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PubMed1983

Prevention of osteonecrosis following renal transplantation by using vitamin D2 (ergocalciferol).

Osteonecrosis is a frequently disabling complication of renal transplantation. Thirty-one of 244 patients (12.7%), who received cadaver renal transplants from 1968 to 1978 developed an osteonecrosis. An analysis of 14 possible risk factors suggested that only the following were significantly more frequent in the osteonecrosis group: greater than 3 pulse doses of 1.2 g prednisolone, serum creatinine greater than 133 mumol/L, steroid-induced diabetes mellitus and second and subsequent transplantation. An important decline in the incidence of osteonecrosis (26.7 per cent to 6.5 per cent) was seen with prophylactic vitamin D2 treatment and the onset of osteonecrosis was on average one year later. Dangerous side effects of the large doses of vitamin D2 were minimal. Hypercalcaemia due to overdosage with vitamin D2 during simultaneous prednisolone therapy was usually mild and returned to normal in a few days by dose reduction.

Ergocalciferols↗

PubMed2006

Alendronate and vitamin D2 for prevention of hip fracture in Parkinson's disease: a randomized controlled trial.

Incidence of a fracture, particularly in the hip joint, is high in elderly women with Parkinson's disease (PD), and this is due to the immobilization-induced bone resorption and vitamin D deficiency with reduced bone mineral density (BMD). The objective of this study was to address the possibility that treatment with alendronate and vitamin D2 may reduce the incidence of hip fractures in elderly women with PD. PD patients were randomly assigned to daily treatment with 5 mg alendronate (n = 144) or a placebo combined with 1,000 IU of vitamin D2 (n = 144) and followed for 2 years. Incidence of hip fractures in the two patient groups during the 2-year follow-up period was studied. At baseline, both groups of patients had low BMD with high levels of serum-ionized calcium and urinary deoxypyridinoline (D-Pyr). Hip fractures occurred in 14 patients in the placebo group and 4 in the alendronate group. The relative risk for hip fractures in the alendronate group as compared with the placebo group was 0.29 (95% CI, 0.10-0.85). The number of hip fracture per 1,000 patient-years was 14 and 49 for the alendronate and placebo groups, respectively. In the alendronate group, serum calcium and urinary D-Pyr levels decreased significantly during the follow-up period, while the levels in the placebo group were increased. BMD increased by 3.1% in the alendronate group and decreased by 2.8% in the placebo group (P < 0.01). Treatment with alendronate and vitamin D2 increases BMD in elderly women with PD and leads to the prevention of hip fractures.

Aged↗

PubMed1980

Serum 25-hydroxyvitamin D in patients with chronic renal failure on long-term treatment with high doses of vitamin D2.

The present study was aimed at answering the following two questions: (1) What is the effect of high dose vitamin D treatment on the serum level of 25-hydroxyvitamin D (25-OH-D) in patients with chronic renal failure (CRF)? (2) Is there any effect of urinary protein loss on the serum 25-OH-D levels during treatment with pharmacological doses of vitamin D? 42 patients with CRF were studied. They were treated conservatively by a low protein diet and received 15 mg of vitamin D2 once a week. Long-term administration of vitamin D caused a significant (5- to 7-fold) increase of plasma 25-OH-D level irrespective of the degree of proteinuria. This increase was noted only during the first 5 months of vitamin D2 treatment. Surprisingly only in some patients moderate hypercalcemia (> 2.75 mmol/l) was found. From the results obtained it is concluded that (1) patients with CRF differ from normal subjects in handling of high doses of vitamin D and (2) high dosage treatment with vitamin D may prevent hypocalcemia in patients with CRF in spite of high proteinuria.

Adult↗

PubMed1997

Characterization of monoglucuronides of vitamin D2 and 25-hydroxyvitamin D2 in rat bile using high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

The characterization of vitamin D2 3-glucuronide, 25-hydroxyvitamin D2 3-glucuronide and 25-hydroxyvitamin D2 25-glucuronide, biliary metabolites obtained from rats dosed with vitamin D2 and 25-hydroxyvitamin D2 per os, was carried out using HPLC-atmospheric pressure chemical ionization (APCI)-MS. The glucuronide obtained from bile specimens was identified by comparison of its chromatographic behaviour with an authentic sample using HPLC-APCI-MS operating in the negative-ion mode. Methylation of the respective fraction with diazomethane gave the methyl ester, which was also confirmed by HPLC-APCI-MS operating in the positive-ion mode. The (M-H)- and (M + NH4)+ ions were monitored in the selected-ion monitoring mode.

25-Hydroxyvitamin D 2↗

PubMed1991

Effects of vitamin D2 analogs on calcium metabolism in vitamin D-deficient rats and in MC3T3-E1 osteoblastic cells.

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.

Alkaline Phosphatase↗

PubMed1982

High-performance liquid chromatography of fat-soluble vitamins: separation and identification of vitamins D2 and D3 and their isomers in food samples in the presence of vitamin A, vitamin E and carotene.

Vitamins D2 and D3 and their corresponding previtamins and provitamins were resolved by reversed-phase high-performance liquid chromatography using a ternary solvent system (acetonitrile-methanol-water) pumped according to a gradient elution programme. The D vitamins were also resolved in the presence of other lipid-soluble vitamins (A, E and K1) and carotene. The peaks were monitored with a UV-visible variable-wavelength detector and were detected at their maximum absorbance, resulting in maximum sensitivity. Lipid-soluble vitamins and carotene were resolved in extracts obtained from oils and butter, thus permitting their identification in a single chromatographic run.

Butter↗

PubMed2003

[Preparation of complex chitosan microcapsule and its application in controlled release of vitamin D2].

In this work a system which consists of chitosan (CS) microcores entrapped within enteric polymer is presented. Vitamin D2, used as a model drug, was efficiently entrapped within CS microcores using spray-drying and then microencapsulated into ethylic cellulose(EC). The morphology and release properties of microcapsules were tested. The influential factors of preparation conditions included molecular weight of chitosan, concentration of chitosan solution, concentration of acetic acid, loading of vitamin D2 were discussed. The results of in vitro release studies showed that the microcapsules prepared in this article could realize sustained release in intestine.

Capsules↗

PubMed1989

Bone mineral content, serum vitamin D metabolite concentrations, and ultraviolet B light exposure in infants fed human milk with and without vitamin D2 supplements.

OBJECTIVE: To monitor ultraviolet B light exposure in human milk-fed infants both with and without supplemental vitamin D2, and to measure longitudinally the bone mineral content, growth, and serum concentrations of calcium, phosphorus, 25-hydroxyvitamin D3, 25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D, and parathyroid hormone. DESIGN: Longitudinal, randomized, double-blind, placebo-controlled study of 6 months' duration. SETTING: Patients from private pediatric practice, Madison, Wisconsin. PATIENTS: Sequential sampling of 46 human milk-fed white infants; 24 received 400 IU/day of vitamin D2, and 22 received placebo. An additional 12 patients were followed who received standard infant formula. Eighty-three percent of patients completed a full 6 months of the study. MEASUREMENTS AND RESULTS: Ultraviolet B light exposure and measurements of growth did not differ between groups. At 6 months, the human milk groups did not differ significantly in bone mineral content or serum concentrations of parathyroid hormone or 1,25-dihydroxyvitamin D, although total 25-hydroxyvitamin D values were significantly less in the unsupplemented human milk group (23.53 +/- 9.94 vs 36.96 +/- 11.86 ng/ml; p less than 0.01). However, 25-hydroxyvitamin D3 serum concentrations were significantly higher in the unsupplemented human milk-fed group compared with the supplemented group (21.77 +/- 9.73 vs 11.74 +/- 10.27 ng/ml, p less than 0.01) by 6 months of age. CONCLUSION: Unsupplemented, human milk-fed infants had no evidence of vitamin D deficiency during the first 6 months of life.

25-Hydroxyvitamin D 2↗

PubMedDate not supplied

[Effect of vitamin D2 on the monooxygenase activity of the rat liver].

Stimulation of lipid peroxidation in the liver microsomal fraction and alteration in the xenobiotic metabolism were found within twelve hrs after a single vitamin D2 administration (960,000 MU/kg) into male rats. The effects observed appear to occur due to the vitamin D2 prooxidative properties.

Animals↗

PubMed2004

Vitamin D2 is much less effective than vitamin D3 in humans.

Vitamins D(2) and D(3) are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market. The relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline. The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng.d/ml (150.5 nmol.d/liter) for vitamin D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).

Adult↗

PubMedDate not supplied

New model of atherosclerosis in sand rats subjected to a high cholesterol diet and vitamin D2.

In order to defeat the atheroresistance in sand rats, 25 animals were given a high cholesterol diet for 45 days, which was then associated with oral treatment with vitamin D2 2000 IU/day for a further 45 days. At days 0, 45 and 90, plasma parameters, and aortic and heart morphology were examined. Results showed at D45 hypercholesterolaemia, increased plasma LDL and VLDL cholesterol, oxidized LDL, triglycerides, free fatty acids (FFA) and calcium levels and moderate hyperinsulinaemia. At D90, plasma-oxidized LDL and FFA were more enhanced, whereas calcium level was reduced. Development of hyperglycaemia was associated with hyperinsulinaemia and insulin resistance. The vitamin D2 administration induced advanced lesions, represented by the degenerescence of elastic lamina, smooth muscle cell proliferation and lipid calcic plaque at an ulcerated stage in most cases. The ischaemic effects were represented by acute myocardial infarction. The potential of the sand rat to develop atherosclerotic lesions at different stages opens the field to therapeutic tests of new anti-atherogenic agents.

Animals↗

PubMed1977

Effect of long-term vitamin D2 treatment on bone morphometry and biochemical values in anticonvulsant osteomalacia.

Quantitative morphometric analyses of iliac crest biopsies from 20 epileptic patients receiving chronic anticonvulsant therapy have been performed before and after 4-8 months of vitamin D2 treatment with 9 000 U per day. Biochemical quantities, including serum 25-hydroxycholecalciferol (25-HCC) and serum parathyroid hormone (iPTH), were measured. The anticonvulsant osteomalacia found in the initial bone biopsies was characterized by an increased amount of ummineralized bone, an increased bone resorption and, contrary to vitamin D deficiency, an increased bone mineralization and bone formation. Bone resorption and bone formation were probably equally increased since the amount of cancellous bone was normal. Except for a slight increase in osteoidcovered surfaces and osteoclastic resorption surfaces, the bone changes were normalized after vitamin D2 treatment, leading to a mean serum level of 25-HCC 2.4 times above normal. Serum iPTH was normal before and unchanged during D2 therapy. The urinary calcium excretion remained decreased. The investigation characterizes anticonvulsant osteomalacia as a specific bone disease different from that of vitamin D deects of vitamin D metabolites on receptor cells.

Adult↗

PubMed1979

Treatment of osteomalacia associated with primary biliary cirrhosis with parenteral vitamin D2 or oral 25-hydroxyvitamin D3.

The histological and biochemical response of osteomalacia has been studied in four patients with primary biliary cirrhosis, who were treated with oral 25-hydroxyvitamin D3, 50 microgram daily, or intramuscular vitamin D2, 150,000 units once weekly, for five to 12 months. All patients showed complete histological healing of osteomalacia, despite rapidly deteriorating liver function in three. Plasma 25-hydroxyvitamin D concentrations were low in all patients before treatment, but became normal during either vitamin therapy. Serum calcium and phosphate levels, and urinary calcium excretion were not always reliable in predicting the histological response to treatment. Serum alkaline phosphatase activity decreased in all patients during vitamin D therapy. We conclude that both high-dose parenteral vitamin D2 and oral 25-hydroxyvitamin D3 may be effective in healing osteomalacia associated with primary biliary cirrhosis. Measurement of plasma 25-hydroxyvitamin D levels during vitamin D therapy provides useful information about 25-hydroxylation of the parent vitamin and intestinal absorption of orally administered 25-hydroxyvitamin D3.

Administration, Oral↗

PubMed1975

The influence of calcium and calcium + vitamin D2 treatment on bone mineral after partial gastrectomy.

Sixty-three men and 23 women who had undergone partial gastrectomy for ulcer disease were randomized into three groups to study the effect of calcium (2 g per day) and calcium + vitamin D2 (1000 IU calciferol per day) treatment for eight months on bone mineral. The Americium-241 gamma ray attenuation method was used to measure the changes in bone mineral density. Calcium and calcium + vitamin D2 increased the bone mineral density statistically significantly in the males, but not in females. Partial gastrectomy causes bone rarefaction, and consequently these patients reach the risk level of bone mineral density for osteoporotic fractures earlier than healthy subjects. The conclusion drawn was that prophylactic treatment is needed after partial gastrectomy. Further study is required, especially of women, to find the most suitable form of treatment for disturbances in bone mineral metabolism after gastric resection.

Aged↗

PubMed1981

Protective effect on vitamin D2 on bone apposition from the inhibitory action of hydrocortisone in rats.

Using the technique of short interval sequential tetracycline labeling, it was documented that the apposition of mineralized bone matrix in adult male Sprague-Dawley rats was inhibited by hydrocortisone. The inhibition occurred as early as six days after the onset of the treatment and was dose dependent over a dose range of 0.62 to 20 mg per kg body weight per day. Vitamin D2 supplements by injection protected bone from this hydrocortisone action. 64 I. U. of vitamin D2 injected daily was able to prevent the inhibition of bone apposition by 20 mg per kg body weight per day of hydrocortisone. The results imply that vitamin D or its metabolites may compete with hydrocortisone in some cellular mechanisms and support the usefulness of vitamin D supplements in the treatment and the prevention of steroid-induced osteoporosis.

Animals↗

PubMed1980

The effect of vitamin D2 on hypocalcemia in patients under chronic hemodialysis.

The effects of vitamin D2 (VD2) on hypocalcemia were studied in 54 hypocalcemic patients (29 males and 25 females) on chronic hemodialysis. Calcium lactate (3 g/day) or VD2 (10,000 IU/day, 50,000 IU/day and 80,000 IU/day) were administered for 4 months in order to correct the hypocalcemia. Serum calcium, phosphate and alkaline phosphatase levels were measured and the effects of VD2 on these parameters of calcium metabolism were followed. 1) Calcium lactate or 10,000 IU/day of VD2 were not effective for the correction of hypocalcemia, while 50,000-80,000 IU/day of VD2 were effective. The effects of VD2 on serum calcium concentrations were dose-dependent, and the normalization of serum calcium concentrations was achieved more rapidly with higher doses of VD2. However, in the group treated with 80,000 IU/day of VD2, many patients developed hypercalcemia, but in the group treated with 50,000 IU/day of VD2, only a few patients did it. From these results, suitable dose (initial and maintenance doses) of VD2 in dialysed patients would be 50,000 IU/day. 2) When the responder group (normal serum calcium levels after 4 months of treatment with 50,000 IU/day of VD2) and the non-responder group serum calcium levels lower than 4.2 mEq/liter on the same condition) were compared, the durations of dialysis were significantly shorter in the former than those in the latter. This fact may suggest that the effects of VD2 administration on hypocalcemia in dialysed patients are partly dependent on the residual renal function concerning the conversion of 25-OH-D3 into 1,25 (OH)2D3.

Adolescent↗

PubMed1979

Naturally occurring vitamin D3 in fish products analysed by HPLC, using vitamin D2 as an international standard.

A chemical method for the analysis of naturally occurring vitamin D is proposed. The unsaponifiable matter of oils and tissues is prepared, cholesterol is partly removed by double precipitation at low temperature in methanol. The vitamin D fraction is collected on an adsorption column by high performance liquid chromatography. The fraction is further purified and the vitamins D2 and D3 are separated on a partition column (reverse phase) by HPLC. Recovery was 89 to 93%, standard deviation 3%. The only vitamin D analogue found in fish oils, livers and fillets, was cholecalciferol (D3). Hence, ergocalciferol (D2) could be used as an internal standard. The provitamins ergosterol and 7-dehydrocholesterol, as well as the previtamins, were separated from the vitamin D-fraction on the adsorption column. Results in the range 0.050 to 134 microgram D3 per gram (2 to 5360 I.U. per gram) are given. One cod liver oil was analysed in a rat bioassay, giving supporting results.

Adsorption↗

PubMed1983

19-nor-10-ketovitamin D derivatives: unique metabolites of vitamin D3, vitamin D2, and 25-hydroxyvitamin D3.

Three metabolites were isolated after incubation of vitamin D3, vitamin D2, or 25-hydroxyvitamin D3 with bovine rumen microbes. They are identified as 5(E)-19-nor-10-ketovitamin D3, 5(E)-19-nor-10-ketovitamin D2, and 5(E)-19-nor-10-keto-25-hydroxyvitamin D3, respectively. The identifications were based on ultraviolet absorbance, mass spectroscopy, and chemical reactivity. All 5(E)-19-nor-10-ketovitamin D derivatives examined had an absorbance maximum at 312 nm and a characteristic fragment in their mass spectra corresponding to loss of 43 amu from their molecular ions. The vitamin D3 metabolite was identical in all essential spectral and chromatographic aspects with authentic synthetic 5(E)-19-nor-10-ketovitamin D3. These metabolites represent a unique pathway of vitamin D metabolism and the first characterized products of microbial vitamin D metabolism. The conversion of vitamin D and its metabolites to their 19-nor-10-keto forms likely represents a detoxification mechanism.

Animals↗