cholecalciferol and Hypercalcemia

Vitamin D deficiency (<20 ng/mL) and insufficiency (20-29 ng/mL) are common among patients with chronic kidney disease (CKD) or undergoing dialysis. In addition to nutritional and sunlight exposure deficits, factors that affect vitamin D deficiency include race, sex, age, obesity and impaired vitamin D synthesis and metabolism. Serum 1,25(OH)₂D levels also decrease progressively because of 25(OH)D deficiency, together with impaired availability of 25(OH)D by renal proximal tubular cells, high fibroblast growth factor (FGF)-23 and decreased functional renal tissue. As in the general population, this condition is associated with increased morbidity and poor outcomes. Together with the progressive decline of serum calcitriol, vitamin D deficiency leads to secondary hyperparathyroidism (SHPT) and its complications, tertiary hyperparathyroidism and hypercalcemia, which require surgical parathyroidectomy or calcimimetics. Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease Improving Global Outcomes (KDIGO) experts have recognized that vitamin D insufficiency and deficiency should be avoided in CKD and dialysis patients by using supplementation to prevent SHPT. Many vitamin D supplementation regimens using either ergocalciferol or cholecalciferol daily, weekly or monthly have been reported. The benefit of native vitamin D supplementation remains debatable because observational studies suggest that vitamin D receptor activator (VDRA) use is associated with better outcomes and it is more efficient for decreasing the serum parathormone (PTH) levels. Vitamin D has pleiotropic effects on the immune, cardiovascular and neurological systems and on antineoplastic activity. Extra-renal organs possess the enzymatic capacity to convert 25(OH)D to 1,25(OH)₂D. Despite many unanswered questions, much data support vitamin D use in renal patients. This article emphasizes the role of native vitamin D replacement during all-phases of CKD together with VDRA when SHPT persists.

Topics: Cholecalciferol; Dialysis; Dietary Supplements; Ergocalciferols; Fibroblast Growth Factor-23; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Parathyroid Hormone; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Vitamin D Deficiency

Public concern over vitamin D deficiency has led to widespread use of over the counter (OTC) vitamin D (-D3 or -D2) supplements, containing up to 10,000 IU/unit dose (400 IU=10μg). Overzealous use of such supplements can cause hypercalcemia due to vitamin D toxicity. Infants are particularly vulnerable to toxicity associated with vitamin D overdose. OTC supplements are not subject to stringent quality control regulations from FDA and high degree of variability in vitamin D content in OTC pills has been demonstrated. Other etiologies of vitamin D induced hypercalcemia include hyperparathyroidism, granulomatous malignancies like sarcoidosis and mutations in the CYP24A1 gene. The differential diagnosis of hypercalcemia should include iatrogenic and genetic etiologies. C24-hydroxylation and C3-epimerization are two important biochemical pathways via which 25-hydroxyvitamin D3 (25(OH)D3) is converted to its metabolites, 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or its C3 epimer, 3-epi-25-OH-D3 respectively. Mutations in the CYP24A1 gene cause reduced serum 24,25(OH)2D3 to 25(OH)D3 ratio (<0.02), elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D3), hypercalcemia, hypercalciuria and nephrolithiasis. Studies in infants have shown that 3-epi-25(OH)D3 can contribute 9-61.1% of the total 25(OH)D3. Therefore, measurements of parathyroid hormone (PTH) and vitamin D metabolites 25(OH)D3, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3 are useful to investigate whether the underlying cause of vitamin D toxicity is iatrogenic versus genetic. Here we report a case of vitamin D3 associated toxicity in a 4-month-old female who was exclusively breast-fed and received an oral liquid vitamin D3 supplement at a dose significantly higher than recommended on the label. The vitamin D3 content of the supplement was threefold higher (6000 IU of D/drop) than listed on the label (2000 IU). Due to overdosing and higher vitamin D3 content, the infant received ∼50,000 IU/day for two months resulting in severe hypercalcemia, hypercalciuria and nephrocalcinosis. We also review the relevant literature on vitamin D3 toxicity in this report.

Topics: Cholecalciferol; Dietary Supplements; Female; Humans; Hypercalcemia; Hypercalciuria; Iatrogenic Disease; Infant; Nephrocalcinosis; Vitamins

The primary source of exposure to cholecalciferol in dogs and cats is ingestion of rodenticide baits with vitamin D3 as the active ingredient. Other sources of this toxin are human medications and rarely, contaminated pet food. Although the reported lethal dose 50% for cholecalciferol is 88 mg/kg, deaths have been seen with an individual exposure of 2 mc g/kg in dogs. Clinical signs are induced by profound hypercalcemia affecting multiple body systems. Clinical presentations may include anorexia, depression, muscle weakness, vomiting, polyuria, polydipsia, dehydration, abdominal pain, hematemesis, melena, and bradycardia. Tissue mineralization may develop if calcium × phosphorous product is greater than 60. Serum testing for hypercalcemia, hyperphosphatemia, and decreased serum parathyroid hormone are confirmatory. Initial treatment relies upon decontamination with emesis induction followed by administration of pulse-dose activated charcoal designed to interfere with the extensive enterohepatic recirculation of toxin. Medical management is designed to decrease serum calcium levels by use of intravenous fluid diuresis with administration of furosemide and prednisolone. Biphosphate pamidronate is used to inhibit calcium release from the bone. Phosphate binders aid in decreasing phosphate availability to interact with calcium. The prognosis is better if treatment is instituted early before development of hypercalcemia and hyperphosphatemia enables tissue mineralization to progress.

Topics: Animals; Cat Diseases; Cats; Cholecalciferol; Dog Diseases; Dogs; Hypercalcemia; Pets; Poisoning; Rodenticides

Vitamin D3 shows a multitude of possible preventive effects in various diseases. Calcitriol, the biologically active form of vitamin D3, affects not only bone metabolism but also acts on the renal renin secretion, the pancreatic insulin production in the beta cells, growth and proliferation of smooth and cardiac muscle cells and the function of lymphocytes and macrophages. Although the human body can synthesise vitamin D3 itself, vitamin D deficiency is common in the German population. Numerous trials studied the association between vitamin D deficiency and different diseases. It is known that even mild forms of vitamin D deficiency increase the risk for cardiovascular diseases or diabetes mellitus. Furthermore, an association with cancer such as pancreatic or colorectal cancer was observed. This is attributed to the influence of vitamin D on cell differentiation, angiogenesis, DNA repair mechanisms and the transcription of numerous genes. In addition, effects of vitamin D deficiency in diseases such as Parkinson's disease, multiple sclerosis and autoimmune diseases are discussed. However, up to now the level of evidence of all these observations is low. There are missing confirmatory randomized controlled trials. Noting the possible preventive effects of vitamin D, a moderate exposure to sunlight to increase vitamin D synthesis can be recommended. Even a controlled supplementation of vitamin D in patients with vitamin D deficiency is considered as reasonable. However, an uncritical substitution of high-dose vitamin D should be avoided because of the risk of hypercalcaemia.

Topics: Calcitriol; Cholecalciferol; Dose-Response Relationship, Drug; Health Promotion; Hypercalcemia; Primary Prevention; Sunlight; Vitamin D; Vitamin D Deficiency

Calcitriol-mediated hypercalcemia resulting from elevated extrarenal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase) activity has not previously been described in giant cell polymyositis.. We report an unusual case of hypercalcemia due to disseminated granulomatous disease in a 62-yr-old woman with profound proximal muscle weakness and weight loss. She was initially diagnosed with vitamin D deficiency myopathy with a low serum 25-hydroxyvitamin D; serum calcium at this time was low-normal. Vitamin D(3) 3000 IU daily was prescribed. One month later, blood work showed new hypercalcemia and hypercalciuria with normalized 25-hydroxyvitamin D. 1,25-dihydroxyvitamin D was high-normal, despite a suppressed PTH, undetectable PTHrP, and essentially normal renal function. Her hypercalcemia resolved, and her strength improved only after prednisone was added to bisphosphonate therapy. Two weeks later, she died from acute congestive heart failure.. Autopsy revealed a disseminated giant cell myositis affecting skeletal, cardiac, and gastrointestinal smooth muscle. Immunohistochemistry localized 1alpha-hydroxylase to the inflammatory infiltrates in skeletal and cardiac muscle.. A review of English publications in Medline and Embase, including a reference search of retrieved articles, revealed that calcitriol-mediated hypercalcemia has been described in over 30 conditions, most of which are granulomatous in nature, ranging from inflammatory conditions and foreign body exposures to infections and neoplasms.. Hypercalcemia resulting from autonomous 1alpha-hydroxylase activity may be unmasked by low-dose vitamin D supplementation and should not be excluded from the differential diagnosis of nonparathyroid causes if the serum calcitriol is inappropriately normal, rather than frankly elevated.

Topics: Calcitriol; Cholecalciferol; Fatal Outcome; Female; Heart Failure; Humans; Hypercalcemia; Middle Aged; Neurologic Examination; Polymyositis; Vitamin D Deficiency

Serum parathyroid hormone concentrations decrease progressively during the first 3 to 6 month after successful renal transplantation. However 1 year after transplantation, persistent hyperparathyroidism is common. Hypercalcemia due to persistent hyperparathyroidism cause graft dysfunction and cardiovascular calcification. Renal transplant recipients with persistent hyperparathyroidism need treatment with vitamin D and calcium, in some cases parathyroidectomy has to be considered.

Topics: Calcinosis; Calcium; Cardiovascular Diseases; Cholecalciferol; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Kidney Transplantation; Parathyroidectomy

Topics: Bone Density Conservation Agents; Cardiovascular Diseases; Cholecalciferol; Diphosphonates; Gastrointestinal Diseases; Hot Flashes; Humans; Hypercalcemia; Jaw Diseases; Macular Edema; Necrosis; Osteoporosis; Raloxifene Hydrochloride; Venous Thrombosis

Glucocorticoid-induced osteoporosis (GIO) is the most common secondary cause of osteoporosis. The use of glucocorticoid (GC) is associated with an increase in bone loss, especially at vertebral spine, and risk of fracture. Active vitamin D(3) (VD(3)) is expected to preserve bone mineral density at vertebral spine, however it is inferior to bisphosphonates (BP) with respect to preventing incidental vertebral fractures. In the guidelines on the management and treatment of GIO in Japan, VD(3) is recommended as the second-lined drug for GIO. The combination of VD(3) and BP is thought to be a beneficial therapy in prevention and or treatment of GIO.

Topics: Anti-Inflammatory Agents; Bone Density; Cholecalciferol; Diphosphonates; Drug Therapy, Combination; Glucocorticoids; Humans; Hypercalcemia; Lumbar Vertebrae; Osteoporosis; Practice Guidelines as Topic; Randomized Controlled Trials as Topic

Topics: Animals; Antibodies; Cholecalciferol; Diagnosis, Differential; Humans; Hypercalcemia; Osteoprotegerin; Palliative Care; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone-Related Protein; Prognosis

In Japan, insufficient calcium (Ca) intake is serious problem for health which may be associated with the high prevalence of osteoporosis among the aged. The intake of most nutrients has been sufficient, however, the Ca intake has never been sufficient. Eggshell Ca has as much as 38% of Ca and low phosphorus content. Eggshell Ca was more soluble than Ca carbonate and was as much as milk products. Eggshell Ca has been shown to exhibit higher absorptivity and availability than Ca carbonate. Furthermore, it has been reported that eggshell Ca is more effective in increasing bone mineral density in ovariectomized osteoporotic rats. These results suggest that eggshell Ca could be beneficial for bone and we propose Ca fortified foods which contain eggshell Ca as a nutraceutical.

Topics: Animals; Bone Density; Bone Resorption; Calcium; Cholecalciferol; Drug Therapy, Combination; Egg Shell; Humans; Hypercalcemia; Intestinal Absorption; Osteoporosis; Parathyroid Hormone; Rats; Solubility

Topics: Biomarkers; Calcium; Cholecalciferol; Dementia; Humans; Hypercalcemia; Hyperparathyroidism; Hyperparathyroidism, Secondary; Hypocalcemia; Hypothyroidism; Parathyroid Hormone; Parathyroidectomy; Phosphorus

Nephrocalcinosis is used to describe renal parenchymal calcification. Causes of nephrocalcinosis include persistent hypercalcemia, hypercalciuria, acid-base disorders, hyperoxaluria and urinary stasis. Patients with nephrocalcinosis initially present no symptom. However, advanced nephrocalcinosis is irreversible and causes impaired renal function. Therefore, careful observation for the presence and progression of nephrocalcinosis is necessary for patients who have risk factors for this disorder.

Topics: Acid-Base Imbalance; Calcium; Cholecalciferol; Humans; Hypercalcemia; Hyperoxaluria; Hyperparathyroidism; Nephrocalcinosis; Risk Factors; Urinary Retention

The etiology, pathophysiology, and diagnosis of hypercalcemia associated with malignant diseases are discussed. In humans, calcium is controlled by three mechanisms: parathyroid hormone, which regulates bone resorption and renal reabsorption of calcium; calcitonin, an antagonist of parathyroid hormone; and cholecalciferol, which regulates calcium absorption from the gastrointestinal tract. Hypercalcemia of malignancy (HCM) results primarily from increased bone resorption by osteoclasts and, to a lesser extent, from increased renal tubular reabsorption. In most tumors, parathyroid hormone-related protein (PTHrP) is the primary mediator of calcium. PTHrP stimulates increased bone resorption by osteoclasts. This stimulation also activates transforming growth factor-beta (TGF-beta), which stimulates tumor cells, thus perpetuating the cycle. Hypercalcemia is usually defined as a serum calcium concentration greater than 12 mg/dL, corrected for the serum albumin concentration. In diagnosing HCM, it is important to rule out other causes of hypercalcemia, such as primary hyperparathyroidism.

Topics: Bone Resorption; Breast Neoplasms; Calcitonin; Calcium; Cholecalciferol; Female; Hematologic Neoplasms; Homeostasis; Humans; Hypercalcemia; Kidney; Lung Neoplasms; Male; Multiple Myeloma; Neoplasms; Parathyroid Hormone

Chronic renal failure is characterized by diminished synthesis of, and resistance to, the active vitamin D metabolite 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3, calcitriol). Calcitriol results from the biotransformation of the precursor 25-hydroxy-vitamin D3 (25(OH)D3) to 1,25(OH)2D3. 25(OH)D3 is synthesized in the liver, and 1alpha-hydroxylase, the rate-limiting enzyme for its biotransformation into the most active metabolite, 1,25(OH)2D3, is located in the kidney. The regulation of 1alpha-hydroxylase in renal failure is not well known. Recent work indicates that, in contrast to previous opinion, 1alpha-hydroxylase is predominantly expressed not in the proximal tubule but in the distal tubule [1]. In vivo, the main stimulatory signal is presumably parathyroid hormone (PTH) and the main inhibitory signal hyperphosphataemia. Both signals are altered in renal failure. There is also evidence that the renal 1alpha-hydroxylase becomes substrate-dependent in patients with renal failure. This means that a higher concentration of the precursor 25(OH)2D3 will result in a higher rate of transformation into the active metabolite 1,25(OH)2D3 in renal patients. Calcitriol is not exclusively synthesized in the kidney, but may also be synthesized in extra-renal tissues, e.g. activated monocytes/macrophages [2], particularly in granuloma [3] as shown by anephric uraemic patients who develop hypercalcaemia and elevated calcitriol concentrations when sarcoidosis [4] or tuberculosis [5] supervenes. On the other hand, calcitriol is less effective in uraemia. This may be to some extent due to diminished expression of vitamin D receptors [6], particularly in parathyroid glands when they undergo nodular transformation [7], but there may also be resistance to calcitriol at the post-receptor level [8]. In a series of elegant experiments [9,10], calcitriol resistance has been related to disturbed genomic effects of active vitamin D because the interaction of the vitamin D receptor ligand complex with vitamin D-responsive elements (VDREs) upstream of vitamin D-regulated genes was disturbed by the action of low molecular weight substances in uraemia, which have not been completely characterized. The role of genetically determined polymorphisms of the vitamin D receptor in the genesis of disturbed calcium metabolism of renal failure is currently unclear.

Topics: Animals; Biomarkers; Calcitriol; Calcium; Calcium Channel Agonists; Cholecalciferol; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hypocalcemia; Parathyroid Hormone; Uremia

To provide further understanding of humoral hypercalcemia in Hodgkin's disease (HD) the authors describe the clinical features and laboratory investigation of three patients recently treated at Massachusetts General Hospital. All were middle-aged men who presented with symptomatic hypercalcemia which led to a diagnosis of bulky intraabdominal HD. None had evidence of bone involvement or hyperparathyroidism. In the two cases tested 1,25(OH)2D3 was elevated at the time of diagnosis. These characteristics are remarkably similar to those of ten patients with HD and probable humoral hypercalcemia described in the literature. The diagnosis of HD was supported in Cases 1 and 3 by genomic blot analysis which showed no evidence of T-cell or B-cell tumor origin. In an in vitro assay, primary tumor medium from Case 1 stimulated dose-dependent bone resorption which was not entirely ascribable to 1,25(OH)2D3. The authors conclude that humoral hypercalcemia in HD predominantly affects males of middle age, that intraabdominal bulky disease is common, and that hypercalcemia appears to be mediated by tumor related production of 1,25(OH)2D3 in concert with a second factor.

Topics: Adult; Aged; Antigens, Differentiation; Antigens, Surface; Cholecalciferol; DNA, Neoplasm; Hodgkin Disease; Humans; Hypercalcemia; Male; Middle Aged; Paraneoplastic Endocrine Syndromes

Topics: Alkalosis; Benzothiadiazines; Calcinosis; Cholecalciferol; Diuretics; Humans; Hypercalcemia; Hyperparathyroidism; Isotretinoin; Lithium; Osteitis Deformans; Sarcoidosis; Sodium Chloride Symporter Inhibitors; Tamoxifen; Tretinoin; Vitamin A

Topics: Animals; Calcium; Cholecalciferol; Diphosphates; Glomerular Filtration Rate; Humans; Hydroxycholecalciferols; Hypercalcemia; Kidney Failure, Chronic; Mitochondria, Liver; Parathyroid Glands; Parathyroid Hormone; Phosphates; Rats

Topics: Animals; Calcitonin; Calcium; Calcium Metabolism Disorders; Cholecalciferol; Diuretics; Extracellular Space; Glomerular Filtration Rate; Glomerulonephritis; Hypercalcemia; Kidney; Kidney Concentrating Ability; Kidney Diseases; Kidney Failure, Chronic; Metabolic Clearance Rate; Mineralocorticoids; Parathyroid Hormone; Sodium

Topics: Calcium; Calcium Metabolism Disorders; Cholecalciferol; Cushing Syndrome; Diagnosis, Differential; Fanconi Syndrome; Fractures, Bone; Glomerular Filtration Rate; Humans; Hypercalcemia; Hyperparathyroidism; Hyperthyroidism; Kidney Calculi; Nephrocalcinosis; Osteitis Deformans; Osteoporosis; Parathyroid Hormone; Sarcoidosis

Topics: Animals; Biological Transport; Calcium; Cholecalciferol; Dactinomycin; Dihydroxycholecalciferols; Ethane; Homeostasis; Hydroxycholecalciferols; Hydroxylation; Hypercalcemia; Hypocalcemia; Intestinal Mucosa; Kidney; Mitochondria; Mitochondrial Swelling; Mixed Function Oxygenases; Organophosphonates; Parathyroid Hormone; Phosphorus; Vitamin D; Vitamin D Deficiency

Topics: Aortic Valve Stenosis; Calcium; Calcium Metabolism Disorders; Cholecalciferol; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hypercalcemia; Hypophosphatemia, Familial; Infant; Kidney; Nutritional Requirements; Pregnancy; Skin; Vitamin D; Vitamin D Deficiency

Topics: Acetates; Animals; Bone and Bones; Bone Resorption; Calcitonin; Cholecalciferol; Depression, Chemical; Femur; Hypercalcemia; Male; Parathyroid Glands; Radiography; Rats; Secretory Rate; Spine; Strontium Isotopes; Vitamin A; Vitamin D

Topics: Animals; Child; Cholecalciferol; Germany, West; Humans; Hypercalcemia; Milk; Prognosis; Radiation Effects; Rickets; Vitamin D

Observational studies suggest that vitamin D deficiency among people living with HIV is associated with a greater risk of disease progression and death. Low levels of vitamin D in pregnancy are also associated with poor fetal and infant growth. Therefore, vitamin D supplementation may improve clinical outcomes for pregnant women living with HIV and improve fetal and postnatal growth for their infants.. We conducted a randomized, triple-blind, placebo-controlled trial of vitamin D3 supplementation among pregnant and lactating women living with HIV in Dar es Salaam, Tanzania (ClinicalTrials.gov NCT02305927). Participants were randomized with 1:1 allocation stratified by study clinic to receive either daily 3,000 IU vitamin D3 supplements or matching placebo supplements from the second trimester of pregnancy (12-27 weeks) until 1 year postpartum. The primary outcomes were (i) maternal HIV progression or death, (ii) small-for-gestational-age (SGA) live births (<10th percentile), and (iii) infant stunting at 1 year of age (length-for-age z-score < -2). We also examined the effect of vitamin D3 supplementation on secondary maternal and infant health outcomes, maternal and infant serum 25-hydroxyvitamin D (25[OH]D) concentrations, and maternal hypercalcemia. An intent-to-treat analysis was used as the primary analytic approach. We enrolled 2,300 pregnant women between June 15, 2015, and April 17, 2018, and follow-up of mothers and infants was completed on October 20, 2019. There were 1,148 pregnant women randomly assigned to the vitamin D3 group, and 1,152 to the placebo group. The proportion of mothers lost to follow-up at 1 year postpartum was 6.6% in the vitamin D3 group (83 of 1,148) and 6.6% in the placebo group (76 of 1,152). The proportion of children lost to follow-up at 1 year of age was 5.5% in the vitamin D3 group (59 of 1,074 live births) and 5.2% in the placebo group (57 of 1,093 live births). There was no difference in the risk of maternal HIV progression or death, with 166 events during 1,461 person-years of follow-up in the vitamin D3 group and 141 events during 1,469 person-years of follow-up in the placebo group (hazard ratio 1.21, 95% CI 0.97 to 1.52, p = 0.09). There was no difference in the risk of SGA birth between the vitamin D3 (229 SGA births among 1,070 live births) and placebo groups (236 SGA births among 1,091 live births) (relative risk 1.03, 95% CI 0.87 to 1.22, p = 0.70). There was also no difference in the risk of infant stunting at 1 year of age between the vitamin D3 (407 events among 867 infants) and placebo groups (413 events among 873 infants) (relative risk 1.00, 95% CI 0.92 to 1.10, p = 0.95). In terms of adverse events, no cases of maternal hypercalcemia were identified. One hypersensitivity reaction to the trial supplements occurred for a pregnant woman in the placebo group. A limitation of our study is that our finding. The trial findings do not support routine vitamin D supplementation for pregnant and lactating women living with HIV in Tanzania.. ClinicalTrials.gov Identifier: NCT02305927.

Topics: Child; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Growth Disorders; HIV Infections; Humans; Hypercalcemia; Infant; Lactation; Pregnancy; Tanzania; Vitamin D; Vitamin D Deficiency

The optimal treatment regimen for correcting 25-hydroxyvitamin D (25OHD) deficiency in children with chronic kidney disease (CKD) is not known. We compared cholecalciferol dosing regimens for achieving and maintaining 25OHD concentrations ≥30 ng/mL in children with CKD stages 2-4.. An open-label, multicentre randomized controlled trial randomized children with 25OHD concentrations <30 ng/mL in 1:1:1 to oral cholecalciferol 3000 IU daily, 25 000 IU weekly or 100 000 IU monthly for 3 months (maximum three intensive courses). In those with 25OHD ≥30 ng/mL, 1000 IU cholecalciferol daily (maintenance course) was given for up to 9 months. Primary outcome was achieving 25OHD ≥30 ng/mL at the end of intensive phase treatment.. Ninety children were randomized to daily (n = 30), weekly (n = 29) or monthly (n = 31) treatment groups. At the end of intensive phase, 70/90 (77.8%) achieved 25OHD ≥30 ng/mL; 25OHD concentrations were comparable between groups (median 44.3, 39.4 and 39.3 ng/mL for daily, weekly and monthly groups, respectively; P = 0.24) with no difference between groups for time to achieve 25OHD ≥30 ng/mL (P = 0.28). There was no change in calcium, phosphorus and parathyroid hormone, but fibroblast growth factor 23 (P = 0.002) and klotho (P = 0.001) concentrations significantly increased and were comparable in all treatment groups. Irrespective of dosing regimen, children with glomerular disease had 25OHD concentrations lower than non-glomerular disease (25.8 versus 41.8 ng/mL; P = 0.007). One child had a 25OHD concentration of 134 ng/mL, and 5.5% had hypercalcemia without symptoms of toxicity.. Intensive treatment with oral cholecalciferol as daily, weekly or monthly regimens achieved similar 25OHD concentrations between treatment groups, without toxicity. Children with glomerular disease required higher doses of cholecalciferol compared with those with non-glomerular disease.

Topics: Child; Cholecalciferol; Dietary Supplements; Humans; Hypercalcemia; Parathyroid Hormone; Renal Insufficiency, Chronic; Vitamin D Deficiency

This trial aimed to analyze the relationship between hyperthyroidism and the morbidity rate of hypercalcemia in the Xindu district, Chengdu, Sichuan province. We observed the level of serum calcium, the bone metabolic and thyroid autoimmune-related antibodies index during vitamin D3 treatment combined with traditional antithyroid drugs (ATD).. Our research included hyperthyroid patients with a first-time diagnosis of Graves diseases (GD) combined with hypercalcemia on the basis of conventional anti-hyperthyroidism therapy, which were randomized into a vitamin D3 group (vitamin D3, 800-1,200 IU/day) and an ATD group (methimazole, 15-30 mg/day). All hyperthyroidism patients with hypercalcemia were analyzed, and changes in serum calcium (Ca2+), parathyroid hormone (PTH), thyroid function, thyroid autoimmune-related antibodies, and 25-dihydroxyvitamin D (25-OHVit D) levels during treatment of thyrotoxicosis with added vitamin D3 were explored.. In total, 184 patients with hyperthyroidism were observed, including 36 (19.57%) patients associated with hypercalcemia, with an age of onset of (56.39±5.80) years old. Twelve (6.52%) of these 36 cases reported digestive symptoms as the first manifestation, and four (2.17%) patients presented with a hypercalcemia crisis as the first manifestation. Serum Ca2+, free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin hormone receptor antibody (TRAb) levels increased in patients with hypercalcemia. Following the addition of vitamin D3 treatment, serum Ca2+, FT3, FT4, and TRAb levels were significantly decreased relative to the ATD group, while the thyroid-stimulating hormone (TSH), PTH, and 25-OHVit D levels were normalized.. Our study highlighted the importance of taking functional digestive disturbance into consideration in hyperthyroidism diagnosis, even in the absence of the typical symptoms. The level of thyroid related antibodies, thyroid function, and bone metabolism in hyperthyroidism patients combined with hypercalcemia could be improved by vitamin D3 adjuvant therapy.. Chinese Clinical Trial Registry: ChiCTR2100047870.

Topics: Cholecalciferol; Graves Disease; Humans; Hypercalcemia; Hyperthyroidism; Middle Aged; Prevalence

Evidence suggests that low vitamin D status may increase the risk of cancer.. To determine if dietary supplementation with vitamin D3 and calcium reduces the risk of cancer among older women.. A 4-year, double-blind, placebo-controlled, population-based randomized clinical trial in 31 rural counties (June 24, 2009, to August 26, 2015-the final date of follow-up). A total of 2303 healthy postmenopausal women 55 years or older were randomized, 1156 to the treatment group and 1147 to the placebo group. Duration of treatment was 4 years.. The treatment group (vitamin D3 + calcium group) received 2000 IU/d of vitamin D3 and 1500 mg/d of calcium; the placebo group received identical placebos.. The primary outcome was the incidence of all-type cancer (excluding nonmelanoma skin cancers), which was evaluated using Kaplan-Meier survival analysis and proportional hazards modeling.. Among 2303 randomized women (mean age, 65.2 years [SD, 7.0]; mean baseline serum 25-hydroxyvitamin D level, 32.8 ng/mL [SD, 10.5]), 2064 (90%) completed the study. At year 1, serum 25-hydroxyvitamin D levels were 43.9 ng/mL in the vitamin D3 + calcium group and 31.6 ng/mL in the placebo group. A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89%) in the vitamin D3 + calcium group and 64 (5.58%) in the placebo group (difference, 1.69% [95% CI, -0.06% to 3.46%]; P = .06). Kaplan-Meier incidence over 4 years was 0.042 (95% CI, 0.032 to 0.056) in the vitamin D3 + calcium group and 0.060 (95% CI, 0.048 to 0.076) in the placebo group; P = .06. In unadjusted Cox proportional hazards regression, the hazard ratio was 0.70 (95% CI, 0.47 to 1.02). Adverse events potentially related to the study included renal calculi (16 participants in the vitamin D3 + calcium group and 10 in the placebo group), and elevated serum calcium levels (6 in the vitamin D3 + calcium group and 2 in the placebo group).. Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/mL, supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years. Further research is necessary to assess the possible role of vitamin D in cancer prevention.. clinicaltrials.gov Identifier: NCT01052051.

Topics: Aged; Calcium; Cholecalciferol; Double-Blind Method; Female; Humans; Hypercalcemia; Incidence; Intention to Treat Analysis; Kaplan-Meier Estimate; Kidney Calculi; Middle Aged; Nebraska; Neoplasms; Osteoporosis, Postmenopausal; Proportional Hazards Models; Sample Size; Time Factors; Vitamin D; Vitamins

Vitamin D supplementation is widely recommended for infants, but the optimal dose remains unclear. High intake may result in hypercalcemia.. We evaluated the incidence of hypercalcemia during the first year of life in a cohort of 987 healthy children who received 10 or 30 μg of vitamin D3 supplementation daily. Ionized calcium (Ca-ion) was analyzed at 6 and 12 months, and serum 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentration at 12 months. Severe hypercalcemia was defined as Ca-ion exceeding the reference limit (1.16-1.39 mmol/L) by 10%.. No severe hypercalcemia occurred. Mild hypercalcemia (1.40-1.52 mmol/L) was present at 6 months in 28% and at 12 months in 2% of infants. At 12 months, 25-OHD ranged between 23 and 241 nmol/L (median 97), and PTH was between undetectable and 104 pg/mL (median 24) and was below the reference range (11.5-78.4 pg/mL) in 11%. 25-OHD and Ca-ion correlated positively (r = 0.149), and 25-OHD was slightly higher in the 12 infants with mild hypercalcemia (median 97 vs. 110 nmol/L, p = 0.046).. Vitamin D3 supplementation of 10 or 30 µg did not cause severe hypercalcemia. Mild hypercalcemia was more prevalent at 6 months than at 12 months, and was associated weakly with 25-OHD at 12 months.

Topics: Calcium; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Hypercalcemia; Incidence; Infant; Infant, Newborn; Male; Prevalence; Rickets

Improving vitamin D (25-OHD) status may be an important modifiable factor that could reduce disability severity, fall-rates and mortality associated after hip fracture surgery. Providing a loading-dose post-surgery may overcome limitations in adherence to daily supplementation.. In this randomized, double-blind, placebo-controlled trial, 218 adults, aged 65-years or older, requiring hip fracture surgery were assigned to receive a single loading-dose of cholecalciferol (250,000 IU vitamin-D3, the REVITAHIP - Replenishment of Vitamin D in Hip Fracture strategy) or placebo, both receiving daily vitamin-D(800 IU) and calcium (500 mg) for 26-weeks. Outcome measures were 2.4 m gait-velocity, falls, fractures, death (Week-4), 25-OHD levels, quality-of-life measure (EuroQoL) and mortality at weeks-2, 4 and 26.. Mean age of 218 participants was 83.9(7.2) years and 77.1 % were women. Baseline mean 25-OHD was 52.7(23.5)nmol/L, with higher levels at Week-2 (73 vs 66 nmol/L; p = .019) and Week-4 (83 vs 75 nmol/L; p = .030) in the Active-group, but not at Week-26. At week-4, there were no differences in 2.4 m gait-velocity (0.42 m/s vs 0.39 m/s, p = .490), fractures (2.7 % vs 2.8 %, p = .964) but Active participants reported less falls (6.3 % vs 21.1 %, χ(2) = 4.327; p = 0.024), with no significant reduction in deaths at week-4 (1 vs 3, p = 0.295), higher percentage reporting 'no pain or discomfort' (96.4 % vs 88.8 %, p = 0.037), and trended for higher EuroQoL-scores (p = 0.092) at week-26. One case of hypercalcemia at week-2 normalised by week-4.. Among older people after hip fracture surgery, the REVITAHIP strategy is a safe and low cost method of improving vitamin-D levels, reducing falls and pain levels.. The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry ANZCTRN ACTRN12610000392066 (Date of registration: 14/05/2010).

Topics: Accidental Falls; Aged; Aged, 80 and over; Australia; Bone Density Conservation Agents; Calcium; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Hip Fractures; Humans; Hypercalcemia; Male; New Zealand; Quality of Life; Survival Rate; Walking Speed

Vitamin D supplementation is recommended for breastfed infants. Maternal supplementation beginning in gestation is a potential alternative, but its efficacy in maintaining infant 25-hydroxyvitamin D [25(OH)D] concentration after birth is unknown.. We determined the effect of 3 doses of maternal vitamin D supplementation beginning in gestation and continued in lactation on infant serum 25(OH)D and compared the prevalence of infant serum 25(OH)D cutoffs (>30, >40, >50, and >75 nmol/L) by dose at 8 wk of age.. Pregnant women (n = 226) were randomly allocated to receive 10, 25, or 50 μg vitamin D₃/d from 13 to 24 wk of gestation until 8 wk postpartum, with no infant supplementation. Mother and infant blood was collected at 8 wk postpartum.. At 8 wk postpartum, mean [nmol/L (95% CI)] infant 25(OH)D at 8 wk was higher in the 50-μg/d [75 (67, 83)] than in the 25-μg/d [52 (45, 58)] or 10-μg/d [45 (38, 52)] vitamin D groups (P < 0.05). Fewer infants born to mothers in the 50-μg/d group had a 25(OH)D concentration <30 nmol/L (indicative of deficiency) than infants in the 25- and 10-μg/d groups, respectively (2% compared with 16% and 43%; P < 0.05). Fewer than 15% of infants in the 10- or 25-μg/d groups achieved a 25(OH)D concentration >75 nmol/L compared with 44% in the 50-μg/d group (P < 0.05). Almost all infants (∼98%, n = 44) born to mothers in the 50-μg/d group achieved a 25(OH)D concentration >30 nmol/L. At 8 wk postpartum, mean maternal 25(OH)D concentration was higher in the 50-μg/d [88 (84, 91)] than in the 25-μg/d [78 (74, 81)] or 10-μg/d [69 (66, 73)] groups (P < 0.05).. Maternal supplementation beginning in gestation with 50 μg vitamin D₃/d protects 98% of unsupplemented breastfed infants against 25(OH)D deficiency (<30 nmol/L) to at least 8 wk, whereas 10 or 25 μg vitamin D/d protects only 57% and 84% of infants, respectively.

Topics: Adult; British Columbia; Calcifediol; Calcium; Child Development; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Fetal Blood; Humans; Hypercalcemia; Infant, Newborn; Intention to Treat Analysis; Lactation; Male; Maternal Nutritional Physiological Phenomena; Patient Compliance; Pregnancy; Pregnancy Complications; Prevalence; Vitamin D Deficiency

There is current interest in the maternal-fetal effects of antenatal vitamin D supplementation, yet little data regarding vitamin D's role in neonatal calcium homeostasis. We determined to assess the effect of high-dose antenatal vitamin D supplementation on fetal and neonatal calcium concentrations.. In a double-blinded, placebo-controlled trial in Bangladesh, 160 pregnant women were randomized to oral vitamin D3 (35,000 IU/wk) or placebo from 26 to 29 wk of gestation.. Total serum calcium (Ca) was higher in cord blood of those supplemented vs. placebo (2.66 ± 0.1 vs. 2.61 ± 0.2 mmol/l; P = 0.04), but the difference in albumin-adjusted calcium was not statistically significant. Change in Ca concentration from birth to day 3 of life was attenuated by vitamin D (-0.10 ± 0.17) compared with placebo (-0.22 ± 0.18 mmol/l; P = 0.02). Maternal 25-hydroxyvitamin D (25(OH)D) (P = 0.04) and cord 25(OH)D (P < 0.01) were associated with day 3 infant Ca, suggesting that the effect of supplementation was mediated by change in maternal-infant vitamin D status. Six infants in each of the supplemented and placebo groups had transient hypercalcemia/hypercalcuria; in all the hypercalcemia/hypercalcuria was asymptomatic, spontaneously resolved, and unassociated with nephrocalcinosis at 1 mo of life.. High-dose antenatal third-trimester vitamin D supplementation attenuated the early postnatal calcium nadir, without increasing the risk of postnatal hypercalcemia.

Topics: Administration, Oral; Biomarkers; Calcium; Cholecalciferol; Dietary Supplements; Double-Blind Method; Drug Administration Schedule; Female; Fetal Blood; Fetus; Gestational Age; Homeostasis; Humans; Hypercalcemia; Hypercalciuria; India; Infant, Newborn; Pregnancy; Pregnancy Trimester, Third; Prenatal Care; Prevalence; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Vitamin D supplementation in infancy is required to support healthy bone mineral accretion. A supplement of 400 IU of vitamin D per day is thought to support plasma 25-hydroxyvitamin D (25[OH]D) concentrations between 40 and 50 nmol/L; some advocate 75 to 150 nmol/L for bone health.. To investigate the efficacy of different dosages of vitamin D in supporting 25(OH)D concentrations in infants.. Double-blind randomized clinical trial conducted among 132 one-month-old healthy, term, breastfed infants from Montréal, Québec, Canada, between March 2007 and August 2010. Infants were followed up for 11 months ending August 2011 (74% completed study).. Participants were randomly assigned to receive oral cholecalciferol (vitamin D3) supplements of 400 IU/d (n=39), 800 IU/d (n=39), 1200 IU/d (n=38), or 1600 IU/d (n=16).. The primary outcome was a plasma 25(OH)D concentration of 75 nmol/L or greater in 97.5% of infants at 3 months. Secondary outcomes included 25(OH)D concentrations of 75 nmol/L or greater in 97.5% of infants at 6, 9, and 12 months; 25(OH)D concentrations of 50 nmol/L or greater across all times; growth; and whole body and regional bone mineral content. Data were analyzed by intention to treat using available data, logistic regression, and mixed-model analysis of variance.. By 3 months, 55% (95% CI, 38%-72%) of infants in the 400-IU/d group achieved a 25(OH)D concentration of 75 nmol/L or greater vs 81%(95% CI, 65%-91%) in the 800-IU/d group, 92% (95% CI, 77%-98%) in the 1200-IU/d group, and 100% in the 1600-IU/d group. This concentration was not sustained in 97.5% of infants at 12 months in any of the groups. The 1600-IU/d dosage was discontinued prematurely because of elevated plasma 25(OH)D concentrations. All dosages established 25(OH)D concentrations of 50 nmol/L or greater in 97% (95% CI, 94%-100%) of infants at 3 months and sustained this in 98% (95% CI, 94%-100%) to 12 months. Growth and bone mineral content did not differ by dosage.. Among healthy, term, breastfed infants, only a vitamin D supplement dosage of 1600 IU/d (but not dosages of 400, 800, or 1200 IU/d) increased plasma 25(OH)D concentration to 75 nmol/L or greater in 97.5% of infants at 3 months. However, this dosage increased 25(OH)D concentrations to levels that have been associated with hypercalcemia.. clinicaltrials.gov Identifier: NCT00381914.

Topics: Administration, Oral; Bone Development; Breast Feeding; Cholecalciferol; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypercalcemia; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Male; Treatment Outcome; Vitamin D; Vitamins

Improvements in antenatal vitamin D status may have maternal-infant health benefits. To inform the design of prenatal vitamin D3 trials, we conducted a pharmacokinetic study of single-dose vitamin D3 supplementation in women of reproductive age.. A single oral vitamin D3 dose (70,000 IU) was administered to 34 non-pregnant and 27 pregnant women (27 to 30 weeks gestation) enrolled in Dhaka, Bangladesh (23°N). The primary pharmacokinetic outcome measure was the change in serum 25-hydroxyvitamin D concentration over time, estimated using model-independent pharmacokinetic parameters.. Baseline mean serum 25-hydroxyvitamin D concentration was 54 nmol/L (95% CI 47, 62) in non-pregnant participants and 39 nmol/L (95% CI 34, 45) in pregnant women. Mean peak rise in serum 25-hydroxyvitamin D concentration above baseline was similar in non-pregnant and pregnant women (28 nmol/L and 32 nmol/L, respectively). However, the rate of rise was slightly slower in pregnant women (i.e., lower 25-hydroxyvitamin D on day 2 and higher 25-hydroxyvitamin D on day 21 versus non-pregnant participants). Overall, average 25-hydroxyvitamin D concentration was 19 nmol/L above baseline during the first month. Supplementation did not induce hypercalcemia, and there were no supplement-related adverse events.. The response to a single 70,000 IU dose of vitamin D3 was similar in pregnant and non-pregnant women in Dhaka and consistent with previous studies in non-pregnant adults. These preliminary data support the further investigation of antenatal vitamin D3 regimens involving doses of ≤70,000 IU in regions where maternal-infant vitamin D deficiency is common.

Topics: Adolescent; Adult; Bangladesh; Calcium; Cholecalciferol; Creatinine; Dietary Supplements; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hypercalcemia; Pregnancy; Serum Albumin; Specimen Handling; Treatment Outcome; Vitamin D Deficiency; Young Adult

Renal osteodystrophy is the major complication in patients with end-stage renal failure. Oral or intravenous vitamin D3 (D3) is given to these patients, but severe hypercalcaemia sometimes interrupts this therapy. This study was undertaken to determine whether the effectiveness and safety of D3 also depend on its dosing time during a repeated treatment.. A higher dose (3 micro g) was given orally to 13 haemodialysis patients at 08.00 h or 20.00 h for 12 months by a randomized, cross-over design.. Three patients were withdrawn due to severe hypercalcaemia after switching from 08.00 h to 20.00 h dosings. The elevation in serum calcium concentration was significantly (P < 0.001) greater during the 08.00 h dosing in the remaining ten patients. Mean serum Ca concentration after the trial was 10.92 (95% confidence interval (CI) 10.79, 11.06) and 9.55 mg dl-1 (95% CI 9.30, 9.71) by 08.00 h and 20.00 h dosing, respectively. On the other hand, the suppression of the elevated serum parathyroid hormone (PTH) and subsequent increment in bone density were significantly greater during the 08.00 h dosing. Mean PTH concentration after the trial was 414 (95% CI 360, 475) and 220 pg ml-1 (95% CI 202, 249) by 08.00 h and 20.00 h dosing, respectively (P = 0.02). Mean increment of bone density after the trial was 22 (95% CI 8, 32) and 57 g cm-3 (95% CI 43, 83) by 08.00 h and 20.00 h dosing, respectively (P = 0.04).. These results indicate that a higher dose of oral D3 is more effective and safe after dosing at evening in patients with renal osteodystrophy.

Topics: Administration, Oral; Adult; Aged; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Chronotherapy; Cross-Over Studies; Double-Blind Method; Female; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

A controlled study of the effects of the potent vitamin-D metabolite, 1, 25-dihydroxycholecalciferol (1,25[OH]2D3), and vitamin D3 was done in 18 non-dialysed patients with chronic renal failure (C.R.F.). Patients with a creatinine clearance below 35 ml/min and mild renal osteodystrophy were selected. After 6 months' observation of the spontaneous course the patients were randomly allocated to 6 months' oral treatment with either 1, 25 (OH)2D3 or vitamin D3 in initial daily doses of 1microgram and 4000 I.U., respectively, combined with 0.5 g calcium. 1,25(OH)2D3 quickly corrected hypocalcaemia, reduced serum-alkaline-phosphatases and serum-immunoreactive-parathyroid-hormone, and more than doubled the urinary excretion rate of calcium. D3 had similar, but less pronounced effects. 7 out of 8 patients on 1,25(OH)2D3, developed hypercalcaemia which necessitated a reduction in dosage. None of the patients on D3 treatment developed hypercalcaemia. The percentage fall in creatinine clearance was greater during treatment than before treatment in all patients on 1, 25 (OH)2D3 (P less than 0.01) and in 7 of 9 patients on vitamin D3 treatment (though the group change here was not significant). Deterioration of renal function is a major limitation of the clinical use of 1, 25(OH)2D3 and D3 in non-dialysed patients with C.R.F. In fact, the decrased formation of 1, 25(OH)2D3 seen in C.R.F. might protect renal function at the expense of abnormalities in mineral metabolism.

Topics: Administration, Oral; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydroxycholecalciferols; Drug Evaluation; Follow-Up Studies; Humans; Hydroxycholecalciferols; Hypercalcemia; Kidney; Kidney Failure, Chronic; Kidney Function Tests

1,25 dihydroxycholecalciferol [1,25(OH)2D3] was studied in a double-blind controlled fashion in patients on chronic dialysis. Serum calcium was unchanged in 16 patients on vitamin D3 (D3) (400 to 1200 IU/day). In 15 patients on 1,25(OH)2D3 (0.5 to 1.5 microgram/day), serum calcium increased from 9.05 +/- .15 to 10.25 +/- .20 mg/dl (p less than 0.001), returning to 9.37 +/- .16 mg/dl (p less than 0.001) in the post control period. Patients on D3 showed no reversible decrease in immunoreactive parathyroid hormone levels, but patients on 1,25(OH)2D3 did, from a control of 1077 +/- 258 to 595 +/- 213 microliter equivalents/ml (p less than 0.01), and returned to 1165 +/- 271 microliter equivalents/ml (p less than 0.005). Nine of 12 patients on D3 who underwent serial iliac-crest biopsies showed histologic deterioration, and six of seven who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium decreased in patients on D3 (p less than 0.05) but not in those on 1,25(OH)2D3. Hypercalcemia occurred in five of 15 patients. We conclude that 1,25(OH)2D3 has a calcemic effect in chronic dialysis patients, decreases levels of immunoreactive parathyroid hormone, and is associated with histologic improvement in bone disease. Thus, 1,25(OH)2D3 is a valuable adjunct to the management of renal osteodystrophy but requires monitoring of serum calcium to avoid hypercalcemia.

Topics: Adult; Alkaline Phosphatase; Antigens; Bone and Bones; Calcium; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Clinical Trials as Topic; Dihydroxycholecalciferols; Double-Blind Method; Female; Humans; Hydroxycholecalciferols; Hypercalcemia; Kidney Failure, Chronic; Male; Middle Aged; Minerals; Parathyroid Hormone; Phosphorus; Renal Dialysis

Topics: Adult; Aspartate Aminotransferases; Cholecalciferol; Chronic Kidney Disease-Mineral and Bone Disorder; Clinical Trials as Topic; Dihydroxycholecalciferols; Double-Blind Method; Female; Humans; Hydroxycholecalciferols; Hypercalcemia; Male; Middle Aged; Renal Dialysis

There is a lack of studies providing comprehensive data on the prevalence of mineral and bone disorders (MBD) laboratory abnormalities after kidney transplantation in Russia.. to obtain real-world data on the prevalence of the main mineral abnormalities among kidney transplant recipients and to revise their concomitant MBD therapy.. This cross-sectional study included 236 patients with successful kidney transplantation. Their serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured.. Only 6.2% of our cohort had all laboratory parameters within the target range, whereas persistent HPT along with hypercalcemia was noted in almost one third of the patients (31%). Normal iPTH levels were observed in 13% cases; 84% of the patients had hyperparathyroidism. The fraction of patients with target iPTH did not differ between the groups with normal and decreased estimated glomerular filtration rate (eGFR) (p=0.118). Hypercalcemia was observed in 29% cases. The serum P level varied significantly in groups with different eGFR (p<0.0001), increasing with declining graft function. Furthermore, 40.7% of patients had ALP above the target range. While 123 patients received active vitamin D (alfacalcidol), 33 received monotherapy with inactive vitamin D (cholecalciferol). The control group consisted of 57 medication-naïve patients. The serum total Ca level varied significantly between the groups (p=0.0006), being higher in patients supplemented with cholecalciferol. The fraction of patients with normocalcemia was lowest in the cholecalciferol group (chi-square, р=0.0018).. The prevalence of biochemical abnormalities after kidney transplantation is high. Alfacalcidol usage may be safer than using cholecalciferol to prevent hypercalcemia development.

Topics: Biomarkers; Bone Diseases; Cholecalciferol; Cross-Sectional Studies; Humans; Hypercalcemia; Kidney Transplantation; Minerals; Parathyroid Hormone; Vitamin D

Denosumab can improve bone health in advanced kidney disease (CKD) but is associated with hypocalcemia. We created a clinical care pathway focused on the safe provision of denosumab in advanced CKD that reduced the risk of hypocalcemia by 37% at our hospital. Similar pathways could be adopted and tested in other centers.. There is an increased risk of hypocalcemia with denosumab in advanced chronic kidney disease (CKD). We aimed to reduce the proportion of patients with advanced CKD who experienced denosumab-induced hypocalcemia at our center.. There were 6 patients with advanced CKD treated with denosumab prior to the implementation of our care pathway (March 2015-October 2020; 83% receiving dialysis). At the time of their denosumab injection, 83% were using 500-1000 mg of calcium, and 83% used 1000-2000 IU of vitamin D. A clinical care pathway focused on the safe provision of denosumab in advanced CKD reduced the risk of hypocalcemia in patients treated in our hospital. Similar pathways could be adopted and tested in other centers.

Topics: Bone Density Conservation Agents; Calcium; Cholecalciferol; Denosumab; Humans; Hypercalcemia; Hyperphosphatemia; Hypocalcemia; Quality Improvement; Renal Insufficiency, Chronic

The beneficial effects of vitamin D3 treatment are known, and its side effects are documented. In connection with the case presentation, we would like to sum up the dangers of excessive vitamin D supplementation, and to draw attention to the shortcomings experienced in everyday medical practice. We discuss the tests required to create a diagnosis of vitamin D intoxication, the differential diagnosis, and present the possible treatment strategies. A 57-year-old female patient was admitted to hospital in November 2020 due to complaints of nausea, vomiting, diarrhea and general weakness. Upon admission, laboratory tests confirmed new-onset kidney damage (eGFR 38 mL/min/1.73 m2), calcium metabolism was not checked. During non-invasive investigations, urinary sediment results showed leukocyturia and non-nephrotic proteinuria, but no clear underlying cause was found. Nephrology consultation suggested acute tubular injury, kidney biopsy was performed, immune serology and serum protein electrophoresis tests were ordered. Despite conservative treatment, her kidney function deteriorated further (eGFR 32 mL/d/1.73 m2). The patient arrived at our department in December 2020 with histological results in progress. Laboratory tests taken on arrival confirmed severe hypercalcemia (tCa 3.22 mmol/L, iCa 1.74 mmol/L), and kidney function was stable (eGFR 33 mL/p/1.73 m2). Intact parathyroid hormone level was below the normal range (0.54 pmol/L), 25-OH-vitamin D level was extremely high (1106.2 nmol/L). The patient then admitted that in October 2020, she received a course of "megadose" parenteral vitamin D, but she could not recall the exact dosage nor wanted to mention the department administering the treatment. We diagnosed vitamin D intoxication. Intravenous saline, furosemide and calcitonin treatment was started. The result of the treatment: serum calcium level normalized (2.52 mmol/L), and kidney functions improved (eGFR 54 mL/p/1.73 m2). Vitamin D treatment was stopped. The patients' serum tCa and vitamin D levels normalized by February 2021, and her kidney functions improved (tCa 2.54 mmol/L, 25-OH-vitamin D 125.0 ng/mL, eGFR 72 mL/p/1.73 m2). Kidney biopsy confirmed the presence of acute tubular necrosis. Granulomatous diseases and multiple myeloma were excluded. The symptoms of vitamin D intoxication are non-specific and varied, each case presents a differential diagnostic challenge. Orv Hetil. 2023; 164(47): 1871-1876.. A D3-vitamin-kezelés jótékony hatásai ismertek, mellékhatásai dokumentáltak. Az esetbemutatás kapcsán kívánjuk ismertetni a túlzó D-vitamin-pótlás veszélyeit, illetve a hétköznapi orvosi gyakorlatban tapasztalt hiányosságokra szeretnénk irányítani a figyelmet. Tárgyaljuk a D-vitamin-intoxikáció kórisméjének megalkotásához, az elkülönítő kórisméhez szükséges vizsgálatokat, valamint bemutatjuk a lehetséges kezelési stratégiákat. Az 57 éves nőbeteget néhány napja tartó hányinger, hányás, hasmenés, általános gyengeség tünetei miatt kezelte más intézmény 2020 novemberében. Felvételekor a laborvizsgálatokban új keletű vesekárosodás (eGFR 38 ml/p/1,73 m2) igazolódott, a kalcium-anyagcsere ellenőrzése nem történt meg. Nefrológiai konzíliuma akut tubuluskárosodást feltételezett, ezért vesebiopszia elvégzésére került sor, immunszerológiai vizsgálatok és a szérumfehérje elektroforézis-vizsgálata történt. A konzervatív kezelés ellenére a vesefunkció romlott (eGFR 32 ml/p/1,73 m2). Folyamatban lévő vizsgálati eredményekkel érkezett a beteg klinikánkra 2020 decemberében. Az érkezésekor végzett laborvizsgálatokban súlyos hypercalcaemia igazolódott (tCa 3,22 mmol/l, iCa 1,74 mmol/l), vesefunkciója stagnált (eGFR 33 ml/p/1,73 m2). Intakt parathormonszintje a normáltartomány alatt volt (0,54 pmol/l), 25-OH-D-vitamin-szintje extrém magasnak bizonyult (1106,2 nmol/l). A beteg ekkor elismerte, hogy 2020. októberben „megadózisú” parenteralis D3-vitamin-kúrában részesült egy harmadik intézményben; a kezelés pontos dózisát nem tudta megnevezni, a kezelést alkalmazó intézmény kilétét nem kívánta felfedni. D3-vitamin-intoxikációt véleményeztünk. Iv. parenteralisan krisztalloid, furoszemid, kalcitonin adásában részesült, melyek hatására szérumkalciumszintje normalizálódott (2,52 mmol/l), vesefunkciói javultak (eGFR 54 ml/p/1,73 m2). Szérum-tCa- és D-vitamin-szintje 2021. februárra normalizálódott, vesefunkciói javultak (tCa 2,54 mmol/l, 25-OH-D-vitamin 125,0 ng/ml, eGFR 72 ml/p/1,73 m2). A vesebiopszia akut tubularis necrosis jelenlétét igazolta. Granulomás gyulladás, myeloma multiplex nem igazolódott. A D-vitamin-intoxikáció tünetei nem specifikusak és változatosak, differenciáldiagnosztikai kihívást jelent egy-egy eset. Orv Hetil. 2023; 164(47): 1871–1876.

Topics: Calcium; Cholecalciferol; Female; Humans; Hypercalcemia; Kidney; Middle Aged; Vitamin D; Vitamins

Vitamin D supplements are readily available as over-the-counter preparations. However, although rare, cases of vitamin D overdose still occur and are associated with nephrocalcinosis and life-threatening hypercalcemia. Errors in manufacturing of nutritional supplements may be a cause of vitamin D intoxication in children. This study aimed to identify factors associated with vitamin D overdose-related nephrocalcinosis in children due to manufacturing errors in supplements.. This retrospective study reviewed medical charts of pediatric patients with non-registered supplement-related vitamin D overdose at a tertiary referral hospital between 2006 and 2011. Clinical and laboratory characteristics of patients with or without nephrocalcinosis were evaluated. Receiver operating characteristics curve and area under the receiver operating characteristics curve were used to determine the most predictive value of each characteristic.. Children with smaller BSAs were more vulnerable to high-dose vitamin D

Topics: Child; Child, Preschool; Cholecalciferol; Humans; Hypercalcemia; Infant; Male; Nephrocalcinosis; Retrospective Studies; Vitamin D; Vitamins

The intent of this study was an evaluation of our effort to reduce the incidence of hypercalcemia in critically ill vitamin D-deficient patients with multiple traumatic injuries given cholecalciferol. Vitamin D deficiency was defined as a serum 25-hydroxy vitamin D concentration (25-OH vit D) of <20 ng/mL. Adult patients (>17 years of age) were given 10,000 IU of cholecalciferol daily with an intended target 25-OH vit D of >19.9 ng/mL. These patients were compared to a historical control group that underwent therapy with a higher target of >29.9 ng/mL. Patients received cholecalciferol via the feeding tube along with enteral nutrition (EN) until the target 25-OH vit D was achieved, EN discontinued, the nutrition support service signed off the patient, or the patient was discharged from the TICU. Patients were included if two consecutive weekly 25-OH vit D were measured. One hundred and three critically ill trauma patients were retrospectively studied. Fifty were given cholecalciferol therapy with the new lower target 25-OH vit D, and 53 were from a historical cohort aiming for the higher target. Hypercalcemia (serum ionized calcium concentration > 1.32 mmol/L) was reduced from 40% (21 out of 53 patients) to 4% (2 out of 50 patients; p < 0.001). None of the hypercalcemic patients were symptomatic. Readjustment of target 25-OH vit D concentration resulted in a ten-fold decrease in the rate of hypercalcemia and improved the safety of cholecalciferol therapy for critically ill patients with traumatic injuries.

Topics: Adult; Calcifediol; Cholecalciferol; Critical Illness; Humans; Hypercalcemia; Retrospective Studies; Vitamin D; Vitamin D Deficiency; Vitamins

There are many causes of hypercalcemia, with hyperparathyroidism and malignancy accounting for 90% of cases. Sarcoidosis and the intake of vitamin D supplements may also cause hypercalcemia, although the occurrence rate is low if only one is involved. We herein report a sarcoidosis patient who developed hypercalcemia after taking cholecalciferol (vitamin D supplement) for a year.. A 62-year-old Japanese man presented with hypercalcemia and acute kidney injury along with symptoms of fatigue and appetite loss while being followed up for sarcoidosis.. We determined that a combination of cholecalciferol supplementation and sarcoidosis had led to hypercalcemia for several reasons. First, hypercalcemia had not been noted when this patient had first been admitted due to sarcoidosis-related respiratory failure several years earlier, which we presumed that was the highest sarcoidosis disease activity. Second, low serum 25-OH Vit.D3 and high 1,25-(OH)2 Vit.D3 levels were noted despite cholecalciferol supplementation for a year, suggesting that 1-α-hydroxylase overexpression caused by sarcoidosis accelerated the conversion from 25-OH Vit.D3 to 1,25-(OH)2 Vit.D3.. Although initially resistant to preservative management, the hypercalcemia promptly improved after starting corticosteroid treatment.. Hypercalcemia and acute kidney injury were normalized after corticosteroid treatment.. We should be aware of patients' medications, especially in patients with granulomatosis disease. The concomitant measurement of 25-OH Vit.D3 and 1,25-(OH)2 Vit.D3 levels is useful for determining the cause of hypercalcemia.

Topics: Acute Kidney Injury; Calcium; Cholecalciferol; Dietary Supplements; Humans; Hypercalcemia; Male; Middle Aged; Mixed Function Oxygenases; Sarcoidosis; Vitamin D

Vitamin D intoxication (VDI) is a well-known cause of hypercalcemia in children and leads to serious kidney, heart, and neurological problems. In the treatment of VDI, the goal is to correct hypercalcemia. Our aim was to evaluate the clinical features of patients with VDI, identify the causes of VDI in our region, and help guide precautions and treatment of VDI.. The medical records of patients with VDI presenting between January 2015 and December 2019 were retrospectively analyzed.. Stoss therapy should not be administered for children of families with problems of adherence to treatment. It should be noted that VDI may develop as a result of improperly produced nutritional supplements. General practitioners and pediatricians must be aware of VDI risks and explain them to parents. Pamidronate is effective for treating VDI in children.

Topics: Child, Preschool; Cholecalciferol; Dietary Supplements; Emergency Medical Services; Female; Fish Oils; Humans; Hypercalcemia; Inappropriate Prescribing; Infant; Male; Parents; Patient Compliance; Professional-Family Relations; Retrospective Studies; Vitamin D Deficiency; Vitamins

Vitamin D deficiency during critical illness has been associated with worsened outcomes. Because most critically ill patients with severe traumatic injuries are vitamin D deficient, we investigated the efficacy and safety of cholecalciferol therapy for these patients.. Fifty-three patients (>17 years of age) admitted to the trauma intensive care unit who had a serum 25-hydroxy vitamin D (25-OH vit D) concentration <20 ng/mL were given 10,000 IU of cholecalciferol daily. Efficacy was defined as achievement of a 25-OH vit D of 30-79.9 ng/mL. Safety was evaluated by the presence of hypercalcemia (serum ionized calcium [iCa] >1.32 mmol/L) or hypervitaminosis D (25-OH vit D >79.9 nmol/L). Patients were monitored for 2 weeks during cholecalciferol therapy.. Twenty-four patients (45%) achieved target 25-OH vit D. No patients experienced hypervitaminosis D. Hypercalcemia occurred in 40% (n = 21) of patients; 2 patients experienced an iCa >1.49 nmol/L. 25-OH vit D was significantly greater for those who developed hypercalcemia (37.2 + 11.2 vs 28.4 + 5.6 ng/mL, respectively, P < 0.001) by the second week of cholecalciferol. Of 24 patients who achieved target 25-OH vit D, 14 (58%) experienced hypercalcemia in contrast to 24% of patients (7 out of 29) who did not achieve target 25-OH vit D (P = 0.024).. Cholecalciferol normalized serum 25-OH vit D concentrations in less than half of patients yet was associated with a substantial proportion of patients with hypercalcemia without hypervitaminosis D.

Topics: Adult; Calcium; Cholecalciferol; Critical Illness; Dose-Response Relationship, Drug; Enteral Nutrition; Female; Humans; Hypercalcemia; Incidence; Intensive Care Units; Male; Middle Aged; Risk Factors; Vitamin D; Vitamin D Deficiency; Vitamins; Wounds and Injuries; Young Adult

Topics: Autoimmunity; Calcium; Cholecalciferol; Humans; Hypercalcemia; Multiple Sclerosis; T-Lymphocytes; Vitamin D

Topics: Cholecalciferol; Dietary Supplements; Humans; Hypercalcemia; Multiple Sclerosis; Vitamin D

Knowledge about complications of chronic ultra-high dose vitamin D supplementation is limited. We report a patient with primary progressive multiple sclerosis (MS) who presented with generalized weakness caused by hypercalcemia after uncontrolled intake of more than 50,000 IU of cholecalciferol per day over several months. Various treatment strategies were required to achieve normocalcemia. However, renal function improved only partly and further progression of MS was observed. We conclude that patients need to be informed about the risks of uncontrolled vitamin D intake and neurologists need to be alert of biochemical alterations and symptoms of vitamin D toxicity.

Topics: Cholecalciferol; Drug-Related Side Effects and Adverse Reactions; Humans; Hypercalcemia; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Renal Insufficiency; Vitamins

Vitamin D3 is a secosteroid hormone produced in the skin in amounts estimated up to 25,000 international units (IUs) a day by the action of UVB radiation on 7-dehydrocholesterol. Vitamin D deficiency is common due to both lack of adequate sun exposure to the skin, and because vitamin D is present in very few food sources. Deficiency is strongly linked to increased risk for a multitude of diseases, several of which have historically been shown to improve dramatically with either adequate UVB exposure to the skin, or to oral or topical supplementation with vitamin D. These diseases include asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. All patients in our hospital have been routinely screened on admission for vitamin D deficiency since July 2011, and offered supplementation to either correct or prevent deficiency. During this time, we have admitted over 4700 patients, the vast majority of whom agreed to supplementation with either 5000 or 10,000 IUs/day. Due to disease concerns, a few agreed to larger amounts, ranging from 20,000 to 50,000 IUs/day. There have been no cases of vitamin D3 induced hypercalcemia or any adverse events attributable to vitamin D3 supplementation in any patient. Three patients with psoriasis showed marked clinical improvement in their skin using 20,000 to 50,000 IUs/day. Analysis of 777 recently tested patients (new and long-term) not on D3 revealed 28.7% with 25-hydroxyvitaminD3 (25OHD3) blood levels < 20 ng/ml, 64.1% < 30 ng/ml, a mean 25OHD3 level of 27.1 ng/ml, with a range from 4.9 to 74.8 ng/ml. Analysis of 418 inpatients on D3 long enough to develop 25OHD3 blood levels > 74.4 ng/ml showed a mean 25OHD3 level of 118.9 ng/ml, with a range from 74.4 to 384.8 ng/ml. The average serum calcium level in these 2 groups was 9.5 (no D3) vs 9.6 (D3), with ranges of 8.4 to 10.7 (no D3) vs 8.6 to 10.7 mg/dl (D3), after excluding patients with other causes of hypercalcemia. The average intact parathyroid hormone levels were 24.2 pg/ml (D3) vs. 30.2 pg/ml (no D3). In summary, long-term supplementation with vitamin D3 in doses ranging from 5000 to 50,000 IUs/day appears to be safe.

Topics: Adult; Aged; Cholecalciferol; Female; Hospitalization; Humans; Hypercalcemia; Male; Middle Aged; Vitamin D Deficiency; Vitamins; Young Adult

Vitamin D insufficiency is highly prevalent among renal transplant recipients and in observational studies is associated with adverse outcomes. Hypercalcemia, usually due to persistent hyperparathyroidism, also commonly occurs in this population and often coexists with vitamin D insufficiency. However, concern that vitamin D supplementation might exacerbate the pre-existing hypercalcemia often leads clinicians to avoid vitamin D supplementation in such patients. This feasibility study aimed to quantify the effect on serum calcium of short-term low-dose cholecalciferol supplementation in a group of renal transplant recipients with a recent history of serum calcium levels >10 mg/dL.. A 2-week, single arm, open-label trial.. Renal transplant follow-up clinic in an Irish University Hospital.. Two weeks of treatment with 1,000 IU cholecalciferol/day.. Change in ionized calcium and urine calcium:creatinine ratio at follow-up compared with baseline.. Mean (standard deviation [SD]) baseline 25 (OH) vitamin D (25 (OH) D) concentration was 15.9 (5.97) ng/mL and mean (SD) baseline serum calcium was 10.50 (0.6) mg/dL. Following the 2-week intervention, median (interquartile range [IQR]) change in serum calcium from baseline was -0.08 (-3.6 to 0.08) mg/dL, P = .3. Mean (SD) ionized calcium decreased from 5.24 (0.32) mg/dL at baseline to 5.16 (0.28) mg/dL, P = .05. Median (IQR) change in the urinary calcium:creatinine ratio was 0.001 (-0.026 to 0.299) mg/mg, P = .88. Median (IQR) change in 25 (OH) D was 3.6 (2.9-6.2) ng/mL, P < .05.. In vitamin D-insufficient renal transplant recipients at risk of hypercalcemia, low-dose short-term oral cholecalciferol supplementation improves 25 (OH) D concentrations without exacerbating hypercalcemia or increasing the urinary calcium:creatinine ratio.

Topics: Adult; Calcium; Cholecalciferol; Creatinine; Dietary Supplements; Feasibility Studies; Female; Humans; Hypercalcemia; Kidney Transplantation; Male; Middle Aged; Prospective Studies; Risk Factors; Transplant Recipients; Vitamin D; Vitamin D Deficiency

Metastatic calcinosis cutis results from abnormal calcium levels leading to the precipitation of insoluble calcium salts in the skin and subcutaneous tissue. Here, we present the case of a 67-year-old man with multiple sclerosis on chronic dexamethasone and concurrent supplementation of calcium and daily cholecalciferol presenting with painful calcified lesions. During initial presentation, corrected calcium was 13.8 mg/dL (reference range: 8.5-10.1 mg/dL), ionised calcium was 1.70 mg/dL (reference range: 1.13-1.32 mg/dL) and 25-hydroxyvitamin D was 41.6 ng/mL (reference range 30-100 ng/mL). Normocalcaemia was restored with the off-label use of denosumab, usually reserved for hypercalcaemia of malignancy and intractable osteoporosis. We discuss potential aetiologies of this patient's hypercalcaemia, calcinosis cutis diagnosis and management and the off-label use of denosumab.

Topics: Calcinosis; Calcium; Cholecalciferol; Denosumab; Dexamethasone; Humans; Hypercalcemia; Male; Middle Aged; Multiple Sclerosis; Off-Label Use; Skin Diseases; Treatment Outcome

Poor vitamin D status is associated with a higher relapse rate and earlier disability in multiple sclerosis. Based on these associations, patients with multiple sclerosis are frequently supplemented with the vitamin D precursor cholecalciferol, although it is unclear whether this regimen is of therapeutic benefit. To model consequences of this common practice, mice were fed for more than 3 months with a low, medium or high dose of cholecalciferol, representative of vitamin D deficiency, modest and disproportionally high supplementation, respectively, in patients with multiple sclerosis. Compared to vitamin D-deprived mice, its moderate supplementation reduced the severity of subsequent experimental autoimmune encephalomyelitis, which was associated with an expansion of regulatory T cells. Direct exposure of murine or human T cells to vitamin D metabolites inhibited their activation. In contrast, mice with 25-(OH) vitamin D levels above 200 nmol/l developed fulminant experimental autoimmune encephalomyelitis with massive CNS infiltration of activated myeloid cells, Th1 and Th17 cells. When dissecting this unexpected outcome, we observed that high, but not medium dose vitamin D had caused mild hypercalcaemia, which rendered T cells more prone to pro-inflammatory activation. Exposing murine or human T cells to equivalent calcium concentrations in vitro enhanced its influx, triggering activation, upregulation of pro-inflammatory gene products and enhanced transmigration across a blood-brain barrier model. These findings suggest that vitamin D at moderate levels may exert a direct regulatory effect, while continuous high dose vitamin D treatment could trigger multiple sclerosis disease activity by raising mean levels of T-cell excitatory calcium.

Topics: Animals; Autoimmunity; Blood-Brain Barrier; Calcifediol; Calcium; Calcium Signaling; Chlorides; Cholecalciferol; Dose-Response Relationship, Drug; Encephalomyelitis, Autoimmune, Experimental; Female; Humans; Hypercalcemia; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Multiple Sclerosis; Phosphates; Sodium; T-Lymphocyte Subsets; Th1 Cells; Th17 Cells; Vitamin D; Vitamin D Deficiency

Mutations of the CYP24A1 gene are associated with alterations in the activity of the enzyme 25-OH-D-24-hydroxylase, resulting in dysfunction of the metabolism of vitamin D. This enzymatic deficiency may cause hypercalcemia, low parathyroid hormone levels, hypercalciuria, nephrolithiasis and nephrocalcinosis. The clinical case of a young woman with recurrent renal lithiasis, hypercalcemia and hypercalciuria is described. These features are linked to deficiency of the enzyme 25-OH-D-24-hydroxylase, therefore to a biallelic mutation of the CYP24A1 gene.

Topics: Adult; Calcium; Cholecalciferol; Citrates; Female; Genotype; Humans; Hypercalcemia; Hypercalciuria; Kidney Calculi; Mutation, Missense; Parathyroid Hormone; Phosphorus; Recurrence; Sequence Deletion; Vitamin D; Vitamin D3 24-Hydroxylase

Malakoplakia is a rare disease characterized by the presence of nongranulomatous macrophage infiltration. In most cases, it affects the urinary tract. Malakoplakia can cause acute kidney injury when it is localized in the kidneys.. Here, we report the case of a 65-year-old female patient with renal malakoplakia responsible for hypercalcemia. During her initial assessment, she was also diagnosed 25-OH vitamin D insufficiency, for which she was prescribed oral cholecalciferol. Three months later, she developed severe hypercalcemia with normal 25-OH vitamin D and parathyroid hormone levels and high 1,25-dihydroxyvitamin D levels.. After a superimposed granulomatous disease was excluded, malakoplakia cells were suspected to be responsible for the abnormal 25-hydroxyvitamin D3 1-alpha-hydroxylase activity, which was confirmed by immunohistochemistry.. Cholecalciferol was stopped, the patient was rehydrated with intravenous physiological saline, and prednisone was initiated to decrease the enzyme activity.. Six months later, she displayed normal serum calcium, 25-OH vitamin D and 1,25-dihydroxyvitamin D levels.. This case illustrates that malakoplakia may exhibit ectopic 25-hydroxyvitamin D3 1-alpha-hydroxylase activity and cause severe hypercalcemia upon vitamin D supplementation. Therefore, such supplementation should not be given in malakoplakia patients without an actual deficiency and requires careful monitoring of serum calcium.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Aged; Calcium; Cholecalciferol; Dietary Supplements; Ectopic Gene Expression; Female; Humans; Hypercalcemia; Kidney Diseases; Malacoplakia; Parathyroid Hormone; Vitamin D Deficiency; Vitamins

Topics: Aged, 80 and over; Cholecalciferol; Confusion; Dietary Supplements; Humans; Hypercalcemia; Male; Parathyroid Hormone; Vitamin D

The aim of this study was to determine whether calcium potentiates acute carbon tetrachloride (CCl4) -induced toxicity. Elevated calcium levels were induced in mice by pre-treatment with cholecalciferol (vitamin D3; V.D3), a compound that has previously been shown to induce hypercalcemia in human and animal models. As seen previously, mice injected with CCl4 exhibited increased plasma levels of alanine aminotransferase, aspartate aminotransferase, and creatinine; transient body weight loss; and increased lipid peroxidation along with decreased total antioxidant power, glutathione, ATP, and NADPH. Pre-treatment of these animals with V.D3 caused further elevation of the values of these liver functional markers without altering kidney functional markers; continued weight loss; a lower lethal threshold dose of CCl4; and enhanced effects on lipid peroxidation and total antioxidant power. In contrast, exposure to V.D3 alone had no effect on plasma markers of liver or kidney damage or on total antioxidant power or lipid peroxidation. The potentiating effect of V.D3 was positively correlated with elevation of hepatic calcium levels. Furthermore, direct injection of CaCl2 also enhanced CCl4-induced hepatic injury. Since CaCl2 induced hypercalcemia transiently (within 3 h of injection), our results suggest that calcium enhances the CCl4-induced hepatotoxicity at an early stage via potentiation of oxidative stress.

Topics: Adenosine Triphosphate; Animals; Body Weight; Calcium; Carbon Tetrachloride; Cholecalciferol; Cytochrome P-450 CYP2E1; Hypercalcemia; Lipid Peroxidation; Liver; Male; Malondialdehyde; Mice; NADP; Oxidative Stress

Long-term severe hyperparathyroidism leads to thinning of cortical bone and cystic bone defects referred to as osteitis fibrosa cystica. Cysts filled with hemosiderin deposits may appear colored as "brown tumors." Osteitis fibrosa cystica and brown tumors are occasionally visualized as multiple, potentially corticalis-disrupting bone lesions mimicking metastases by bone scintigraphy or. We report a case of a 72-year-old white woman who presented with malaise, weight loss, and hypercalcemia. She had a history of breast cancer 7 years before. The practitioner, suspecting bone metastases, initiated bone scintigraphy, which showed multiple bone lesions, and referred her to our hospital for further investigations. Laboratory investigations confirmed hypercalcemia but revealed a constellation of primary hyperparathyroidism and not hypercalcemia of malignancy; in the latter condition, a suppressed rather than an increased value of parathyroid hormone would have been expected. A parathyroid adenoma was found and surgically removed. The patient's postoperative course showed a hungry bone syndrome, and brown tumors were suspected. With the background of a previous breast cancer and lytic, partly corticalis-disrupting bone lesions, there was a great concern not to miss a concomitant malignant disease. Biopsies were not diagnostic for either malignancy or brown tumor. Six months after the patient's neck surgery, imaging showed healing of the bone lesions, and bone metastases could be excluded.. This case shows essential differential diagnosis in a patient with hypercalcemia and multiple bone lesions. Whenever multiple, fluorodeoxyglucose-avid bone lesions are found, malignancy and metabolic bone disease should both be included in the differential diagnosis. Fluorodeoxyglucose-avid and corticalis-disrupting lytic lesions also occur in benign bone disease. There may be very few similar cases with heterogeneous and widespread bone lesions reported in the literature, but we think our patient's case is particularly remarkable for its detailed imaging and the well-documented course.

Topics: Aged; Bone Neoplasms; Breast Neoplasms; Calcium; Cholecalciferol; Diagnosis, Differential; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Osteitis Fibrosa Cystica; Parathyroid Neoplasms; Parathyroidectomy; Positron Emission Tomography Computed Tomography; Treatment Outcome; Vitamins

Recent evidence suggests that 1α,25-dihydroxyvitamin D3 (calcitriol, VD3), the active form of vitamin D (VD), can inhibit the proliferation of microorganisms. In the present study, we conducted in vitro experiments and utilized in vivo murine models to investigate the antimalarial activity of VD3 and its analog, 22-oxacalcitriol (22-OCT), which was designed to cause less hypercalcemia than VD3. VD3 and 22-OCT treatments effectively resolved a Plasmodium chabaudi (Pc) infection in wild-type mice. Reduced parasitemia was observed during the acute phase of infection in the presence of VD3 and 22-OCT, followed by a delayed peak during the chronic stage of infection. Some anti-Pc activity was observed in VD receptor knockout (KO) mice. VD3 and 22-OCT also completely inhibited the proliferation of P. falciparum (Pf) in human red blood cells in vitro. Plasma levels of interferon (IFN)-γ in VD3-treated B10 and B6 mice were lower than those in vehicle-treated animals, and VD3 resolved a Pc infection in IFN-γ-KO mice, which greatly improved survival. These data suggest that the protective effects of VD3 are elicited through an IFN-γ-independent mechanism. Effective antiplasmodial doses of VD3 and 22-OCT resulted in a loss of body weight in mice. This loss in body weight occurred concomitantly with the development of hypercalcemia. Zoledronic acid partially attenuated VD3-induced hypercalcemia and abrogated the antiparasitic effects of VD3. This study highlights a potential therapeutic role for VD3 in the treatment of malarial infections and shows that hypercalcemia is excellent indicator of the antiplasmodial activity of VD3.

Topics: Acute Disease; Animals; Antimalarials; Body Weight; Calcitriol; Cholecalciferol; Chronic Disease; Diphosphonates; Erythrocytes; Humans; Hypercalcemia; Imidazoles; Interferon-gamma; Malaria; Mice; Mice, Inbred BALB C; Mice, Knockout; Parasitemia; Plasmodium chabaudi; Receptors, Calcitriol; Zoledronic Acid

In the 1930's and 1940's, vitamin D was reported to be an effective treatment for a number of diseases, including asthma, psoriasis, rheumatoid arthritis, rickets and tuberculosis. High doses were used, 60,000 to 300,000 IU a day for asthma, and 200,000 to 600,000 IU a day for rheumatoid arthritis. Toxicity from hypercalcemia occurred after prolonged oral dosing with these supraphysiologic doses. Assays for measuring vitamin D in the blood were not available, and blood levels of vitamin D associated with hypercalcemia were unknown. A 2011 report on vitamin D toxicity showed that hypercalcemia resolved when 25-hydroxyvitamin D (25OHD) blood levels dropped below 400ng/ml in 2 patients with blood levels ranging from 645ng/ml to 1220ng/ml after accidental ingestion of massive doses of vitamin D. We now know that vitamin D is made in the skin in amounts ranging up to 25,000 IU a day with exposure to UVB radiation. There is little data on the safety and blood levels of 25OHD and calcium after prolonged daily intake of amounts of vitamin D in this range. In this report, one subject took increasing daily doses of vitamin D3 for 6 years starting in April 2009: 6500 IU for 6 months; increasing to 10,000 IU for 13 months; 20,000 IU for 24 months; 40,000 IU for 12 months; 50,000 IU for 10 months, and 60,000 IU since October 2014. 25OHD blood levels were 28, 81, 204, 216, 225, 166, and 218ng/ml. Subject 2 began 10,000 IU in Nov 2011, increased to 20,000 IU in Feb 2014, 25,000 IU in June 2014, and 30,000 IU in Oct 2014, and then decreased to 20,000 IU in June 2015. 25OHD blood levels were 96.6, 161.1 and 106.9ng/ml. He reported marked clinical improvement in his asthma. Subject 3 started on daily 10,000 IU in Sept 2013, increasing to 20,000 IU on Nov 2013. 25OHD blood levels were 31.4, 102, 164, 148, and 143ng/ml. No one developed hypercalcemia or any adverse events. The major finding of this case series is prolonged daily dosing of vitamin D3 with doses of 10,000 to 60,000 IU was safely tolerated.

Topics: Administration, Oral; Adult; Calcium; Cholecalciferol; Humans; Hypercalcemia; Male; Parathyroid Hormone; Vitamin D; Vitamins

Topical agents containing vitamin D3 (VD3) analogues such as calcipotriol, maxacalcitol and tacalcitol and the combination of calcipotriol/betamethasone dipropionate (betamethasone) are prescribed for patients with psoriasis. However, they are known to occasionally cause hypercalcemia, and the frequency of hypercalcemia is suggested to vary according to the VD3 analogue used. In this study, to address the reason for these differences, the calcemic effects of maxacalcitol-, calcipotriol- and calcipotriol/betamethasone-containing ointments in rats were evaluated. The serum calcium levels in rats treated with ointments containing maxacalcitol, but not calcipotriol or calcipotriol/betamethasone, were significantly elevated, which is consistent with clinical observations. The serum concentration of VD3 analogue in rats treated with ointments containing calcipotriol and calcipotriol/betamethasone was lower than that in rats treated with maxacalcitol-containing ointment. Thus, the calcemic effects appear to be associated with the systemic exposure of VD3 analogues in rats. To understand the mechanism underlying the different systemic exposures of VD3 analogues, skin permeation and metabolic stability of VD3 analogues were evaluated. The cumulative amount of calcipotriol permeated through rat skin was significantly lower than that of maxacalcitol. On the other hand, the metabolic clearance of calcipotriol in rat hepatocytes was higher than that of maxacalcitol. Similar results were obtained using human skin and human hepatocytes. The current study demonstrates that the lower calcemic effects of calcipotriol- and calcipotriol/betamethasone-containing ointments are caused by the low systemic exposure of calcipotriol according to low skin permeability and rapid hepatic elimination after topical application.

Topics: Administration, Topical; Animals; Cholecalciferol; Hypercalcemia; Liver; Male; Ointments; Permeability; Rats; Rats, Sprague-Dawley; Skin

Hypercalcemia associated with lymphomas can be secondary to increased calcitriol [1,25(OH)2 vitamin D3], PTHrP, or osteolytic metastases.. A case of calcitriol-mediated hypercalcemia secondary to non-Hodgkin lymphoma in a patient with postsurgical hypoparathyroidism is presented.. Single patient managed at a tertiary health care facility in the United States.. A 55-year-old white woman had a total thyroidectomy and radioiodine ablation for a 3.5-cm follicular carcinoma. Surgery was complicated by permanent hypoparathyroidism treated with calcium, calcitriol, and cholecalciferol. For over 16 years she had no evidence of either residual thyroid tissue in the neck or metastasis. Her corrected serum calcium levels were appropriately maintained in the low-normal range. During a routine clinic visit, she had mild hypercalcemia; calcium and cholecalciferol were reduced by 50%, while calcitriol was continued. Two weeks later, she presented with nausea, abdominal pain, and multiple rapidly enlarging cervical and axillary lymph nodes with elevated calcium and calcitriol. A fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography scan and lymph node biopsy were diagnostic for non-Hodgkin lymphoma.. Calcium and calcitriol were stopped; hypercalcemia was corrected with iv fluids. Chemotherapy resulted in an excellent response within 7 weeks; calcitriol normalized, and the patient developed recurrent hypocalcemia. Positron emission tomography/computed tomography scans at 7 weeks and 3 months after treatment documented near-complete resolution of the lesions. Outcome and Result: Sixteen months after the treatment of lymphoma, the patient remains free of disease and is on calcium, calcitriol, and cholecalciferol.. Clinicians should have a high index of suspicion for malignancy when patients presents with rapid and high elevations of serum calcium.

Topics: Adenocarcinoma, Follicular; Calcitriol; Calcium; Cholecalciferol; Female; Humans; Hypercalcemia; Hypocalcemia; Hypoparathyroidism; Lymphoma, Non-Hodgkin; Middle Aged; Thyroid Neoplasms; Thyroidectomy; Treatment Outcome

Topics: Aged, 80 and over; Bone Density Conservation Agents; Calcitriol; Calcium Carbonate; Cholecalciferol; Denosumab; Female; Fractures, Bone; Humans; Hypercalcemia; Hypocalcemia; Medication Errors; Renal Insufficiency, Chronic; Tetany

Pediatric cases of vitamin D intoxication (VDI) with dietary supplements have not been previously reported. We report on 7 children with VDI caused by consumption of a fish oil supplement containing an excessively high dose of vitamin D due to a manufacturing error. Seven children aged between 0.7 and 4.2 years were admitted with symptoms of hypercalcemia. Initial median (range) serum concentrations of calcium and 25-hydroxyvitamin D were 16.5 (13.4-18.8) mg/dL and 620 (340-962) ng/mL, respectively. Repeated questioning of the parents revealed use of a fish oil that was produced recently by a local manufacturer. Analysis of the fish oil by gas chromatography/mass spectrometry revealed that the vitamin D3 content was ~4000 times the labeled concentration. Estimated daily amounts of vitamin D3 intake varied between 266,000 and 800,000 IU. Patients were successfully treated with intravenous hydration, furosemide, and pamidronate infusions. With treatment, serum calcium returned to the normal range within 3 days (range: 2-7 days). Serum 25-hydroxyvitamin D levels normalized within 2 to 3 months. Complications, including nephrocalcinosis, were not observed throughout the 1-year follow-up. In conclusion, errors in manufacturing of dietary supplements may be a cause of VDI in children. Physicians should be aware of this possibility in unexplained VDI cases and repeatedly question the families about dietary supplement use. To prevent the occurrence of such unintentional incidents, manufacturers must always monitor the levels of ingredients of their products and should be rigorously overseen by governmental regulatory agencies, as is done in the pharmaceutical industry.

Topics: Biomarkers; Child, Preschool; Cholecalciferol; Dietary Supplements; Female; Fish Oils; Humans; Hypercalcemia; Infant; Male; Turkey; Vitamin D; Vitamins

Epidemiological studies suggest that vitamin D deficiency is common in patients with primary hyperparathyroidism (PHPT). They have higher levels of serum parathyroid hormone (PTH) and markers of bone turnover and fractures are more frequent than vitamin D-replete patients. However, there are concerns that Vitamin D repletion might exacerbate pre-existent hypercalcaemia. Therefore, we aimed to determine if vitamin D replacement improved biochemical indices of calcium metabolism without worsening underlying hypercalcaemia.. This is a prospective, observational study based on routine clinical practice, set up in a secondary care centre. 45 consecutive patients with mild biochemical hypercalcaemia due to PHPT and hypovitaminosis D were enrolled. The mean age of the cohort was 61 years (range 25-85 years), predominately Asian (32 patients) and female (41 patients). They received 20,000 IU of oral cholecalciferol, once a week, for 3 months. Calcium, phosphate, alkaline phosphatase and PTH were measured at baseline, 4, 8 and 12 weeks following treatment. Vitamin D levels were obtained at baseline and at 12 weeks, after they completed their treatment.. Vitamin D levels normalised at week 12 (mean ± SD, 18.8 ± 9.4 versus 76 ± 20 nmol/L, p = 0.0001) and PTH levels improved following treatment completion (21.2 ± 10 versus 16.2 ± 6 pmol/L, p = 0.026). There was no significant increase in serum calcium levels during vitamin D supplementation.. High doses of oral cholecalciferol normalised vitamin D levels without worsening underlying hypercalcaemia in individuals with PHPT.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcifediol; Calcium; Cholecalciferol; Cohort Studies; Dietary Supplements; Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Male; Middle Aged; Parathyroid Hormone; Secondary Care Centers; Severity of Illness Index; United Kingdom; Vitamin D Deficiency

Vitamin D deficiency is common. It causes osteomalacia, may contribute to osteoporosis and is an independent risk factor for cancer, diabetes, multiple sclerosis, cardiovascular disease and all-cause mortality. We describe patients with a history of sarcoidosis who developed acute kidney injury due to hypercalcaemia following treatment with colecalciferol.

Topics: Acute Kidney Injury; Adult; Cholecalciferol; Humans; Hypercalcemia; Male; Sarcoidosis; Vitamin D Deficiency; Vitamins

Topics: Aged, 80 and over; Calcium; Cholecalciferol; Diagnosis, Differential; Diphosphonates; Female; Glomerular Filtration Rate; Humans; Hypercalcemia; Osteoporosis; Renal Insufficiency, Chronic

Vitamin D deficiency is highly prevalent in India. This has set off a trend among medical practitioners to prescribe vitamin D supplements empirically. Whilst this approach is generally safe, in predisposed individuals it may lead to hypervitaminosis D. Here we present a case where empirical use of high dose vitamin D supplementation had serious consequences highlighting the need to use vitamin D therapy judiciously and to remain vigilant for side-effects in high-risk individuals.

Topics: Aged, 80 and over; Cholecalciferol; Female; Humans; Hypercalcemia; Vitamin D Deficiency; Vitamins

Vitamin D toxicity from unactivated vitamin D (calciferol) therapy is currently a rare cause of hypercalcaemia. However, the frequency of this event may increase as high-dose unactivated vitamin D preparations become available. Prolonged vitamin D toxicity can cause reversible hypercalcaemia and partially reversible renal impairment. Parathyroid hormone may not be suppressed with unactivated vitamin D toxicity, especially if renal disease coexists.

Topics: Acute Kidney Injury; Aged; Cholecalciferol; Disease Progression; Female; Humans; Hypercalcemia; Time Factors

Topics: Antitubercular Agents; Biomarkers; Calcifediol; Calcitriol; Calcium; Cholecalciferol; Dietary Supplements; Glucocorticoids; Humans; Hypercalcemia; Male; Middle Aged; Prednisolone; Severity of Illness Index; Treatment Outcome; Tuberculosis, Pleural; Tuberculosis, Pulmonary; Vitamin D Deficiency

Topics: Adult; Calcium; Cholecalciferol; Female; Humans; Hypercalcemia; Obesity; Parathyroid Hormone; Radiography; Sarcoidosis; Vitamin D; Vitamin D Deficiency

To report a case of hypervitaminosis D resulting in hypercalcemia and acute kidney injury in a 70-year-old female who was prescribed a standard dose of vitamin D but given a toxic dose of vitamin D 50,000 IU (1.25 mg) daily resulting from a dispensing error.. A 70-year-old female in her usual state of health was instructed to begin supplementation with vitamin D 1000 IU daily. Three months later she developed confusion, slurred speech, unstable gait, and increased fatigue. She was hospitalized for hypercalcemia and acute kidney injury secondary to hypervitaminosis D. All vitamin D supplementation was discontinued and 5 months after discharge, the patient's serum calcium and vitamin D concentrations, as well as renal function, had returned to baseline values. Upon review of the patient's records, it was discovered that she had been taking vitamin D 50,000 IU daily.. There is an increased interest in vitamin D, resulting in more health care providers recommending--and patients taking--supplemental vitamin D. Hypervitaminosis D is rarely reported and generally only in the setting of gross excess of vitamin D. This report highlights a case of hypervitaminosis D in the setting of a prescribed standard dose of vitamin D that resulted in toxic ingestion of vitamin D 50,000 IU daily due to a dispensing error. As more and more people use vitamin D supplements, it is important to recognize that, while rare, hypervitaminosis D is a possibility and dosage conversion of vitamin D units can result in errors.. Health care providers and patients should be educated on the advantages and risks associated with vitamin D supplementation and be informed of safety measures to avoid hypervitaminosis D. In addition, health care providers should understand dosage conversion regarding vitamin D and electronic prescribing and dispensing software should be designed to detect such errors.

Topics: Acute Kidney Injury; Aged; Cholecalciferol; Confusion; Drug Dosage Calculations; Ergocalciferols; Female; Fractures, Bone; Humans; Hypercalcemia; Medication Errors; Treatment Outcome

In the present work the effect of subcutaneous administration of 250, 500 and 750 microg (10.000, 20.000 and 30.000 IU, respectively) of vitamin D3 (calciferol) daily for eight days, on serum concentrations of vitamin D3 and 25-hydroxyvitamin D3 (25-OH-D3) and on serum and tissue concentrations of Ca, Zn, Cu and Fe in 45 white male Wistar rats, aged 12 weeks and weighing 180-200 g, have been studied. The group control was integrated by 15 healthy rats with similar characteristics (strain, gender, age and weight) that treated animals. Administration of high doses of calciferol produced a hypervitaminosis D characterized by a significant (p < 0.05) increase in serum vitamin D3 and 25-OH-D3, diverse clinical signs (such as, anorexia, marked loss of body weight, bloody diarrhea, bilateral conjunctivitis, and death), hypercalcemia, hypozincaemia, hypercupremia, hypoferraemia and an alteration in the tissue distribution of Ca, Zn, Cu and Fe as compared with untreated controls. Hypercalcemia and inflammation are prominent findings in hypervitaminosis D. Inflammation or infection induce systemic changes, collectively known as the acute phase response. Among the varied alterations that together produce this response are hypoferraemia, hypozincaemia and hypercupremia. It is likely that these responses are mediated, in part, by production and release of cytokines such as interleukin 1, interferons (IFN-alpha), interleukin 6 (11-6) and tumor necrosis factor (TNF). The development of hypoferraemia during inflammation requires hepcidin, an iron regulatory hormone, a disulfide-rich peptide, produced in the liver in response to the release of I1-6 during inflammation/infection. In conclusion, our results provide evidence that short-term administration of high doses of vitamin D determined diverse clinical signs and produced a marked increase of serum vitamin D3 and 25-OH-D3 and a marked alteration in the serum and tissue concentrations of Ca, Zn, Cu, and Fe. These changes depend on the doses given of vitamin D.

Topics: Animals; Calcifediol; Calcium; Cholecalciferol; Copper; Hypercalcemia; Injections, Subcutaneous; Iron; Kidney; Liver; Male; Rats; Rats, Wistar; Vitamins; Zinc

Vitamin D(3) analogues were shown to be beneficial for osteoporosis and other indications, but their narrow therapeutic window between efficacy and hypercalcemia has limited their clinical utility. A nonsecosteroidal, tissue-selective, orally bioavailable, vitamin D receptor (VDR) ligand was ascertained to be efficacious in bone while having modest calcemic effects in vivo. This compound (VDRM2) potently induced Retinoid X Receptor alpha (RXR)-VDR heterodimerization (EC(50) = 7.1 +/- 1.6 nM) and induced osteocalcin promoter activity (EC(50) = 1.9 +/- 1.6 nM). VDRM2 was less potent in inducing Ca(2+) channel transient receptor potential cation channel, subfamily V, member 6 (TRPV6) expression (EC(50) = 37 +/- 12 nM). VDRM2 then was evaluated in osteopenic ovariectomized (OVX) rats and shown to dose-dependently restore vertebral bone mineral density (BMD) from OVX to sham levels at 0.08 microg/kg per day. Hypercalcemia was observed at a dose of 4.6 microg/kg per day of VDRM2, suggesting a safety margin of 57 [90% confidence interval (CI) 35-91]. 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D], ED71, and alfacalcidol restored BMD at 0.030, 0.0055, and 0.046 microg/kg per day, respectively, whereas hypercalcemia was observed at 0.22, 0.027, and 0.23 microg/kg per day, indicating a safety margin of 7.3, 4.9, and 5.0, respectively (90% CIs 4.1-13, 3.2-7.7, and 3.5-6.7, respectively). Histomorphometry showed that VDRM2 increased cortical bone area and stimulated the periosteal bone-formation rate relative to OVX at doses below the hypercalcemic dose. By contrast, ED71 increased the periosteal bone-formation rate only above the hypercalcemic dose. VDRM2 suppressed eroded surface on trabecular bone surfaces at normal serum calcium dosage levels, suggesting dual anabolic and antiresorptive activity. In summary, vitamin D analogues were more potent than VDRM2, but VDRM2 had a greater safety margin, suggesting possible therapeutic potential.

Topics: Animals; Binding, Competitive; Biological Assay; Biomechanical Phenomena; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Cholecalciferol; Female; Humans; Hypercalcemia; Ligands; Luciferases; Osteocalcin; Protein Multimerization; Rats; Rats, Sprague-Dawley; Receptors, Calcitriol; Retinoid X Receptors; Transcriptional Activation; Treatment Outcome; TRPV Cation Channels

Cytochrome P450scc metabolizes vitamin D3 to 20-hydroxyvitamin D3 (20(OH)D3) and 20,23(OH)(2)D3, as well as 1-hydroxyvitamin D3 to 1alpha,20-dihydroxyvitamin D3 (1,20(OH)(2)D3). It also cleaves the side chain of 7-dehydrocholesterol producing 7-dehydropregnenolone (7DHP), which can be transformed to 20(OH)7DHP. UVB induces transformation of the steroidal 5,7-dienes to pregnacalciferol (pD) and a lumisterol-like compounds (pL).. To define the biological significance of these P450scc-initiated pathways, we tested the effects of their 5,7-diene precursors and secosteroidal products on leukemia cell differentiation and proliferation in comparison to 1alpha,25-dihydroxyvitamin D3 (1,25(OH)(2)D3). These secosteroids inhibited proliferation and induced erythroid differentiation of K562 human chronic myeloid and MEL mouse leukemia cells with 20(OH)D3 and 20,23(OH)(2)D3 being either equipotent or slightly less potent than 1,25(OH)(2)D3, while 1,20(OH)(2)D3, pD and pL compounds were slightly or moderately less potent. The compounds also inhibited proliferation and induced monocytic differentiation of HL-60 promyelocytic and U937 promonocytic human leukemia cells. Among them 1,25(OH)(2)D3 was the most potent, 20(OH)D3, 20,23(OH)(2)D3 and 1,20(OH)(2)D3 were less active, and pD and pL compounds were the least potent. Since it had been previously proven that secosteroids without the side chain (pD) have no effect on systemic calcium levels we performed additional testing in rats and found that 20(OH)D3 had no calcemic activity at concentration as high as 1 microg/kg, whereas, 1,20(OH)(2)D3 was slightly to moderately calcemic and 1,25(OH)(2)D3 had strong calcemic activity.. We identified novel secosteroids that are excellent candidates for anti-leukemia therapy with 20(OH)D3 deserving special attention because of its relatively high potency and lack of calcemic activity.

Topics: Animals; Antineoplastic Agents; Calcifediol; Cell Line, Tumor; Cell Proliferation; Cholecalciferol; Cholesterol Side-Chain Cleavage Enzyme; Dehydrocholesterols; Gene Expression Regulation, Leukemic; HL-60 Cells; Humans; Hypercalcemia; Mice; Pregnenolone; U937 Cells

Pathologic fractures in children may be due to various causes. Rarely, it may be the presenting symptom of neurofibromatosis. A misdiagnosis of Rickets and Vitamin D supplementation in such a case may wreak havoc in the form of iatrogenic hypervitaminosis D. We report one such case.

Topics: Child, Preschool; Cholecalciferol; Diagnostic Errors; Female; Fractures, Spontaneous; Humans; Hypercalcemia; Neurofibromatosis 1; Rickets

Tenofovir-containing antiviral therapy might result in acute renal failure and is able to induce tubular dysfunction with hypocalcemia. On the other hand, hypercalcemia induced by intoxication with colecalciferol has been described to induce renal failure in HIV-positive individuals as well. Here, the authors describe the unusual case of reversible renal failure due to hypercalcemia in a patient with low-dose colecalciferol substitution treated with tenofovir.. A 31-year-old HIV-positive female, CDC stage C3, was admitted to the authors' hospital with progressive renal failure and hypercalcemia. Antiretroviral therapy consisted of tenofovir and emtricitabine in combination with efavirenz. Additionally, she was on low-dose vitamin D(3) substitution (25 microg/d) and calcium supplementation (500 mg/d) due to systemic steroid treatment.. Additionally to regular control of renal function, serologic level of calcium should be supervised in patients concomitantly treated with tenofovir and colecalciferol.

Topics: Acquired Immunodeficiency Syndrome; Acute Kidney Injury; Adenine; Adrenal Cortex Hormones; Adult; AIDS-Related Opportunistic Infections; Alkynes; Anti-HIV Agents; Antitubercular Agents; Benzoxazines; Calcium; Cholecalciferol; Cyclopropanes; Deoxycytidine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Emtricitabine; Female; Humans; Hypercalcemia; Immune Reconstitution Inflammatory Syndrome; Kidney Function Tests; Mycobacterium avium-intracellulare Infection; Organophosphonates; Osteoporosis; Tenofovir

1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] is capable of inhibiting the proliferation of acute myelogenous leukemia (AML). However, toxicity of hypercalcemia has limited the use of 1,25(OH)2D3 in clinical trials. We have evaluated 11 synthesized vitamin D3 analogs for their ability to inhibit clonal growth of HL-60 myeloid leukemic cells. Among the 11 vitamin D3 analogs, HY-11 (code name) showed the most potent antileukemic activity with 2.5x10(-6) M of IC50, however, it did not affect the cellular growth of normal peripheral blood mononuclear cells until 10(-6) M. Flow cytometric analysis indicated that HY-11 induced the G1 arrest in a dose-dependent manner, which was mediated via inactivation of CDK4 and CDK6 in association with up-regulation of CDKI (cyclin-dependent kinase inhibitor), p27 and Rb protein. Induction of apoptosis was mediated via caspase-3 pathway in HY-11-treated HL-60. In addition, HY-11 enhanced the expression of TGF-beta1, TGF-beta receptor type I and II and vitamin D3 receptor (VDR). VDR expression was increased by TGF-beta1, suggesting that TGF-beta1 might be involved in the antiproliferative effect of HY-11 on HL-60 cells by autocrine and paracrine regulation. Serum calcium levels were within normal limit when HY-11 was given intraperitoneally (i.p.) every other day for 5 weeks to BALB/c mice at the doses of 10(-7), 10(-6)and 10(-5) M. HY-11 inhibited the growth of WEHI-3BD+ mouse leukemic cells in vitro, and syngeneic BALB/c mice that received WEHI-3BD+ mouse leukemic cells and HY-11 had a significantly longer survival without producing hypercalcemia compared to control group. In summary, HY-11 is a vitamin D3 analog that inhibited the proliferation of human AML cell line, HL-60, through induction of cell cycle arrest, triggering apoptosis as well as modulation of TGF-beta1 and its receptors. In particular, HY-11 significantly increased the survival of mice that had myeloid leukemia without producing hypercalcemia.

Topics: Animals; Antineoplastic Agents; Calcium; Cell Line, Tumor; Cell Proliferation; Cholecalciferol; HL-60 Cells; Humans; Hypercalcemia; Leukemia, Myeloid; Male; Mice; Mice, Inbred BALB C; Models, Chemical; Neoplasm Transplantation

The tolerable upper intake level (UL) for vitamin D is 50 mcg/d (2000 iu/d) in North America and in Europe. In the United Kingdom a guidance level exists for vitamin D, 25 mcg/d (1000 iu/d), defined as the dose "of vitamins and minerals that potentially susceptible individuals could take daily on a life-long basis, without medical supervision in reasonable safety." Exposure of skin to sunshine can safely provide an adult with vitamin D in an amount equivalent to an oral dose of 250 mcg/d. The incremental consumption of 1 mcg/d of vitamin D3 raises serum 25-hydroxyvitamin D [25(OH)D ] by approximately 1 nmol/L (0.4 microg/L). Published reports suggest toxicity may occur with 25(OH)D concentrations beyond 500 nmol/L (200 microg/L). Older adults are advised to maintain serum 25(OH)D concentrations >75 nmol/L. The preceding numbers indicate that vitamin D3 intake at the UL raises 25(OH)D by approximately 50 nmol/L and that this may be more desirable than harmful. The past decade has produced separate North American, European, and U.K. reports that address UL or guidance-level values for vitamin D. Despite similar well-defined models for risk assessment, each report has failed to adapt its message to new evidence of no adverse effects at higher doses. Inappropriately low UL values, or guidance values, for vitamin D have hindered objective clinical research on vitamin D nutrition, they have hindered our understanding of its role in disease prevention, and restricted the amount of vitamin D in multivitamins and foods to doses too low to benefit public health.

Topics: Adult; Animals; Calcifediol; Cholecalciferol; Dietary Supplements; Food, Fortified; Humans; Hypercalcemia; Nutrition Policy; Nutritional Requirements; Sunlight; Vitamin D; Vitamin D Deficiency

The conflicting results of previous evaluations of the influence of hypercalcemia on thyroid C-cells and the absence of reports on its influence on calcitonin (CT)-producing cells of the airways prompted this study. It aims to evaluate the activity and changing dynamics in CT-producing cells in rat thyroid glands and lungs after prolonged hypercalcemia. The hypercalcemia was induced by an intraperitoneal injection of 100,000IU of vitamin D(3) (Vigantol), Merck). Control and experimental rats were examined after 1, 7 and 14 days. Calcium and CT concentrations were measured in blood plasma. Paraffin wax embedded sections of thyroid and lungs were stained with hematoxylin and eosin. CT was detected immunohistochemically in thyroid C-cells and lung endocrine cells. Results showed increased calcium and CT concentrations in rat blood after vitamin D(3) administration, a statistically significant reduction in number of CT-positive cells in the thyroid with indications of their increased activity, and a statistically non-significant reduction of the number of cells immunopositive for CT in lungs after 1 day, and an increase after 7 days, compared to the control group. Lack of an obvious correlation in lung neuroendocrine cells among the rats with hypercalcemia may indicate the presence of other, perhaps local, functions for calcitonin.

Topics: Animals; Calcitonin; Cholecalciferol; Hypercalcemia; Lung; Male; Rats; Rats, Wistar; Thyroid Gland

Topics: Cerebral Palsy; Cholecalciferol; Female; Growth Disorders; Humans; Hypercalcemia; Infant; Male; Muscle Hypotonia; Pregnancy; Prenatal Exposure Delayed Effects

Freshwater mud eel, Amphipnous cuchia, were injected intraperitoneally daily with 100 ng of vitamin D3/100 g body weight and maintained in media containing either no calcium or different calcium concentrations. The eels were killed after 1, 3, 5, 10 and 15 days following the treatment and their serum calcium levels were measured. The ultimobranchial glands were fixed and processed using the routine paraffin method for histological studies. The results of the present study indicate that vitamin D3 can induce hypercalcaemia in eels kept in different calcium environments. Also, the ultimobranchial glands became hyperactive following vitamin D3 treatment. It is concluded that in mud eels, the gland has a calcium-regulating function.

Topics: Animals; Calcium; Cholecalciferol; Eels; Environment; Female; Fish Diseases; Fresh Water; Hypercalcemia; Male; Ultimobranchial Body

Topics: Animals; Cholecalciferol; Diabetes Mellitus, Type 1; Humans; Hypercalcemia; Infant, Newborn; Islets of Langerhans; Mice; Mice, Inbred NOD

In calcium homeostasis, vitamin D3 is a potent serum calcium-raising agent which in vivo regulates both calcitonin (CT) and parathyroid hormone (PTH) gene expression. Serum calcium is the major secretagogue for CT, a hormone product whose biosynthesis is the main biological activity of thyroid C-cells. Taking advantage of this regulatory mechanism, long-term vitamin D3-induced hypercalcemia has been extensively used as a model to produce hyperactivation, hyperplasia and even proliferative lesions of C-cells, supposedly to reduce the sustained high calcium serum concentrations. We have recently demonstrated that CT serum levels did not rise after long-term hypervitaminosis D3. Moreover, C-cells did not have a proliferative response, rather a decrease in CT-producing C-cell number was observed. In order to confirm the inhibitory effect of vitamin D3 on C-cells, Wistar rats were administered vitamin D3 chronically (25,000 IU/d) with or without calcium chloride (CaCl2). Under these long-term vitamin D3-hypercalcemic conditions, calcium, active metabolites of vitamin D3, CT and PTH serum concentrations were determined by RIA; CT and PTH mRNA levels were analysed by Northern blot and in situ hybridization; and, finally, the ultrastructure of calciotrophic hormone-producing cells was analysed by electron microscopy. Our results show, that, in rats, long term administration of vitamin D3 results in a decrease in hormone biosynthetic activities of both PTH and CT-producing cells, albeit at different magnitudes. Based upon these results, we conclude that hypervitaminosis D3-based methods do not stimulate C-cell activity and can not be used to induce proliferative lesions of calcitonin-producing cells.

Topics: Administration, Oral; Analysis of Variance; Animals; Blotting, Northern; Calcitonin; Calcium; Cholecalciferol; Hypercalcemia; Immunohistochemistry; Male; Microscopy, Electron; Parathyroid Hormone; Radioimmunoassay; Rats; Rats, Wistar; RNA, Messenger; Time Factors

Topics: Adult; Cholecalciferol; Diagnosis, Differential; Dietary Supplements; Humans; Hypercalcemia; Male; Nonprescription Drugs; Vitamin D

The chronotherapeutic effects of 1-alpha-(OH) vitamin D3, a pro-drug of 1,25(OH)2 vitamin D3 (1,25(OH)2D3), were evaluated by repeated dosing of the drug in aged stroke-prone spontaneously hypertensive male rats, a model of osteoporosis. Animals (7 months old) were kept in rooms with a 12-h light/dark cycle. Drug (0.5 microg/kg) or vehicle was given once daily at 2 or 14 h after lights on for 3 months. The severity of adverse effects such as body weight loss, hypercalcemia and hyperphosphatemia was significantly less when the drug was given at 14 h after lights on (14 HALO). Serum 1,25(OH)2 vitamin D3 concentrations of 2 h after lights on (2 HALO) group and 14 HALO group did not differ significantly after dosing. The decrease in parathyroid hormone (PTH) level 12 weeks after the start of the study was greater in the 14 HALO group than in the 2 HALO group. Urinary excretion of inorganic Ca and P in the 2 HALO group was greater than that in the 14 HALO group. Urinary excretion of deoxypyridiniline, an index of the bone resorption capacity of osteoclasts, was much suppressed in the 14 HALO group, suggesting that the efficacy of vitamin D3 for suppressing bone resorption might vary with the dosing time. The increase in bone density of both femurs, determined by dual-energy X-ray absorption at the end of the study, was greater in the 14 HALO group than in the 2 HALO group. This is the first study to show the dosing time-dependent efficacy and toxicity of active vitamin D3 in an animal model of osteoporosis. These results indicate that a chronopharmacological approach is beneficial for establishing a more effective and/or safer regimen of active vitamin D3 for the treatment of osteoporosis.

Topics: Aging; Amino Acids; Animals; Body Weight; Bone Density; Calcium; Cholecalciferol; Chronotherapy; Disease Models, Animal; Hypercalcemia; Hypertension; Male; Osteoporosis; Parathyroid Hormone; Phosphates; Rats; Rats, Inbred SHR; Steroid Hydroxylases; Time Factors; Weight Loss

The objectives of this study were to develop a novel approach to postmortem diagnosis of cholecalciferol (CCF) toxicosis in dogs using kidney, bile, and urine samples, and to differentiate CCF from ethylene glycol (EG) toxicosis. To achieve these objectives, specimens collected from 2 previous laboratory studies in which dogs were given a single oral toxic dose of CCF (8.0 mg/kg) were used. For EG toxicosis, historical data from the previous 13 years (1985-1998) were reviewed and confirmed cases of EG toxicosis were selected. The historical data were used to compare trace mineral concentrations, specifically of calcium and phosphorus to differentiate between intoxications caused by CCF from that caused by EG in dogs. Kidneys, bile, and urine from dogs that died of CCF toxicosis were analyzed for 25 monohydroxy vitamin D3 (25(OH)D3) and 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) and compared to known control unexposed dogs. Results of this study show that biliary and renal 25(OH)D3 concentrations and renal calcium to phosphorus ratio are of diagnostic value in dogs exposed to toxic concentrations of CCF. The renal calcium to phosphorus ratio was <0.1 in normal dogs, 0.4-0.9 in dogs that died of CCF toxicosis, and >2.5 in dogs that died of EG toxicosis.

Topics: Animals; Bile; Calcium; Cholecalciferol; Diagnosis, Differential; Dog Diseases; Dogs; Ethylene Glycol; Hypercalcemia; Kidney; Phosphorus; Tissue Distribution; Urinalysis

To determine whether pamidronate disodium can reduce vitamin D3-induced hypercalcemia in dogs and whether combination treatment with calcitonin is more effective than treatment with pamidronate alone.. 20 clinically normal male Beagles.. All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were assigned randomly to 4 groups of 5 dogs each. Dogs were given 0.9% NaCl solution IV (group 1), calcitonin SC and 0.9% NaCl solution IV (group 2), pamidronate and 0.9% NaCl solution IV (group 3), or a combination of all 3 agents (group 4). Dogs were observed for 28 days, and serial blood and urine samples were collected for determination of serum biochemical, electrolyte, and 25(OH)D3 values, CBC, and urine mineral excretion. Samples of kidney, stomach, lung, aorta, liver, duodenum, and brain were evaluated by light microscopy and quantitative mineral analysis.. Two dogs in group 1 were euthanatized 4 days after CCF administration because of severe clinical signs of disease. Dogs in group 3 lost less weight and had significantly lower serum phosphorus, total and ionized calcium, and urinary zinc concentrations, compared with dogs in group 1. On day 4, serum urea nitrogen concentration was significantly lower in dogs of groups 3 and 4, compared with dogs in group 1. Mild to moderate mineralization of kidneys and stomach were observed in the 2 group-1 dogs euthanatized on day 4.. Pamidronate administration effectively prevents CCF-induced hypercalcemia and mineralization of soft tissues.. Pamidronate is a potentially useful antidote against CCF toxicosis in dogs.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Blood Chemical Analysis; Calcitonin; Cholecalciferol; Creatinine; Diphosphonates; Dog Diseases; Dogs; Hypercalcemia; Ion-Selective Electrodes; Kidney Cortex; Male; Pamidronate; Radioimmunoassay; Random Allocation; Urea; Zinc

Vitamin D is required for the normal development of teeth and bones. When there is excess vitamin D, systemic and dental changes may occur. This is a case report of a girl who experienced hypercalcemia secondary to excess vitamin D derived from the consumption of milk that was incorrectly fortified. The changes in the permanent dentition to date are enamel hypoplasia and focal pulp calcification. These changes correspond to the timing of the toxemia caused by hypervitaminosis D.

Topics: Animals; Bone Development; Child; Cholecalciferol; Dental Enamel Hypoplasia; Dental Pulp Calcification; Female; Food, Fortified; Humans; Hypercalcemia; Milk; Nephrocalcinosis; Odontogenesis; Tooth Calcification; Tooth Discoloration

Many papers have reported that chronic hypercalcemia induced either by large doses of vitamin D or by the administration of calcium or parathormone, produces hypertrophy and hyperplasia of C cells. However, more recent studies suggest that the effect of elevated calcium or 1.25(OH)2D3 concentration on the production of calcitonin may be more complex than previously suspected. To assess the validity of such a response an experimental model, where hypercalcemia was induced with vitamin D3 overdose, was designed. Male Wistar rats were administered vitamin D3 chronically (50,000 IU per 100 ml of drinking water with or without CaCl2). Serum calcium and calcitonin levels were determined. C cells were stained by immunohistochemistry using calcitonin and neuronal specific enolase (NSE) antibodies and their percentage was calculated by a morphometric analysis. We also investigated the ultrastructural characteristic of the C cells under experimental conditions. C cells did not have a proliferative response rather a decrease in their number was observed after 1 month of treatment with 25,000 IU of vitamin D3 (1.55 vs 2.43% in control animals) and 3 months with vitamin plus CaCl2 (2.27% vs 3.62% in control animals). In addition, no significant changes in serum calcitonin levels were observed during the experimental period. We conclude that rat C cells do not respond with hypertrophic and hyperplastic changes in a hypercalcemic state due to an intoxication with vitamin D3.

Topics: Animals; Calcitonin; Calcium; Calcium Chloride; Cell Count; Cholecalciferol; Cytoplasmic Granules; Hypercalcemia; Immunohistochemistry; Male; Phosphopyruvate Hydratase; Rats; Rats, Wistar; Thyroid Gland

We report on a 61-year-old woman with coexisting early stage primary gastric plasmacytoma and sarcoidosis with hypercalcaemia. Laboratory data on admission showed hypercalcaemia, with 12.8 mg/dl, parathyroid hormone-related peptide (PTHrP) 1.2 pmol/l, C-PTHrP 69.5 pmol/l, and 1,25-dihydroxyvitamin D3 46.7 pg/ml. Neoplastic plasma cells proliferated in the propria mucosa of the stomach, showed a monoclonal immunoglobulin of cytoplasmic IgA (lambda light chain) and were positive for leucocyte common antigen and epithelial membrane antigen on paraffin section prepared from a stomach biopsy specimen. Russel bodies were present, as were crystals. Abundant sarcoid granulomas were observed in many of the regional lymph nodes around the stomach and in the dermis of a skin nodule. The patient underwent subtotal gastrectomy with administration of antimyeloma chemotherapy. We suggest that the hypercalcaemia in this patient was due to PTHrP production by neoplastic plasma cells.

Topics: Cholecalciferol; Female; Humans; Hypercalcemia; Immunohistochemistry; Middle Aged; Neoplasm Proteins; Parathyroid Hormone-Related Protein; Plasmacytoma; Proteins; Sarcoidosis; Stomach Neoplasms

Two cases of vitamin D3 intoxication in piglets are described. The dietary concentrations of vitamin D3 were 265 and 435 thousand IE/kg. Decreased feed intake, growth depression and polyuria or polydypsia were observed. In some animals hypercalcemia and symptoms of impaired renal function were found. Pathological findings included calcinosis of several tissues and degenerative damage.

Topics: Animal Feed; Animals; Calcinosis; Cholecalciferol; Feeding and Eating Disorders; Foodborne Diseases; Hypercalcemia; Kidney; Swine; Swine Diseases

Topics: Bone Density; Calcitriol; Cholecalciferol; Dose-Response Relationship, Drug; Ergocalciferols; Female; Fractures, Spontaneous; Humans; Hydroxycholecalciferols; Hypercalcemia; Osteoporosis, Postmenopausal; Spinal Fractures; Vitamin D

1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25(OH)2D3) has recently been reported to exert a toxic effect on both rat and human glioma cell lines. However the potential clinical use of 1 alpha,25(OH)2D3 in the treatment of glioma is impaired by its potent hypercalcemic effects. We have therefore investigated the effects on glioma cell growth of several vitamin D3 analogues which have previously been shown to be less calcemic in vivo than 1 alpha,25(OH)2D3. The present study shows that several analogues are able to induce, in vitro, the death of rat glioma cells (C6.9). The compound KH 1060 appears to be the most effective in the induction of cell death, while MC 1288 and CB 1093 are as potent as 1 alpha,25(OH)2D3. EB 1089 was somewhat less effective than 1 alpha,25(OH)2D3 and MC 903, which is currently used in the treatment of psoriasis, has only a weak activity on C6.9 cells. The effective doses used are around 10(-9) M for 1 alpha,25(OH)2D3 and 10(-10) M for KH 1060. Interestingly, the toxic effect exerted by 1 alpha,25(OH)2D3 and its analogues is accompanied by several of the biochemical features of apoptosis, such as DNA fragmentation and induction of the c-myc protooncogene. These findings, together with the fact that the therapies currently available for glioma are only palliative, suggest that 1 alpha,25(OH)2D3 analogues such as KH 1060, EB 1089 or CB 1093, alone or in combination with other therapeutic approaches, could be of potential interest in the treatment of brain glial tumors.

Topics: Animals; Calcitriol; Calcium; Cell Death; Cholecalciferol; DNA Damage; DNA, Neoplasm; Drug Screening Assays, Antitumor; Gene Expression; Genes, myc; Glioma; Homeostasis; Hypercalcemia; Rats; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured

Hypercalcemia is often associated with a urinary concentration defect. During antidiuresis, organic osmolytes [sorbitol, myo-inositol, taurine, and glycerophosphorylcholine (GPC)] accumulate in the renal inner medulla and are essential for urinary concentration. To clarify the relationship between organic osmolytes and urinary concentration defect in hypercalcemia, examination was made of the effects of hypercalcemia on renal medullary osmolytes content. Rats were put in a state of hypercalcemia by a calcium-rich diet supplemented with CaCO3 (2.5%/wt) and daily s.c. injection of 1.25(OH)2VitD3 (1.6 micrograms/kg). They were killed on days 7 and 14. Hypercalcemia induced a urinary concentration defect. Myo-inositol, sorbitol, and GPC contents in the renal medulla were significantly reduced. Aldose reductase activity decreased significantly. Hypercalcemia would thus appear to directly affect renal medullary content of organic osmolytes, thereby modifying renal concentration ability.

Topics: Aldehyde Reductase; Animals; Calcium, Dietary; Cholecalciferol; Chromatography, High Pressure Liquid; Hypercalcemia; Kidney Concentrating Ability; Kidney Medulla; Male; Osmolar Concentration; Rats; Rats, Wistar; Time Factors

Topics: Animals; Bone Resorption; Cholecalciferol; Depression, Chemical; Diphosphonates; Disease Models, Animal; Female; Hypercalcemia; Imidazoles; Ovariectomy; Pamidronate; Parathyroidectomy; Rats; Thyroidectomy; Zoledronic Acid

Thyroid and parathyroid glands from normal adult sheep and sheep with vitamin D3-induced hypercalcemia were evaluated immunohistochemically for the presence of parathyroid hormone-related protein (PTHrP) and calcitonin (CT). Thyroid follicular cells, C-cells, and parathyroid chief cells stained moderately to strongly positive for PTHrP in both groups of sheep. C-cells were identified as cells positive for cytoplasmic staining of CT. Staining of C-cells for calcitonin in hypercalcemic sheep was diminished in intensity. The data demonstrated that PTHrP is present in the sheep thyroid and parathyroid glands. PTHrP may function as a local paracrine factor in these organs, but its staining intensity was not affected by the induction of hypercalcemia.

Topics: Animals; Calcitonin; Cholecalciferol; Hypercalcemia; Immunoenzyme Techniques; Immunohistochemistry; Male; Parathyroid Hormone-Related Protein; Proteins; Sheep; Thyroid Gland

Naked mole-rats have no access to obvious sources of vitamin D and therefore have an impoverished vitamin D status. In an investigation into the effects of vitamin D supplementation, inadvertently supraphysiological doses of 130,000 times the normal dose of vitamin D were administered. Within 5 days animals appeared lethargic, with reduced food intake. All but one of the seven animals were killed and blood was collected. Plasma vitamin D metabolites 25(OH)D and 1,25(OH)2D and calcium were determined. Both vitamin D metabolite concentrations exceeded the upper limits of sensitivity of the assays (> 100 ng/ml 25(OH)D and > 210 pg/ml 1,25(OH)2D). Active calcium uptake in the intestine was evident along with concomitant increases in calcium concentration in plasma, bone, and teeth. The remaining animal survived, but showed scab-like formations in the skin around the lower jaw and along the nipple line. X-ray analyses revealed calcium deposition in these cornified regions, although there was no evidence of metastatic calcification in other tissues. Deposition of excess calcium in skin that is regularly sloughed off and in teeth that are continuously worn down and replaced may reduce the vitamin D-induced hypercalcaemia and thus alleviate the effects of vitamin D intoxication.

Topics: Animals; Calcinosis; Calcium; Cholecalciferol; Hypercalcemia; Rodent Diseases; Rodentia; Skin Diseases; Tooth

In vitro, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) induces differentiation of HL-60 cells and inhibits their proliferation as well as the proliferation of leukemic cells from patients. In vivo, the survival of mice challenged with syngeneic leukemic cells is enhanced by treatment with 1,25(OH)2D3. Patients treated with 1,25(OH)2D3 develop hypercalcemia at a serum level of 2 x 10(-10) mol/l which is a concentration too low to achieve an antileukemic effect in vitro. Several interesting vitamin D3 analogs have recently been developed. We initially examined the effect of 1,25(OH)2-16ene-23yne-19-nor-26,27-F6-D3 and 24a,26a,27a-tri-homo-22,24-diene-1-alpha,25-(OH)2-D3 on clonal growth and differentiation of HL-60 cells. Each of the analogs had comparable effects on clonal growth with 50% inhibition (ED50) at concentrations of 0.2-0.5 x 10(-9) M; 1,25(OH)2D3 was about 20- to 50-fold less active in inhibiting growth. Differentiation was determined by induction of superoxide production, as measured by nitroblue tetrazolium (NBT) reduction and by expression of a macrophage-specific enzyme (alpha napthyl acetate esterase (ANAE)). The 24a,26a,27a-tri-homo-22,24-diene-1-alpha,25-(OH)2-D3 and 1,25(OH)2-16ene-23yne-19-nor-26,27-F6-D3 were about 5- to 14-fold more potent than 1,25(OH)2D3. The hypercalcemia inducing side-effects of these analogs and three other previously identified, extremely potent vitamin D3 compounds, as well as 1,25(OH)2D3, were studied. The analogs were administered intraperitoneally every other day (qod) for 5 weeks; serum was collected weekly and Ca2+ measured by atomic absorption spectrophotometry. The highest tolerated dose of each analog leaving all mice alive was for 1,25(OH)2D3: 0.25 micrograms; 1,25(OH)2-24a,26a,27a-tri-homo-22,24-diene-D3: 0.25 micrograms; and 1,25(OH)2-16ene-23yne-19-nor-26,27-F6-D3: 0.0625 micrograms. Another hexafluoro compound with potent abilities to induce differentiation (1,25(OH)2-16ene-23yne-26,27-F6-D3) was very toxic, all mice died in the second week while receiving 0.0625 micrograms qod. Prior studies showed that the most potent compound in inducing differentiation of HL-60 was 1,25(OH)2-20-epi-D3; but it is very toxic as only one mouse survived a dose of > or = 0.0125 micrograms qod for 5 weeks. 1,25(OH)2-16ene-23yne-D3 is an extremely active inducer of differentiation but, on the other hand, it has low potential to produce hypercalcemia; mice maintained normal serum calcium levels even while receiving 2 microg

Topics: Animals; Bone Marrow; Bone Marrow Cells; Calcium; Cell Differentiation; Cell Division; Cholecalciferol; Clone Cells; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Mice; Mice, Inbred BALB C; Tumor Cells, Cultured

To determine whether 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] exerts unique biologic effects on bone, we examined the effects of the vitamin D metabolites, 24R,25(OH)2D3 and 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], on the hypophosphatemic (Hyp) mouse, a model for X-linked hypophosphatemic rickets in humans. The Hyp mice were administered 1-10,000 micrograms/kg/day of 24R,25(OH)2D3, 0.01-10 micrograms/kg/day of 1 alpha,25(OH)2D3, or vehicle alone, given daily for 28 days by intraperitoneal injection. 24R,25(OH)2D3 at doses of 1-1000 micrograms/kg/day had dose-dependent effects in increasing bone size, dry bone weight, and bone mineral content without causing hypercalcemia. 1 alpha,25(OH)2D3 at doses of 1 or 10 micrograms/kg/day, which we considered to have activity similar to that of 1000 micrograms/kg/day of 24R,25(OH)2D3 with respect to cell differentiation activity, caused severe bone resorption and hypercalcemia. At 0.1 microgram/kg/day, 1 alpha,25(OH)2D3 increased bone size, similarly to a dose of 1000 micrograms/kg/day of 24R,25(OH)2D3, without significantly affecting dry bone weight or bone mineral content, as did 1000 micrograms/kg/day of 24R,25(OH)2D3. These findings suggest that 24R,25(OH)2D3 exerts unique activity in the Hyp mouse rather than merely mimicking the activity of 1 alpha,25(OH)2D3.

Topics: Animals; Bone Density; Bone Development; Calcitriol; Cholecalciferol; Disease Models, Animal; Drug Administration Schedule; Hypercalcemia; Hypophosphatemia; Injections, Intraperitoneal; Male; Mice; Mice, Inbred C57BL; Radiography

Compounds that induce cancer cells to differentiate are clinically effective for several types of malignancies. The 1,25-dihydroxyvitamin D3[1,25(OH)2D3(C)] induces leukemic cells, including HL-60, to differentiate and/or no longer proliferate, but it causes hypercalcemia. Development of vitamin D analogs that are more potent in their abilities to affect leukemic cells without causing greater hypercalcemia, may be useful therapeutically. A novel analog [1,25(OH)2-16ene-D3(HM)] has a double bond between C-16 and C-17; it appears to be an extremely effective antileukemic agent with the same or fewer effects on serum calciums. We define the potency of this compound and compare it with seven, previously reported, potent analogs of 1,25(OH)2D3. HM inhibited clonal growth of HL-60 cells by 50% at 1.5 x 10(-11) M. This was about equipotent to 1,25(OH)2-16ene-23yne-D3(V), about 100-fold more potent than many of the other analogs, and 1000-fold more potent than 1,25(OH)2D3. The rank order of leukemic inhibitory activity was: 1,25(OH)2-16ene-D3(HM) > or = 1,25(OH)2- 16ene-23yne-D3(V) > 1,25(OH)2-23ene-D3(EX) = 1,24(OH)2-22ene-24-cyclopropyl-D3(BT) = 22-oxa- 1,25(OH)2D3(EU) = 1,25(OH)2-24-homo-D3(ER) > 1,25(OH)2D3(C) > 1,25(OH)2-24- dihomo-D3(ES). The rank order of their effects on induction of differentiation of HL-60 cells, as measured by superoxide production and nonspecific esterase activity, was similar to their antiproliferative activities. In contrast, each analog slightly stimulated proliferation of normal human myeloid clonal growth. Serum calcium levels were the same or slightly less when either 1,25(OH)2-16ene-D3(HM) or 1,25(OH)2D3 (0.0625, 0.125, or 0.25 microgram) was given intraperitoneally to mice for 5 weeks. HM bound to 1,25(OH)2D3 receptors about 1.5-fold more avidly than 1,25(OH)2D3. In fact, this vitamin D3 appears to be the most avid binder to 1,25(OH)2D3 receptors that has been identified to date. In contrast, HM had a greater than 50-fold lower affinity for the D-binding proteins as compared with 1,25(OH)2D3, thus increasing the availability of the compound for target tissues. Further differentiation experiments showed that HM was more potent than 1,25(OH)2D3 in the presence of serum, but was equipotent in serum-free conditions. Taken together, our experiments suggest that 1,25(OH)2-16ene-D3(HM) may be more potent than 1,25(OH)2D3(C) because of its higher affinity to the 1,25(OH)2D3 receptors and its low affinity to the D-binding protein prese

Topics: Antineoplastic Agents; Calcitriol; Calcium; Cell Differentiation; Cell Division; Cell Line; Cholecalciferol; Dose-Response Relationship, Drug; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Molecular Structure; Structure-Activity Relationship; Tumor Cells, Cultured; Tumor Stem Cell Assay; Vitamin D-Binding Protein

A case of sarcoidosis is described which presented with hypercalcaemia and renal insufficiency. Initially, a calciol intoxication was diagnosed, because a high daily intake was suspected. However, vitamin D3 metabolites in the blood revealed normal concentrations of calcidiol, but extremely high concentrations of calcitriol. These features rejected the first diagnosis and pointed to high endogenous calcitriol production, which may take place in granulomatous diseases. This is caused by an increased 1-alpha-hydroxylation reaction in activated macrophages. Eventually, muscle biopsy revealed non-caseating granulomas, confirming the diagnosis of sarcoidosis.

Topics: Aged; Calcitriol; Cholecalciferol; Diagnosis, Differential; Female; Humans; Hypercalcemia; Muscles; Poisoning; Renal Insufficiency; Sarcoidosis

Vitamin D has been added to milk in the United States since the 1930s to prevent rickets. We report the unusual occurrence of eight cases of vitamin D intoxication that appear to have been caused by excessive vitamin D fortification of dairy milk.. Medical records were reviewed and a dietary questionnaire was sent to eight patients who had unexplained hypervitaminosis D. Vitamin D analyses with high-performance liquid chromatography were performed on samples of the patients' serum, the dairy milk they drank, and the vitamin D concentrate added to the milk.. All eight patients drank milk produced by a local dairy in amounts ranging from 1/2 to 3 cups (118 to 710 ml) daily. All had elevated serum 25-hydroxyvitamin D concentrations (mean [+/- SD], 731 +/- 434 nmol per liter [293 +/- 174 ng per milliliter]). Six of the eight patients had elevated serum vitamin D3 concentrations. Of the eight patients, seven had hypercalcemia and one had hypercalciuria but normocalcemia (mean serum calcium, 3.14 +/- 0.51 mmol per liter [12.6 +/- 2.1 mg per deciliter]). Analysis of the dairy's vitamin D-fortified milk revealed concentrations of vitamin D3 (cholecalciferol) that ranged from undetectable to as high as 232,565 IU per quart (245,840 IU per liter). An analysis of the concentrate that was used to fortify the milk, labeled as containing vitamin D2 (ergocalciferol), revealed that it contained vitamin D3.. Hypervitaminosis D may result from drinking milk that is incorrectly and excessively fortified with vitamin D. Milk that is fortified with vitamin D must be carefully monitored.

Topics: Adult; Aged; Aged, 80 and over; Animals; Calcifediol; Calcium; Cholecalciferol; Diet; Ergocalciferols; Female; Food, Fortified; Humans; Hypercalcemia; Male; Milk; Surveys and Questionnaires; Vitamin D

Pamidronate (disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate, CGP 23339A, CAS 57248-88-1) has been show to provide a potent antihypercalcemic effect through the inhibition of calcium release from the bone. The time course study on the antihypercalcemic effect of pamidronate was performed using a rat hypercalcemia model induced by orally administered cholecalciferol. The onset of the antihypercalcemic effect was observed within 48 h after a single i.v. injection of pamidronate at 1 mg/kg and this effect was sustained for 19 days. The time course of the antihypercalcemic effect of pamidronate in combination with calcitonin was also examined in the same model. The onset of the antihypercalcemic effect was observed within 4 h after combination therapy with a single i.v. injection of pamidronate at 1 mg/kg and successive i.m. injections of calcitonin at 3.2 IU/kg and the effect was of sufficient duration. These results suggest that pamidronate has a pronounced effect in controlling hypercalcemia and provides a long-lasting effect by a single i.v. administration. Moreover, the use of pamidronate in combination with calcitonin may be useful when a quicker onset of action is required clinically.

Topics: Animals; Body Weight; Calcitonin; Calcium; Cholecalciferol; Diphosphonates; Female; Hypercalcemia; Pamidronate; Phosphates; Rats; Rats, Inbred Strains

The mineralization process was investigated in the aortic wall of hypercalcemic rabbits. The elevated calcium level in serum was induced by intramuscular injection of vitamin D3. The animals were killed at different times of the experiment (max. 246 d). The freeze-dried tissue homogenates were used for elemental composition studies by means of proton induced X-ray emission (PIXE) and atomic absorption spectroscopy. The structural information was obtained from infrared (IR) and X-ray diffraction (XRD) spectra. Moreover, the ascending part of the aortic arch was separated and used for micro-PIXE (PIXE in combination with proton microprobe) and histochemical examinations. It was found that hypercalcemia (blood serum Ca content elevated by about 20%) induced calcification of the aortic wall. The mineral phase within the aortic wall consisted of Ca-P salts. The Ca/P ratio continuously increased during the experiment and approached 2 after 246 d of the vitamin D3 treatment. The IR and XRD studies made possible the identification of the complex phase composition of the samples. The hydroxyapatite crystals were detected after 196 days, however, in earlier phases of the experiment, amorphous calcium phosphate, dicalcium phosphate dihydrate and octacalcium phosphate were also observed. On the basis of the data obtained, the mechanism of the precipitation and growth of inorganic deposits in the tunica media of the aortic wall was discussed.

Topics: Animals; Aortic Diseases; Calcinosis; Calcium; Calcium Phosphates; Cholecalciferol; Hypercalcemia; Phosphorus; Rabbits; Spectrometry, X-Ray Emission

Hypercalcaemia occurs in two forms: mild and severe. In the mild form, usually in young infants the characteristic signs of the severe from (Williams syndrome) are absent, and thus it may cause diagnostic difficulties. Because of that, in infants with muscular hypotonia, growth arrest, constipation and apathy the possibility of idiopathic hypercalcaemia, apart from rickets, should be considered.

Topics: Cholecalciferol; Drug Hypersensitivity; Female; Humans; Hypercalcemia; Infant; Medication Errors; Rickets

Vitamin D3, 25(OH) vitamin D3 and 1,25 (OH)2D3 were administered daily to unfed male Bufo andersoni for 15 days which resulted in a significant hypercalcemia and hyperphosphatemia in a dose-dependent fashion. 1,25(OH)2D3 is more potent than the other metabolites. The treatment activated ultimobranchial gland but induced degenerative changes in parathyroid of the toads.

Topics: Animals; Bufonidae; Calcifediol; Calcitriol; Calcium; Cholecalciferol; Dose-Response Relationship, Drug; Hypercalcemia; Male; Parathyroid Glands; Phosphates; Ultimobranchial Body

Hyperplasia and hypertrophy of C cells were demonstrated in sheep with hypercalcaemia induced by administration of vitamin D3 (2 million I.U. per day). After treatment with vitamin D3 for 10, 20 or 30 days, serum calcium values increased to 10.28, 11.86 and 10.44 mg per dl, respectively, compared to a normal concentration of around 9 mg per dl. Immunohistochemical reactions of calcitonin, chromogranin A and calcitonin gene-related peptide (CGRP) decreased, whereas intense neurone-specific enolase (NSE) immunoreactivity was noted in C cells. Immunohistochemical staining with anti-calcitonin, anti-chromogranin A, anti-CGRP and anti-NSE antisera was useful to demonstrate the functional state of stimulated C cells in sheep with hypercalcaemia.

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Calcium; Cholecalciferol; Chromogranin A; Chromogranins; Hypercalcemia; Hyperplasia; Hypertrophy; Phosphopyruvate Hydratase; Sheep; Thyroid Gland

The effects of different treatment regimens and the influence of parental height on the statural growth of 40 patients with hereditary vitamin D-resistant hypophosphatemic rickets were investigated. Three treatment regimens, each with oral phosphate, were used: vitamin D (0.5 to 2 mg/day), calcidiol (50 to 200 micrograms/day), and 1 alpha-hydroxyvitamin D3 (1 to 3 micrograms/day). Mean duration of follow-up was 9.5 +/- 5.1 years. The results show that (1) there was no acceleration of growth before puberty for the majority of children treated with vitamin D (12/16) or calcidiol (13/15), whereas 1 alpha-hydroxyvitamin D3 promoted catch-up growth in 10 of 16 patients; (2) height gain during puberty was normal, irrespective of the treatment; (3) most vitamin D-treated male and female subjects and calcidiol-treated male subjects had short adult stature, but the majority (75%) of the 1 alpha-hydroxyvitamin D3-treated groups had normal stature; (4) parental stature had little influence on the adult height of male subjects, but that of affected girls was positively correlated (p less than 0.002) with mid-parental height. These results demonstrate that 1 alpha-hydroxyvitamin D3 is superior to vitamin D or calcidiol for improvement of stature of patients with hypophosphatemic vitamin D-resistant rickets, and indicate the importance of parental height in determining the adult height of affected girls.

Topics: Body Height; Child, Preschool; Cholecalciferol; Ergocalciferols; Female; Growth; Humans; Hypercalcemia; Hypophosphatemia, Familial; Male; Parathyroid Hormone; Parents; Phosphates; Phosphorus; Puberty; Retrospective Studies; Vitamin D

Hypercalcemia secondary to cholecalciferol rodenticide toxicosis was identified in two dogs. The first dog died shortly after admission. The second dog responded to treatment with sodium chloride solution, prednisolone, furosemide, and calcitonin. Treatment was needed for a longer period than anticipated and the serum calcium concentration did not stabilize for approximately one month. Although not conclusively demonstrated, calcitonin was considered the cause of severe anorexia. This new class of rodenticides has great toxic potential for dogs, and it is recommended that serum calcium concentration be carefully monitored as treatment for hypercalcemia is gradually withdrawn.

Topics: Animals; Cholecalciferol; Dog Diseases; Dogs; Female; Hypercalcemia; Male; Rodenticides

Calcitonin was used in conjunction with saline diuresis, furosemide, and prednisone in treatment of a dog that consumed a rodenticide that contained cholecalciferol and has been touted as safe for nontarget species. This report shows that the rodenticide is toxic to dogs and that salmon calcitonin is a useful treatment for the often refractory hypercalcemia induced by vitamin D toxicosis.

Topics: Animals; Calcifediol; Calcitonin; Cholecalciferol; Combined Modality Therapy; Dog Diseases; Dogs; Fluid Therapy; Hypercalcemia; Male; Rodenticides

The in vivo immunoregulating activity and the hypercalcemic action of 4 synthetic analogues of vitamin D3 with an oxygen atom in the side chain were compared with those of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] in mice. Oral administration of these vitamin D3 compounds augmented the primary immune response, induced by immunization with a suboptimal number of sheep erythrocytes, without inducing hypercalcemia. The order of the in vivo potency to induce the immune response was 22-oxa-1 alpha,25(OH)2D3 greater than 1 alpha,25(OH)2D3 not equal to 20-oxa-1 alpha,25(OH)2D3 not equal to 22-oxa-1 alpha(OH)D3 greater than 1 alpha(OH)D3 not equal to 20-oxa-1 alpha(OH)D3. 22-Oxa-1 alpha,25(OH)2D3 was about 50 times more potent than 1 alpha,25(OH)2D3 in inducing the in vivo primary immune response, but the former was only 1/100 as active as the latter in inducing hypercalcemia. These results suggest that the immunoregulating activity of vitamin D compounds can be separated structurally from their hypercalcemic action in vivo.

Topics: Animals; Calcitriol; Calcium; Cholecalciferol; Dose-Response Relationship, Drug; Ergocalciferols; Female; Hypercalcemia; Immune System; Mice; Mice, Inbred BALB C

Vitamin D3 in the presence of calcium lactate induced significant hypercalcemia and hyperphosphatemia while calcitonin in the presence of a chelating agent (EGTA) induced hypocalcemia and hypophosphatemia in the rat lens. The physiologic significance of these changes in relation to cataract formation was understood by correlating the ratio of calcium and phosphate in the rat lens with the similar ratio obtained from human cataractous lenses of cortical and nuclear types.

Topics: Animals; Calcitonin; Calcium; Cataract; Cholecalciferol; Egtazic Acid; Humans; Hypercalcemia; Lactates; Lactic Acid; Lens, Crystalline; Male; Phosphates; Rats

Male Fischer-344 rats, 21 days old, were fed diets containing 0 (LOD), 2,200 (CONT), or 440,000 (HID) international units of vitamin D3 per kilogram for 12 weeks. [Ca] was measured in plasma, CSF, brain, and choroid plexus. In addition, 45Ca and 36Cl transfer coefficients (KCa and KCl) for uptake from blood into CSF and brain were determined. Although plasma ionized [Ca]s in LOD and HID rats were 50% and 136%, respectively, of values in CONT animals, CSF and brain [Ca]s ranged from only 85% to 110% of respective CONT values. Choroid plexus [Ca] was increased by 37% after HID diet, but was decreased only 10% after LOD. KCa values at CSF, parietal cortex, and pons-medulla were negatively correlated with plasma ionized [Ca], whereas KCl values at CSF and brain were not different between the diet groups. The findings demonstrate that central nervous system [Ca] is maintained during chronic hypo- or hypercalcemia by saturable transport of Ca at brain barrier membranes. This transport does not seem to involve modulation by 1,25-dihydroxyvitamin D3.

Topics: Animals; Brain; Calcium; Calcium Radioisotopes; Chlorides; Cholecalciferol; Choroid Plexus; Diet; Hypercalcemia; Hypocalcemia; Male; Potassium; Rats; Rats, Inbred F344; Sodium; Vitamin D

Hypercalcemia (12.0 to 18.3 mg/dl) was detected in 3 cats that had eaten a rodenticide that contained cholecalciferol. Clinical signs included lethargy, anorexia, vomiting, and polydipsia. Treatment with furosemide and fluids administered IV resulted in normalization of the serum calcium concentration and in remission of the clinical signs in 2 cats. One cat with a serum calcium concentration of 18.3 mg/dl did not have clinical signs, was not treated, and was reportedly normal 9 months after initial examination. We attributed the uniformly favorable outcome of exposure to the rodenticide in these cats to the small quantity of the toxin ingested.

Topics: Animals; Cat Diseases; Cats; Cholecalciferol; Hypercalcemia; Male; Rodenticides

We examined the calcium contents of desheathed peripheral nerve, perineurial sheath, and whole sciatic nerve in the frog as a function of the steady-state plasma concentration of ionized calcium. Chronic hypocalcemia was induced by parathyroidectomy and by bathing frogs in a phosphate medium. Chronic hypercalcemia was induced by administering vitamin D3 and by bathing frogs for up to 2 wk in medium containing 50 mM CaCl2. Calcium was measured with a calcium-sensitive electrode and by atomic absorption spectroscopy. The calcium contents (mmol/kg wet wt) in whole nerve, desheathed nerve, and the perineurial sheath varied linearly with slopes of 0.72, 0.71, and 1.72, respectively, with plasma concentration (mM) of ionized calcium, which ranged from 0.3 to 8.0 mM. In the same animals the calcium content in the cerebrum was independent of plasma calcium between 0.5 and 1.5 mM but rose at higher plasma concentrations. Our results indicate that net calcium concentration in the frog peripheral nerve is not regulated during chronic hypocalcemia and hypercalcemia, whereas brain calcium is regulated at plasma calcium concentrations less than 1.5 mM. The lack of calcium regulation in the nerve is attributed to the lack of calcium regulation in the endoneurial compartment.

Topics: Animals; Brain Chemistry; Calcium; Cholecalciferol; Homeostasis; Hypercalcemia; Hypocalcemia; Male; Rana pipiens; Sciatic Nerve; Spectrophotometry, Atomic

Topics: Calcium; Calcium Channel Blockers; Cholecalciferol; Diuretics; Homeostasis; Humans; Hypercalcemia; Hypocalcemia; Kidney; Nephrons

Topics: Cholecalciferol; Ergocalciferols; Female; Humans; Hypercalcemia; Kidney; Kidney Diseases; Middle Aged; Parathyroid Hormone

The effect of a daily intramuscular injection of vitamin D3 (2000 IU/100 g b.wt) on serum calcium level was investigated in Varanus flavescens. This treatment evoked hypercalcaemia on day 3 which progressed up to day 7. At day 14 a decline was noticed in the serum calcium level which was followed by a rise from day 21 to day 28.

Topics: Animals; Calcium; Cholecalciferol; Hypercalcemia; Lizards; Time Factors

The reported coincidence of primary hyperparathyroidism and cholelithiasis led us to investigate the effects of acute and chronic hypercalcemia on bile secretion in cats. Acute hypercalcemia (6-7 mmol/liter) was induced by an intravenous calcium infusion. Chronic hypercalcemia (3-4 mmol/liter) was induced and maintained for 8-10 weeks by treatment with subcutaneous vitamin D3, oral dihydrotachysterol, and feeding a calcium-rich diet. Bile secretion was then studied in acute experiments. We found that calcium concentrations in serum and hepatic bile were similar during all experimental normo- or hypercalcemic conditions (y = 1.12x - 0.85; r = 0.76). Biliary volume outputs were significantly decreased during both acute (P less than 0.002) and chronic (P less than 0.05) hypercalcemia compared with normocalcemic controls. Acute hypercalcemia also decreased total bile acid outputs (P less than 0.05), but had no effect on biliary bile acid concentrations. The inhibitory effect of acute hypercalcemia on biliary fluid and bile acid secretion was dose dependent and not antagonized by atropine. These findings suggest that calcium is secreted in hepatic bile at similar concentrations as present in the serum and that elevations of serum calcium concentration inhibit biliary volume and bile acid secretion in cats. Similar effects of hypercalcemia on bile composition in humans might promote calcium salt precipitation in bile.

Topics: Acute Disease; Animals; Bile; Bile Acids and Salts; Calcium; Calcium, Dietary; Cats; Cholecalciferol; Chronic Disease; Dihydrotachysterol; Female; Hypercalcemia; Male

Vitamin D intoxication, which may result from zealous intake of health food supplements, may cause metastatic calcification. This is the first reported case of a patient with vitamin D intoxication who had massive gastric uptake of [99mTc]MDP, but no lung uptake, with histologic documentation of the metastatic calcification by gastric biopsy. It is probable that the metastatic calcification was a highly metabolic process in this patient since the gastric uptake resolved within 3 wk when serum calcium and phosphate had returned to normal.

Topics: Bone and Bones; Calcinosis; Cholecalciferol; Female; Gastric Mucosa; Humans; Hypercalcemia; Lung; Middle Aged; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Stomach; Stomach Diseases; Technetium Tc 99m Medronate

Topics: Adult; Chemical Industry; Cholecalciferol; Cholestyramine Resin; Dexamethasone; Humans; Hydrocortisone; Hypercalcemia; Male; Occupational Diseases; Prednisolone

Topics: Animals; Cholecalciferol; Endocrine Glands; Fishes; Hypercalcemia; Hyperplasia; Male

Topics: Cholecalciferol; Drug Hypersensitivity; Female; Humans; Hypercalcemia; Infant; Male; Syndrome

Hypercalcaemia in six patients with sarcoidosis was associated with elevated circulating 1,25-dihydroxy vitamin D3 (187-475 pmol/l): the concentration of this metabolite of vitamin D was a function of the concentration of its precursor, 25-hydroxy vitamin D which remained within the normal range. Corticosteroids, in reducing serum calcium, eliminated this abnormal substrate--product relationship by rapidly reducing circulating 1,25-dihydroxy vitamin D3 while having no effect on 25-hydroxy vitamin D. The fall in circulating 1,25-dihydroxy vitamin D3 preceded the fall of calcium. Studies on the clearance of exogenous 1,25-dihydroxy vitamin D3 indicated that during hypercalcaemic episodes, the plasma disappearance time of the sterol was delayed and that this reverted to normal with steroid therapy. Administration of vitamin D3 to these patients with sarcoidosis increased the circulating concentration of 1,25-dihydroxy vitamin D3 and this resulted in hypercalcaemia, thus accounting for their hypersensitivity to vitamin D and sunlight.

Topics: Adult; Aged; Calcifediol; Calcitriol; Cholecalciferol; Humans; Hydrocortisone; Hypercalcemia; Light; Male; Metabolic Clearance Rate; Middle Aged; Prednisolone; Sarcoidosis

Topics: Calcitriol; Calcium; Cholecalciferol; Dihydroxycholecalciferols; Granuloma; Humans; Hypercalcemia

Topics: Acute Kidney Injury; Aged; Bone Marrow Diseases; Cholecalciferol; Female; Humans; Hypercalcemia; Osteoporosis; Sarcoidosis

Chick embryos were injected in the yolk sac at various ages with various doses of different vitamin D3 metabolites. Serum concentrations of total calcium and inorganic phosphate were determined 24 h after the injection and histological and electron microscopic studies of the tibiae were conducted 3-6 days after. Confirming previous results, the injection of 1,25(OH)2D3 was found to produce significant hypercalcemia and hypophosphatemia. The dose required to produce these effects decreased with age: 100 ng on the 9th day, 50 ng on the 11th, and 10 ng on the 15th. This finding is interpreted as resulting from the fact that the specialized cells in the chorionic epithelium which are considered to be involved in mineral resorption from the shell differentiate between the 11th and 13th days. Although no bone changes were observed in embryos injected before the 11th day, a rim of unmineralized trabeculae (osteoid) was observed at the periphery of the cortex of the tibial diaphysis in the embryos which had been injected after that age. Thus, in embryos injected on the 11th day with 100 ng 1,25(OH)2D3, the trabeculae formed between the 11th and 14th day remained unmineralized until the 15th or 16th day at which time they completed their mineralization. In the embryos injected on the 14th day, the alterations were more severe and could be produced with doses 10 times smaller than those required when the injections were made on the 11th day. At all ages, the doses that produced an osteoid rim also induced hypercalcemia and hypophosphatemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bone and Bones; Chick Embryo; Cholecalciferol; Hypercalcemia; Osteogenesis; Phosphates

Ultrastructural studies on rat thyroid demonstrated two types of secretory granules in parafollicular cells. In control animals were significantly more frequent strong osmophilic granules of approximately 130 nm in diameter than weak osmophilic granules of approximately 200 nm in diameter. Number and ratio of granules of the two types varied greatly in parafollicular cells. Administration of vitamin D3 induced a depletion of strong osmophilic granule number while the larger, weak osmophilic secretory granules continued to be stored. Immunocytochemical tests detected calcitonin in the small, strong osmophilic granules and showed that calcitonin content decreased after vitamin D3 administration. The obtained results suggest that the smaller, strong osmophilic granules contain calcitonin only, while the larger, weak osmophilic ones may contain somatostatin only.

Topics: Animals; Cholecalciferol; Histocytochemistry; Hypercalcemia; Immunologic Techniques; Male; Rats; Thyroid Gland; Vitamin D

Topics: Acute Kidney Injury; Cholecalciferol; Humans; Hypercalcemia; Infant; Male

Topics: Acute Kidney Injury; Cholecalciferol; Humans; Hypercalcemia; Infant; Male

Vitamin D3 metabolites and iPTH were measured in 26 patients at various times after renal transplantation. Hypercalcaemia (serum Ca greater than 2.62 mmol/L, 14 patients) was associated with hyperparathyroidism (p less than 0.02) and raised 1,25(OH)2D3 (p less than 0.05) but raised 1,25(OH)2D3 was also found in most patients in the normocalcaemic group. Lower 25(OH)D3 concentrations were found in the group with normal 1,25(OH)2D3 compared to the group with elevated 1,25(OH)2D3 (p less than 0.05). Low values of 24,25(OH)2D3 were found in both the normocalcaemic and hypercalcaemic patients (p less than 0.002). Impaired creatinine clearance (less than or equal to 55 ml/min, mean: 38 ml/min) was not associated with reduced 1,25(OH)2D3. No difference in D3 metabolites was found between hypophosphataemic and normophosphataemic patients.

Topics: Adult; Cholecalciferol; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Hypercalcemia; Kidney Diseases; Kidney Transplantation; Parathyroid Hormone

Topics: Animals; Calcium; Calcium Chloride; Cholecalciferol; Fish Diseases; Fishes; Hypercalcemia; Male

Vitamin D intoxication was induced in chicks by treatment with large amounts of radioactive cholecalciferol (vitamin D3) either by s.c. injections or by stomach tube. Hypercalcemia and nephrocalcinosis were present, confirming toxicity. The distribution of cholecalciferol and its metabolites in the tissues of the intoxicated birds was compared with that in birds that were treated with physiological amounts of radioactive cholecalciferol. Treatment with pharmacological doses resulted in marked elevation of cholecalciferol and its metabolites in all tissues examined, including elevation of 1 alpha,25-dihydroxycholecalciferol in the intestine. The predominant form of cholecalciferol in these birds was found to be the unchanged vitamin, whereas in birds treated with physiological doses 25-hydroxycholecalciferol was the predominant metabolite. The route of vitamin administration was found to be of importance only when pharmacological doses were given: generally, higher levels were noted when administered via s.c. injections than via stomach tube, except in the arteries. It is suggested that in vitamin D intoxication, the factor responsible for the pathological changes in soft tissues is cholecalciferol itself. High levels of 1 alpha,25-dihydroxycholecalciferol may be responsible for the hypercalcemia.

Topics: Animals; Bone and Bones; Chickens; Cholecalciferol; Hypercalcemia; Injections; Intestines; Intubation; Kidney; Liver; Male; Nephrocalcinosis; Vitamin D

Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.

Topics: 25-Hydroxyvitamin D 2; Animals; Calcifediol; Calcium; Cattle; Cattle Diseases; Cholecalciferol; Ergocalciferols; Female; Hydroxycholecalciferols; Hydroxyproline; Hypercalcemia; Injections, Intramuscular; Labor, Obstetric; Magnesium; Phosphorus; Pregnancy

Nineteen rats were parathyroidectomized by electrocauterization, resulting in pronounced hypocalcaemia. Seven of these rats were then given vitamin D3 in a dose causing hypercalcaemia, while 7 received a dose which normalized serum calcium and 5 received no vitamin D. Ten further animals were sham-operated and were not given any extra vitamin D. The experimental period was 16 weeks. No significant differences in serum gastrin values were found between the different groups. Quantitative studies of the antral gastrin cells showed no difference in the number of gastrin cells per unit volume or unit segment between the different groups of vitamin-D-treated animals and sham-operated animals. However, the number of gastrin cells per unit segment was significantly higher in the hypocalcaemic animals than in the sham-operated animals, as a result of an increase in mucosal thickness. The amount of antral mucosal gastrin did not differ between the different groups. Thus the results of this study indicate that experimentally induced hypercalcaemia in parathyroidectomized rats does not influence the serum gastrin, the number of gastrin cells or antral gastrin.

Topics: Animals; Cell Count; Cholecalciferol; Gastrins; Hypercalcemia; Male; Parathyroid Glands; Pyloric Antrum; Rats; Rats, Inbred Strains

Topics: Bone and Bones; Child; Cholecalciferol; Humans; Hypercalcemia; Rickets; Vitamin D

Topics: Calcifediol; Cholecalciferol; Humans; Hypercalcemia; Infant; Infant, Low Birth Weight; Infant, Newborn; Rickets

Topics: Administration, Oral; Cholecalciferol; Female; Humans; Hypercalcemia; Infant; Rickets

Topics: Animals; Bone Neoplasms; Cholecalciferol; Cyclic AMP; Diagnosis, Differential; Humans; Hypercalcemia; Hyperparathyroidism; Mice; Neoplasms; Paraneoplastic Syndromes; Parathyroid Hormone; Peptides

A role for calciferol in zinc homeostasis was investigated by radioisotope uptake and compartmental analysis techniques. cholecalciferol was injected into rats 4-5 days prior to radioisotopic study of rapidly exchangeable pools (< 4 h). Kidney, liver, and duodenum had significant increases in zinc uptake rates. Bone and skeletal muscle had significant decreases. No other tissues had significant differences. Compartmental analysis models generated by the SAAM-25 digital computer program suggested a decrease in the fractional tissue to plasma coefficient to be the mechanism for the observed changes in the serum zinc concentration and tissue zinc accumulation rates. It is not clear whether this is a specific effect of calciferol on zinc homeostasis or is a nonspecific response which may reflect some role for zinc in calciferol metabolism.

Topics: Animals; Cholecalciferol; Homeostasis; Hypercalcemia; Male; Models, Biological; Rats; Tissue Distribution; Vitamin D; Zinc; Zinc Radioisotopes

Topics: Child; Cholecalciferol; Humans; Hypercalcemia; Hypertension; Infant; Kidney Diseases; Rickets

Calcium balance studies and measurement of 25-hydroxyvitamin D3 (25[OH]D3) levels were performed on a vitamin D intoxicated, hypoparathyroid patient before, during, and after successful management of hypercalcemia with oral prednisone therapy. Prednisone effected a dramatic reduction in both mean serum calcium levels and mean 24-hour urinary calcium excretion within four days on two separate occasions. No changes were apparent in fecal calcium excretion. Calcium balance became less negative with prednisone treatment. Levels of 25(OH) D3 during the same period did not change. Decreased calcium mobilization from bone best accounted for the glucocorticoid-mediated amelioration of hypercalcemia.

Topics: Calcium; Calcium, Dietary; Cholecalciferol; Female; Humans; Hypercalcemia; Hypoparathyroidism; Middle Aged; Prednisone; Vitamin D

A sensitive, precise assay for vitamin D in plasma is described. Three to five milliliters of plasma were extracted with methanol:methylene chloride (2:1). The lipid extract was chromatographed on Sephadex LH-20 and then on lipidex-5000 columns. After high pressure liquid chromatography with a reverse phase chromatographic system, vitamin D2 and vitamin D3 were quantitated by ultraviolet absorbance. We used this assay system for monitoring daily changes of vitamin D3 in plasma of two Jersey cows after four intramuscular doses (15 x 10(6) IU) of vitamin D3 administered at weekly intervals. Basal vitamin D in plasma was 3.2 +/- .99 ng/ml with a range of 1.7 to 4.9 ng/ml. Vitamin D3 in plasma remained relatively low (10 to 45 ng/ml) the week after the first vitamin D3 injection. Vitamin D3 was high (130 to 234 ng/ml) after the second, third, and fourth injections. Vitamin D3 decreased steadily to 88 ng/ml by 38 days after the fourth vitamin D3 injection. Phosphorus in plasma increased sharply to a plateau at 9.5 mg/100 ml during the week after the second vitamin D3 injection and returned to normal (4.5 mg/100 ml) at the end of the experiment. Calcium, however, gradually increased to 14.0 mg/100 ml 20 days after the fourth vitamin D3 injection. Both animals remained hypercalcemic (calcium 11.5 mg/100 ml) during the experiment.

Topics: Animals; Calcium; Cattle; Cholecalciferol; Chromatography, High Pressure Liquid; Colorimetry; Ergocalciferols; Female; Hypercalcemia; Injections, Intramuscular; Lipids; Phosphorus; Time Factors

Under short duration hypercalcemia induced by pharmacological doses of vitamin D3 significant ultrastructural changes were observed in the renomedullary interstitial cells of rats. The most striking alteration was the degranulation of these cells accompanied with the increase in volume of the rough and smooth-surfaced endoplasmic reticulum, enlargement of the Golgi apparatus and occurence of osmiophilic inclusions probably of lipid nature in mitochondria. The ultrastructural changes can be regarded as an expression of the increase of a synthetic and secretory activity of the renomedullary interstitial cells and they may be associated with an enhanced production of prostaglandins or other lipid hormonal substances than prostaglandins under condition of hypercalcemia.

Topics: Animals; Cholecalciferol; Hypercalcemia; Kidney Medulla; Male; Prostaglandins; Rats; Time Factors

Topics: Animals; Binding, Competitive; Cholecalciferol; Chromatography, High Pressure Liquid; Dihydroxycholecalciferols; Dose-Response Relationship, Drug; Ergocalciferols; Hydroxycholecalciferols; Hypercalcemia; Male; Protein Binding; Radioligand Assay; Rats

Acute massive vitamin D overdosage occurred in a family after eating food cooked in a nut oil containing 5 million units of vitamin D3/ml. The plasma vitamin D was 55 and 60 i.u./ml in the father and mother respectively, and 9.6 i.u./ml in their 11-month-old infant (normal range, 0--1.6 i.u/ml). All the family presented with symptoms of hypercalcaemia and the infant responded quickly to prednisone. After steroids had failed to control the hypercalcaemia in the parents, neutral phosphate was successful, although necessary for 9 months. Before phosphate therapy it was shown that both parents were in strongly negative calcium balance, indicating that the vitamin D was mobilizing calcium from bone. Eleven years later all 3 patients are well but a renal biopsy in one of them shows persistent nephrocalcinosis.

Topics: Acute Disease; Adult; Cholecalciferol; Female; Humans; Hypercalcemia; Infant; Male; Nephrocalcinosis; Nuts; Oils; Phosphates; Prednisone

The analysis of the serum calcium and phosphate level changes in intact Vitamin D--dosed animals showed the increasing serum calcium values without any concomitant change in serum phosphate concentration. The observed discrepancy of intestinal phosphate transport in vitro and in vivo studies together with the effect of Vitamin D towards normalizing serum phosphate level in TPTX Vitamin D--dosed animals suggest the presence of Vitamin D as some phosphate regulatory factor. The participation of the possible role of 25 OH D3 in the observed phenomenon is under current investigations. In PTH supressed hypercalcemic conditions we did not reproduce, with the usage of 1alpha--OH D3, the regulatory effect of 1,25 (OH) 2D3 described by Garabedian et al. /1/.

Topics: Animals; Calcium; Cholecalciferol; Duodenum; Hydroxycholecalciferols; Hypercalcemia; In Vitro Techniques; Intestinal Absorption; Jejunum; Parathyroid Glands; Phosphates; Rats; Thyroidectomy; Time Factors

25-Hydroxyvitamin D (25-OHD) levels were measured in 39 patients with metabolic bone disease or hypoparathyroidism who had been treated with a constant high dose of vitamin D2 or D3 for at least 12 weeks. Plasma 25-OHD levels rose with increasing dosage, the relationship between dose and plasma level being approximately linear whether or not the dose was expressed on a weight-corrected basis. A therapeutic range of 25-OHD to be expected when patients with these conditions are treated with vitamin D has been established. There may be certain exceptions in which plasma 25-OHD levels within the range are associated with either an inadequate response to treatment or, conversely, the hypercalcaemia of vitamin D toxicity. There was no correlation between plasma calcium level and 25-OHD concentration in the group of patients studied. There was also no difference between the dose/25-OHD relationship of patients treated with vitamin D2 and that of patients receiving vitamin D3. Ten patients were started on treatment with large doses of vitamin D during the period of the study. The rate of rise of plasma 25-OHD was followed during treatment. The incremental rise in 25-OHD was calculated at the end of the first week of treatment in terms of dose per unit body weight. The rate of rise of plasma 25-OHD level was highly correlated with the dose used. Plasma 25-OHD levels after one weeks' treatment were only 15-20% of the expected steady-state level on the same dosage. The importance of a high priming dose when a rapid response is needed is thus emphasised.

Topics: Adolescent; Adult; Aged; Body Weight; Bone Diseases; Child; Child, Preschool; Cholecalciferol; Dose-Response Relationship, Drug; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hypercalcemia; Hypoparathyroidism; Infant; Male; Middle Aged; Vitamin D

Hypercalcemia is a potentially life-threatening metabolic disorder which may be effectively treated once its presence is recognized and its probable cause determined. The family physician should be aware of the various clinical circumstances in which hypercalcemia occurs and the appropriate initial therapy for patients who are symptomatic at the time of diagnosis. This paper provides a clear approach to the pathogenesis, diagnosis, and management of this problem.

Topics: Calcitonin; Calcium; Cholecalciferol; Homeostasis; Humans; Hypercalcemia; Parathyroid Hormone

Topics: Aged; Calcium; Cholecalciferol; Ergocalciferols; Esophagus; Female; Humans; Hypercalcemia; Hypoparathyroidism; Laryngectomy; Male; Middle Aged; Parathyroid Hormone; Pharyngectomy; Postoperative Complications; Vitamin D

Topics: Bone Development; Calcification, Physiologic; Cholecalciferol; Humans; Hypercalcemia; Infant; Male; Rickets; Skull

Topics: Aged; Antineoplastic Agents; Bone Neoplasms; Calcinosis; Calcitonin; Cholecalciferol; Cyclophosphamide; Ergocalciferols; Fractures, Spontaneous; Humans; Hypercalcemia; Kidney Calculi; Lung Neoplasms; Male; Neoplasm Metastasis; Osteitis Deformans; Plicamycin; Podophyllin; Quinones; Sarcoma; Vitamin D

Topics: Acid Phosphatase; Animals; Cholecalciferol; Cholinesterases; Chronic Disease; Esterases; Histocytochemistry; Hypercalcemia; Male; Rats; Thyroid Gland

Topics: Animals; Calcium; Cholecalciferol; Hypercalcemia; Leydig Cell Tumor; Male; Methods; Neoplasm Transplantation; Neoplasms, Experimental; Parabiosis; Parathyroid Glands; Parathyroid Hormone; Rats; Stimulation, Chemical; Thyroid Gland; Thyroidectomy; Time Factors; Transplantation, Homologous

Topics: Animals; Cholecalciferol; Hypercalcemia; Kidney Glomerulus; Microscopy, Electron; Rats

Topics: Animals; Calcium; Cholecalciferol; Gluconates; Hypercalcemia; Male; Rats; Thyroid Gland

Topics: Adult; Aged; Bone Diseases; Calcitonin; Child; Cholecalciferol; Ergocalciferols; Humans; Hypercalcemia; Metabolic Diseases; New Zealand; Organophosphonates; Osteitis Deformans; Osteomalacia; Osteoporosis; Parathyroid Hormone; Sarcoidosis; Vitamin D; Vitamin D Deficiency

Topics: Animals; Calcitonin; Calcium; Chlorates; Cholecalciferol; Gluconates; Hypercalcemia; Karyometry; Male; Mathematics; Rats; Thyroid Gland; Time Factors

Topics: Animals; Calcitonin; Calcium; Cholecalciferol; Chromatin; Cytoplasm; Dogs; Endoplasmic Reticulum; Epithelial Cells; Female; Glycogen; Histocytochemistry; Hypercalcemia; Hyperplasia; Hypertrophy; Male; Microscopy, Electron; Parathyroid Glands; Thyroid Gland

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Bone and Bones; Calcium; Calcium Isotopes; Cholecalciferol; Deficiency Diseases; Hydroxycholecalciferols; Hypercalcemia; Intestinal Mucosa; Intestine, Small; Kidney; Lipid Metabolism; Liver; Male; Osteomalacia; Phosphorus; Rats; Rickets; Tritium; Urine

Topics: Cholecalciferol; Female; Glucagon; Humans; Hypercalcemia; Infant

Topics: Administration, Oral; Animals; Bone Diseases; Cholecalciferol; Diet; Ergocalciferols; Gout; Haplorhini; Hypercalcemia; Kidney; Macaca; Nephrocalcinosis; Uric Acid; Vitamin A Deficiency

Topics: Animals; Calcium; Calcium, Dietary; Chickens; Cholecalciferol; Chromatography, Gas; Chromatography, Gel; Hydroxycholecalciferols; Hypercalcemia; Kidney; Male; Mass Spectrometry; Methods; Methylation; Silicon; Spectrophotometry, Ultraviolet; Swine

Topics: Age Factors; Alkaline Phosphatase; Calcium; Cholecalciferol; Humans; Hypercalcemia; Infant, Newborn; Infant, Newborn, Diseases; Phosphorus; Rickets

Topics: Adenylyl Cyclases; Anticonvulsants; Calcitonin; Calcium; Cholecalciferol; Cyclic AMP; Diagnosis, Differential; Humans; Hydroxycholecalciferols; Hypercalcemia; Hyperparathyroidism; Osteitis Deformans; Osteitis Fibrosa Cystica; Osteomalacia; Parathyroid Hormone; Pseudohypoparathyroidism; Radioimmunoassay; Thyroid Neoplasms

Topics: Animals; Calcium; Calcium, Dietary; Cattle; Cholecalciferol; Female; Homeostasis; Hypercalcemia; Male; Parathyroid Hormone; Phosphates; Stimulation, Chemical; Thyroid Gland; Thyroidectomy; Thyroxine

Topics: Animals; Bone Resorption; Calcitonin; Cholecalciferol; Hypercalcemia; Male; Parathyroid Glands; Rats; Secretory Rate; Stimulation, Chemical; Strontium Isotopes; Thyroid Gland; Thyroidectomy; Tibia

Topics: Carbon Isotopes; Cholecalciferol; Chromatography; Humans; Hypercalcemia; Nephrectomy; Osteomalacia; Sarcoidosis; Time Factors; Tritium; Vitamin D

Topics: Animals; Calciphylaxis; Cholecalciferol; Dihydrotachysterol; Ergocalciferols; Female; Heart; Hypercalcemia; Kidney; Male; Nephrocalcinosis; Pregnancy; Pregnancy, Animal; Rats; Reserpine

Topics: Cholecalciferol; Ergocalciferols; Humans; Hypercalcemia; Hypoparathyroidism; Vitamin D

Topics: Adenine Nucleotides; Animals; Bone and Bones; Bone Resorption; Calcium; Calcium Isotopes; Cholecalciferol; Culture Techniques; Cyclic AMP; Depression, Chemical; Glucagon; Hypercalcemia; Hypocalcemia; Male; Parathyroid Glands; Parathyroid Hormone; Rats; Thyroidectomy

Topics: Age Factors; Animals; Animals, Newborn; Biological Assay; Bone and Bones; Bone Development; Calcitonin; Calcium; Cholecalciferol; Hypercalcemia; Hypocalcemia; Rats; Secretory Rate; Thyroid Gland

Topics: Animals; Body Weight; Calcium; Calcium Chloride; Cholecalciferol; Dogs; Female; Hypercalcemia; Injections, Intramuscular; Male; Microscopy, Electron; Mitosis; Parathyroid Glands; Thyroid Gland; Time Factors

Topics: Animals; Aortic Diseases; Calcinosis; Calcium Phosphates; Cholecalciferol; Crystallization; Female; Hypercalcemia; Nephrocalcinosis; Organophosphonates; Rats

Topics: Acidosis; Alkaline Phosphatase; Animals; Bone and Bones; Bone Development; Bone Resorption; Calcitonin; Calcium; Cholecalciferol; Chromium Isotopes; Citrates; Cortisone; Dogs; Hydrochloric Acid; Hydrogen-Ion Concentration; Hypercalcemia; Hypocalcemia; Metatarsus; Microradiography; Osteoclasts; Parathyroid Hormone; Perfusion; Phosphates; Phosphorus; Thyroxine

Topics: Animals; Bone and Bones; Calcitonin; Calcium; Cholecalciferol; Hypercalcemia; Male; Parathyroid Glands; Parathyroid Hormone; Rats; Stimulation, Chemical; Thyroidectomy; Triiodothyronine

Topics: Animals; Calcium; Cholecalciferol; Hypercalcemia; Hypocalcemia; Neoplasm Metastasis; Parathyroid Glands; Rats; Sarcoma, Experimental; Thyroidectomy

Topics: Alkaline Phosphatase; Animals; Calcitonin; Calcium; Cholecalciferol; Decalcification, Pathologic; Female; Hypercalcemia; Phosphates; Potassium; Rats; Sodium; Stimulation, Chemical; Thyroid Gland

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Calcinosis; Cholecalciferol; Diphosphates; Female; Hypercalcemia; Kidney; Phosphates; Rats

Topics: Animals; Aortic Diseases; Bone Resorption; Calcinosis; Calcium Phosphates; Chemical Phenomena; Chemical Precipitation; Chemistry; Cholecalciferol; Diphosphates; Hypercalcemia; Mice; Organophosphonates; Pyrophosphatases; Rats

Topics: Animals; Bone and Bones; Bone Resorption; Calcitonin; Calcium Chloride; Cholecalciferol; Hypercalcemia; Parathyroid Hormone; Rats; Strontium Isotopes; Tibia

Topics: Animals; Blood Chemical Analysis; Bone and Bones; Calcium; Cholecalciferol; Ergocalciferols; Hypercalcemia; Phosphorus; Poultry; Rickets; Tetracycline

Topics: Cholecalciferol; Drug Prescriptions; Humans; Hypercalcemia; Infant; Prescriptions; Toxicology; Vitamin D