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PubMed1985

Different actions of vitamin D2 and D3 on bone metabolism in patients treated with phenobarbitone/phenytoin.

In 22 epileptic outpatients treated for at least 1 year with phenobarbitone/phenytoin the local and total bone mass, together with serum and urinary indices of calcium metabolism, were measured before and during treatment with either vitamin D2 or D3, 4,000 IU daily for 24 weeks. The results showed a distinct difference in the action of the two vitamins on bone metabolism during anti-convulsant treatment. The bone mass increased during treatment with vitamin D2, whereas the vitamin D3-treated patients showed unchanged values of bone mass, but an increased excretion rate of calcium, probably caused by increased intestinal calcium absorption. The data demonstrate that vitamins D2 and D3 (or their metabolites) have quantitative different effects in patients treated with phenobarbitone/phenytoin.

Adult↗
PubMed1985

The effect of prednisolone on kidney calcification in vitamin D-treated rats.

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.

Animals↗
PubMed1987

Calcium, vitamin D-endocrine system, and parathyroid hormone in black and white males.

The serum and urinary calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and parathyroid hormone (PTH) were studied in healthy black and white males living in Belgium, and the results were compared to data in blacks of similar age living in Zaïre. Dietary calcium and vitamin D were estimated in a sub-sample of blacks and whites examined in Belgium. Compared to whites (9.51 +/- 0.28 mg%) serum calcium was somewhat lower in blacks (9.26 +/- 0.27 mg% in Belgium; 9.19 +/- 0.48 mg% in Zaïre). The 24 hour urinary calcium excretion averaged 215.0 +/- 16.7 mg% in whites and was higher (P less than 0.05 or less) than in blacks (115 +/- 71 mg% in Belgium; 36 +/- 33 mg% in Zaïre). The serum 25OHD levels were similar in whites and blacks evaluated in Zaïre, both being higher (P less than 0.05 or less) than in blacks living in Belgium. In the latter blacks, an inverse correlation was observed between the 25OHD level and the duration of the stay in a temperate climate. Parathyroid hormone levels were slightly higher in blacks living in Belgium than in the other two groups of subjects. The serum levels of 1,25(OH)2D3 and human vitamin D-binding protein were similar in the three groups of subjects. Dietary calcium averaged 541 +/- 152 mg/day in blacks and was significantly (P less than 0.001) less than in whites (1,203 +/- 508 mg/day), whereas no significant difference was observed in dietary vitamin D intake between blacks and whites. It is concluded that calcium intake is low in blacks but stimulation of parathyroid hormone and 1,25(OH)2D3 required to achieve normocalcemia does not occur.

25-Hydroxyvitamin D 2↗
PubMed1987

Effect of aging on vitamin D stores and bone density in women.

It has been suggested that the decrease in vitamin D stores with aging is a contributory cause of age-related osteoporosis. We studied this question by measuring bone mineral density (BMD) of the mid-radius, distal radius, and lumbar spine assessed by single and dual photon absorptiometry in 122 women, aged 33-94 years, selected from a random sample of Rochester, MN residents. We measured serum 25-hydroxyvitamin D (25OHD), the major storage form of vitamin D, as well as 25OHD3 (representing both endogenous and exogenous sources of vitamin D), and 25OHD2 (representing only exogenous sources). Both baseline serum total 25OHD (r = -0.29, P less than 0.001) and the metabolite 25OHD3 (r = -0.41, P less than 0.001), were negatively associated with age at baseline. After adjusting for the effect of age by multiple regression analysis, there was no association between serum levels of 25OHD2, 25OHD3, or total 25OHD and BMD for any of the three skeletal scanning sites. Thus, in a northern American population we cannot demonstrate that reduced bioavailability of vitamin D plays a major role in age-related bone loss.

25-Hydroxyvitamin D 2↗
PubMed1975

The effect of fluoride alone or fluoride followed by calcium and vitamin D on disuse osteoporosis of the rat tail vertebrae.

The therapeutic effect of fluoride alone or fluoride followed by calcium and vitamin D administration on the osteoporosis induced by immobilization of the rat tail vertebrae was investigated. Tail immobilization was carried out by musclectomy and tendectomy. After 60 days of immobilization, the vertebrae were examined for bone mass, breaking strength, ash percentage and Ca, P and F content. NaF or Ca and vitamin D as separate treatments improved the osteoporosis induced by immobilization. The effects of NaF treatment were more pronounced than those of Ca and vitamin D. NaF and NaF followed by Ca and vitamin D produced a similar degree of improvement in breaking strength. The fact that fluoride and calcium and vitamin D were administered separately and sequentially may explain the absence of a synergistic effect.

Animals↗
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↗
PubMed2004

Effect of oral vitamin D2 yearly bolus on hip fracture risk in elderly women: a community primary prevention study.

BACKGROUND AND AIMS: Vitamin D deficiency is a well-known risk for hip fracture, and vitamin D insufficiency is so frequent in the elderly that population-wide preventive intervention would be useful. The objective of the study was to evaluate the efficacy of vitamin D bolus on hip fracture incidence in elderly women. METHODS: All women aged > 65 years registered at Health District 20 of the Regione Veneto, Italy, were eligible for this quasi-experimental, prospective community intervention study. A vial containing 400,000 IU vitamin D2 (Ostelin 800, Teofarma, Italy) was offered for oral administration to all women in the winters of 2000-2001 and 2001-2002. The only exclusion criteria for treatment were age and gender, and the control group included women who did not participate in the Health District initiative. Analysis of hip fracture incidence was carried out for 4 years, from 1999 to 2002. Patients with incident hip fracture were identified as soon as they were admitted to one of the 3 hospitals of the health district and interviewed regarding their participation in the vitamin D preventive intervention program. In 120 of the women (age range 68-90 years), serum concentrations of 25-OH vitamin D were measured from October to June, both before and 1 and 4 months after vitamin D administration. RESULTS: 23,325 and 24,747 women received the vitamin D bolus during winters 2000-2001 and 2001-2002 respectively, i.e. 45-47% of eligible women. The proportion of women who accepted the bolus declined with advancing age, from 50-55% in women aged 60-70 years to 22-26% in those aged > 90 years. The two-year intervention on the community decreased the incidence of fracture by 10% (p = 0.050) in comparison with the previous two years. The age-adjusted risk reduction (RR) of hip fracture during 2001 and 2002 in women who had received vitamin D, with respect to women who had not, decreased by 17% (p = 0.056) and 25% (p = 0.005) respectively. The RR was considerably greater and statistically significant over both 2001 and 2002 in the cohort aged > 75 years. 25-OH vitamin D concentrations, in the subset of women in whom it was measured, rose significantly (p < 0.0001) by 9 ng/ml over 4 months after administration. CONCLUSION: Despite several obvious limitations due to its nature, this study sufficiently documents that yearly vitamin D bolus supplements, given as primary prevention to elderly Caucasian women, may decrease the incidence of hip fracture. For its probable safety and excellent feasibility and cost-effectiveness, this primary intervention has a great potential for generalisability.

Administration, Oral↗
PubMed1999

[Disseminated ischemic necrosis and livedo racemosa in a chronic dialysis patient with calciphylaxis].

Calciphylaxis occurred in a 40-year old female patient with end-stage renal failure. The patient developed livedo racemosa ("livedo reticularis") with painful skin necrosis and ulcers involving multiple areas of the hip and legs after 22 years of hemodialysis. X-ray-examinations revealed calcinosis of peripheral arteries, especially of the pelvis, thigh and hands, while histological examinations showed a fibrosis and calcinosis of small subcutaneous arteries. A generalized cutaneous microangiopathy could be demonstrated by transcutaneous oxygen pressure measurements. Laboratory data showed a moderate secondary hyperparathyroidism with mild elevation of calcium-phosphate product. In addition to the hemodialysis an attempt was made to improve the microcirculation by vasoactive drugs. The clinical course was characterized by slow healing of the ulcers and occurrence of new areas of cutaneous necrosis. Calciphylaxis is a rare late complication in patients with advanced, often end-stage renal failure. It has characteristic histopathological features and is frequently, but not always, associated with a disturbed calcium and phosphorus metabolism and mildly elevated levels of parathyroid hormone. Calciphylaxis is classified as a special type of metastatic calcinosis.

Adult↗
PubMed1998

Fluoride salts are no better at preventing new vertebral fractures than calcium-vitamin D in postmenopausal osteoporosis: the FAVOStudy.

Although fluoride salts have been shown to be capable of linearly increasing spinal bone mineral density (BMD) in postmenopausal osteoporosis, the effects of this gain in density on the vertebral fracture rate remain controversial. We conducted a 2-year multicenter, prospective, randomized, double-masked clinical trial in 354 osteoporotic women with vertebral fractures (mean age 65.7 years). They received either fluoride (208 patients), given as sodium fluoride (50 mg/day) or as monofluorophosphate (200 mg/day or 150 mg/day), or a placebo (146 patients). All patients received daily supplements of 1 g of calcium (Ca) and 800 IU of vitamin D2 (D). A 1-year open follow-up on Ca-D was obtained in 124 patients. After 2 years the fluoride group and the Ca-D group had increased their lumbar BMD by 10.8% and 2.4% respectively (p = 0.0001). However, the rate of patients with at least one new vertebral fracture, defined by semiquantitative assessment and evaluable on an intention-to-treat basis in 89% of patients, was similar in the fluoride groups and the Ca-D group. No difference between the three fluoride regimens was found. The percentage of patients with nonvertebral fractures was not different in the fluoride and Ca-D groups (1.9% and 1.4% respectively for hip fractures). A lower limb pain syndrome occurred more frequently in the fluoride groups. In the 124 patients followed for 1 year after cessation of fluoride therapy, the percentage of patients with at least one new vertebral fracture after 36 months was identical to the percentages in the previous fluoride group and the Ca-D group. We conclude that fluoride-Ca-D regimen was no more effective that Ca-D supplements for the prevention of new vertebral fractures in women with postmenopausal osteoporosis.

Aged↗
PubMed2003

Effect of vitamins D2 and D3 supplement use on serum 25OHD concentration in elderly women in summer and winter.

Vitamin D2 and D3 are generally considered equipotent in humans. A few studies have reported that serum 25OHD levels are higher in vitamin D3- compared with vitamin D2-supplemented subjects. As both vitamin D2 and D3 supplements are commonly used by elderly in United States, in the present study we determined the effect of self-reported vitamin D2 and vitamin D3 supplement use on serum total 25OHD levels according to season in elderly women aged 65-77 years. Serum total 25OHD levels were determined in winter and summer in unsupplemented women ( N = 307) and in women who reported taking vitamin D2 ( N = 56) and vitamin D3 ( N = 55) supplements by competitive protein binding assay. In vitamin D2-supplemented women, the contribution of vitamin D2 and D3 to the mean serum total 25OHD level was assessed by HPLC. In summer, there were no significant differences in the mean total serum 25OHD levels (ng/ml) among the vitamin D2 (32 +/- 2.1), vitamin D3 (36.7 +/- 1.95), and unsupplemented (32.2 +/- 0.95) groups. In winter, the mean serum total 25OHD levels were higher in women on vitamin D2 (33.6 +/- 2.34, P < 0.05) and vitamin D3 (29.7 +/- 1.76, NS) supplements compared with unsupplemented women (27.3 +/- 0.72). In vitamin D2-supplemented women, about 25% of the mean serum total 25OHD was 25OHD2, in both summer and winter. Twelve percent of unsupplemented women and 3.6% of vitamin D-supplemented women had a mean serum total 25OHD level below 15 ng/ml in winter. In elderly subjects, both vitamin D2 and Vitamin D3 supplements may contribute equally to circulating 25OHD levels, with the role of vitamin D supplement use being more predominant during winter.

Aged↗
PubMed2006

Calcification inhibitors and Wnt signaling proteins are implicated in bovine artery smooth muscle cell calcification in the presence of phosphate and vitamin D sterols.

Administration of active vitamin D sterols to treat secondary hyperparathyroidism in patients with chronic kidney disease receiving dialysis has been associated with elevated serum calcium and phosphorus levels, which may lead to increased risk of vascular calcification. However, calcimimetics, by binding to the parathyroid gland calcium-sensing receptors, reduce serum parathyroid hormone, calcium, phosphorus, and the calcium-phosphorus product. Using cultured bovine aorta vascular smooth muscle cells (BASMCs), an in vitro model of vascular calcification, we compared calcification levels and gene expression profiles after exposure to the phosphate source ss-glycerolphosphate (BGP), the active vitamin D sterols calcitriol and paricalcitol, the calcimimetic R-568, or BGP with the active vitamin D sterols or R-568. Cells exposed to BGP (10 mM) alone or with calcitriol or paricalcitol showed dose-dependent BASMC calcification. No change in calcification was observed in cultures exposed to BGP with R-568, consistent with the observed lack of calcium-sensing receptor expression. Microarray analysis using total cellular RNA from cultures exposed to vehicle or BGP in the absence and presence of 10(-8) M calcitriol or paricalcitol for 7 days showed that cells exposed to BGP with calcitriol or BGP with paricalcitol had virtually identical gene expression profiles, which differed from those of cells treated with BGP or vehicle alone. Several osteoblast- and chondrocyte-associated genes were modulated by BGP and vitamin D exposure. In this study, exposure of BASMCs to phosphate and active vitamin D sterols induced calcification and changes in expression of genes associated with mineralized tissue.

Alkaline Phosphatase↗