin activity in pancreatic juice of chicken

The results of studying the interaction of calcium and pancreatic enzymes in 46-week-old Hisex white chickens are presented. It is shown that intestinal absorption of calcium is accompanied by endogenous excretion of calcium with digestive juices. The effect of calcium on tryptic activity in an in vitro experiment was determined. In the experiment, different doses of calcium (5.0; 7.5; 0.5; 12.5 and 25.0 mg) were injected into the pancreatic juice of chickens, previously diluted with physiological solution 10 times. The number of repetitions in each variant of the experiment was 20 times. For the experiment, 2-aqueous calcium chloride (Chimmed, RF) was used. Trypsin activity was determined by the kinetic method. The content of calcium was determined with a Sinnowa BS-3000P biochemical analyzer (China) and a set for the determination of calcium in the blood of animals DIAKON-VET (RF). It was found that pancreatic juice of chickens contains up to 2.9 ± 0.03 mmol of calcium/l, which is comparable to the level of calcium in the blood serum of 1.99 ± 0.10 – 3.13 ± 0.20 mmol/l. The inhibiting effect of calcium on the tryptic activity was found. A five-fold increase in calcium in pancreatic juice of chickens reduces the activity of trypsin by 34.7%. According to the analysis of variance, the concentration of calcium in pancreatic juice affects tryptic activity, the reliability of the effect is confirmed by 92%. A stable negative correlation was established between calcium content in pancreatic juice and activity of trypsin r = –0.78, which is consistent with the correlation of the corresponding parameters in the blood. These findings serve as evidence that calcium together with proteases can be regarded as an element that regulates metabolic processes in chickens.

Intestinal Calcium Absorption.

In this article, we focus on mammalian calcium absorption across the intestinal epithelium in normal physiology. Intestinal calcium transport is essential for supplying calcium for metabolism and bone mineralization. Dietary calcium is transported across the mucosal epithelia via saturable transcellular and nonsaturable paracellular pathways, both of which are under the regulation of 1,25-dihydroxyvitamin D3 and several other endocrine and paracrine factors, such as parathyroid hormone, prolactin, 17β-estradiol, calcitonin, and fibroblast growth factor-23. Calcium absorption occurs in several segments of the small and large intestine with varying rates and capacities. Segmental heterogeneity also includes differential expression of calcium transporters/carriers (e.g., transient receptor potential cation channel and calbindin-D9k ) and the presence of favorable factors (e.g., pH, luminal contents, and gut motility). Other proteins and transporters (e.g., plasma membrane vitamin D receptor and voltage-dependent calcium channels), as well as vesicular calcium transport that probably contributes to intestinal calcium absorption, are also discussed. © 2021 American Physiological Society. Compr Physiol 11:1-27, 2021.

MO054EFFICACY OF ORAL PHOSPHATE SUPPLEMENTATION IN CHILDREN WITH HEREDITARY HYPOPHOSPHATEMIC RICKETS WITH HYPERCALCIURIA

Abstract Background and Aims Hereditary hypophosphatemic rickets with hypercalciuria (HHRH; MIM #241530) is an autosomal recessive renal phosphate-wasting disorder caused by mutations in the SLC34A3/NPT2c gene. HHRH characterized by increased urinary phosphate excretion leading to hypophosphatemic rickets, short stature and elevated serum 1,25(OH)2D levels which result in hypercalciuria leads to nephrocalcinosis/urolithiasis due to enhanced intestinal calcium absorption and reduced PTH-dependent calcium reabsorption in the distal renal tubules. Treatment of HHRH involves administration of oral phosphate supplements alone to normalize of serum phosphate, alkaline phosphatase activity (ALP), PTH levels, urine calcium excretion for prevention of renal calcifications and progression of rickets. Currently there is no consensus on the optimal dose of oral phosphate in patients with HHRH. The aim of the study was to evaluate the efficacy of oral phosphate supplements in Russian cohort of children with HHRH. Method 9 children (7M/2F) with homozygous (n=6) and compound heterozygous (n=3) SLC34A3 mutations from unrelated families were examined. Treatment with oral phosphate supplements was started at the median age of patients 12.0 (IQR: 9.0; 13.0) years. The median dosage of oral phosphate supplements was 14.1 (IQR: 13.8; 14.8) mg/kg/day based on elemental phosphorus. The duration of follow-up was 36.0 (IQR: 16; 49) months. Blood electrolytes levels, ALP, PTH and 24-hour-urine excretion of calcium were evaluated in all children. ALP Z-scores were calculated using age- and sex-specific mean/standard deviation (SD) lab reference data. Bone mineral density with Z-score were measured in lumbar spine and whole body for all patients using a dual energy X-ray absorptiometry device. Molecular genetic analysis was performed in all children using by next generation sequencing. Results The median SD score of height at the first and last follow-up was -1.35 (IQR: -1.8; -0.87) and -1.51 (IQR: -2.0; -0.66) (p=0.6), respectively, short stature had 33.3% (3/9) of patients at first and 44.4% (4/9) at last follow-up (p=0.7). Treatment with low doses of oral phosphate supplements did not led to normalization of serum phosphorus:1.05 (IQR: 0.97; 1.39) vs. 0.93 (IQR: 0.81; 1.27) mmol/l (p=0.13), PTH: 8.3 (IQR: 5.8; 13.8) vs. 12.9 (IQR: 12.0; 16.0) pg/ml (p=0.34), Z-score in lumbar spine: -1.2 (IQR: -2.7; -0.1) vs. -1.8 (IQR: -2.8; -1.1) (p=0.48) and Z-score in total body: -2.1 (IQR -2.6; -1.5) vs. -2.4 (IQR: -3.0; -2.0) (p=0.37). Hypercalciuria had 88.8% (8/9) of children (0.15 (IQR: 0.12; 0.19) mmol/kg/day) at first follow-up and 44.4% (4/9) (0.09 (IQR: 0.08; 0.16) mmol/kg/day) in last examination (p=0.13). ALP blood levels were elevated in all patients (9/9) at first and most recent visit, but ALP Z-score were significant lower at last follow-up: 3.9 (IQR: 1.2; 5.1) vs. 0.57 (IQR: -0.36; 2.1) (p=0.04). There were significant correlations between doses of oral phosphate supplements and ALP Z-score (r=-0.68; p=0.04) and total body Z-score (r=0.78; p=0.03). There was no significant correlations between ALP Z-score and total body Z-score (r=-0.3) or lumbar spine Z-score (r=-0.1). Conclusion The present study demonstrated that treatment of HHRH with low doses (&amp;lt;20 mg/kg/day) of oral phosphorus supplements led to decreasing of ALP Z-score in 7/9 (77.8%) and hypercalciuria in 5/9 (55.6%) of patients. However, that therapy didn’t improve significantly height and severity of rickets, as well didn’t led to normalization of serum phosphorus in children with HHRH. It is therefore conceivable that higher daily doses of phosphate supplements are needed to normalize all clinical and radiological features of disease. Lack of association between ALP Z-score and bone mineral density severity on radiographs limits the value of serum ALP as the indicator of rickets activity.

Importance of Extra-Renal CYP24A1 Expression for Maintaining Mineral Homeostasis

Calcium homeostasis involves a complex interplay between kidneys, parathyroid glands, intestine and bone. Specifically, 1,25(OH)2D3 is a key calciotropic hormone which stimulates intestinal calcium absorption. A growing body of evidence suggests that circulating levels of 1,25(OH)2D3 depend not only on its synthesis under the action of PTH in the kidneys, but also its catabolism by 24-hydroxylase, herein referred to as CYP24A1. The clinical importance of CYP24A1 has been demonstrated by human loss-of-function mutations, which lead to severe hypercalcemia due to exaggerated levels of 1,25(OH)2D3. Despite its growing importance, little is known about its tissue-specific contributions to normal vitamin D metabolism. To explore the physiology of CYP24A1 and delineate renal-specific effects of CYP24A1 in calcium metabolism, we generated a mouse with constitutive kidney-specific deletion of Cyp24a1 (Six2Cre-Cyp24flox). Six2 marks the nephron progenitor population throughout nephrogenesis. We hypothesized that hypercalcemia as seen in CYP24A1 inactivating mutations is related to lack of both renal and extrarenal expression, and that renal deletion does not lead to severe hypercalcemia. To confirm Cyp24a1 deletion, we measured mRNA expression in the kidney using qPCR and RNA in situ hybridization. All mice were fed a standard commercial rodent diet and followed longitudinally for five months with interval calcium measurements. At time of termination, serum PTH levels were measured along with vitamin D-dependent calcium transporters as a functional measure of 1,25(OH)2D3 action. Cyp24a1 expression was significantly knocked down in total kidneys from Six2Cre-Cyp24flox mice as compared to intestinal expression suggesting successful gene deletion. Compared to age-matched wildtype controls, Six2Cre-Cyp24flox mice were mildly but persistently hypercalcemic (diff between means= 0.46 mg/dL, p-value: 0.03, n=8 per group). As expected, 1,25D-dependent calcium transporters in the kidney (Calb1, Trpv5, Slc8a1, Atp2b1) and intestine (Trpv6, s100g) were all increased, consistent with increased systemic 1,25(OH)2D3 activity. PTH levels were appropriately suppressed in the Six2Cre-Cyp24flox mice (diff between means=83 pg/mL, p-value 0.2, n=9 control, n=3 exp) as were renal cyp27b1 mRNA expression. These data suggest that renal CYP24A1 is important for systemic 1,25(OH)2D3 regulation, but the lack of severe hypercalcemia supports critical contributions of extra-renal CYP24A1.

Acromegaly and non\u2010parathyroid hormone\u2010dependent hypercalcemia: a case report and literature review

BackgroundHypercalcemia associated with acromegaly is mostly parathyroid hormone (PTH)-dependent, being caused by parathyroid hyperplasia or adenoma, which are common in individuals with multiple endocrine adenomatosis-1 (MEN-1). The rare occurrence of non-PTH-dependent hypercalcemia associated with acromegaly is attributable to complex factors involving increased intestinal calcium absorption, enhanced bone calcium release, and reduced urinary calcium elimination. Although patients with acromegaly often have mild hyperphosphatemia and hypercalciuria, clinically significant hypercalcemia is extremely rare.Case presentationHere we present a case of non-PTH-dependent hypercalcemia associated with a growth hormone- (GH) and prolactin- (PRL) co-secreting pituitary macroadenoma. A 37-year-old Chinese man presented with a 6-year history of increasing ring and shoe sizes and was referred to the West China Hospital of Sichuan University for treatment of acromegaly. Pituitary magnetic resonance imaging (MRI) showed a 2.0 × 1.7 × 1.9 cm macroadenoma. Laboratory examinations revealed high serum concentrations of GH and PRL with mild hypercalcemia, hyperphosphatemia, hypercalciuria, inhibited PTH concentration, and increased bone turnover markers. Administration of cabergoline together with somatostatin resulted in sharp decreases in his GH, PRL, and serum and urinary calcium concentrations. These values were further reduced 5 months later and his PTH and bone turnover markers gradually returned to within the normal range.ConclusionsMild hyperphosphatemia and hypercalciuria are common in individuals with acromegaly and deserve attention because they may contribute to osteoporosis and urolithiasis. However, overt hypercalcemia is rare in such individuals. It is usually attributable to a coexisting parathyroid hyperplasia or adenoma, rarely being non-PTH-dependent. In such cases, the hypercalcemia is attributable to excessive PRL and hypogonadism and reverses with remission of acromegaly.

Parathyroid Disease in Pregnancy and Lactation: A Narrative Review of the Literature.

Pregnancy and lactation are characterized by sophisticated adaptations of calcium homeostasis, aiming to meet fetal, neonatal, and maternal calcium requirements. Pregnancy is primarily characterized by an enhancement of intestinal calcium absorption, whereas during lactation additional calcium is obtained through resorption from the maternal skeleton, a process which leads to bone loss but is reversible following weaning. These maternal adaptations during pregnancy and lactation may influence or confound the presentation, diagnosis, and management of parathyroid disorders such as primary hyperparathyroidism or hypoparathyroidism. Parathyroid diseases are uncommon in these settings but can be severe when they occur and may affect both maternal and fetal health. This review aims to delineate the changes in calcium physiology that occur with pregnancy and lactation, describe the disorders of calcium and parathyroid physiology that can occur, and outline treatment strategies for these diseases in the above settings.

A Review of the Occurrence and Mechanisms of Induction of Osteoporosis Following Spinal Cord Injury

Introduction: Spinal cord injury (SCI) causes devastating injuries in patients. The main mechanisms of the pathogenesis of secondary injury include nerve degeneration, gliosis, and inflammation. Spinal cord injury induces a disorder or failure in several organs due to the vital role of the spinal cord in regulating bodily functions. Osteoporosis is a consequence of spinal cord injury that occurs in the vast majority of patients with spinal cord injury. Articles on the related topic were searched in the following databases: Science Direct, Scopus, Springer Science, PubMed and Google scholar to have been used in writing from this review article. A total of 120 related research papers, including quantitatve and qualitative researches in English, from the last 57 years papers (1962- 2019) were included in this study. The review article is written according to 120 articles and the keywords “Spinal cord injury, Osteoporosis, Inflammation, Osteoblast and Osteoclast”. Conclusion: Although weight loss is an important factor in the development of osteoporosis following SCI, inflammation, nerve damage, and hormonal changes also contribute to this process. Hormonal changes mediated by SCI may contribute to postoperative osteoporosis with several mechanisms. These mechanisms included: increased renal excretion and decreased intestinal absorption of calcium, consequently, a negative balance of calcium ions; Vitamin D deficiency; impair the function of the gonads and inhibits the osteoanabolic (ossification) activity of sex steroids; elevated blood leptin; Pituitary suppression of parathyroid hormone, and bone loss following SCI may (at least in part) be caused directly by insulin resistance and insulin-like growth factor.

Historical weather data as a biocultural indicator of ancient vitamin D deficiency in human skeletal remains in the United States.

Vitamin D is a pro-hormone that is activated by ultraviolet B (UVB) radiation through direct exposure to the skin. Vitamin D plays a large role in calcium and phosphorus absorption in the small intestines, directly influencing blood-calcium homeostasis and skeletal health. Individuals who do not receive enough UVB radiation do not have adequate blood calcium levels leading to a cascade of metabolic deficiencies and health problems, including bone diseases like rickets and osteomalacia. Many biocultural variables may affect vitamin D exposure. For this presentation, I will explore how weather and geographic location affect the likelihood of individuals living in the past being vitamin D deficient. I analyzed twelve states above and twelve states below the Mason-Dixon Line which were settled during the 19th century. To examine historic weather data I extracted average temperature, UV index, and zenith angle data by year, season, and state. Data were analyzed using ANOVA and PCA. Preliminary results show weather data significantly varies by northern and southern state, which may indicate that state of residence can directly impact vitamin D status.

Vitamin D in liquid food supplements: are labels in line with RDA?

Introduction Nowadays, it has been observed an increase consumption in vitamins and food supplements (FS). In Portugal, in 2018, more than 2 million individuals reported the intake of these products [1]. Media has been given a particular attention to the high prevalence of vitamin D (VitD) deficiency, which may explain its highest consumption [2]. This vitamin increases intestinal calcium absorption and plays a central role in its homeostasis. Although vitD toxicity is uncommon, being a fat-soluble vitamin, excessive supplementation may result in body accumulation and toxicity [3]. The aim of this study is to evaluate if daily dose of vitamin D claimed in FS labels is in conformity with the recommended daily allowances (RDA) for this vitamin defined by European Union Directive and Portuguese legislation [4]. Materials and methods A total of 65 FS sold in Portuguese pharmacies, health shops, supermarkets and on the internet were examined for indicated daily intake and dosage of vitamin D. Selection criteria included: oral liquid pharmaceutical forms, for adults or paediatric consumption containing vitD in its composition, as mentioned in the label, regardless of the purpose of the FS. Results 35 (54%) FS presented vitD label doses above RDA and six (9%) of them indicated a daily dose ≥ the tolerable upper intake level defined by EFSA (UL = 100 μg/day) (Figure 1). Figure 1. NIR calibration curve used to predict the amorphous fraction of OLZ. Discussion and conclusions VitD label dose far exceeded RDA value in most of the FS evaluated and some exceeded UL defined by EFSA. Currently, the economic operators who place FS on the market are the responsible for the safety and the authenticity of label data. Attending that these products are often taken without any medical supervision or counselling and vitD excess may trigger adverse effects and also considering that some of these liquid formulations are for children consumption, it increases the concern about FS safety, it is imperative that the daily doses of this vitamin are reviewed in FS, in accordance to RDA values. FS should be under the same quality control of pharmaceuticals, regarding FS consumers health.

Diet-induced iron deficiency in rats impacts small intestinal calcium and phosphate absorption.

Recent reports suggest that iron deficiency impacts both intestinal calcium and phosphate absorption, although the exact transport pathways and intestinal segment responsible have not been determined. Therefore, we aimed to systematically investigate the impact of iron deficiency on the cellular mechanisms of transcellular and paracellular calcium and phosphate transport in different regions of the rat small intestine. Adult, male Sprague-Dawley rats were maintained on a control or iron-deficient diet for 2weeks and changes in intestinal calcium and phosphate uptake were determined using the in situ intestinal loop technique. The circulating levels of the hormonal regulators of calcium and phosphate were determined by ELISA, while the expression of transcellular calcium and phosphate transporters, and intestinal claudins were determined using qPCR and western blotting. Diet-induced iron deficiency significantly increased calcium absorption in the duodenum but had no impact in the jejunum and ileum. In contrast, phosphate absorption was significantly inhibited in the duodenum and to a lesser extent the jejunum, but remained unchanged in the ileum. The changes in duodenal calcium and phosphate absorption in the iron-deficient animals were associated with increased claudin 2 and 3 mRNA and protein levels, while levels of parathyroid hormone, fibroblast growth factor-23 and 1,25-dihydroxy vitamin D3 were unchanged. We propose that iron deficiency alters calcium and phosphate transport in the duodenum. This occurs via changes to the paracellular pathway, whereby upregulation of claudin 2 increases calcium absorption and upregulation of claudin 3 inhibits phosphate absorption.

Uptake of Vitamins D2, D3, D4, D5, D6, and D7 Solubilized in Mixed Micelles by Human Intestinal Cells, Caco-2, an Enhancing Effect of Lysophosphatidylcholine on the Cellular Uptake, and Estimation of Vitamins D' Biological Activities.

Vitamins D have various biological activities, as well as intestinal calcium absorption. There has been recent concern about insufficient vitamin D intake. In addition to vitamins D2 and D3, there are lesser-known vitamins D4–D7. We synthesized vitamins D5–D7, which are not commercially available, and then evaluated and compared the mixed micelles-solubilized vitamins D uptake by Caco-2 cells. Except for vitamin D5, the uptake amounts of vitamins D4–D7 by differentiated Caco-2 cells were similar to those of vitamins D2 and D3. The facilitative diffusion rate in the ezetimibe inhibited pathway was approximately 20% for each vitamin D type, suggesting that they would pass through the pathway at a similar rate. Lysophosphatidylcholine enhanced each vitamin D uptake by approximately 2.5-fold. Lysophosphatidylcholine showed an enhancing effect on vitamin D uptake by reducing the intercellular barrier formation of Caco-2 cells by reducing cellular cholesterol, suggesting that increasing the uptakes of vitamins D and/or co-ingesting them with lysophosphatidylcholine, would improve vitamin D insufficiency. The various biological activities in the activated form of vitamins D4–D7 were estimated by Prediction of Activity Spectra for Substances (PASS) online simulation. These may have some biological activities, supporting the potential as nutritional components.

Genetic Disorders of Bone or Osteodystrophies of Jaws-A Review.

Bone is a specialized form of connective tissue, which is mineralized and made up of approximately 28% type I collagen and 5% noncollagenous matrix proteins. The properties of bone are very remarkable, because it is a dynamic tissue, undergoing constant renewal in response to mechanical, nutritional, and hormonal influences. In 1978, “The International Nomenclature of Constitutional Diseases of Bone” divided bone disorders into two broad groups: osteochondrodysplasias and dysostoses. The osteochondrodysplasia group is further subdivided into two categories: dysplasias (abnormalities of bone and/or cartilage growth) and osteodystrophies (abnormalities of bone and/or cartilage texture). The dysplasias form the largest group of bone disorders, hence the loose term “skeletal dysplasia” that is often incorrectly used when referring to a condition that is in reality an osteodystrophy or dysostosis. The word “dystrophy” implies any condition of abnormal development. “Osteodystrophies,” as their name implies, are disturbances in the growth of bone. It is also known as osteodystrophia. It includes bone diseases that are neither inflammatory nor neoplastic but may be genetic, metabolic, or of unknown origin. Recent studies have shown that bone influences the activity of other organs, and the bone is also influenced by other organs and systems of the body, providing new insights and evidencing the complexity and dynamic nature of bone tissue. The 1,25-dihydroxyvitamin D3, or simply vitamin D, in association with other hormones and minerals, is responsible for mediating the intestinal absorption of calcium, which influences plasma calcium levels and bone metabolism. Diagnosis of the specific osteodystrophy type is a rather complex process and various biochemical markers and radiographic findings are used, so as to facilitate this condition. For diagnosis, we must consider the possibility of lesions related to bone metabolism altered by chronic renal failure (CRI), such as the different types of osteodystrophies, and differentiate from other possible neoplastic and/or inflammatory pathologies. It is important that the dentist must be aware of patients medical history, suffering from any systemic diseases, and identify the interference of the drugs and treatments to control them, so that we can able to perform the correct diagnosis and propose the most adequate treatment and outcomes of the individuals with bone lesions.