Gastrointestinal Calcium Absorption Research Articles

Transcriptomic and Proteomic Analyses Reveal New Insights into Regulatory Mechanisms of Strontium in Bovine Chondrocytes.

Strontium (Sr) is a trace element found mainly in bone, and it performs a dual action by promoting bone formation and inhibiting bone resorption. Sr has been used to evaluate the gastrointestinal calcium (Ca) absorption capacity of dairy cows due to the similar physicochemical properties of the two elements. However, the possible effects of Sr on dairy cows remain unclear. This study aimed to explore the potential regulatory mechanism of Sr in bovine chondrocytes by performing transcriptomic and proteomic analyses. A total of 111 genes (52 up-regulated and 59 down-regulated) were identified as significantly altered (1.2-fold change and p < 0.05) between control and Sr-treated groups. Moreover, LC-MS-based proteomic analysis detected 286 changed proteins (159 up-regulated and 127 down-regulated) between the control and Sr-treated groups (1.2-fold change and p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations of a combination analysis of the transcriptomic and proteomic data revealed that the genes were predominantly involved in chondrocyte proliferation and differentiation, fat metabolism, the inflammation process, and immune responses. Overall, our data reveal a potential regulatory mechanism of strontium in bovine chondrocytes, thus providing further insights into the functions and application of Sr in ruminants.

ASSOCIATION OF VITAMIN D DEFICIENCY TO SEVERITY OF COVID-19 : A SYSTEMATIC REVIEW

As a pathogen invades, phagocytes quickly respond, but the adaptive immune response is more specific. Antigen-recognizing cytotoxic T cells control this immunological response. Cytotoxic T cells kill infection. These cells participate in humoral, antiparasitic, and antiviral immune responses. Balanced nutrition helps the immune system fight infections and neoplastic cells. Research describes how the immune system and defensive mechanisms defend the body from invaders, especially with optimal diet. Respiratory tract infections can worsen chronic diseases, increasing mortality. Vitamin D reduces respiratory infections, including pneumonia, through numerous mechanisms. UVB exposure converts 7-dehydrocholesterol into fat-soluble vitamin D. The liver converts it to 25(OH)D, which the kidneys or other organs convert to calcitriol 1, 25(OHD). Bones and teeth need vitamin D. Vitamin D aids bone metabolism, gastrointestinal calcium and phosphorus absorption, and the immune system, according to in vitro research. Most studies indicate COVID-19 severity with vitamin D levels below 12. Vitamin D pills benefit COVID-19 patients.

Metabolic Bone Disease of Prematurity.

Metabolic Bone Disease of Prematurity.

Evaluation of Relationship between Vitamin D Supplementation Treatment and Hypercalciuria in Patients with Kidney Stones

Background: Vitamin D, especially calcitriol (its active metabolite), increases gastrointestinal calcium absorption. Because urinary calcium excretion is associated with calcium absorption in the gastrointestinal tract; vitamin D metabolites could theoretically cause hypercalciuria. The aim of this study was to investigate the relationship between treatment and vitamin D supplementation on the rate of hypercalciuria in patients. Method: In the present double-blind randomized clinical trial, 90 patients (male-female) with urinary stones and serum vitamin D levels less than 30 ng/mL were evaluated. Patients were randomLy divided into two groups of 45 patients. One group was given 50,000 units of oral vitamin D weekly for up to 8 weeks. For the other group, the drug was given as a placebo for up to 8 weeks. Sampling was performed one month after the end of treatment. The data garnered from hospital records were inserted into SPSS software for analysis.Results: In the present study, the mean age of the subjects was 39.78 years. Also, out of 90 patients, 52 were male and 38 were female. Blood PTH levels decreased significantly after treatment in vitamin D group (P <0.001). Also, serum levels of vitamin D in this group showed a significant increase (P <0.001). However, in this study urinary calcium levels after treatment did not show significant changes (P = 0.680).Conclusion: The present study showed that in people with a history of kidney stones, taking vitamin D supplement alone for people with lower than standard serum levels of vitamin D did not show any significant difference in calcification. As a result, the therapeutic dose of this drug is recommended in patients with kidney stones according to the condition.

Hypervitaminosis A: A Rare Cause of Hypercalcemia

Abstract Introduction: Hypercalcemia is a rather common clinical problem and a majority of cases are found to be secondary to primary hyperparathyroidism and malignancy. A rare cause of hypercalcemia is associated with high levels of vitamin A and thought to be secondary to the effect of vitamin A on bone to stimulate osteoclastic resorption or inhibit osteoblastic formation. Clinical Case: A 54 year-old male with a past medical history of CKD stage 3 secondary to medullary sponge kidney presented for hypercalcemia. He complained of chronic constipation, joint pain, mood changes and recurrent kidney stones. Reported multivitamin use (including 1000mcg of vitamin A) for years but was discontinued one year prior to visit. Lab work showed calcium of 11.5 mg/dL (8.7–10.2mg/dL), albumin 4.9 g/dL (3.8–4.9g/dL), elevated 24h urine calcium, eGFR 40 mL/min/1.73, parathyroid hormone 5 pg/mL (15-65pg/mL,) normal 1,25-OH vit D and 25-OH vit D, PTHrP &amp;lt;2.0 pmol/L, serum protein electrophoresis unremarkable. His vitamin A level was elevated to 103 ug/dL (20.1–62.0ug/dL). CT chest showed no findings concerning for sarcoidosis. Bone density scan showed normal bone mineral density. Patient diagnosed with hypercalcemia secondary to elevated vitamin A levels. Current limited literature shows stopping the vitamin A supplement will normalize vitamin A levels and correct the hypercalcemia. This patient had discontinued his multivitamin 1 year prior and vitamin A remained elevated, thought to be due to his poor kidney function. Treatment was targeted at improving his hypercalcemia and reducing his symptoms. He was prescribed a one-week course of prednisone 40 mg daily. His calcium level improved to 10.5 mg/dL. Prednisone was reduced to 20 mg daily with normalization of calcium to 10.3 mg/dL (8.7–10.2mg/dL). Conclusion: Hypercalcemia is a rare but known complication of vitamin D toxicity. The liver, kidney and adrenal glands store vitamin A and it is excreted in the urine. Liver and kidney disease pose higher risk of vitamin A toxicity. We present a unique case of Hypercalcemia secondary to elevated vitamin A levels in a patient with moderate chronic kidney disease who was not taking excessive amounts of vitamin A and whose calcium and vitamin A did not normalize once vitamin A supplements were discontinued. The CKD 3 may have reduced vitamin A clearance and increased its toxicity. Hypercalcemia is not the only concern regarding vitamin A toxicity, the increasing use of dietary supplements and over the counter medications may pose significant risks for osteoporosis and bone fractures. A high clinical suspicion and thorough workup to exclude other causes of hypercalcemia is warranted to diagnose hypervitaminosis A as the etiology. Steroids can reduce gastrointestinal absorption of calcium, however, its role in vitamin A toxicity remains unclear. Further research is needed to investigate the appropriate treatment for these patients.

Elucidating the effect of specific surface area on the gastrointestinal absorption of nanostructured calcium through Calcium-45 in vivo radiotracing

Low dietary calcium intake and absorption may increase the risk of hypocalcaemia disease states. Reducing the particle size of calcium-containing powders and increasing the specific surface area (SSA), may have high oral calcium bioavailability. The absorption of a single dose of different sized calcium carbonate nanoparticles was traced in Sprague-Dawley rats with radioactive calcium-45 (half-life = 162.6 days, β− endpoint = 258 keV; 100%). Four calcium carbonate formulations (calcium-45) were administered to Sprague-Dawley rodents (6 per treatment; n = 24). The groups were [45Ca]CaCO3 SSA 3 m2/g, [45Ca]CaCO3 36 m2/g, [45Ca]CaCO3 64 m2/g and a separate [45Ca]CaCO3 36 m2/g formulation produced by flame assisted pyrolysis. Blood and urine were sampled periodically, and organs collected and analysed after euthanasia. No changes in SSA or crystallinity were observed when powders before or after irradiation were compared. The [45Ca]CaCO3 64 m2/g formulation presented with higher levels in blood 2 h after administration and a higher liver and femur concentration. These findings suggest [45Ca]CaCO3 64 m2/g could lead to increased oral bioavailability.

Higher Bioavailability of Calcium in Chickens With a Novel In-Feed Pharmaceutical Formulation

Egg production and egg shell quality decrease toward the end of the first laying cycle in hens (approximately by week 80). Even so, farmers often choose to work a second cycle with them. Defective egg shell production has been mainly linked to a decrease in gastrointestinal absorption of calcium. Here we studied pharmaceutically-designed modified-release small pellets (FOLAs) containing calcium to improve calcium bioavailability (F). The influence of FOLA alone or with capsicum-oleoresin was studied in a total of 400 Bovans-White hens randomly divided into four groups of 20 laying hens each and with five replicates per group (n = 100) as follows: (1) control group (GC) receiving a diet containing basal levels of 4.1% of calcium-carbonate; (2) group GF treated as GC but with the same dose of calcium-carbonate in FOLA; (3) group GFc5 was treated as GF but with 6 ppm of capsicum-oleoresin (500,000 Scoville Heat Units [SHU]); and (4) group GFc10 treated as GFc5 but with 1,000,000 SHU capsicum-oleoresin. Plasma concentrations of calcium were determined during 5 days at predetermined times sampling more often on days 1 and 5 for blood plasma kinetics of calcium. Relative bioavailability (Fr) values based on the area under the serum calcium concentration vs. time curve (AUC) were obtained and compared to GC. The AUC was statistically different among all groups (P < 0.5), but the GFc10 had the greatest Fr (194%), with serum calcium concentrations ranging from 25.37 to 31.2 μg/dL. Calcium residence time (RT) between GC and GF showed no statistical differences while GFc5 and GFc10 had statistically superior RT values. Simultaneously, the number of shell-less eggs per group and their thickness was evaluated by utilizing the same groups but with 150 hens per group on 6 days. Shell-less eggs decreased to zero in Group GFc10 and produced eggs with the greatest shell thickness from day 2 onwards. The inclusion of calcium-carbonate in the pharmaceutical form FOLA induced higher serum calcium concentrations (GF, GFc5, and GFc10) particularly during the night-phase of the hen's cycle—this coincides with the time at which egg shell formation occurs.

Current evidence for vitamin D in intestinal function and disease.

Vitamin D activity is associated with the modulation of a wide variety of biological systems, in addition to its roles in calcium homeostatic mechanisms. While vitamin D is well known to promote gastrointestinal calcium absorption, vitamin D also plays a role in attenuating and/or preventing the progression of several gastrointestinal diseases including Crohn’s disease, ulcerative colitis, and colorectal cancer, and may also play a role in chemotherapy-induced intestinal mucositis. The pro-differentiation, immunomodulatory, and anti-inflammatory effects of vitamin D, which has been reported in numerous circumstances, are key potential mechanisms of action in the prevention of gastrointestinal disorders. While the debate of the effectiveness of vitamin D to treat bone pathologies continues, the clinical importance of vitamin D therapy to prevent gastrointestinal disorders should be investigated given current evidence, using both nutritional and pharmaceutical intervention approaches.Impact statementThe non-skeletal functions of vitamin D play an important role in health and disease. The anti-inflammatory properties and maintenance of intestinal function fulfilled by vitamin D impact other systems in the body though downstream processing. This review provides insight into the mechanisms underpinning the potential benefits of vitamin D in both maintaining intestinal homeostasis and associated diseased states.

MON-516 Skeletal Fluorosis from Fluorocarbon Inhalation

Background: Skeletal fluorosis (SF) is endemic in many places, especially where well water is rich in fluoride (F) from volcanic rock. SF is rare in the US, where it has unusual causes. The impact of F on the skeleton is conditioned by calcium and vitamin D sufficiency. Clinical Case: A 51-year-old obese man with chronic opiate use was referred for secondary hyperparathyroidism detected after right femoral neck and left proximal femur fractures, and displaced humeral fracture which healed poorly with radial nerve entrapment. Oncologic evaluation was negative, including intraoperative bone biopsy. He reported longstanding diffuse musculoskeletal pain, drank 72 oz of cola daily, and consumed little dietary calcium. Physical exam showed Ht 1.7 m, BMI 46, no dental abnormalities, deformed right humerus, diminished right wrist dorsiflexion, and an antalgic gait. DXA BMD Z-score was +7.4 at the spine and +0.4 at the “1/3” radius. At femur fracture, corrected serum calcium was 7.8 mg/dL (8.5-10.1) and alkaline phosphatase (ALP) 1080 U/L (46-116). After 5 months of calcium and vitamin D supplementation, calcium was 9.4 mg/dL, ALP 539 U/L, phosphorus 3.7 mg/dL (2.3-4.7), 25(OH)D 20.6 ng/mL (30-100), PTH 327 pg/mL (8.7-77.1), and creatinine 0.62 mg/dL (0.72-1.25). Hepatitis C Ab and PSA were normal. Elevated serum C-telopeptide 2513 pg/mL (87-345) and osteocalcin greater than 300 ng/mL (9-38) indicated rapid bone turnover. Bone scan showed increased uptake at the left hip fracture site, 2 ribs, and periarticular areas. Radiographic skeletal survey revealed diffuse osteosclerosis. Mutation analysis for high turnover sclerotic skeletal disease was negative, including examination of OPG, exon 1 of RANK and a NSG high bone mass panel. Initially, F exposure history was negative, however serum and urine F levels were elevated at 118 mcmol/L (0-4) and 42.6 mg/L (0.3-3.2), respectively. His mother confided that he had “huffed” difluoroethane containing computer cleaner for 2 years several times daily to control pain. Subsequently, right femur fracture required intramedullary fixation, several weeks rehabilitation, and generous doses of calcium and vitamin D3. Routine nondecalcified histology showed reactive bone with reticulin and collagen fibrosis. 24-hour urine of 3.43 liters contained calcium less than 68.6 mg and F 91.6 mg (0.2-3.2 mg/L). Conclusion: Inhalant abuse of fluorocarbons is known. However, literature concerning the skeletal effects is scant. Our patient’s positive bone balance together with low calcium intake could explain his secondary hyperparathyroidism. High phosphorus in colas may also have decreased gastrointestinal calcium absorption. Deposition of fluorohydroxyapatite in the skeleton likely explained our patient’s skeletal fragility.

Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and Hip Fracture Risk among Patients on Hemodialysis.

An association between proton pump inhibitor (PPI) use and hip fracture risk has been described in the general population, where the primary causative hypothesis focuses on impaired gastrointestinal calcium absorption. The impact of acid suppressor use on hip fracture risk in a high-risk subset, patients with ESKD requiring hemodialysis, is unknown and could help further distinguish the reason for higher susceptibility among PPI users. Using the US Renal Data System, we identified all hip fracture events recorded between 2009 and 2014 among patients dependent on hemodialysis. Eligible cases were matched on index date with ten controls. We identified PPI and histamine-2 receptor antagonist use from Medicare Part D claims covering 3 years before the index date and stratified according to proportion of days covered by filled prescriptions. Using logistic regression with multiple imputation for missing data, we estimated unadjusted and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). We studied 4551 cases and 45,510 controls. Patients were older, more likely to be female and white, and had shorter dialysis vintage; fewer were obese. A larger proportion of patients had any prior PPI (70% versus 63%) or histamine-2 receptor antagonist (25% versus 23%) use. Use of PPI was associated with higher risk of hip fracture (adjusted OR, 1.19; 95% CI, 1.11 to 1.28). This association remained within subgroups of low, moderate, and high PPI use, yielding adjusted ORs of 1.16 (95% CI, 1.06 to 1.27), 1.21 (95% CI, 1.11 to 1.31), and 1.19 (95% CI, 1.08 to 1.31), respectively. Among patients with ESKD on hemodialysis, PPIs and not histamine-2 receptor antagonists were associated with hip fracture events.

Evidence of disordered calcium metabolism in adolescent girls with type 1 diabetes: An observational study using a dual-stable calcium isotope technique

Type 1 diabetes (T1D) is associated with skeletal abnormalities including low bone density and increased fracture risk. The pathophysiology underlying T1D related skeletal fragility remains unknown. The objective of this study was to use a dual-stable calcium isotope method to investigate the effects of T1D on calcium absorption and estimated calcium retention in adolescent females. Twenty adolescent females with T1D were admitted for a 24-h calcium absorption study using oral (44Ca) and intravenous (42Ca) stable isotopes for determination of percent gastrointestinal calcium absorption and estimated calcium retention. Five out of twenty participants were found to have negative estimated calcium retention. Participants with negative calcium retention had greater urinary calcium excretion [202mg/d (IQR: 178–213)] compared to those with positive calcium retention [101.5mg/d (IQR: 82–122)], p=0.01, but similar calcium intake and percent calcium absorption. With the exception of one outlier, 24-h urine calcium was significantly associated with hemoglobin A1c (Pearson's r=0.55, p=0.02). 50% of participants consumed less than the RDA for calcium; fractional calcium absorption was inversely correlated with calcium intake in participants not meeting the RDA (Spearman's rho −0.65, p=0.04). In conclusion, one-quarter of adolescent girls with T1D were found to have negative estimated calcium retention at a time when bone mineral accrual should be ongoing. This appeared to be the result of excess urinary calcium excretion as opposed to diminished gastrointestinal calcium absorption. Insufficient calcium availability for bone deposition during adolescence could impair bone mineral accrual and contribute to skeletal fragility.Trial registered: ClinicalTrials.gov Reg No. NCT03156179

Tetany Secondary to the Use of a Proton-Pump Inhibitor

Introduction: Chronic PPI use has been reported to cause hypocalcemia, bone density loss and osteoporoticrelated fractures but an acute drop in serum calcium level with PPI use is rare. We present a rare case of symptomatic hypocalcemia with 2 weeks use of PPI. Case Report: 61-year-old female with past medical history of hypothyroidism and hypoparathyroidism secondary to thyroidectomy and parathyroidectomy came to the emergency department(ED) with complaints of spasm and twitching of her upper extremities associated with lethargy and difficulty ambulation. 2 weeks prior to this presentation patient had upper endoscopy done for dyspepsia which showed antral erythema and stomach biopsies came back positive for Helicobacter Pylori gastritis. Patient started taking omeprazole after the endoscopy and later she was given antibiotics treatment for Helicobacter Pylori which she started taking three days prior to the ED presentation. Prior to initiate the omeprazole patient's serum calcium was 8.1 mg/DL. The patient has been taking magnesium citrate 200 mg two times a day and calcium carbonate 1200 mg daily with meals since surgery. No recent change in the dosage of these medications. In ED, EKG done showed QT prolongation, serum calcium was 5.7 mg/DL, magnesium was 1.7 mg/DL and albumin was 3.3 g/DL Thyroid function was within normal limit and parathyroid hormone(PTH) was Discussion Gastric acidic PH is required for absorption of the calcium. Calcium carbonate is a widely use form of calcium supplement which become soluble in the gastric acidic PH and then get absorb in the small intestine. PPI increase the gastric PH so decrease the absorption of calcium which later can cause hypocalcemia. This effect is more seen in the patient with low PTH as it plays a key role in maintaining the serum calcium level within normal limit by stimulating bone resorption, renal tubular calcium reabsorption, and by enhancing gastrointestinal absorption of calcium. The patients with hypoparathyroidism when take PPI their serum calcium needs to be closely monitored to avoid the life threatening complication of hypocalcemia and should be advised to take calcium citrate as a calcium supplement which does not require gastric acidic PH.

Zeolite A effect on calcium homeostasis in growing goats.

The purpose of this study was to investigate the influence of 2 different concentrations of zeolite A on calcium homeostasis. Seventeen growing goats were divided into 3 groups. Whereas the control group (5 animals) received no supplementation, 2 treatment groups were supplemented with zeolite A at either 1.2 (6 animals) or 1.6 g/kg BW (6 animals), respectively. Blood and urine samples were continually drawn and bone mineral density was measured weekly by peripheral quantitative computed tomography. After 3 wks, the animals were slaughtered and samples were taken from the rumen, duodenum, and kidneys. Plasma concentrations of phosphate ( < 0.001), magnesium ( < 0.001), and 1.25-dihydroxycholecalciferol ( < 0.01) as well as renal excretion of phosphate ( < 0.05) were significantly lower in the treatment groups compared with the control group. Although bone resorption was increased in both treatment groups ( < 0.05), no alterations in bone structure were detected. Determination of gastrointestinal absorption of calcium by Ussing chamber technique and quantification of RNA and protein expression of genes known to be involved in active calcium absorption did not reveal any stimulating effect of zeolite. Plasma calcium concentrations were not altered, probably because of the sufficient dietary calcium supply. However due to the effects of zeolite on 1,25 dihydroxycholecalciferol, bone metabolism and serum concentrations of phosphate and magenesium shown in the present study, potential negative long-termin effects on the animals should be considered whenever rations with zeolite are designed.

69-Year-Old Woman With Confusion and Fatigue

Resident in Internal Medicine, Mayo School of Graduate Medical Education, Rochester, MN (H.M.K.); Advisor to resident and Consultant in Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN (A.E.K.). A 69-year-old woman presented to her primary care physicianwith a 4-day history of fatigue and dizziness. She was 45 minutes late for her appointment because she had trouble driving to the office. She reported no motor or sensory deficits but had difficulty with coordination. Review of systems was positive for dysuria and urinary frequency. She did not have fever, chills, weight or appetite changes, respiratory, cardiac, or gastrointestinal symptoms, or recent head trauma. The patient’s medical history was remarkable for hypertension, hyperlipidemia, type 2 diabetes mellitus, osteoporosis, and gastroesophageal reflux disease. Medications included metoprolol tartrate, lisinopril with hydrochlorothiazide, lovastatin, cholecalciferol, and as-needed calcium carbonate. She had smoked half a pack of cigarettes per day for 40 years but had quit smoking 6 years previously. She didnot use alcohol or illicit drugs. On examination, the patient was afebrile with a blood pressure of 104/67 mm Hg, heart rate of 76 beats/min, respiratory rate of 17 breaths/min, oxygen saturation of 94% while breathing room air, and body mass index (calculated as weight in kilograms divided by height inmeters squared) of 39 kg/m. Shewas alert and oriented to person, place, and time. Her speech was dysarthric, and she had difficulty following simple commands. Her coordination was impaired with symmetric dysmetria on finger-to-nose testing, heel-kneeshin testing, and rapid alternating movements. Cranial nerves II through XII were intact. Results of motor and sensory examinations were within normal limits. Reflexes were symmetric. Lymph node, thyroid, cardiac, respiratory, gastrointestinal, musculoskeletal, and skin examinations identified no abnormalities.

Corrigendum

CorrigendumCorrigendumPublished Online:01 Mar 2014https://doi.org/10.1152/ajprenal.zh2-7325-corr.2014Original articleMoreSectionsPDF (323 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations Volume 306, January 1, 2014Volume 75. January 1, 2014Behets GJ, Dams G, Damment SJ, Martin P, De Broe ME, D'Haese PC. Differences in gastrointestinal calcium absorption after the ingestion of calcium-free phosphate binders. Am J Physiol Renal Physiol 306: F61–F67, 2014. First published November 6, 2013; doi: 10.1152/ajprenal.00219.2013—On p. F64, Fig. 1 was printed erroneously. The correct version of Fig. 1 and its legend appear below.Fig. 1.Ionized calcium levels (top), calciuria (middle), and phosphaturia (bottom) in animals with normal renal function (NRF) treated for 8 days with phosphate-binding agents followed by a 6-day washout period. *P< 0.05, sevelamer vs. cellulose; °P < 0.05, calcium vs. cellulose.Download figureDownload PowerPointThis article has no references to display. Download PDF Previous Back to Top FiguresReferencesRelatedInformation Related ArticlesDifferences in gastrointestinal calcium absorption after the ingestion of calcium-free phosphate binders 01 Jan 2014American Journal of Physiology-Renal Physiology More from this issue > Volume 306Issue 5March 2014Pages F568-F568 Copyright & PermissionsCopyright © 2014 the American Physiological Societyhttps://doi.org/10.1152/ajprenal.zh2-7325-corr.2014History Published online 1 March 2014 Published in print 1 March 2014 Metrics

Effects of 25-hydroxyvitamin D3 on localisation and extent of gastrointestinal calcium absorption in dairy cattle

The combination of 25-hydroxyvitamin D3 (25-OHD3) and a diet negative in dietary cation anion difference (DCAD) has recently been shown to have beneficial effects on peripartal calcium (Ca) homeostasis in dairy cows. To further elucidate the underlying mechanisms, it was the aim of the experiments to investigate the effects of 25-OHD3 in combination with DCAD values about –70 meq/kg DM on pre-duodenal and overall gastrointestinal Ca absorption. A group of six ruminally fistulated lactating cows equipped with a cannula in the proximal duodenum were assigned to three dietary treatments (Control diet, anionic salts, anionic salts +25-OHD3) of 5 weeks each. Urine and faeces were collected quantitatively and flow of duodenal contents was calculated by applying chromium oxide. Blood samples were taken at regular intervals. Treatment with anionic salts and 25-OHD3 resulted in an increased Ca net absorption from the total gastrointestinal tract, which was mainly due to respective increases in intestinal Ca absorption. Furthermore, anionic salts and 25-OHD3-treated animals had significantly higher plasma phosphate concentrations and lower plasma levels of CrossLaps and the overall net absorption of phosphorus was significantly higher in these animals. From these data, it can be concluded that anionic salts in combination with 25-OHD3 positively influence the overall net Ca and phosphorus absorption, which is obviously associated with a reduced mobilisation of bone minerals as indicated by decreases in plasma CrossLaps concentrations.

Differences in gastrointestinal calcium absorption after the ingestion of calcium-free phosphate binders

Both calcium-containing and noncalcium-containing phosphate binders can increase gastrointestinal calcium absorption. Previously, we observed that lanthanum carbonate administration to rats with renal failure is not associated with increased calciuria. Additionally, lanthanum carbonate treatment in dialysis patients has been associated with a less pronounced initial decrease in serum parathyroid hormone compared with other phosphate binders. For 8 days, male Wistar rats received a diet supplemented with 2% lanthanum carbonate, 2% sevelamer, 2% calcium carbonate, or 2% cellulose. Calciuria was found to be increased in animals with normal renal function treated with sevelamer or calcium carbonate but not with lanthanum carbonate. In animals with renal failure, cumulative calcium excretion showed similar results. In rats with normal renal function, serum ionized calcium levels were increased after 2 days of treatment with sevelamer, while calcium carbonate showed a smaller increase. Lanthanum carbonate did not induce differences. In animals with renal failure, no differences were found between sevelamer-treated, calcium carbonate-treated, and control groups. Lanthanum carbonate, however, induced lower ionized calcium levels within 2 days of treatment. These results were confirmed in normal human volunteers, who showed lower net calcium absorption after a single dose of lanthanum carbonate compared with sevelamer carbonate. In conclusion, these two noncalcium-containing phosphate-binding agents showed a differential effect on gastrointestinal calcium absorption. These findings may help to improve the management of calcium balance in patients with renal failure, including concomitant use of vitamin D.

Hereditary hypophosphatemic rickets with hypercalciuria and nephrolithiasis—Identification of a novel SLC34A3/NaPi‐IIc mutation

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is characterized by rickets, hyperphosphaturia, hypophosphatemia, elevated 1,25-dihydroxyvitamin-D, increased gastrointestinal calcium absorption and hypercalciuria. Serum calcium, 25-hydroxyvitamin-D and PTH levels are normal. Here we describe a boy with HHRH, nephrolithiasis, and compound heterozygosity for one previously described mutation (g.4225_50del) and a novel splice mutation (g.1226G>A) in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. The patient's mother and grandmother are carriers of g.4225_50del, and both have a history of nephrolithiasis associated with hypercalciuria and elevated 1,25-dihydroxyvitamin-D. His three siblings (2-6 years old), who are also carriers of g.4225_50del, have hypercalciuria but so far their renal ultrasounds are normal. Thus, SLC34A3/NaPi-IIc mutations appear to be associated with variable phenotypic changes at presentation, which can include recurrent nephrolithiasis.

Gastrointestinal calcium absorption in sheep is mostly insensitive to an alimentary induced challenge of calcium homeostasis

For ruminants, marked differences to monogastric species have been described concerning the localisation and vitamin D sensitivity of gastrointestinal calcium absorption, particularly with respect to the forestomach compartment. Therefore, we investigated gastrointestinal calcium transport of sheep as influenced by a dietary calcium restriction and/or a supraphysiological dosage of exogenous calcitriol. Using the Ussing chamber technique, we determined calcium and mannitol flux rates to differentiate between para- and transcellular calcium transport in rumen, duodenum, jejunum and colon. Expression of epithelial calcium channels, calbindin-D(9K), and basolateral extrusion mechanisms was determined by quantitative RT-PCR and Western blot analysis. Active calcium transport could be demonstrated in jejunum and rumen. A significant stimulation of jejunal calcium absorption was only observed in animals treated with calcitriol. The alimentary calcium restriction alone did not result in significant effects indicating a less effective intestinal adaptation to alimentary calcium restriction than observed in monogastric animals. The observed ruminal calcium transport was not affected at all, neither by the diet nor the calcitriol treatment. Furthermore, no significant expression of epithelial calcium channels or calbindin-D(9K) could be detected in the rumen; therefore it is concluded that calcium transport in the forestomachs is probably mediated by a different, so far unknown mechanism.

Gastrointestinal calcium absorption after ingestion of non calcium containing phosphate binders

Gastrointestinal calcium absorption after ingestion of non calcium containing phosphate binders