vitamin-d-2 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

Previous studies have demonstrated the safety and efficacy of using Paricalcitol for the treatment of secondary hyperparathyroidism (SHPT) in patients on dialysis. The aim of the current meta-analysis was to assess the safety and efficacy of Paricalcitol for the management of SHPT in patients with chronic kidney disease (CKD) not yet on dialysis. A secondary aim was to determine if sufficient data was available to assess the effect of Paricalcitol for the management of proteinuria.. A meta-analysis was conducted using the Cochrane Collaboration's RevMan 4.2 software.. Paricalcitol is effective in lowering PTH in patients with CKD not yet on dialysis and is also effective in lowering proteinuria in diabetic CKD patients. However, we uncovered a safety signal identifying an elevated calcium phosphate product and a trend towards the development of hypercalcemia. A phosphate elevation was not demonstrated because the target used in the clinical studies was a P > 5.5 mg/dl, a value appropriate for dialysis patients and not CKD patients.. Although Paricalcitol is effective in lowering PTH, we advise caution in the use of any active Vitamin D analogues in patients with CKD because of the potential risk of exacerbating vascular calcification.

Topics: Bone Density Conservation Agents; Ergocalciferols; Glomerular Filtration Rate; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hyperphosphatemia; Kidney Failure, Chronic; Proteinuria; Randomized Controlled Trials as Topic; Risk; Treatment Outcome; Vitamin D

Observational data indicate that newer vitamin D compounds such as paricalcitol can suppress serum intact parathyroid hormone (iPTH) and reduce proteinuria in patients with CKD. To systematically evaluate the efficacy and safety of paricalcitol for CKD, we conducted a meta-analysis of the published randomized controlled trials (RCTs).. MEDLINE, Embase, the Cochrane Library, and article reference lists were searched for RCTs that compared paricalcitol with placebo in the treatment of patients with stage 2-5 CKD. The quality of the studies was evaluated using the Jadad method. The results are summarized as risk ratios (RRs) for dichotomous outcomes or mean differences for continuous outcomes.. Nine studies (832 patients) were included. Compared with placebo, paricalcitol suppressed serum iPTH (RR, 6.37; 95% confidence interval [95% CI], 4.64-8.74; P<0.001) and reduced proteinuria (RR, 1.68; 95% CI, 1.25-2.25; P<0.001). Compared with the control group, the RR for hypercalcemia associated with paricalcitol use was 2.25 (95% CI, 0.81-6.26; P=0.12). Patients receiving paricalcitol therapy did not have an increased risk of endocrine system and cardiovascular system adverse effects (RR, 1.07; 95% CI, 0.84-1.36; P=0.58).. We confirm that paricalcitol suppresses iPTH and lowers proteinuria in patients with stage 2-5 CKD without an increased risk of adverse events. A trend toward increased hypercalcemia did not reach statistical significance, but may be clinically relevant. A randomized trial is needed to determine if paricalcitol affects the development of ESRD or mortality.

Topics: Biomarkers; Chi-Square Distribution; Chronic Disease; Ergocalciferols; Evidence-Based Medicine; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Kidney Diseases; Odds Ratio; Parathyroid Hormone; Proteinuria; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome

Recent evidence suggests that the traditional syndromes known as renal osteodystrophy, secondary hyperparathyroidism, and vitamin D deficiency are related to mortality in persons with moderate to advanced chronic kidney disease (CKD). The so-called 'kidney bone disease', also known as 'mineral and bone disorders', is defined to include bone disorders, mineral disarrays, and vascular calcification. We have identified 14 common and clinically relevant conditions of contemporary nature that are related to the kidney bone disease, including calcitriol (active vitamin D) deficiency, 25(OH)-vitamin D deficiency, biochemical hyperparathyroidism, relatively low parathyroid hormone (PTH) level, increased serum alkaline phosphatase (hyperphosphatasemia), elevated fibroblast growth factor (FGF)-23, high turnover bone disease, adynamic bone disease, uremic osteoporosis, vascular calcification, hyper- and hypophosphatemia, and hyper- and hypocalcemia. We present a critical review of these 14 conditions with emphasis on patient survival and other pertinent clinical outcomes. We also review unresolved controversies surrounding the management of these conditions by administration of nutritional vitamin D (ergocalciferol and cholecalciferol), vitamin D receptor activators (calcitriol, alphacalcidiol, doxercalciferol), D-mimetics (paricalcitol, maxacalcitol), calcimimetics (cinacalcet), recombinant PTH (teriparatide), and receptor activator of nuclear factor-kappaB ligand modulators (denosumab); compare mortality predictability of PTH and alkaline phosphatase; and examine potential risks of bone disorders and mineral disarrays in CKD patients.

Topics: Alkaline Phosphatase; Calcinosis; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hyperphosphatemia; Hypocalcemia; Hypophosphatemia; Kidney Failure, Chronic; Minerals; Osteoporosis; Parathyroid Hormone; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

Although researchers first identified the fat-soluble vitamin cholecalciferol almost a century ago and studies have now largely elucidated the transcriptional mechanism of action of its hormonal form, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], we know surprisingly little about mechanisms of vitamin D toxicity. The lipophilic nature of vitamin D explains its adipose tissue distribution and its slow turnover in the body (half-life approximately 2 mo). Its main transported metabolite, 25-hydroxyvitamin D(3) [25(OH)D(3)], shows a half-life of approximately 15 d and circulates at a concentration of 25-200 nmol/L, whereas the hormone 1alpha,25(OH)(2)D(3) has a half-life of approximately 15 h. Animal experiments involving vitamin D(3) intoxication have established that 25(OH)D(3) can reach concentrations up to 2.5 mumol/L, at which it is accompanied by hypercalcemia and other pathological sequelae resulting from a high Ca/PO(4) product. The rise in 25(OH)D(3) is accompanied by elevations of its precursor, vitamin D(3), as well as by rises in many of its dihydroxy- metabolites [24,25(OH)(2)D(3); 25,26(OH)(2)D(3); and 25(OH)D(3)-26,23-lactone] but not 1alpha,25(OH)(2)D(3). Early assumptions that 1alpha,25(OH)(2)D(3) might cause hypercalcemia in vitamin D toxicity have been replaced by the theories that 25(OH)D(3) at pharmacologic concentrations can overcome vitamin D receptor affinity disadvantages to directly stimulate transcription or that total vitamin D metabolite concentrations displace 1alpha,25(OH)(2)D from vitamin D binding, increasing its free concentration and thus increasing gene transcription. Occasional anecdotal reports from humans intoxicated with vitamin D appear to support the latter mechanism. Although current data support the viewpoint that the biomarker plasma 25(OH)D concentration must rise above 750 nmol/L to produce vitamin D toxicity, the more prudent upper limit of 250 nmol/L might be retained to ensure a wide safety margin.

Topics: Animals; Bone Density Conservation Agents; Ergocalciferols; Half-Life; Humans; Hypercalcemia; Metabolic Clearance Rate; Risk Factors; Toxicology; Vitamin D

Drug-induced hypercalcemia is caused by increased bone resorption (vitamin D and vitamin A intoxication), increased calcium absorption in the gastrointestinal tract (vitamin D intoxication, excessive intake of calcium) or increased calcium reabsorption in the renal tubules (thiazide diuretics). When vitamin D (D(2) or D(3)) intoxication develops, the hypercalcemia persists for more than several months. Therefore, short-acting active vitamin D (1alpha-OHD(3), 1,25- (OH) (2)D(3)) are clinically used. Recently, various analogs of 1,25- (OH) (2)D(3) with potent differentiation stimulating activity on keratinocytes but insufficient calcium-movilizing activity have been developed (tacalcitol, calcipotriol, 22-oxacalcitriol). However, severe hypercalcemia may develop when these ointments were abundantly applied to patients with psoriasis since the agents can be easily absorbed through the skin lesions.

Topics: Bone Resorption; Ergocalciferols; Humans; Hypercalcemia; Psoriasis; Steroid Hydroxylases; Vitamin D

A strict control of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) is indicated to avoid serious complications linked to osteitis fibrosa and other parathyroid-hormone (PTH)-related bodily disturbances. However, such a control is often achieved only at the price of unacceptably high plasma calcium and phosphorus levels and the risk of soft tissue calcification, even when using the novel, so-called 'non-hypercalcemic' vitamin D analogs. The advent of a new class of drugs, the calcimimetics, should allow a more adequate control of the disturbed calcium-phosphorus metabolism in CKD patients. In my opinion, the calcimimetics will not replace currently used medications but will be a valuable supplement to presently available treatment options for this major complication in patients with renal failure.

Topics: Calcitriol; Cinacalcet; Clinical Trials as Topic; Drug Synergism; Ergocalciferols; Humans; Hydroxycholecalciferols; Hypercalcemia; Hyperparathyroidism, Secondary; Intestinal Absorption; Kidney Failure, Chronic; Liver; Naphthalenes; Phosphates; Receptors, Calcitriol; Receptors, Calcium-Sensing; Vitamin D; Vitamin D Deficiency

In patients with primary hyperparathyroidism, a definite diagnosis is the first step in the management strategy and relies on appropriately selected and carefully interpreted laboratory tests. Parathyroid hormone assays are being increasingly performed as part of the routine evaluation of osteoporosis. In this setting, laboratory tests are often consistent with primary hyperparathyroidism but should be interpreted with caution. Bone mineral density measurements are useful for assessing the impact of primary hyperparathyroidism. The recommended bone mineral density cutoffs for selecting patients requiring parathyroidectomy were lowered in 2003, and the number of surgically treated patients has increased as a result. Parathyroidectomy remains the treatment of choice given the low mortality associated with this procedure and the absence of pharmacological alternatives suitable for long-term use.

Topics: Bone Density; Bone Diseases, Metabolic; Ergocalciferols; Humans; Hypercalcemia; Hyperparathyroidism; Osteoporosis; Parathyroidectomy; Postoperative Period

Topics: Biomarkers; Chromatography, High Pressure Liquid; Diagnosis, Differential; Ergocalciferols; Humans; Hypercalcemia; Hypocalcemia; Osteomalacia; Phosphorus Metabolism Disorders; Reference Values; Rickets; Specimen Handling; Vitamin D

Described herein is a case of oncogenic osteomalacia that ran a course of at least 16 years before curative resection of a mixed mesenchymal tumor. Hypercalcemic hyperparathyroidism developed in the patient, and review of the literature indicated that this occurs in about 10 percent of reported cases. Changes in serum parathyroid hormone levels with and without phosphate supplement therapy and before and after tumor resection suggested that both the high intake of phosphate and the effect of the neoplasm on vitamin D bioactivation engendered the parathyroid overactivity. Despite marked hyperparathyroidism, serum 1,25-dihydroxyvitamin D levels were subnormal preoperatively but showed a sevenfold increase within 48 hours of tumor resection. Thereafter, a gradual increase in the maximal tubular reabsorption of phosphate occurred during several months. Biopsy of the iliac crest confirmed that tumor removal was followed by resolution of osteomalacia, but there was no accompanying increase in vertebral mineral density as assessed by quantitative computed tomography or in total-body bone mineral as measured with dual-photon absorptiometry. The findings presented are consistent with secretion by the tumor of a factor with a short half-life that is potent enough to inhibit renal 25-hydroxyvitamin D-1 alpha-hydroxylase despite hyperparathyroidism. The resulting subnormal circulating 1,25-dihydroxyvitamin D levels may have secondarily contributed to decreased renal tubular reabsorption of phosphate.

Topics: Chronic Disease; Combined Modality Therapy; Dihydroxycholecalciferols; Ergocalciferols; Female; Homeostasis; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Mesenchymoma; Middle Aged; Osteomalacia; Phosphates; Soft Tissue Neoplasms

Topics: Adolescent; Adult; Alkaline Phosphatase; Asia; Calcium; Clinical Enzyme Tests; England; Ergocalciferols; Female; Humans; Hypercalcemia; Hypocalcemia; Male; Osteomalacia; Parathyroid Glands; Parathyroid Hormone; Pregnancy; Pregnancy Complications; Rickets; 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: Acidosis, Renal Tubular; Adenoma; Adult; Alkaline Phosphatase; Anuria; Bicarbonates; Bone Diseases; Calcium; Ergocalciferols; Female; Glomerulonephritis; Glycosuria; Humans; Hypercalcemia; Hyperparathyroidism; Hypertension, Renal; Kidney Failure, Chronic; Kidney Transplantation; Parathyroid Glands; Parathyroid Neoplasms; Phosphates; Renal Dialysis; Sodium; Transplantation, Homologous

Elevated intact parathyroid hormone (iPTH) levels can contribute to morbidity and mortality in children with chronic kidney disease (CKD). We evaluated the pharmacokinetics, efficacy, and safety of oral paricalcitol in reducing iPTH levels in children with stages 3-5 CKD.. Children aged 10-16 years with stages 3-5 CKD were enrolled in two phase 3 studies. The stage 3/4 CKD study characterized paricalcitol pharmacokinetics and compared the efficacy and safety of paricalcitol with placebo followed by an open-label period. The stage 5 CKD study evaluated the efficacy and safety of paricalcitol (no comparator) in children with stage 5 CKD undergoing dialysis.. In the stage 3/4 CKD study, mean peak plasma concentration and area under the time curve from zero to infinity were 0.13 ng/mL and 2.87 ng•h/((or ng×h/))mL, respectively, for 12 children who received 3 μg paricalcitol. Thirty-six children were randomized to paricalcitol or placebo; 27.8% of the paricalcitol group achieved two consecutive iPTH reductions of ≥30% from baseline versus none of the placebo group (P = 0.045). Adverse events were higher in children who received placebo than in those administered paricalcitol during the double-blind treatment (88.9 vs. 38.9%; P = 0.005). In the stage 5 CKD study, eight children (61.5%) had two consecutive iPTH reductions of ≥30% from baseline, and five (38.5%) had two consecutive iPTH values of between 150 and 300 pg/mL. Clinically meaningful hypercalcemia occurred in 21% of children.. Oral paricalcitol in children aged 10-16 years with stages 3-5 CKD reduced iPTH levels and the treatment was well tolerated. Results support an initiating dose of 1 μg paricalcitol 3 times weekly in children aged 10-16 years.

Topics: Adolescent; Bone Density Conservation Agents; Calcium; Child; Double-Blind Method; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hyperphosphatemia; Kidney Failure, Chronic; Male; Parathyroid Hormone; Phosphorus; Renal Dialysis; Treatment Outcome

The objective of this study was to determine the maximum tolerated dose and safety of LR-103, a Vitamin D analogue, in patients with advanced cancer.. In Step A, patients received oral LR-103 once daily in 14-day cycles with intra-patient dose escalation per accelerated dose escalation design. Dose limiting toxicity for Step A was defined as ≥grade 2 hypercalcemia and/or >grade 2 other toxicities. Starting dose was 5 µg/day. Step B used a 3+3 design starting at Step A maximum tolerated dose with 28-day cycles. Dose limiting toxicity was defined as ≥grade 3 hypercalcemia or any grade 3 or 4 non-hematologic toxicity, except hypercalciuria.. Twenty-one patients were enrolled; eight were treated in Step A. At dose level 3 (15 µg/day), two patients had dose limiting toxicity. One had grade 4 hyperuricemia. The other had grade 4 GGT plus grade 3 alkaline phosphatase, fatigue and urinary tract infection (UTI). Dose level 2 (10 µg/day) was the maximum tolerated dose for Step A and was starting dose for Step B. The dose was escalated to dose level 5 (30 µg/day) with a patient experiencing grade 3 dose limiting toxicity of hypercalcemia. The study was discontinued before reaching the maximum tolerated dose due to sponsor decision. Modest increases in serum osteocalcin and calcium and decrease in parathyroid hormone were noted. Best response was stable disease; four patients were on therapy for six months or longer.. Step A dose limiting toxicities limited accelerated dose escalation. The maximum tolerated dose of LR-103 was not reached prior to study termination and this agent is no longer being developed.

Topics: Aged; Aged, 80 and over; Alkaline Phosphatase; Antineoplastic Agents; Calcium; Dose-Response Relationship, Drug; Ergocalciferols; Female; Humans; Hypercalcemia; Hypercalciuria; Male; Maximum Tolerated Dose; Middle Aged; Muscle Fatigue; Neoplasms; Osteocalcin; Parathyroid Hormone; Urinary Tract Infections

Secondary hyperparathyroidism (SHPT) is one of the major complications of chronic kidney disease (CKD) and is associated with elevated serum intact parathyroid hormone (iPTH). Calcitriol, a non-selective vitamin D receptor agonist (VDRA) that suppresses iPTH is used for SHPT treatment, but its use is frequently complicated by hypercalcemia. Paricalcitol, a selective VDRA, demonstrated efficacy in iPTH suppression compared to maxacalcitol in a Phase 2 study (M11-609) in Japanese subjects. The current larger Phase 3 study (M11-517), evaluated the efficacy of intravenous paricalcitol injection compared to intravenous maxacalcitol injection with respect to iPTH and calcium control using a non-inferiority primary endpoint. In this double-blind, double-dummy, parallel-group study, eligible Japanese CKD subjects with SHPT on hemodialysis were randomized 1:1 to receive intravenous paricalcitol or intravenous maxacalcitol injections for 12 weeks. Dynamic allocation of subjects on the basis of screening iPTH levels was used to ensure equal distribution of subjects with iPTH <500 pg/mL and ≥500 pg/mL into the two treatment groups. 255 subjects were randomized to receive paricalcitol (N = 127) or maxacalcitol (N = 128). Primary efficacy analysis indicated that 27.7% in the paricalcitol group vs. 30.5% in the maxacalcitol group (95% CI -14.34% to 8.79%, P = 0.353) achieved target iPTH in the last 3 weeks without hypercalcemia during treatment, failing to achieve the non-inferiority margin of -5% that was set based upon agreement with the PMDA. Both intravenous paricalcitol and maxacalcitol were effective in reducing iPTH and provided similar safety profiles; however, non-inferiority for paricalcitol vs. maxacalcitol was not demonstrated.

Topics: Aged; Calcitriol; Calcium; Double-Blind Method; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Injections, Intravenous; Male; Middle Aged; Parathyroid Hormone; Receptors, Calcitriol; Renal Dialysis; Renal Insufficiency, Chronic

Vitamin D seems to protect against cardiovascular disease, but the reported effects of vitamin D on patient outcomes in CKD are controversial. We conducted a prospective, double blind, randomized, placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular (LV) mass in patients with stages 3-5 CKD with LV hypertrophy. Subjects with echocardiographic criteria of LV hypertrophy were randomly assigned to receive either oral paricalcitol (1 μg) one time daily (n=30) or matching placebo (n=30) for 52 weeks. The primary end point was change in LV mass index over 52 weeks, which was measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volume, echocardiographic measures of systolic and diastolic function, biochemical parameters of mineral bone disease, and measures of renal function. Change in LV mass index did not differ significantly between groups (median [interquartile range], -2.59 [-6.13 to 0.32] g/m(2) with paricalcitol versus -4.85 [-9.89 to 1.10] g/m(2) with placebo). Changes in LV volume, ejection fraction, tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities, and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups. However, paricalcitol treatment significantly reduced intact parathyroid hormone (P<0.001) and alkaline phosphatase (P=0.001) levels as well as the number of cardiovascular-related hospitalizations compared with placebo. In conclusion, 52 weeks of treatment with oral paricalcitol (1 μg one time daily) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD.

Topics: Aged; Alkaline Phosphatase; Blood Pressure; Double-Blind Method; Echocardiography; Ergocalciferols; Female; Humans; Hypercalcemia; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Parathyroid Hormone; Prospective Studies; Renal Insufficiency, Chronic; Ventricular Dysfunction, Left

Vitamin D deficiency is a common problem worldwide. Several studies have shown an association between vitamin D deficiency and the increased risk of metabolic syndrome. No previous study has compared the efficacy and safety of ergocalciferol at 40,000 versus 20,000 IU/week in patients with metabolic syndrome.. To evaluate the efficacy of ergocalciferol supplementation on serum 25-hydroxyvitamin D [25(OH)D] concentrations and to examine safety parameters in metabolic syndrome patients.. Outpatient department of Phramongkutklao Hospital, Bangkok, Thailand.. A randomized, double-blinded, parallel study was conducted in metabolic syndrome patients with vitamin D deficiency [25(OH)D <20 ng/mL]. Ninety patients were randomly assigned into three groups of 30 patients each. Group 1 was given two capsules of placebo/week, group 2 was given ergocalciferol 20,000 IU/week, and group 3 was given ergocalciferol 40,000 IU/week for 8 weeks.. serum 25(OH)D concentrations, serum calcium, safety, and corrected QT (QTc) interval.. Of the 90 patients enrolled, 84 patients completed the study. At the end of the study, the mean serum 25(OH)D in groups 2 and 3 significantly increased from the baseline (15.1 and 14.3 to 26.8 and 30.0 ng/mL, respectively). The increase in serum 25(OH)D in groups 2 and 3 were comparable and significantly greater than that of the placebo group. The percentage number of patients achieving normal vitamin D levels in groups 1, 2 and 3 were 3.3, 33.3, and 60.0 %, respectively, which were significantly different between groups (p < 0.001). Adverse reactions in both ergocalciferol treatment groups were not different from the placebo group (p > 0.05). Serum calcium levels did not change within and between groups of treatment. No significant change in QTc was observed in any patient.. Both 20,000 and 40,000 IU/week of ergocalciferol supplementation for 8 weeks were able to increase serum 25(OH)D concentrations significantly. However, more patients in the ergocalciferol 40,000 IU/week treatment group achieved a normal serum 25(OH)D level than in the group which received 20,000 IU/week. Clinicians would have informed of choosing the dosing regimen of ergocalciferol in metabolic syndrome patients.

Topics: 25-Hydroxyvitamin D 2; Aged; Arrhythmias, Cardiac; Calcifediol; Calcium; Dietary Supplements; Double-Blind Method; Ergocalciferols; Female; Humans; Hypercalcemia; Incidence; Male; Metabolic Syndrome; Middle Aged; Thailand; Time Factors; Vitamin D Deficiency

Calcitriol is used to treat secondary hyperparathyroidism in patients with CKD. Paricalcitol is less calcemic and phosphatemic in preclinical studies and in some trials in dialysis patients, but head-to-head comparisons in nondialysis patients are lacking. A large meta-analysis of trials concluded that these agents did not consistently reduce parathyroid hormone (PTH) and increased the risk of hypercalcemia and hyperphosphatemia. Therefore, the objective of this multicenter trial was to compare the rate of hypercalcemia between calcitriol and paricalcitol, while suppressing PTH 40%-60%.. Patients with stages 3-4 CKD (n=110) with a PTH level >120 pg/ml were recruited and randomized to 0.25 μg/d of calcitriol or 1 μg/d of paricalcitol between April 2009 and July 2011. Subsequent dose adjustments were by protocol to achieve 40%-60% PTH suppression below baseline. The primary endpoint was the rate of confirmed hypercalcemia of >10.5 mg/dl between groups.. Forty-five patients in each group completed the 24 weeks of treatment. Both agents suppressed PTH effectively (-52% with paricalcitol and -46% with calcitriol; P=0.17), although the paricalcitol group reached a 40% reduction in PTH sooner at a median 8 weeks (interquartile range [IQR], 4, 12) versus 12 weeks (IQR, 8, 18; P=0.02) and had a lower pill burden of 240 (IQR, 180, 298) versus 292 (IQR, 231, 405; P=0.01). Confirmed hypercalcemia was very low in both groups (three with paricalcitol and one with calcitriol) and was not significantly different (P=0.36). Both groups had small increases in calcium and phosphorus levels (0.3-0.4 mg/dl in each electrolyte) and significant decreases in alkaline phosphatase, a marker of high bone turnover, with no significant differences between groups.. These results show that both calcitriol and paricalcitol achieved sustained PTH and alkaline phosphatase suppression in stages 3-4 CKD, with small effects on serum calcium and phosphorus and a low incidence of hypercalcemia.

Topics: Aged; Calcitriol; Ergocalciferols; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Incidence; Kidney Failure, Chronic; Middle Aged

The vitamin D hormone, [1,25(OH) 2D, calcitriol], inhibits proliferation and angiogenesis in breast cancer but its therapeutic use is limited by hypercalcemia. Synthetic analogs of 1,25(OH) 2D that are less calcemic, such as paricalcitol (19-nor-1,25-Dihydroxyvitamin D 2), are used to treat hyperparathyroidism associated with chronic kidney disease. We sought to determine the safety and feasibility of taking oral paricalcitol with taxane-based chemotherapy in women with metastatic breast cancer (MBC). Oral paricalcitol was considered safe if it did not result in excessive toxicity, defined as grade 3 or higher serum calcium levels. It was considered feasible if the majority of women could take eight weeks of continuous therapy in the first three months. Serum calcium was monitored weekly and the paricalcitol dose was adjusted based on its calcemic effect. Intact parathyroid hormone (iPTH) was monitored as a marker of paricalcitol activity. Twenty-four women with MBC were enrolled. Twenty women (83%) received eight weeks of continuous therapy. Paricalcitol was well-tolerated with no instances of hypercalcemia grade 2 or greater. Fourteen women (54%) were able to escalate the dose. The dose range of paricalcitol in the first 3 mo was 2-7 ug/day. Serum iPTH levels at baseline were significantly higher in women with serum 25-Hydroxyvitamin D (25-OHD) levels less than 30 ng/ml (96.4 ± 40.9 pg/ml) vs. 46.2 ± 20.3 pg/ml (p = 0 0.001) (iPTH reference 12-72 pg/ml). We conclude that paricalcitol is safe and feasible in women with MBC who are receiving chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Dose-Response Relationship, Drug; Ergocalciferols; Feasibility Studies; Female; Humans; Hypercalcemia; Lymphatic Metastasis; Middle Aged; Taxoids; Treatment Outcome

Vitamin D is associated with decreased cardiovascular-related morbidity and mortality, possibly by modifying cardiac structure and function, yet firm evidence for either remains lacking.. To determine the effects of an active vitamin D compound, paricalcitol, on left ventricular mass over 48 weeks in patients with an estimated glomerular filtration rate of 15 to 60 mL/min/1.73 m(2).. Multinational, double-blind, randomized placebo-controlled trial among 227 patients with chronic kidney disease, mild to moderate left ventricular hypertrophy, and preserved left ventricular ejection fraction, conducted in 11 countries from July 2008 through September 2010.. Participants were randomly assigned to receive oral paricalcitol, 2 μg/d (n =115), or matching placebo (n = 112).. Change in left ventricular mass index over 48 weeks by cardiovascular magnetic resonance imaging. Secondary end points included echocardiographic changes in left ventricular diastolic function.. Treatment with paricalcitol reduced parathyroid hormone levels within 4 weeks and maintained levels within the normal range throughout the study duration. At 48 weeks, the change in left ventricular mass index did not differ between treatment groups (paricalcitol group, 0.34 g/m(2.7) [95% CI, -0.14 to 0.83 g/m(2.7)] vs placebo group, -0.07 g/m(2.7) [95% CI, -0.55 to 0.42 g/m(2.7)]). Doppler measures of diastolic function including peak early diastolic lateral mitral annular tissue velocity (paricalcitol group, -0.01 cm/s [95% CI, -0.63 to 0.60 cm/s] vs placebo group, -0.30 cm/s [95% CI, -0.93 to 0.34 cm/s]) also did not differ. Episodes of hypercalcemia were more frequent in the paricalcitol group compared with the placebo group.. Forty-eight week therapy with paricalcitol did not alter left ventricular mass index or improve certain measures of diastolic dysfunction in patients with chronic kidney disease.. clinicaltrials.gov Identifier: NCT00497146.

Topics: Aged; Chronic Disease; Double-Blind Method; Ergocalciferols; Female; Glomerular Filtration Rate; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Parathyroid Hormone; Treatment Outcome; Ventricular Function, Left; Vitamin D Deficiency; Vitamins

Optimal treatment for secondary hyperparathyroidism (SHPT) has not been defined. The IMPACT SHPT (ClinicalTrials.gov identifier: NCT00977080) study assessed whether dose-titrated paricalcitol plus supplemental cinacalcet only for hypercalcaemia is superior to cinacalcet plus low-dose vitamin D in controlling intact parathyroid hormone (iPTH) levels in patients with SHPT on haemodialysis.. In this 28-week, multicentre, open-label Phase 4 study, participants were randomly selected to receive paricalcitol or cinacalcet plus low-dose vitamin D. Randomization and analyses were stratified by mode of paricalcitol administration [intravenous (IV) or oral]. The primary efficacy end point was the proportion of subjects who achieved a mean iPTH value of 150-300 pg/mL during Weeks 21-28.. Of 272 subjects randomized, 268 received one or more dose of study drug; 101 in the IV and 110 in the oral stratum with two or more values during Weeks 21-28 were included in the primary analysis. In the IV stratum, 57.7% of subjects in the paricalcitol versus 32.7% in the cinacalcet group (P = 0.016) achieved the primary end point. In the oral stratum, the corresponding proportions of subjects were 54.4% for paricalcitol and 43.4% for cinacalcet (P = 0.260). Cochran-Mantel-Haenszel analysis, controlling for stratum, revealed overall superiority of paricalcitol (56.0%) over cinacalcet (38.2%; P = 0.010) in achieving iPTH 150-300 pg/mL during Weeks 21-28. Hypercalcaemia occurred in 4 (7.7%) and 0 (0%) of paricalcitol-treated subjects in the IV and oral strata, respectively. Hypocalcaemia occurred in 46.9% and 54.7% of cinacalcet-treated subjects in the IV and oral strata, respectively.. Paricalcitol versus cinacalcet plus low-dose vitamin D provided superior control of iPTH, with low incidence of hypercalcaemia.

Topics: Administration, Intravenous; Administration, Oral; Aged; Bone Density; Bone Density Conservation Agents; Calcium; Cinacalcet; Drug Therapy, Combination; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Male; Middle Aged; Naphthalenes; Parathyroid Hormone; Receptors, Calcitriol; Renal Dialysis; Renal Insufficiency, Chronic; Treatment Outcome; Vitamin D

We compared the effects of calcitriol and doxercalciferol, in combination with either calcium carbonate or sevelamer, on bone, mineral, and fibroblast growth factor-23 (FGF-23) metabolism in patients with secondary hyperparathyroidism. A total of 60 pediatric patients treated with peritoneal dialysis were randomized to 8 months of therapy with either oral calcitriol or doxercalciferol, combined with either calcium carbonate or sevelamer. Bone formation rates decreased during therapy and final values were within the normal range in 72% of patients. A greater improvement in eroded surface was found in patients treated with doxercalciferol than in those given calcitriol. On initial bone biopsy, a mineralization defect was identified in the majority of patients which did not normalize with therapy. Serum phosphate concentrations were controlled equally well by both binders, but serum calcium levels increased during treatment with calcium carbonate, and serum parathyroid hormone levels were decreased by 35% in all groups. Baseline plasma FGF-23 values were significantly elevated and rose over fourfold with calcitriol and doxercalciferol, irrespective of phosphate binder. Thus, doxercalciferol is as effective as calcitriol in controlling serum parathyroid hormone levels and suppressing the bone formation rate. Sevelamer allows the use of higher doses of vitamin D. Implications of these changes on bone and cardiovascular biology remain to be established.

Topics: Adolescent; Bone and Bones; Bone Density Conservation Agents; Calcitriol; Calcium Carbonate; Chronic Kidney Disease-Mineral and Bone Disorder; Drug Therapy, Combination; Ergocalciferols; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hyperphosphatemia; Kidney Failure, Chronic; Longitudinal Studies; Male; Osteogenesis; Parathyroid Hormone; Polyamines; Sevelamer

We conducted a phase II trial of doxercalciferol, a vitamin D2 analogue, in 15 patients with MDS. Each received doxercalciferol 12.5 microg orally daily for 12 weeks. Nine of 15 patients completed the prescribed course and of these, six had stable disease. No patient had a response (IWG criteria) and overall eight patients experienced progressive disease while on therapy. Two patients with chronic myelomonocytic leukemia (CMML) had a marked rise in monocytes on study. Overall the treatment was well tolerated. One patient was removed from study due to hypercalcemia. We conclude that short-term treatment with doxercalciferol has limited activity in patients with MDS.

Topics: Aged; Aged, 80 and over; Disease Progression; Ergocalciferols; Humans; Hypercalcemia; Leukemia, Myelomonocytic, Chronic; Middle Aged; Myelodysplastic Syndromes; Treatment Failure

Management of secondary hyperparathyroidism has included the use of active vitamin D or vitamin D analogs for the suppression of parathyroid hormone (PTH) secretion. Although, these agents are effective, therapy is frequently limited by hypercalcemia, hyperphosphatemia, and/or elevations in the calcium-phosphorus (Ca x P) product. In clinical studies, paricalcitol was shown to be effective at reducing PTH concentrations without causing significant hypercalcemia or hyperphosphatemia as compared to placebo. A comparative study was undertaken in order to determine whether paricalcitol provides a therapeutic advantage to calcitriol.. A double-blind, randomized, multicenter study comparing the safety and effectiveness of intravenous paricalcitol and calcitriol in suppressing PTH concentrations in hemodialysis patients was performed. A total of 263 randomized patients were enrolled at domestic and international sites. Following the baseline period, patients with serum Ca x P < 75, and a PTH level > or =300 pg/mL were randomly assigned to receive either paricalcitol or calcitriol in a dose-escalating fashion for up to 32 weeks. Dose adjustments were based on laboratory results for PTH, calcium, and Ca x P. The primary end point was the greater than 50% reduction in baseline PTH. Secondary end points were the occurrence of hypercalcemia and elevated Ca x P product.. Paricalcitol-treated patients achieved a > or =50% reduction from baseline PTH significantly faster than did the calcitriol-treated patients (P = 0.025) and achieved a mean reduction of PTH into a desired therapeutic range (100 to 300 pg/mL) at approximately week 18, whereas the calcitriol-treated patients, as a group, were unable to achieve this range. Moreover, paricalcitol-treated patients had significantly fewer sustained episodes of hypercalcemia and/or increased Ca x P product than calcitriol patients (P = 0.008).. Paricalcitol treatment reduced PTH concentrations more rapidly with fewer sustained episodes of hypercalcemia and increased Ca x P product than calcitriol therapy.

Topics: Adult; Aged; Calcitriol; Calcium Channel Agonists; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Incidence; Male; Middle Aged; Parathyroid Hormone

This Phase I study of 1alpha-hydroxyvitamin D(2), an p.o. administered vitamin D analogue, in patients with advanced hormone-refractory prostate cancer was designed to assess the toxicity, pharmacokinetic and biological markers of drug activity, and lastly tumor response data to recommend a dose for Phase II studies. 1alpha-Hydroxyvitamin D(2) was administered daily at doses ranging from 5 to 15 microg/day. Patients were monitored for toxicity and tumor response, and blood and urine samples were collected for pharmacokinetics (1alpha,25-dihydroxyvitamin D(2) levels) and other parameters of biological activity (bone markers, parathyroid hormone, urine calcium, and serum phosphorus levels). Twenty-five patients were enrolled. Main toxicities were hypercalcemia with associated renal insufficiency. No other significant toxicity was seen. Pharmacokinetics showed an increase in the active metabolite 1alpha,25-dihydroxyvitamin D(2) that reached a plateau by week 4 despite continuous drug dosing. Elevation in daily urinary calcium excretion and serum phosphorus levels was seen, whereas a decrease in serum parathyroid hormone was evident. Two patients showed evidence of a partial response, whereas 5 others achieved disease stabilization for > or =6 months. 1alpha-Hydroxyvitamin D(2) was well tolerated with main toxicities being hypercalcemia and renal insufficiency. All of the toxicity was reversible with drug discontinuation. Evidence for drug activity was seen in surrogate markers, and pharmacokinetic analysis showed substantial increases in vitamin D metabolite levels among the various cohorts. Whereas the defined maximum tolerated dose was not reached, the recommended Phase II dose was 12.5 microg/day given continuously.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Calcium; Cohort Studies; Drug Resistance, Neoplasm; Ergocalciferols; Humans; Hypercalcemia; Kidney Failure, Chronic; Male; Middle Aged; Neoplasm Proteins; Osteocalcin; Parathyroid Hormone; Phosphorus; Prodrugs; Prostate-Specific Antigen; Prostatic Neoplasms; Salvage Therapy; Treatment Outcome

Vitamin D therapy for patients with end-stage renal disease (ESRD) on hemodialysis therapy has relied on patient dry weight to determine the initial dose of medication. Obtaining a patient's dry weight can be difficult, and no correlation has been established between a patient's body weight and severity of secondary hyperparathyroidism. We conducted a double-blind, double-dummy, randomized, 12-week, multicenter trial to compare the incidence of hypercalcemia (single occurrence) between two dosing regimens: one regimen based on baseline intact parathyroid hormone (iPTH; PTH/80) level, and the other regimen based on patient body weight (0.04 microgram/kg). One hundred twenty-five adult patients with ESRD on maintenance hemodialysis therapy were enrolled at multiple sites. Before treatment, all patients were required to have PTH levels of 300 pg/mL or greater, calcium levels of 8.0 mg/dL or greater and 10.5 mg/dL or less, and a calcium x phosphorus (Ca x P) product of 70 or less. Patients were randomized to one of two regimens: the nonrandomized treatment was also administered as a placebo dummy. No incidence of hypercalcemia occurred in either treatment group during the study. Patients treated according to the formula iPTH/80 required fewer dose adjustments and achieved the first of four consecutive reductions from baseline PTH level of 30% or greater more rapidly than patients treated based on body weight (P = 0.0306). Incidences of elevated Ca x P product levels were similar between treatment groups. Treatment with paricalcitol injection based on degree of secondary hyperparathyroidism incurred no greater risk for hypercalcemia and achieved meaningful therapeutic results with fewer dose adjustments than dosing based on patient body weight.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Body Weight; Calcium; Confidence Intervals; Double-Blind Method; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis

Paricalcitol (19-nor-1alpha-25-dihydroxyvitamin D2), a new vitamin D analog developed for the treatment of secondary hyperparathyroidism, was evaluated in three double-blind, placebo-controlled, dose-escalating, randomized multicenter trials. A total of 78 patients (40 Paricalcitol injection, 38 placebo) achieved treatment phase eligibility, which included intact parathyroid hormone (iPTH) > or = 400 pg/ml, normalized serum calcium levels between 8.0 and 10.0 mg/dl, and calcium x phosphorus product values less than 75. Study end points included a decrease in iPTH of at least 30% or a maximum of five dose escalations. After a 4-wk washout, paricalcitol or placebo was administered intravenously three times per week after dialysis for 12 wk. Study drug was started at a dose of 0.04 microg/kg and was increased by 0.04 microg/kg every 2 wk to a maximal allowable dose of 0.24 microg/kg or until at least a 30% decrease in serum iPTH was achieved. The dose of paricalcitol that decreased iPTH by at least 30% became the maintenance dose. Of 40 patients receiving paricalcitol, 27 (68%) had at least a 30% decrease in serum iPTH for 4 consecutive weeks, compared with three of 38 patients (8%) receiving placebo (P < 0.001). For patients who received 12 wk of treatment with paricalcitol, the levels of iPTH decreased significantly from 795+/-86 to 406+/-106 pg/ml (P < 0.001), whereas the values for PTH were 679+/-41 pg/ml before and 592+/-41 pg/ml after 12 wk of therapy in patients receiving placebo (P=NS). Also, there was a significant difference between treatment groups for the change from baseline PTH levels (P < 0.001). Paricalcitol treatment resulted in a significant reduction in serum alkaline phosphatase from 148+/-23 U/L to 101+/-14 U/L (P < 0.001) in patients treated for 12 wk compared with 120+/-9 U/L to 130+/-11 U/L (P=NS) in patients receiving placebo for 12 wk. Importantly, hypercalcemia did not occur before achieving target serum iPTH levels in any of the paricalcitol-treated patients. There was no significant difference for the change from baseline in serum phosphorus within or between treatment groups. There was no significant difference in adverse events between the paricalcitol and placebo-treated groups. These studies demonstrate that paricalcitol safely and effectively suppresses iPTH levels in hemodialysis patients. This second generation vitamin D analog may have a wider therapeutic window than current vitamin D preparations, and thus may allow redu

Topics: Adult; Aged; Aged, 80 and over; Alkaline Phosphatase; Calcium; Double-Blind Method; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Renal Dialysis; Safety

The circulating concentrations of calcium, phosphorus, and vitamin D metabolites were measured in 25 infants (fifteen to 30 days of age) with congenital hypothyroidism before treatment or during the first 6 months of thyroxine therapy. Five of the children before treatment and four during the early 3 months of treatment had mild hypercalcemia (10.8 to 12.4 mg/dl). Hypercalcemia before treatment did not appear to be related to the vitamin D status of the infant nor to an alteration in vitamin D metabolism, but to the presence of a residual thyroid secretion. In contrast, hypercalcemia during thyroxine therapy was related to vitamin D supplementation, even though the serum calcium concentration could not be correlated with the circulating concentration of any of the vitamin D metabolites assayed and obvious changes in vitamin D metabolism could not be demonstrated.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Alkaline Phosphatase; Calcitriol; Calcium; Congenital Hypothyroidism; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hypercalcemia; Hypothyroidism; Infant, Newborn; Phosphorus; Thyroid Hormones; Thyrotropin; Thyroxine; Time Factors; Vitamin D

Topics: Alkaline Phosphatase; Calcium; Calcium, Dietary; Clinical Trials as Topic; Depression, Chemical; Ergocalciferols; Humans; Hydrocortisone; Hypercalcemia; Phosphorus; Prednisone; Tuberculosis

Topics: Calcium; Calcium, Dietary; Child; Clinical Trials as Topic; Ergocalciferols; Female; Humans; Hypercalcemia; Parathyroid Hormone; Phosphates; Pseudohypoparathyroidism; Thyroidectomy

Options for chronic treatment of hypoparathyroidism include calcitriol, recombinant human parathyroid hormone, and high-dose vitamin D (D2). D2 is used in a minority of patients because of fear of prolonged hypercalcemia and renal toxicity. There is a paucity of recent data about D2 use in hypoparathyroidism.. Compare renal function, hypercalcemia, and hypocalcemia in patients with hypoparathyroidism treated chronically with either D2 (D2 group) or calcitriol.. A retrospective study of patients with hypoparathyroidism treated at the University of Maryland Hospital. Participants were identified by a billing record search with diagnosis confirmed by chart review. Thirty patients were identified; 16 were treated chronically with D2, 14 with calcitriol. Data were extracted from medical records.. Serum creatinine and calcium, hospitalizations, and emergency department (ED) visits for hypercalcemia and hypocalcemia.. D2 and calcitriol groups were similar in age (58.9 ± 16.7 vs 50.9 ± 22.6 years, P = 0.28), sex, and treatment duration (17.8 ± 14.2 vs 8.5 ± 4.4 years, P = 0.076). Hospitalization or ED visits for hypocalcemia occurred in none of the D2 group vs four of 14 in the calcitriol group (P = 0.03); three in the calcitriol group had multiple ED visits. There were no differences between D2 and calcitriol groups in hospitalizations or ED visits for hypercalcemia, serum creatinine or calcium, or kidney stones.. We found less morbidity from hypocalcemia in hypoparathyroid patients treated chronically with D2 compared with calcitriol and found no difference in renal function or morbidity from hypercalcemia. Treatment with D2 should be considered in patients with hypoparathyroidism, particularly in those who experience recurrent hypocalcemia.

Topics: Adult; Aged; Calcitriol; Calcium; Creatinine; Emergency Service, Hospital; Ergocalciferols; Female; Hospitalization; Humans; Hypercalcemia; Hypocalcemia; Hypoparathyroidism; Kidney Calculi; Male; Middle Aged; Nephrocalcinosis; Renal Insufficiency; Retrospective Studies; Vitamins

Topics: Azathioprine; Ergocalciferols; Female; Humans; Hypercalcemia; Middle Aged; Prednisone; Sarcoidosis; Severity of Illness Index; Treatment Outcome; Vitamin D; Vitamin D Deficiency

We have synthesized a novel vitamin D receptor agonist VS-105 ((1R,3R)-5-((E)-2-((3αS,7αS)-1-((R)-1-((S)-3-hydroxy-2,3-dimethylbutoxy)ethyl)-7α-methyldihydro-1H-inden-4(2H,5H,6H,7H,7αH)-ylidene)ethylidene)-2-methylenecyclohexane-1,3-diol). Preparation of a-ring phenylphosphine oxide 11, followed by Wittig-Horner coupling of 11 with the protected 25-hydroxy Grundmann's ketone 22 generated the precursor 12. Deprotection of the TBDMS groups of 12 produced the target compound VS-105. The biological profiles of VS-105 were evaluated using in vitro assays (VDR receptor binding, VDR reporter gene and HL-60 differentiation) in comparison to calcitriol (the endogenous hormone) or paricalcitol. Furthermore, the PTH suppressing potency and hypercalcemic side effects of VS-105 were evaluated in the 5/6 nephrectomized uremic rats in comparison to paricalcitol. Combining various changes at 20-epi, 22-oxa, 24-methyl, and 2-methylene yielded VS-105 that not only is highly potent in inducing functional responses in vitro, but also effectively suppresses PTH in a dose range that does not affect serum calcium in the 5/6 nephrectomized uremic rats.

Topics: Animals; Calcitriol; Calcium; Cell Differentiation; Ergocalciferols; HL-60 Cells; Humans; Hypercalcemia; Parathyroid Hormone; Rats; Receptors, Calcitriol

Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models.. Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3) xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR) antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN) activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K) activity independently of PPAR-gamma protein.. Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Calcium; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Citric Acid; Down-Regulation; ErbB Receptors; Ergocalciferols; Fatty Acid Synthases; Fatty Acids; Female; Homeostasis; Humans; Hypercalcemia; L-Lactate Dehydrogenase; Malonyl Coenzyme A; Membrane Potential, Mitochondrial; Mice; Molecular Dynamics Simulation; Molecular Sequence Data; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Rats; Receptors, Calcitriol; Safety; Signal Transduction; Xenograft Model Antitumor Assays

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

Secondary hyperparathyroidism is a common complication in patients with chronic kidney disease. Treatment with paricalcitol, a selective vitamin D receptor (VDR) activator, has shown benefits in these patients by adequately reducing PTH levels with minimal changes in serum calcium and phosphorus. The aim of this study was to assess the effectiveness and safety of paricalcitol in chronic renal disease patients (CKD grades 3 and 4).. A study of our experience with paricalcitol was conducted in normal clinical practice in patients over 18 years diagnosed with grade 3 or 4 chronic kidney disease. Patients were periodically evaluated every 3 months. The primary endpoint of effectiveness was to obtain two consecutive decreases of ≥30% in iPTH with respect to baseline values. The secondary endpoints were fulfilment of the objectives in accordance with the Spanish Society of Nephrology (SEN) and Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines, as well as the relationship between the effectiveness of the treatment and different patient variables. Safety was studied by means of hypercalcaemia events.. The primary study endpoint was achieved in 54.3% of patients. In addition, another 16.3% of patients had reduced iPTH by more than 30% at the 3rd visit. Therefore, 70.6% of patients reduced their iPTH levels by more than 30% in 6 months. The relationship between treatment success and both glomerular filtration rate and body mass index was significant. There were few adverse events, although hypercalcaemia was found in 5.4% of patients.. Treatment with paricalcitol is effective in controlling secondary hyperparathyroidism in non-dialysed patients with a wide safety margin.

Topics: Aged; Aged, 80 and over; Body Mass Index; Calcium; Chronic Disease; Diabetic Nephropathies; Dose-Response Relationship, Drug; Drug Evaluation; Endpoint Determination; Ergocalciferols; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Kidney Diseases; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Retrospective Studies; Severity of Illness Index; Treatment Outcome

The outcome-predictability of baseline and instantaneously changing serum calcium in hemodialysis patients has been examined. We investigated the mortality-predictability of time-averaged calcium values to reflect the 'cumulative' effect of calcium burden over time.. We employed a Cox model using up-to-5-year (7/2001-6/2006) time-averaged values to examine the mortality-predictability of cumulative serum calcium levels in 107,200 hemodialysis patients prior to the use of calcimimetics, but during the time where other calcium-lowering interventions, including lower dialysate calcium, were employed.. Both low (<9.0 mg/dl) and high (>10.0 mg/dl) calcium levels were associated with increased mortality (reference: 9.0 to <9.5 mg/dl). Whereas mortality of hypercalcemia was consistent, hypocalcemia mortality was most prominent with higher serum phosphorus (>3.5 mg/dl) and PTH levels (>150 pg/ml). Higher paricalcitol doses shifted the calcium range associated with the greatest survival to the right, i.e. from 9.0 to <9.5 to 9.5 to <10.0 mg/dl. African-Americans exhibited the highest death hazard ratio of hypocalcemia <8.5 mg/dl, being 1.35 (95% CI: 1.22-1.49). Both a rise and drop in serum calcium over 6 months were associated with increased mortality compared to the stable group.. Whereas in hemodialysis patients cumulatively high or low calcium levels are associated with higher death risk, subtle but meaningful interactions with phosphorus, PTH, paricalcitol dose and race exist.

Topics: Adult; Aged; Black or African American; Bone Density Conservation Agents; Cause of Death; Ergocalciferols; Female; Humans; Hypercalcemia; Hypocalcemia; Kidney Failure, Chronic; Longitudinal Studies; Male; Middle Aged; Parathyroid Hormone; Predictive Value of Tests; Proportional Hazards Models; Renal Dialysis; Time Factors

Vitamin D compounds are effective in managing elevated PTH levels in secondary hyperparathyroidism (SHPT) of renal failure. However, undesired increases in serum calcium and phosphorus associated with compounds such as calcitriol [1,25(OH)2D3] has prompted a search for compounds with improved safety profiles. 1alpha,24(S)(OH)2D2 (1,24(OH)2D2) is a vitamin D2 metabolite with low calcium-mo bilizing activity in vivo. We studied the efficacy of 1,24(OH)2D2 in mice lacking the CYP27B1 enzyme [25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase)], a novel vitamin D deficiency model with SHPT.. 1alpha-OHase-deficient (-/-) mice and normal (+/-) heterozygous littermates re ceived 1,24(OH)2D2 (100, 300, 1000, and 3000 pg/g/day) or 1,25(OH)2D3 (30, 300, and 500 pg/g/day) for 5 weeks via daily sc injection. Control groups received vehicle.. Vehicle-treated 1alpha-OHase-deficient mice were hypocalcemic and had greatly elevated serum PTH. 1,24(OH)2D2 at doses above 300 pg/g/day normalized serum calcium, serum PTH, bone growth plate morphology, and other bone parameters. No hy percalcemia was observed at any dose of 1,24(OH)2D2 in normal or 1alpha-OHase-deficient animals. In contrast, 1,25(OH)2D3 at only 30 pg/g/day normalized calcemia, serum PTH, and bone parameters, but at higher doses completely suppressed PTH and caused hypercalcemia in both 1alpha-OHase-deficient and normal mice. Treatment with 500 pg/g/day of 1,25(OH)2D3 also induced osteomalacia in normal animals.. 1,25(OH)2D3 was maximally active at 10-fold lower doses than 1,24(OH)2D2, but induced hypercalcemia and osteomalacia at high doses. 1,24(OH)2D2 normalized serum calcium, serum PTH, and bone histomorphometry without hypercalcemia in 1alpha-OHase-deficient mice with SHPT.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Animals; Bone and Bones; Calcinosis; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Ergocalciferols; Femur; Hypercalcemia; Hyperparathyroidism, Secondary; Mice; Mice, Transgenic; Parathyroid Hormone; Vitamin D Deficiency

Vitamin D deficiency is common in CKD and dialysis patients. Studies suggest a physiologic autocrine and/or paracrine role for 1,25(OH)D produced via 1alpha-hydroxylase in tissues such as vascular smooth muscle, breast, prostate, and bone marrow. Studies have not yet defined the optimal dose and duration of vitamin D necessary to replete and maintain stores in dialysis patients, or whether it is safe or beneficial.. We performed a review of the prevalence of vitamin D deficiency and the safety and effectiveness of ergocalciferol oral supplementation (vitamin D(2), 50,000 IU monthly) given to hemodialysis patients during dialysis May to October 2005 in St. Louis (latitude 38 degrees ).. Among the 119-patient cohort present for the entire 6 months, 25(OH)D was (mean +/- SD) 16.9 +/- 8.5 ng/ml, (91% < 30 ng/ml) and increased to 53.6 +/- 16.3 ng/ml (p < 0.001), (95% > 30 ng/ml, and none > 100 ng/ml). Initial versus 6 mo. serum calcium (9.1 +/- 0.56 vs. 9.2 +/- 0.70), phosphorus (5.25 +/- 1.38 vs. 5.11 +/- 1.31), Ca x P, and paricalcitol dose (10.3 +/- 9.6 vs. 11.3 +/- 9.2 mcg/week) were not significantly different. No hypercalcemia could be attributed to supplementation. Mean hemoglobin did not change significantly (11.96 +/- 1.4 vs. 11.69 +/- 1.4, p = 0.124), but most patients experienced a reduced weekly epoetin dose. Epoetin dose decreased in 64% of patients, and increased in 28%.. We conclude that the vast majority of hemodialysis patients are vitamin D-deficient; monthly ergocalciferol 50,000 IU is safe and effective in normalizing serum 25(OH)D levels and may have an epoetin-sparing effect.

Topics: Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Comorbidity; Drug Administration Schedule; Ergocalciferols; Female; Humans; Hypercalcemia; Kidney Failure, Chronic; Male; Middle Aged; Missouri; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; Vitamin D Deficiency

Absorption of calcium carbonate in the fasting state has been reported to be significantly compromised in subjects with achlorhydria. Although calcium carbonate malabsorption in the fasting state cannot be predicted, it might be corrected if the compound is administered with meals. However, administering calcium carbonate with meals is logistically challenging in long-term care facilities.. The aim of this study was to report the case of a woman who was transitioned to calcium citrate and subsequently experienced symptomatic severe hypercalcemia.. An 89-year-old female resident of the Wisconsin Veterans Home, a skilled nursing facility in King, Wisconsin, was receiving long-term treatment with ergocalciferol (vitamin D2) 50,000 IU/d. The patient also was receiving calcium carbonate supplements in the morning, and she rarely ate breakfast (fasting state). The patient was transitioned from 2000 mg/d of elemental calcium as carbonate to 1230 mg/d as citrate.. After being switched from calcium carbonate to calcium citrate, the patient developed severe symptomatic hypercalcemia (16.8 mg/dL), the primary cause of which was the administration of an inappropriately high dose of vitamin D.. We report a case of symptomatic severe hypercalcemia in a skilled nursing facility resident treated with an inappropriately high daily dose of vitamin D. Hypercalcemia manifested when calcium carbonate was replaced with calcium citrate.

Topics: Aged, 80 and over; Calcium Carbonate; Calcium Citrate; Ergocalciferols; Fasting; Female; Homes for the Aged; Humans; Hypercalcemia; Skilled Nursing Facilities; Vitamins

Parathyromatosis, consisting of hyperfunctioning parathyroid tissues scattered throughout the neck, is a rare cause of recurrent hyperparathyroidism after parathyroidectomy. Medical management of patients with parathyromatosis usually is ineffective. Repeated surgery often is necessary, but generally is unsuccessful. We describe a case of parathyromatosis as a cause for recurrent hyperparathyroidism. A 32-year-old woman with a history of end-stage renal disease on hemodialysis therapy for 13 years developed secondary hyperparathyroidism requiring subtotal parathyroidectomy. Three years later, hyperparathyroidism relapsed. A technetium Tc 99m-sestamibi scan showed remnant parathyroid tissue on the left inferior thyroid lobe. Percutaneous ethanol infusion therapy failed to suppress parathormone excess, and neck exploration was performed. Histological examination of pathological lesions confirmed the diagnosis of parathyromatosis. Despite extended resection of multiple parathyroid nodules, symptoms worsened, leading progressively to severe morbidity. Imaging studies at this point showed widespread hyperfunctioning parathyroid tissue within the neck. The patient refused a third operation; thus, we resorted to coadministration of paricalcitol, a less hypercalcemic vitamin D analogue, and ibandronate, a new-generation bisphosphonate. Parathormone secretion was suppressed partially with this regimen, even at the expense of hypercalcemia and hyperphosphatemia. Sustained normalization of hormone levels and normocalcemia were accomplished only after substitution of ibandronate for the calcimimetic agent cinacalcet. The question of whether calcimimetics may maximize the chance of complete cure of parathyromatosis, especially when surgical treatment fails or is not feasible, remains to be answered by future studies.

Topics: Adult; Bone Density Conservation Agents; Diphosphonates; Disease Progression; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism; Ibandronic Acid; Kidney Failure, Chronic; Renal Dialysis; Reoperation

Topics: Aged; Bone Diseases, Metabolic; Calcium Carbonate; Dietary Supplements; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism

To investigate the effectiveness of the vitamin D analogues 1,25-(OH)(2)-16-ene-23-yne vitamin D(3) (16,23-D(3)) and 1alpha-hydroxyvitamin D(2) (1alpha-OH-D(2)) in inhibiting retinoblastoma growth in large tumors in a xenograft model and with prolonged use in a transgenic model.. For the large-tumor study, the xenograft athymic mouse/human retinoblastoma cell (Y-79) model was used. Subcutaneous tumors were allowed to grow to an average volume of 1600 mm(3). Systemic treatment with 1 of the vitamin D analogues or with vehicle (control groups) was carried out for 5 weeks. For the long-term study, transgenic beta-luteinizing hormone-large T antigen (LHbeta-Tag) mice were systemically treated with 1 of the 2 compounds or vehicle (control groups) for up to 15 weeks. Tumor size and signs of toxicity were assessed.. In the large-tumor study, tumor volume ratios for the 1alpha-OH-D(2) and 16,23-D(3) groups were significantly lower than those for controls (P<.002). No significant differences in tumor volume were seen between the 1alpha-OH-D(2) and 16,23-D(3) groups (P =.15). In the long-term study, the 1alpha-OH-D(2) group showed significantly smaller tumor size compared with its control (P<.001). No significant difference was seen between the 16,23-D(3) group and its control. Some toxic effects related to hypercalcemia were seen in both studies.. In athymic mice in the large-tumor study, both 1alpha-OH-D(2) and 16,23-D(3) were effective in inhibiting tumor growth compared with controls. In the long-term study, 1alpha-OH-D(2) inhibited tumor growth but 16,23-D(3) did not. Effective doses of both compounds caused hypercalcemia and a significant increase in mortality. Clinical Relevance Use of 1alpha-OH-D(2) inhibited tumor growth in large tumors and with long-term treatment compared with controls. Because of hypercalcemia-related toxic effects seen in the present experiments, in clinical trials, serum calcium levels should be carefully monitored. This analogue may require use with drugs that lower serum calcium levels or use of relatively lower doses or skipped doses. The ideal alternative solution would be to identify vitamin D analogues that retain the antineoplastic action without the calcemic activity.

Topics: Animals; Antineoplastic Agents; Calcitriol; Disease Models, Animal; Ergocalciferols; Hypercalcemia; Mice; Mice, Nude; Mice, Transgenic; Retinal Neoplasms; Retinoblastoma; Survival Rate; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

The efficacy of the vitamin D analog paricalcitol has mainly been shown in short-term studies. There are limited data regarding long-term treatment with this agent. This purpose of this study was to determine long-term effects of paricalcitol therapy on parathyroid hormone (PTH) suppression and serum levels of calcium, phosphorus and calcium-phosphorus product (Ca x P).. Patients who received paricalcitol for > or = 3 months had the following data collected: demographics, drug dosage, serum PTH, corrected serum calcium concentration, serum phosphorus concentrations and serum Ca x P values.. Sixteen patients received paricalcitol for a mean of 18 months. The mean +/- SD dose of paricalcitol was 0.13 +/- 0.12 mcg/kg. The mean +/- SD pre-paricalcitol serum PTH concentration was 705 +/- 423 pg/mL. PTH concentration did not change significantly over the duration of treatment (mean +/- SD: 821 +/- 480 pg/mL). The number of patients who had at least one corrected serum calcium concentration > or = 11.5 mg/dL, one serum phosphorus concentration > or = 6.5 mg/dL, or one Ca x P level > or = 70 were 75%, 94% and 82%, respectively. Hypercalcemia and elevated Ca x P value resulted in a mean of 17% of doses being withheld during therapy.. During the study, PTH was not adequately suppressed by paricalcitol. This was primarily attributed to withholding paricalcitol doses due to elevated serum calcium and Ca x P levels.

Topics: Adult; Calcium; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Phosphorus Metabolism Disorders; Renal Dialysis

Paricalcitol was evaluated for the treatment of secondary hyperparathyroidism (SHPT) in a long-term, prospective, open-label study of 37 patients with end-stage renal failure resistant to intravenous calcitriol. All patients had an intact parathyroid hormone (iPTH) level of 600 pg/mL or greater before being converted from calcitriol to paricalcitol therapy. Paricalcitol therapy was initiated at a 1:4 calcitriol to paricalcitol dose conversion ratio for the initial 14 patients and a 1:3 dose ratio for the next 23 patients. Subsequent dosing was based on iPTH, calcium, and phosphorus determinations. All patients underwent hemodialysis three times weekly and received structured nutritional counseling. Mean iPTH level (baseline, 901 +/- 58 pg/mL) decreased rapidly during the initial 2 months and was 165 +/- 24 pg/mL at 16 months. Alkaline phosphatase levels decreased from 280 +/- 27 IU at baseline to 65 +/- 12 IU at 16 months. Mean calcium and phosphorus levels did not change significantly over the 16 months of paricalcitol therapy. The baseline mean calcium level of 9.4 +/- 0.2 mg/dL increased to 9.7 +/- 0.2 mg/dL (P = 0.86), and phosphorus level decreased from 6.1 +/- 0.2 to 5.8 +/- 0.2 mg/dL (P = 0.77). The greater paricalcitol doses afforded by the initial dose conversion ratio of 1:4 produced unacceptably rapid iPTH suppression and subsequent hypercalcemia. Mean doses of paricalcitol decreased six- to sevenfold throughout the course of therapy while maintaining acceptable iPTH suppression. Eight patients developed hypercalcemia, which successfully managed by dietary counseling, phosphate-binder adjustment, and paricalcitol dose reduction. Six patients developed hyperphosphatemia; 3 patients responded adequately to dietary manipulation and phosphate binders, but 3 patients had repeated episodes. Three patients did not respond adequately to paricalcitol therapy and required parathyroidectomy. In summary, paricalcitol was successful at controlling SHPT in patients resistant to calcitriol therapy with minimal impact on calcium and phosphorus homeostasis. The 1:3 initial dose conversion provided the smoothest iPTH control with only a single episode of hypercalcemia in patients treated with this initial dose. Doses of paricalcitol decreased over time.

Topics: Calcitriol; Calcium; Dietary Proteins; Drug Resistance; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Phosphorus; Prospective Studies; Renal Dialysis; Serum Albumin

The present experiments were conducted to compare the relative hypercalciuric and hypercalcemic activities of 1,24-dihydroxyvitamin D(2) [1,24-(OH)(2)D(2)], 1,24-dihydroxyvitamin D(3) [1, 24-(OH)(2)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] in 7-week-old rats. The rats were dosed orally with each sterol for 7 days at a rate of 1 ng/g body weight/day. We also monitored the effect of the three compounds on the induction of mRNA for CaATPase and for 25-hydroxyvitamin D-24-hydroxylase in the kidney and intestine, on plasma vitamin D metabolite levels, and on the capacity to evoke modification in the vitamin D receptor/retinoic acid X receptor (VDR/RXR) heterodimer conformation. Plasma calcium was elevated in the rats treated with 1,24-(OH)(2)D(3) and 1, 25-(OH)(2)D(3), but not in the 1,24-(OH)(2)D(2)-dosed rats. Urinary calcium was elevated significantly (relative to controls) in all groups. The order of hypercalciuric activity was 1,25-(OH)(2)D(3) >/= 1,24-(OH)(2)D(3) >/= 1,24-(OH)(2)D(2) > control. Duodenal plasma membrane calcium ATPase (PMCA) mRNA was elevated to a similar extent in all groups relative to controls. Duodenal 24-hydroxylase mRNA was elevated in all groups relative to controls; however, the elevations were significantly higher in the 1,24-(OH)(2)D(3) and 1, 25-(OH)(2)D(3) groups compared with the 1,24-(OH)(2)D(2) group. Kidney 24-hydroxylase also was elevated significantly in the 1, 24-(OH)(2)D(3)- and 1,25-(OH)(2)D(3)-treated rats but not in the 1, 24-(OH)(2)D(2)-treated rats. Recombinant human vitamin D receptor (hVDR) extracts were incubated with saturating concentrations of 1, 24-(OH)(2)D(2), 1,24-(OH)(2)D(3), and 1,25-(OH)(2)D(3) and subsequently analyzed by electrophoretic mobility shift assay (EMSA). Overall binding was comparable for all metabolites; however, the 1, 24-(OH)(2)D(2) complex exhibited distinctly altered mobility relative to 1,24-(OH)(2)D(3) and 1,25-(OH)(2)D(3), suggestive of an effect on hVDR/hRXR conformation. These data suggest that 1, 24-(OH)(2)D(2) is not as potent as either of the vitamin D(3) sterols at affecting hypercalcemia or hypercalciuria in young growing rats; however, 1,24-(OH)(2)D(2) can evoke other biological responses similar to the vitamin D(3) sterols. These different responses may be related to the alterations in conformation state of the hVDR/hRXR heterodimer.

Topics: Analysis of Variance; Animals; Binding, Competitive; Calcitriol; Calcium; Dihydroxycholecalciferols; Ergocalciferols; Hypercalcemia; Male; Rats; Receptors, Calcitriol; RNA, Messenger; Vitamin D

19-Nor-1,25(OH)(2)D(2) (19-norD(2)) has been shown to suppress parathyroid hormone effectively, but with lower calcemic activity than 1,25(OH)(2)D(3). The present study investigated potential mechanisms to explain the reduced calcemic response to 19-norD(2). Tissue localization of [(3)H]19-norD(2) or[(3)H]1,25(OH)(2)D(3) after a single injection was not different. Intestinal calcium absorption and bone mobilization, measured in vitamin D-deficient rats 24 h after single injections of 60 or 600 pmol of 19-norD(2) or 1,25(OH)(2)D(3), were enhanced to a similar degree by the two compounds. However, when normal rats were treated every other day with 240 pmol of 19-norD(2) or 1,25(OH)(2)D(3), increases in serum calcium were identical 24 h after the first injection but diverged thereafter with significantly lower serum calcium in the 19-norD(2)-treated rats by 5 d. Intestinal calcium absorption and bone calcium mobilization were reassessed in vitamin D-deficient rats after seven daily injections of 600 pmol of 19-norD(2) or 1, 25(OH)(2)D(3), and both parameters were significantly lower in the 19-norD(2)-treated rats. Pharmacokinetic analysis after seven daily injections of 600 pmol of 19-norD(2) or 1,25(OH)(2)D(3) showed similar localization to the intestine and bone. In addition, intestinal vitamin D receptor levels were not different after 1 wk of treatment with 19-norD(2) or 1,25(OH)(2)D(3). In conclusion, the low calcemic activity of 19-norD(2) seems to be due to an acquired, postreceptor resistance of the intestine and bone to chronic treatment with the analog.

Topics: Animals; Bone Resorption; Calcitriol; Calcium; Ergocalciferols; Hypercalcemia; Injections; Intestinal Absorption; Intestinal Mucosa; Male; Rats; Receptors, Calcitriol; Time Factors; Tissue Distribution; Vitamin D Deficiency

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

A 76-year-old female patient who had been taking vitamin D2 100,000 U/day for more than 14 years due to hypoparathyroidism following total throidectomy was admitted because of protracted hypercalcemia. On admission, the levels of serum vitamin D2 (99.8 ng/ml) and 25-OHD2 (356 ng/ml) were very high, and 1,25-(OH)2D2 was low (4.0-18.7 pg/ml). Serum D3' 25-OHD3 and 1,25-(OH)2D3 were below the normal range. Despite intensive hydration with saline, intravenous hyperalimentation with phosphate- and calcium-free nutrients, and administration of glucocorticoid and calcitonin, the hypercalcemia persisted, accompanied by hypoproteinemia, edema, pleural effusion and congestive heart failure. The serum D2 and 25-OHD2 concentrations remained high and were accompanied by a gradual increase in 1,25-(OH)2D2 (121 pg/ml), which further increased after the administration of bisphosphonate (pamidronate) to 183 pg/ml. Seventeen months later, serum calcium and 1,25-(OH)2D2 were normalized but serum D2 and 25-OHD2 remained high. The serum 24,25-(OH)2D2/25-OHD2 ratio was relatively constant throughout her clinical course, whereas the low serum 1,25-(OH)2D2/25-OHD2 ratio at admission gradually increased during admission, suggesting that the increase in serum 1,25-(OH)2D2 is due to increased production rather than decreased degradation. The administration of pamidronate further increased serum 1,25-(OH)2D2. These features of the clinical course demonstrate that the 1,25-dihydroxyvitamin D concentration in hypercalcemic patients with protracted vitamin D intoxication may be decreased, normal or increased. Possible factors responsible for a protracted increase in serum 1,25-(OH)2D2 are body weight loss, hypoproteinemia, and phosphate depletion. In addition, some bisphosphonates would certainly promote PTH-independent production of 1,25-(OH)2D2.

Topics: Aged; Ergocalciferols; Female; Humans; Hypercalcemia; Hypoparathyroidism

A 55-year-old patient with hypercalcemic crisis due to gastric carcinoma with bone marrow metastasis was treated with bisphosphonate (pamidronate) and calcitonin. Urinary excretion of parathyroid hormone-related protein (PTHrP) was increased. When normocalcemia had been attained, intravenous hyperalimentation was started, in which 1,000 U vitamin D2 was inadvertently supplemented on days 5-18, On days 15-18, hypercalcemia rapidly recurred, accompanied by markedly increased serum levels of 25-OHD2 (9.1 ng/dl) and 1,25-(OH)2D2 (161 pg/ml). This clinical course suggests that PTHrP, like PTH, stimulated 1 alpha-hydroxylase activity and produced excessive 1,25-(OH)2D2. Vitamin D should not be administered to patients with malignancy-associated hypercalcemia, particularly that due to PTHrP-producing tumors.

Topics: Calcitriol; Contraindications; Diphosphonates; Ergocalciferols; Humans; Hypercalcemia; Male; Middle Aged; Neoplasm Proteins; Pamidronate; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Parenteral Nutrition, Total; Protein Biosynthesis; Stomach Neoplasms

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

Slices of the thyroid gland were impregnated with silver nitrate and stained with hematoxylin. Separate calculation of the index of calchicin mitosis of the follicular and parafollicular (C-) cells was made. The material of 37 mature albino rats was analyzed. Calcium-rich diet was given to 22 animals during 10 days. Different levels of hypercalcemia were achieved by different doses of vitamin D2 (from 1 to 10 thousand MU daily, 11 experimental groups). The mitotic index of C-cells was found to grow but under mild hypercalcemia (10% of the control level). Further elevation of the calcium concentration in blood was followed by a decrease of the amount of the dividing parafollicular cells down to control values. In rats fed by the diet optimal for the stimulation of C-cells division (11 rats, 2000 MU as a daily dosage of vitamin D2) within the interval from 1 to 10 days increased mitotic activity of the follicular cells was found from the 3rd day, while that of C-cells only as late as the 9th-10th day. In all the experimental rats the mitotic index of the follicular thyrocytes was 3.5-4 times as high as the mitotic index of C-cells. Relatively not high proliferative activity of parafollicular cells might be due to their pronounced polyfunctional character and their participation in complex paracrine interactions with other cell elements of the thyroid gland.

Topics: Animals; Calcium, Dietary; Cell Division; Ergocalciferols; Hypercalcemia; Male; Mitosis; Rats; Thyroid Gland; Time Factors

The effects of 1 alpha-hydroxyvitamin D2 on calcium metabolism in vivo and of 1 alpha, 25-dihydroxyvitamin D2, which is an active metabolite of 1 alpha-hydroxyvitamin D2, on bone metabolism in vitro was studied and compared with that of 1 alpha-hydroxyvitamin D3 or 1 alpha,25-dihydroxyvitamin D3. 1 alpha-Hydroxyvitamin D2 and 1 alpha-hydroxyvitamin D3 was equally potent in stimulating intestinal calcium transport by using the everted sac method and of calcium mobilization from bone in vitamin D-deficient rats. On the other hand, the hypercalcemic activity of 1 alpha-hydroxyvitamin D2 was much lower than that of 1 alpha-hydroxyvitamin D3 in normal mice and rats. 1 alpha,25-Dihydroxyvitamin D2 and 1 alpha,25-dihydroxyvitamin D3 stimulated alkaline phosphatase activity in osteoblastic MC3T3-E1 cells and bone resorption in newborn mouse calvaria maintained in organ culture. These results show that 1 alpha-hydroxyvitamin D2 as well as 1 alpha-hydroxyvitamin D3 promote calcium absorption and may accelerate bone remodelling via direct action on osteoblasts. In addition, they suggest that 1 alpha-hydroxyvitamin D2 may be more useful than 1 alpha-hydroxyvitamin D3 for the treatment of senile osteoporosis, because hypercalcemia is one of the major side effects of 1 alpha-hydroxyvitamin D3.

Topics: Alkaline Phosphatase; Animals; Animals, Newborn; Bone Remodeling; Bone Resorption; Calcitriol; Calcium; Cells, Cultured; Ergocalciferols; Hydroxycholecalciferols; Hypercalcemia; Intestinal Absorption; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Organ Culture Techniques; Osteoblasts; Rats; Rats, Inbred Strains; Skull; Stimulation, Chemical; Vitamin D Deficiency

Biological activity of 24-epi-1 alpha,25-dihydroxyvitamin D-2 (24-epi-1,25(OH)2D2) and 1 alpha,25-dihydroxyvitamin D-7 (1,25(OH)2D7), the 22,23-dihydro derivative of the former compound, was investigated. Both of the vitamin D derivatives stimulated intestinal calcium transport and calcium mobilization from bones in rats; however, the effect was about 50% of that of 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)2D3). On the other hand, 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 inducement of HL-60 human leukemia cell differentiation was comparable to that of 1,25(OH)2D3. Accordingly, the differentiation-inducing activity of 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 was much greater than their ability to stimulate calcium metabolism. In contrast to 1,25(OH)2D3, 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 exerted little hypercalcemic activity in mice. These results suggest that both vitamin D derivatives will be useful as anti-tumor agents.

Topics: Alkaline Phosphatase; Animals; Bone and Bones; Calcium; Cell Differentiation; Cell Division; Cell Line; Ergocalciferols; Humans; Hypercalcemia; Intestinal Mucosa; Male; Mice; Mice, Inbred ICR; Rats; Rats, Inbred Strains; Vitamin D

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

Because of the recently observed augmentation of medullary hypoxic injury by calcium in isolated perfused rat kidneys (Kidney Int 34:186-194, 1988), renal morphology of chronic, prolonged hypercalcemia was investigated in vivo. Rats were treated with repeated injections of vitamin D2 (400,000 units/week) for two to eight weeks. Chronic elevation of plasma calcium from 2.1 to 2.8 mmol/liter (P less than 0.001) was associated by a fall in maximal urine osmolality with no change in glomerular filtration rate. The most significant morphological alterations occurred in the inner stripe of the outer medulla; these changes were characterized by a sequence of active injury with subsequent destruction and atrophy of the medullary thick ascending limbs, fibroblastic and lymphocytic infiltration, and secondary dilatation of collecting ducts. Similar changes occurred in the medullary rays. These alterations were accompanied by increased renal prostanoid production and a predisposition to acute kidney failure from indomethacin. Because of its selective occurrence in zones of poorest oxygen supply, this inner stripe injury may derive from vulnerability to hypoxia and may play a role in some chronic nephropathies.

Topics: Animals; Chronic Disease; Ergocalciferols; Hypercalcemia; Hypoxia; Kidney Diseases; Kidney Medulla; Prostaglandins; Rats; Rats, Inbred Strains

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

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

Topics: Acute Kidney Injury; Aged; Chilblains; Ergocalciferols; Frostbite; Humans; Hypercalcemia; Male

Vitamin D2 (40,000 IU) per 100 g body weight was administered daily in male albino rats. The levels of calcium and inorganic phosphate were determined in serum and lens. Lens calcium was elevated in the treated rats by 40%.

Topics: Animals; Ergocalciferols; Hypercalcemia; Lens Diseases; Male

Hypercalcemia is associated with impaired urinary concentrating ability. To explore the mechanism(s) by which hypercalcemia impairs chloride transport in the loop of Henle, we carried out in vivo microperfusion of the loop segment in Sprague-Dawley rats rendered acutely hypercalcemic (12.1 +/- 0.1 mg/dliter) by calcium gluconate infusion. Control rats were infused with sodium gluconate and had normal plasma calcium (8.0 +/- 0.2 mg/dliter). Compared to control, fractional chloride reabsorption was decreased (61 +/- 4 to 50 +/- 3%; P less than 0.05) and early distal chloride increased 74 +/- 6 to 98 +/- 3 mEq/liter (P less than 0.001) in hypercalcemia. During hypercalcemia, infusion of verapamil failed to increase fractional chloride reabsorption (49 +/- 4%; P less than 0.05) or decrease early distal chloride (95 +/- 2; P less than 0.05) toward control values. Similarly, indomethacin did not improve fractional chloride reabsorption (48 +/- 4%; P less than 0.05) or distal chloride concentration (93 +/- 7; P less than 0.05). In control rats infused with Ringers HCO3, the addition of calcium 8.0 mEq/liter to the perfusate increased early distal calcium (9.22 to 3.11 mEq/liter) but was associated with no change in fractional chloride reabsorption (-6 +/- 6%) and a slight decrease in early distal chloride (-9 +/- 3 mEq/liter; P less than 0.05). These data are consistent with the hypothesis that an elevated plasma, not luminal calcium, concentration impairs chloride reabsorption in the loop segment, primarily the ADH-stimulated component. This may have an important role in the urinary concentrating defect of hypercalcemia.

Topics: Animals; Biological Transport, Active; Calcium; Calcium Gluconate; Chlorides; Ergocalciferols; Hypercalcemia; Indomethacin; Kidney Concentrating Ability; Kidney Tubules; Loop of Henle; Male; Rats; Rats, Inbred Strains; Verapamil

Topics: Drug Administration Schedule; Ergocalciferols; Female; Humans; Hypercalcemia; Infant; Male; Rickets

A patient received 2.5 mg vitamin D2 daily for 10 years and presented with increasing skeletal pain and hypercalcaemia. The limbs were painful to touch especially at the insertions of ligaments and tendons, and radiographs showed osteosclerosis with calcification in the periosteum, blood vessels, tendoachilles and plantar fascia. Bone histomorphometry showed increased amounts of osteoid and defective mineralisation despite hypercalcaemia, hyperphosphataemia and raised serum concentrations of vitamin D metabolites. A negative external calcium balance was documented in the presence of enhanced intestinal calcium absorption and an increase in urinary hydroxyproline excretion. Cortisone improved calcium balance and corrected the hypercalcaemia by reducing serum 1,25-dihydroxyvitamin D levels and urinary hydroxyproline excretion.

Topics: Bone and Bones; Calcium; Ergocalciferols; Female; Humans; Hypercalcemia; Middle Aged; Osteomalacia; Syndrome; Vitamin D

A lipid indistinguishable from 1,24(R)-dihydroxyvitamin D3 [1,24(R)-(OH)2D3] was found in serum and tumor extracts from a hypercalcemic patient with a small cell carcinoma of the lung. The lipid comigrated with authentic 1,24(R)-(OH)2D3 on high performance liquid chromatography using both straight and reverse phase columns and competed with tritiated 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3)] for binding to intestinal 1,25-(OH)2D3 receptor. Increasing doses of the lipid factor from tumor and authentic 1,24(R)-(OH)2D3 gave parallel responses in a bone resorption assay, as assessed by 45Ca release from prelabeled mouse calvaria. The lipid factor from the patient's serum and authentic 1,24(R)-(OH)2D3 had identical biological activities in the receptor binding and bone resorption assays. In addition, the mechanisms of action of this lipid factor and 1,24(R)-(OH)2D3 were indistinguishable. Bone resorption by both was inhibited by calcitonin, and neither the lipid factor nor authentic 1,24(R)-(OH)2D3 affected cAMP content in osteoblast-like bone cells derived from mouse calvaria. The estimated concentrations of the 1,24(R)-(OH)2D3-like lipid, expressed as 1,24(R)-(OH)2D3 were 11 ng/g tumor wet wt by the receptor binding assay and 9.2 ng/g tumor wet wt by the bone resorption assay. The mean serum concentration was 1.4 +/- 0.3 (+/- SD) ng/ml (n = 3) by the receptor binding assay. No activity was detected in either bioassay when extracts of nontumor tissues from this patient or tumor extracts and sera from one hypercalcemic and four normocalcemic cancer patients were tested. The mean serum 1,25-(OH)2D level was low (6.4 +/- 0.5 pg/ml; n = 2), and serum 1,24(R),25-(OH)3D in this patient was high (103 pg/ml) compared to normocalcemic cancer patients, in whom the mean serum 1,25-(OH)2D level was 27 +/- 12 pg/ml (n = 4) and the 1,24(R),25(OH)3D level was 28 +/- 1.3 pg/ml (n = 4). Thus, the 1,24(R)-(OH)2D3-like lipid may be a substrate for metabolic conversion to 1,24(R),25-(OH)3D in vivo. These results provide evidence for the presence of a novel metabolite of vitamin D3, 1,24(R)-(OH)2D3. Detection of this bone-resorbing lipid in both tumor and serum suggests, but does not prove, that the tumor secreted this bioactive lipid into the circulation and that the high level of circulating bone-resorbing lipid was related to the hypercalcemia in this patient.

Topics: Animals; Bone and Bones; Bone Resorption; Calcium; Carcinoma, Small Cell; Chromatography, High Pressure Liquid; Cyclic AMP; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hypercalcemia; In Vitro Techniques; Lipids; Lung Neoplasms; Male; Mice; Middle Aged; Paraneoplastic Endocrine Syndromes; Radioligand Assay

Vitamin D metabolites were measured on admission in eight patients intoxicated with ergocalciferol (serum calcium 3.01-4.05 mmol/l) and also during the subsequent 2 months in six of the eight. Serum concentrations of 25-hydroxyergocalciferol, on admission, were grossly elevated in all patients (range 583-1843 nmol/l). Serum calcium concentration was related significantly only to the concentration of 25-hydroxyergocalciferol (P = 0.003). Concentrations of 25-hydroxyergocalciferol in serum were significantly related to those of calciferol (P = 0.004). Elevated initial concentrations of 1,25-dihydroxycalciferol, mainly as 1,25-dihydroxyergocalciferol, were found in seven of the eight patients (range 179-313 pmol/l). It is suggested that the hypercalcaemia in these patients may be explained by the action of 25-hydroxyergocalciferol at high concentration in competing for 1,25-dihydroxycalciferol receptors, thus exerting a biological effect per se, and also by increasing the synthesis of 1,25-dihydroxycalciferol through a mass-action effect on the renal 1 alpha-hydroxylase.

Topics: 25-Hydroxyvitamin D 2; Adolescent; Adult; Aged; Calcium; Ergocalciferols; Female; Humans; Hypercalcemia; Male; Middle Aged; Vitamin D

1,25(OH)2D3 induces 25(OH)D3-24-hydroxylase (24-OHase) in cultured skin fibroblasts from normal subjects. We evaluated 24-OHase induction by 1,25(OH)2D3 in skin fibroblasts from 10 normal subjects and from four unrelated patients with hereditary resistance to 1,25(OH)2D or vitamin D-dependent rickets type II (DD II). Fibroblasts were preincubated with varying concentrations of 1,25(OH)2D3 for 15 h and were then incubated with 0.5 microM [3H]25(OH)D3 at 37 degrees C for 30 min; lipid extracts of the cells were analyzed for [3H]24,25(OH)2D3 by high performance liquid chromatography and periodate oxidation. Apparent maximal [3H]24,25(OH)2D3 production in normal cell lines was 9 pmol/10(6) cells per 30 min and occurred after induction with 10(-8) M 1,25(OH)2D3. 24-OHase induction was detectable in normal fibroblasts at approximately 3 X 10(-10) M 1,25(OH)2D3. [3H]24,25(OH)2D3 formation after exposure to 1,25(OH)2D3 was abnormal in fibroblasts from all four patients with DD II. In fibroblasts from two patients with DD II, [3H]24,25(OH)2D3 formation was unmeasurable (below 0.2 pmol/10(6) cells per 30 min) at 1,25(OH)2D3 concentrations up to 10(-6) M. Fibroblasts from the other two patients with DD II required far higher than normal concentrations of 1,25(OH)2D3 for detectable [3H]24,25(OH)2D3 induction. In one, [3H]24,25(OH)2D3 production reached 2.9 pmol/10(6) cells per 30 min at 10(-6) M 1,25(OH)2D3 (30% normal maximum at 10(-6) M 1,25(OH)2D3). In the other, [3H]24,25(OH)2D3 production achieved normal levels, 7.3 pmol/10(6) cells per 30 min after 10(-6) M 1,25(OH)2D3. The two patients whose cells had a detectable 24-OHase induction by 1,25(OH)2D3 showed a calcemic response to high doses of calciferols in vivo. Our current observations correlate with these two patients' responsiveness to calciferols in vivo and suggest that their target organ defects can be partially or completely overcome with extremely high concentrations of 1,25(OH)2D3. The two patients whose cells showed no detectable 24-OHase induction in vitro failed to show a calcemic response to high doses of calciferols in vivo.. (a) the measurement of 24-OHase induction by 1,25(OH)2D3 in cultured skin fibroblasts is a sensitive in vitro test for defective genes in the 1,25(OH)2D effector pathway. (b) This assay provides a useful tool for characterizing the target tissue defects in DD II and predicting response to calciferol therapy.

Topics: Alopecia; Calcitriol; Cells, Cultured; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Enzyme Induction; Ergocalciferols; Fibroblasts; Humans; Hypercalcemia; Rickets; Skin; Steroid Hydroxylases; Vitamin D3 24-Hydroxylase

Metabolites of vitamin D were measured in plasma from 83 patients with idiopathic infantile hypercalcaemia syndrome who were mentally handicapped but had normal calcium values at the time of the study. No significant difference was detected in the mean plasma concentrations of 25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D3, or 25,26-dihydroxyvitamin D3 between patients and age matched controls. The mean plasma concentration of 25-hydroxyvitamin D3 was significantly lower in patients than controls but this may be a secondary phenomenon related to less sunlight exposure. In addition, two hypercalcaemic patients with this syndrome were studied during the first year of life, and were found to have normal concentrations of vitamin D metabolites. These findings do not support a role for abnormal vitamin D metabolism in the pathogenesis of this syndrome.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Adolescent; Calcitriol; Calcium; Child; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hypercalcemia; Infant; Intellectual Disability; Male; Syndrome; Vitamin D

Glucocorticoids are often used to treat hypercalcemia due to vitamin D overdosage. We measured the effect of 1.5 mg/day of prednisolone on the amount of calcium deposited in the kidney of rats dosed with either 500 ng/d or 2000 ng/day of 1-alpha OHD2 or 1-alpha OHD3. The rats were given a diet containing 0.3% calcium and 0.5% phosphate. A second group of rats received 2000 ng/d of the vitamin D analogs and a diet which contained only 0.02% calcium. After 6 weeks, rats given the vitamin D analogs had two to six times more calcium in the kidney compared with the controls (0.096-0.276 mg vs. 0.240-1.064 mg). When a pharmacological dose of prednisolone was added to treatment, calcium in renal tissue increased to 0.305-3.083 mg. The urinary output of calcium seemed to be increased by prednisolone whereas the serum calcium was lowered. It appears that glucocorticoids given at the same time as vitamin D compounds increases the risk for nephrocalcinosis possibly due to increased amounts of calcium in the urine.

Topics: Animals; Calcinosis; Calcitriol; Calcium, Dietary; Disease Models, Animal; Ergocalciferols; Hypercalcemia; Kidney; Male; Prednisolone; Rats; Rats, Inbred Strains; Uremia

Topics: Aged; Cataract; Ergocalciferols; Humans; Hypercalcemia; Male

Two patients with disseminated coccidioidomycosis and hypercalcemia are presented. One patient studied showed normal levels of 25-hydroxyvitamin D with depressed levels of 1 alpha,25-dihydroxyvitamin D. The serum calcitonin level was appropriate for the level of serum calcium, and the serum parathyroid hormone level was suppressed with elevation of the nephrogenous cAMP level. Intestinal absorption of calcium was elevated at 63 percent. Hypercalcemia and hypercalciuria persisted despite a 300 mg calcium diet. An osteotropic substance similar to the humoral hypercalcemia of malignancy is postulated.

Topics: 25-Hydroxyvitamin D 2; Adult; Calcitonin; Calcium; Coccidioidomycosis; Ergocalciferols; Female; Humans; Hypercalcemia; Intestinal Absorption; Male

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

Topics: Aged; Enzyme Induction; Ergocalciferols; Female; Glutethimide; Humans; Hypercalcemia; Microsomes, Liver

A 9-month-old boy who had the mild form of idiopathic infantile hypercalcemia was observed for 18 months. During the initial hypercalcemic stage, the serum concentration of 25-hydroxyvitamin D was normal. Urinary levels of cyclic adenosine monophosphate (cAMP) were low, and the serum concentrations of the dihydroxyl metabolites of vitamin D were appropriate to the high serum calcium concentration, with low 1,25-dihydroxyvitamin D and relatively high 24,25- and 25,26-dihydroxyvitamin D levels. Throughout the study period, there was a close positive correlation between the magnitude of the urinary cAMP excretion and the serum level of 1,25-dihydroxyvitamin D. The results indicate that excessive vitamin D intake leading to high serum levels of 25-hydroxyvitamin D are not decisive factors in the pathogenesis of idiopathic infantile hypercalcemia.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Calcitriol; Cyclic AMP; Dihydroxycholecalciferols; Ergocalciferols; Humans; Hypercalcemia; Infant; Male; Phosphates; Phosphorus; Vitamin D

The authors report on a new case of severe hypercalcaemia induced by prolonged oral treatment with high doses of vitamin D2. (6 mg/day for 9 months). Blood calcium level did not return to normal until 6 months after the drug was discontinued. The plasma concentration of 25 (OH) D was more than three times the normal value and remained very high throughout the observation period. The plasma concentration of 24, 25 (OH)2 D was slightly raised during treatment but became normal after 15 days, while that of 1,25 (OH)2 D, the active form of vitamin D, remained normal throughout, suggesting that the pathogenesis of vitamin D-induced hypercalcaemia is probably complex.

Topics: 25-Hydroxyvitamin D 2; Aged; Ergocalciferols; Female; Humans; Hypercalcemia; Vitamin D

Hypercalcaemia developed in 21 patients due to vitamin-D poisoning; 2 were poisoned twice and 2 were poisoned three times. All patients had taken milligram doses of vitamin D, which for 5 patients was inappropriate. For the other 16 patients (mainly with hypoparathyroidism) milligram doses of vitamin D were appropriate; the patients were poisoned either early in therapy, trying to correct the plasma-calcium too quickly, or, later, because of failure to follow up patients properly. 2 patients died as a result of their intoxication. Constant vigilance is essential when patients are taking large doses of vitamin D.

Topics: Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Follow-Up Studies; Humans; Hypercalcemia; Hyperparathyroidism; Iatrogenic Disease; Osteomalacia; Osteoporosis; Patient Dropouts; Self Administration; Self Medication

Central nervous system disorders are not uncommon in patients with hyperparathyroidism and hypercalcaemia. Usually these consist of neuropsychiatric disturbances but acute encephalopathies and seizures may occur. A rare manifestation is cerebral infarction. A patient is presented with neuroradiological evidence of infarction caused by cerebral arterial spasm which appears related to hypercalcaemia due to hypervitaminosis D. Arterial spasm is suggested as a possible aetiological factor in focal neurological lesions associated with hypercalcaemia.

Topics: Brain Edema; Calcium; Cerebral Angiography; Cerebral Infarction; Ergocalciferols; Female; Humans; Hypercalcemia; Ischemic Attack, Transient; Middle Aged

Topics: Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Ergocalciferols; Humans; Hypercalcemia; Male

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

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

Topics: Animals; Calcitonin; Ergocalciferols; Hypercalcemia; Male; Rats; Somatostatin; Thyroid Gland

Mean plasma 1(alpha),25-dihydroxyvitamin D[1(alpha),25(OH)(2)D] was significantly increased and serum parathyroid hormone was suppressed in three patients with sarcoidosis and hypercalcemia. Prednisone lowered the mean plasma 1(alpha),25(OH)(2)D to normal range and corrected the hypercalcemia. To elucidate the mechanism for the increased sensitivity to vitamin D in this disorder, the effects of orally-administered vitamin D(2) were determined in seven normal subjects, four patients with sarcoidosis and normal calcium metabolism and three patients with sarcoidosis and a history of hypercalcemia who were normocalcemic when studied. Serum and urinary calcium, serum 25-hydroxyvitamin D (25-OHD), plasma 1(alpha),25(OH)(2)D and, in some studies, calcium balance were measured. Vitamin D(2), 250 mug a day for 12 d, produced little, if any, change in mean plasma 1(alpha),25(OH)(2)D and in urinary calcium in the normals and in the patients with normal calcium metabolism. In contrast, vitamin D(2) produced increases in plasma 1(alpha),25(OH)(2)D from concentrations which were within the normal range (20-55 pg/ml) to abnormal values and increased urinary calcium in two patients with abnormal calcium metabolism. In an abbreviated study in the third patient, vitamin D(2), 250 mug a day for 4 d, also increased plasma 1(alpha),25(OH)(2)D abnormally from a normal value. There was a highly significant correlation between plasma 1(alpha),25(OH)(2)D and urinary calcium. Serum 25-OHD and serum calcium remained within the normal range in all subjects and patients. These findings provide evidence that the defect in calcium metabolism in sarcoidosis probably results from impaired regulation of the production and(or) degradation of 1(alpha),25(OH)(2)D. Prednisone may act to correct the abnormal calcium metabolism by reducing circulating 1(alpha),25(OH)(2)D.

Topics: Adult; Aged; Calcium; Calcium Metabolism Disorders; Dihydroxycholecalciferols; Ergocalciferols; Female; Humans; Hydroxycholecalciferols; Hypercalcemia; Male; Middle Aged; Prednisone; Sarcoidosis

Eight cases of vitamin-D poisoning are described. In six patients this therapy was unnecessary and in the remaining two patients inadequate supervision of the treatment resulted in overdosage. In five cases the history of vitamin-D therapy was either unknown or not appreciated by the referring clinician so that three surgical procedures of dubious value were performed on two patients. Large doses of vitamin D should only be used when strictly indicated and on the understanding that close biochemical and clinical supervision is necessary.

Topics: Adolescent; Adult; Aged; Calcinosis; Diagnosis, Differential; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism; Male; Middle Aged; Risk

Long term hypercalcaemia was induced in F. pennanti by alternate day intramuscular injections of 50,000 IU of vitamin D2 and by giving them 1% CaCl2 solution prepared in tap water to drink. The controls were not injected with vitamin D2 and were given tap water. The serum calcium levels at various stages of the experiment (1-29 days) show increased values as compared with those of control animals. The calcitonin cells in the treated animals generally exhibit an increase in their number up to the 15th day. Mitotic figures are also encountered between the 7th and the 15th day of treatment. This exhibits the increase in the number of C cells. Constant calcium challenge results in increased quantities of secretory granules among these cells up to the 15th day and in degranulation from the 17th day onwards. It also causes degenerative changes in a certain number of C cells. The parathyroids exhibit atrophic changes (25 days onwards) due to chronic hypercalcaemia. For short term hypercalcaemia, animals were injected intravenously with 1 ml of 10% solution of calcium gluconate. The calcitonin cells do not exhibit any change during the first half hour but thereafter they exhibit progressive degranulation, resulting in marked degranulation after 5 hours of the injection. The parathyroids remain unaffected throughout the experiment and show no histological change.

Topics: Animals; Calcitonin; Calcium; Ergocalciferols; Female; Hypercalcemia; Male; Parathyroid Glands; Sciuridae; Stimulation, Chemical; Thyroid Gland; 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

Topics: Diagnosis, Differential; Ergocalciferols; Female; Humans; Hypercalcemia; Hypocalcemia; Middle Aged; Tetany

Topics: Calcium; Child; Diet; Dihydrotachysterol; Ergocalciferols; Humans; Hypercalcemia; Hypocalcemia; Hypoparathyroidism; Magnesium; Male; Phosphorus; Vitamin D

Topics: Adult; Attitude to Health; Ergocalciferols; Furosemide; Humans; Hypercalcemia; Male; Recurrence; Self Medication; Substance-Related Disorders

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

Topics: Calcium; Ergocalciferols; Female; Humans; Hypercalcemia; Hypoparathyroidism; Hypothyroidism; Middle Aged; Parathyroid Hormone; Prednisone; Thyroid (USP); Vitamin D

Topics: Aged; Cataract; Ergocalciferols; Humans; Hypercalcemia; Male

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: 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; Calcium; Dogs; Ergocalciferols; Extracellular Space; Female; Furosemide; Hypercalcemia; Injections, Intravenous; Kidney Function Tests; Parathyroid Hormone; Potassium; Sodium; Time Factors; Water-Electrolyte Balance

Topics: Acute Kidney Injury; Adult; Ergocalciferols; Female; Humans; Hypercalcemia; Hypoparathyroidism; Kidney Function Tests; Vitamin D

Topics: Aged; Ergocalciferols; Female; Humans; Hypercalcemia; Male; Osteoporosis; Tablets

Topics: Calcium; Cellulose; Dehydration; Diet Therapy; Drug Combinations; Ergocalciferols; Humans; Hypercalcemia; Injections, Intramuscular; Male; Middle Aged; Osteoarthritis; Prednisolone; Sodium; Vitamin D

Topics: Animals; Chemical and Drug Induced Liver Injury; Ergocalciferols; Hypercalcemia; Kidney; Liver; Rats

Topics: Aged; Calcium; Carbimazole; Ergocalciferols; Exophthalmos; Female; Goiter; Humans; Hypercalcemia; Hyperthyroidism; Prednisolone; Thyroidectomy

Topics: Adult; Bone and Bones; Calcium; Calcium Metabolism Disorders; Chronic Disease; Decalcification, Pathologic; Ergocalciferols; Female; Glomerulonephritis; Humans; Hypercalcemia; Male; Middle Aged; Osteoporosis; Paralysis; Phosphates; Polycystic Kidney Diseases; Pyelonephritis; Radiography; Renal Dialysis; Uremia

Topics: Administration, Oral; Adult; Age Factors; Aged; Calcium; Calcium Carbonate; Ergocalciferols; Female; Gluconates; Humans; Hypercalcemia; Injections, Intramuscular; Lactates; Male; Time Factors

Topics: Adenoma; Adult; Aged; Calcium; Carcinoma, Papillary; Creatinine; Ergocalciferols; Female; Humans; Hypercalcemia; Hypoparathyroidism; Parathyroid Neoplasms; Pharmaceutical Vehicles; Postoperative Complications; Stimulation, Chemical; Thyroid Neoplasms; Thyroidectomy

Porcine calcitonin was used to treat three patients with hypercalcaemia due to vitamin D intoxication. In two patients a rapid and sustained fall to normal in serum calcium occurred within three days, in the third patient normocalcaemia was achieved in seven days. In view of its rapid and sustained effect calcitonin may be of value in the urgent treatment of hypercalcaemia due to vitamin D intoxication.

Topics: Aged; Animals; Back Pain; Calcitonin; Ergocalciferols; Female; Humans; Hypercalcemia; Hypoparathyroidism; Middle Aged; Poisoning; Swine; Vitamin D

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

Topics: Blood Urea Nitrogen; Brain; Calcium; Electroencephalography; Ergocalciferols; Female; Humans; Hypercalcemia; Hypocalcemia; Hypoparathyroidism; Middle Aged; Phosphorus; Seizures; Thyroidectomy

Topics: Animals; Bone Resorption; Calcium; Calcium, Dietary; Ergocalciferols; Hydroxylation; Hypercalcemia; Kidney; Nephrectomy; Parathyroid Glands; Parathyroid Hormone; Phosphates; Rats; Vitamin D Deficiency

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

Topics: Adult; Aged; Ergocalciferols; Humans; Hypercalcemia; Hyperparathyroidism; Hypocalcemia; Hypoparathyroidism; Ischemia; Middle Aged; Muscular Atrophy; Myelin Sheath; Neoplasms; Peripheral Nerves; Sensation; Vibration

Topics: Adult; Biological Transport; Bone and Bones; Calcium; Cell Membrane Permeability; Diabetic Retinopathy; Ergocalciferols; Female; Heart Failure; Humans; Hypercalcemia; Peritoneal Dialysis; Peritoneum; Phosphorus; Solutions; Uremia

Topics: Analysis of Variance; Animals; Body Weight; Bone Resorption; Calcium; Diet; Dihydrotachysterol; Ergocalciferols; Hypercalcemia; Intestinal Absorption; Kidney; Magnesium; Phosphorus; Rats; Rats, Inbred Strains; Stomach; Tibia; Time Factors

Topics: Animals; Cardiovascular System; Cortisone; Ergocalciferols; Female; Gonadal Steroid Hormones; Hypercalcemia; Pregnancy; Rats

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

Topics: Animals; Ergocalciferols; Female; Glycosaminoglycans; Hydronephrosis; Hypercalcemia; Kidney; Nephrocalcinosis; Rats; Sulfates; Sulfur Isotopes; Urinary Calculi

Topics: Animals; Calcium; Calcium Chloride; Ergocalciferols; Golgi Apparatus; Hypercalcemia; Injections, Intramuscular; Microscopy, Electron; Parathyroid Glands; Rats; Thyroid Gland

Topics: Analysis of Variance; Animals; Bone and Bones; Bone Diseases; Cyclic AMP; Depression, Chemical; Enteral Nutrition; Ergocalciferols; Hypercalcemia; Hypocalcemia; Hypoglycemia; Hypolipidemic Agents; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Nephrectomy; Pancreatectomy; Parathyroid Glands; Phosphates; Rats; Thiophenes; Thyroidectomy

Topics: Animals; Calcinosis; Calciphylaxis; Calcium; Cornea; Edetic Acid; Ergocalciferols; Eye Diseases; Hypercalcemia; Phosphorus; Rabbits; Sulfonic Acids; Ultraviolet Rays; Uveitis; Vitamin D

Topics: Acute Disease; Aged; Basilar Artery; Calcium; Cerebrovascular Disorders; Diagnosis, Differential; Ergocalciferols; Female; Humans; Hypercalcemia; Hypoparathyroidism; Neurologic Manifestations

Topics: Adult; Aged; Blood Urea Nitrogen; Bone Resorption; Calcium; Chlorothiazide; Diuretics; Ergocalciferols; Female; Humans; Hypercalcemia; Hyperparathyroidism; Male; Methyclothiazide; Middle Aged; Osteoporosis; Pregnancy; Pregnancy Complications

Topics: Abscess; Adrenal Insufficiency; Adult; Calcium; Chloramphenicol; Citrates; Citric Acid Cycle; Empyema; Empyema, Tuberculous; Ergocalciferols; Female; Furunculosis; Humans; Hypercalcemia; Hypocalcemia; Intestinal Absorption; Isoniazid; Klebsiella Infections; Lung Abscess; Lupus Vulgaris; Lymphadenitis; Male; Middle Aged; Paronychia; Penicillins; Pleurisy; Prednisone; Streptomycin; Suppuration; Tuberculosis, Pulmonary

Topics: Calcium, Dietary; Diet Therapy; Ergocalciferols; Glomerular Filtration Rate; Humans; Hypercalcemia; Infant; Kidney Concentrating Ability; Male; Mother-Child Relations; Phosphorus; Prednisone; Rickets

Topics: Adrenal Cortex Hormones; Adult; Calcium; Diet Therapy; Ergocalciferols; Female; Goiter; Humans; Hypercalcemia; Hypocalcemia; Inositol; Kidney Failure, Chronic; Male; Middle Aged; Nephrocalcinosis; Thyroidectomy; Time Factors; Vitamin D

Topics: Anemia; Animals; Ascorbic Acid; Breast Feeding; Child, Preschool; Environment; Ergocalciferols; Female; Fish Oils; Food Additives; Housing; Humans; Hypercalcemia; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Milk; Rickets; Scotland; Social Conditions; United Kingdom; Vitamin D; Vitamin D Deficiency

Topics: Adult; Calcium; Ergocalciferols; Female; Humans; Hypercalcemia; Hypocalcemia; Hypoparathyroidism; Lactates; Male; Middle Aged

Topics: Animals; Anura; Branchial Region; Calcium; Endocrine Glands; Ergocalciferols; Hypercalcemia; Hyperplasia; Hypertrophy; Male; Seasons

Topics: Animals; Anura; Branchial Region; Calcitonin; Endocrine Glands; Ergocalciferols; Hypercalcemia; Male; Microscopy, Electron; Mitosis

Topics: Adolescent; Adrenal Insufficiency; Adult; Child; Child, Preschool; Dihydrotachysterol; Ergocalciferols; Female; Humans; Hypercalcemia; Hypoparathyroidism; Male; Rickets; Vitamin D

Topics: Animals; Aorta; Bone and Bones; Brain; Calcium Isotopes; Dogs; Electrolytes; Ergocalciferols; Hypercalcemia; Liver; Magnesium; Muscles; Myocardium; Nerve Tissue; Pancreas; Radioisotopes

Topics: Alkaline Phosphatase; Blood; Bone and Bones; Calcium; Calcium, Dietary; Diagnosis, Differential; Ergocalciferols; Humans; Hypercalcemia; Hyperparathyroidism; Hyperparathyroidism, Primary; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intellectual Disability; Pathology; Phosphorus; Radiography; Rickets

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

Topics: Calcium; Ergocalciferols; Female; Humans; Hypercalcemia; Infant

Topics: Child; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Ergocalciferols; Hypercalcemia; Rickets; Tetany; Toxicology; Vitamins

Topics: Child; Emigration and Immigration; Ergocalciferols; Food Additives; Health Education; Humans; Hypercalcemia; Rickets; Toxicology; United Kingdom

Topics: Absorption; Blood; Calcium; Calcium, Dietary; Creatine; Creatinine; Diet; Diet Therapy; Ergocalciferols; Gastrointestinal Tract; Hypercalcemia; Hyperparathyroidism; Inositol; Kidney Diseases; Kidney Function Tests; Metabolism; Pharmacology; Phosphates; Phytic Acid; Sarcoidosis; Sodium; Toxicology; Urine; Vitamin D

Topics: Child; Drug-Related Side Effects and Adverse Reactions; Ergocalciferols; Humans; Hypercalcemia; Hypertension; Kidney Function Tests; Poisoning; Toxicology

Topics: Blood Chemical Analysis; Bone and Bones; Calcium; Calcium, Dietary; Cortisone; Ergocalciferols; Feces; Gastric Juice; Gastrointestinal Tract; Hypercalcemia; Hyperparathyroidism; Hyperparathyroidism, Primary; Pharmacology; Surgical Procedures, Operative; Urine

Topics: Bronchitis; Drug Hypersensitivity; Ergocalciferols; Humans; Hypercalcemia; Infant; Rickets; Toxicology; Vitamin D; Vitamins

Topics: Cataract; Dihydrotachysterol; Ergocalciferols; Humans; Hypercalcemia; Lens, Crystalline; Tetany

Topics: Adrenal Cortex Hormones; Biochemical Phenomena; Biochemistry; Ergocalciferols; Humans; Hypercalcemia; Hyperparathyroidism; Movement Disorders; Neoplasms; Sarcoidosis; Thyroid Diseases; Vitamin D

Topics: Abdominal Wall; Calcium; Ergocalciferols; Food; Gastric Juice; Humans; Hypercalcemia; Skin; Vitamin D

Topics: Ascorbic Acid; Ergocalciferols; Humans; Hypercalcemia; Nervous System Diseases; Urine; Vitamins

Topics: Calcium; Ergocalciferols; Humans; Hypercalcemia; Kidney