Fractures in the men of a Veterans Administration Nursing Home: relation to 1,25-dihydroxyvitamin D.

One hundred fifty-three men, age 48-96, 86% white, had resided in this Nursing Home for an average of 6.3 years (range 1.3-36) as of August 1984. At that time, we reviewed their medical charts to record the numbers and sites of fractures which had been diagnosed during the preceding 1 to 5 years of Nursing Home residence, the duration of this period depending on the duration of institutionalization. In addition, a clinical database was compiled comprising 70 attributes, including diagnoses, drugs, plasma (serum) chemistries, and measures of hematologic, nutritional, and functional status. Fractures during the studied period of Nursing Home residence had occurred in 24 of 153 men; six residents had experienced two or more fractures. Fracture rates in hip, spine, and wrist were 2564, 366, and 549 per 100,000 patient years, respectively. The total fracture rate, hip fracture rate, and limb fracture rate were five to 11 times higher than in the age-matched general population of white men in the United States; in Rochester, MN; in Dundee, England; in Oxford, England; or in Finland. Univariate statistical analysis showed that the rates for hip fracture or for fracture at any site were significantly associated with 13 attributes: directly with age, plasma somatomedin C, blood urea N, serum creatinine, serum uric acid, serum 25-hydroxyvitamin D (25-OH-D), degree of functional impairment, and chronic urinary tract infection, and inversely with serum 1,25-dihydroxyvitamin D [1,25-(OH)2-D], serum albumin, hematocrit, and hemoglobin. There was not a significant correlation with the number of falls/month which occurred during the 7 months after August 1984. After the effect of age was partialed out, somatomedin C, 25-OH-D, 1,25-(OH)2-D, and the diagnosis of urinary tract infection were still significantly related to the occurrence of fractures. The fact that Nursing Home fracture cases had significantly higher blood urea nitrogen and 25-OH-D, and significantly lower 1,25-(OH)2-D, than their non-fracture counterparts suggests that impaired renal production of the latter vitamin D metabolite contributed to the excessive rate of fractures.     

Effects of ergocalciferol supplementation on the concentration of vitamin D and its metabolites in human milk

The effect of maternal ergocalciferol (vitamin D2) supplementation on the concentrations of vitamin D, 25-hydroxyvitamin D (25-OH-D), 24R,25-dihydroxyvitamin D [24,25-(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25-(OH)2D] in their milk was studied. Vitamin D2, D3, 25-OH-D2 and 25-OH-D3 were simultaneously determined by high performance liquid chromatography, and the determination of 24,25-(OH)2D and 1,25-(OH)2D was performed by competitive protein binding assay and radioreceptor assay, respectively, after separation of the D2 and D3 compounds. After healthy lactating mothers had received a daily oral dose of vitamin D2 (1,200 IU/d) for 4 wk, the concentrations of vitamin D2, D3 and the metabolites were determined in their plasma and milk. Although the plasma levels of 25-OH-D2 were significantly increased, the increase in milk was relatively small. On the other hand, the increase of vitamin D2 levels in milk was greater than that of 25-OH-D2 in milk after supplementation. The levels of 1,25-(OH)2D in milk was lower after 5 wk of lactation than after 1 wk of lactation, regardless of maternal vitamin D2 supplementation. When total antirachitic activities in milk were calculated, only a very slight increase was observed as a result of supplementation.     

Determinants of vitamin D status in patients with hip fracture and in elderly control subjects

The factors that influence vitamin D status were investigated in 125 patients with hip fracture and in 74 elderly control subjects. The serum concentrations of 25-hydroxyvitamin D [25(OH)D] varied with sunshine score and were paralleled by serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. The control subjects showed a higher sunshine score and higher serum 24(OH)D levels than the patients with hip fracture. Dietary vitamin D intake was similar in both groups (mean 115 IU/d). A positive correlation between vitamin D intake and serum 25(OH)D was observed in the patients with low sunshine exposure. It appeared from this relation that dietary vitamin D intake should be approximately 300 IU/d to maintain an adequate serum (25(OH)D concentration. Vitamin D status was very poor in patients who were institutionalized before hip fracture. Multiple regression analysis on serum 25(OH)D confirmed the primary role of sunshine exposure as determinant of vitamin D status. The principal determinants of serum 1,25(OH)2D were serum 25(OH)D, serum creatinine, and serum phosphate.     

Metabolism of vitamin D: current status.

There has been much progress in our understanding of the metabolism of vitamin D. It is now clear that vitamin D3 can be produced in the skin or ingested in the diet. It accumulates very rapidly in the liver where it undergoes 25-hydroxylation, yielding 25-OH-D3, the major circulating metabolite of the vitamin. 25-OH-D3 proceeds to the kidney where it undergoes one of two hydroxylations. If there is a biological need for calcium or for phosphate the kidney is stimulated to convert 25-OH-D3 to the 1,25-(OH)2-D3, a calcium and phosphate mobilizing hormone. If, however, the animal has sufficient supplies of calcium and phosphate, the l-hydroxylase is shut down and instead the 25-OH-D3 is converted to a 24,25-(OH)2D3. The role of the 24,25-(OH)2D3 remains unknown; it may be an intermediate in the inactivation-excretion mechanism. 1,25-(OH)2D3 proceeds to the intestine where it stimulates intestinal calcium transport and intestinal phosphate transport. It also stimulates bone calcium mobilization and probably has other effects yet to be discovered in such tissues as muscle. The 25-OH-D3-l-hydroxylase, which is located exclusively in renal mitochondria, has been shown to be a three component system involving a flavoprotein, an iron-sulfur protein (renal ferredoxin), and a cytochrome P-450. This system has been successfully solubilized, the components isolated, and reconstituted. The 24-hydroxylase, however, has not yet been thoroughly studied. 1,25-(OH)2D3 is necessary for the appearance of the 24-hydroxylase; parathyroid hormone represses 24-hydroxylation. It is possible that the 24-hydroxylase represents the major regulated enzyme, so that its presence or absence may determine whether 1,25-(OH)2D3 is produced. Two metabolic pathways for 1,25-(OH)2D3 are known, conversion by the 24-hydroxylase to 1,24,25-(OH)3D3, and conversion of 1,25-(OH)2D3 to an unknown substance. In the latter instance, there occurs loss of a side chain piece, including at least one of the 26 and 27 carbons. Whether 1,25-(OH)2D3 must be metabolized further before it carries out all of its functions has yet to be established. The primary excretion route of vitamin D3 is via the bile into the feces. Urinary excretion appears small in magnitude and no excretion products have yet been identified positively. Much remains to be learned concerning the metabolism and function of vitamin D and its metabolites. This should therefore, prove to be a fruitful area of investigation for many years to come, especially since 1,25-(OH)2D3, 25-OH-D3, and lalpha-OH-D3 have been shown to be effective in a number of metabolic bone disease states.     

Vitamin D status: effects on parathyroid hormone and 1, 25-dihydroxyvitamin D in postmenopausal women

BACKGROUND: Low serum 25-hydroxyvitamin D ?25(OH)D concentrations are commonly found in the elderly and are associated with hip fracture. Treatment with vitamin D and calcium can reduce the risk of fracture. The relation between the rise in parathyroid hormone (PTH) with age and the decrease in 25(OH)D is not clear. Neither is there any consensus on the serum concentration of 25(OH)D required for bone health. OBJECTIVE: Our objective was to study the relations between serum PTH, serum vitamin D metabolites, and other calcium-related variables in postmenopausal women. DESIGN: This was a cross-sectional study of 496 postmenopausal women without vertebral fractures attending our menopausal osteoporosis clinics. RESULTS: PTH was significantly positively related to age and serum 1, 25-dihydroxyvitamin D ?1,25(OH)(2)D and inversely related to 25(OH)D and plasma ionized calcium. There was a step-like increase in PTH as serum 25(OH)D fell below 40 nmol/L. In women with 25(OH)D concentrations >40 nmol/L, 1,25(OH)(2)D was positively related to 25(OH)D; in women with 25(OH)D concentrations 40 nmol/L, 1,25(OH)(2)D was most closely (inversely) related to plasma creatinine. Therefore, with serum 25(OH)D concentrations increasingly <40 nmol/L, serum 1,25(OH)(2)D becomes critically dependent on rising concentrations of PTH. CONCLUSION: The data suggest that aging women should maintain 25(OH)D concentrations >40 nmol/L (which is the lower limit of our normal range for healthy young subjects) for optimal bone health.     

Vitamin D status and concentrations of serum vitamin D metabolites and osteocalcin in elderly patients with femoral neck fracture: a follow-up study

Vitamin D status and the serum osteocalcin concentration in patients with femoral neck fractures were studied as follows. Thirty-seven elderly patients (P) with fracture of the femoral neck were studied, whereas 24 age-matched persons (C) seen at the out-patient department for non-orthopaedic reasons served as controls. The dietary intake of vitamin D, estimated using a vitamin D score based on food items known to be the main sources of vitamin D, was significantly lower in the patients than in the controls. There was no difference in the serum 25-hydroxy-vitamin D (25-OH-D) (P: 22.3 +/- 7.5 nmol/l; C: 27.5 +/- 13.5) or the serum 1,25-dihydroxy-vitamin D3 concentration (P: 86 +/- 43 pmol/l; 31) C: 85 +/- 31) between the groups. The 25-OH-D concentration was, however, low as compared to reference values, suggesting vitamin D deficiency in both groups. There was no difference in the serum osteocalcin concentration between the groups (P: 3.1 +/- 1.7 micrograms/l; C: 3.4 +/- 1.5). One year later the serum osteocalcin concentrations (5.9 +/- 2.2 micrograms/l, n = 11) was significantly higher (P less than 0.005) in the patients than at the time of the fracture (3.2 +/- 2.2 micrograms/l), indicating an active bone turnover in the patients still present 1 year after the fracture.     

The biological activity of 25-hydroxycholecalciferol and 1,25--dihydroxycholecalciferol for rainbow trout (Salmo gairdneri)

Dietary 25-hydroxycholecalciferol (25-hydroxycholecalciferol (25-OH-D3) and 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] showed vitamin D activity in rainbow trout. However, inclusion of dietary cholecalciferol (vitamin D3 or D3), ergocalciferol (vitamin D2 or D2), 25-OH-D3 or 1,25-(OH)2D3 did not result in the presence of detectable levels of vitamin D or 25-OH-D in the blood plasma of the fish. Fish fed the diet devoid of vitamin D over an extended period of time showed symptoms of a droopy-tail or "lordosis-like" syndrome that appeared to be related to muscle weakness since x-ray examination indicated no abnormality in vertebral development. The requirement for vitamin D as cholecalciferol was in excess of 1600 IU/kg diet and may be as high as, or higher than 2400 IU/kg diet.     

The effect of 1,25-dihydroxycholecalciferol on the changes of bone gamma-carboxyglutamic acid-containing protein in bone and serum of developing chick

The effects of 1,25-dihydroxycholecalciferol(1,25-(OH)2-D3) injection into developing chick embryos on bone gamma-carboxyglutamic acid-containing protein (BGP) levels in bone and serum were observed in relation to those on calcium metabolism using chick embryos and chicks aged from 13 days' incubation to 7 days of age. Chick BGP was determined by radioimmunoassay using antiserum to purified chick BGP. The injection of 1,25-(OH)2-D3 into the developing chick embryos of 13 days' incubation resulted in the increases of bone BGP levels at hatching and at 2 days of age. However, the distribution of bone BGP at hatching was not influenced by 1,25-(OH)2-D3. On the other hand, serum BGP levels were significantly increased by 1,25-(OH)2-D3 at 14, 15, 18 days' incubation and at 2 days of age. The early changes of serum BGP levels after 1,25-(OH)2-D3 treatment were correlated with the increases of serum calcium concentrations and the decreases of inorganic phosphorus concentrations. These results suggest that 1,25-(OH)2-D3 may directly or indirectly mediate BGP synthesis or secretion associated with calcium metabolism.     

Bone marrow and serum concentrations of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1 alpha,25-dihydroxyvitamin D in patients with leukemia and normal subjects

Concentrations of 25-hydroxyvitamin D (25-OH-D), 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in bone marrow and serum of patients with leukemia and normal subjects were assayed. There were highly significant correlations between the bone marrow and serum concentrations of the respective vitamin D metabolites. Especially, the concentrations of 25-OH-D and 1,25(OH)2D in the bone marrow gave very similar values to those in serum. This is a big advantage in controlling the bone marrow levels of vitamin D metabolites in patients with leukemia, because doctors can calculate the bone marrow levels from the serum levels of the respective vitamin D metabolites without bone marrow aspiration. When 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) was administered orally to eight patients with leukemia, clinical conditions were improved in seven patients: four complete remissions (CR), one partial response (PR), and two minor responses (MR) without severe hypercalcemia. The results suggest that the therapy with 1 alpha-OH-D3 is fairly effective for curing human leukemia although it is not dramatic.     

Concentrations of vitamin D-binding protein and vitamin D metabolites in plasma of patients with liver cirrhosis

Plasma levels of vitamin D-binding protein (DBP) and vitamin D metabolites in patients with decompensated and compensated liver cirrhosis were assayed. Plasma levels of DBP in the decompensated group were significantly lower than those in the compensated group, but both were lower than the normal range. The plasma levels of 25-hydroxyvitamin D (25-OH-D) and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in the compensated group were within the respective normal ranges, whereas both values in the decompensated group were significantly lower than those in the compensated group. Most of 25-OH-D (higher than 96%) was confirmed to be circulated as a bound form with DBP in the plasma of not only the compensated but also the decompensated group. When vitamin D2 was given to the decompensated group, a significant increase of 1,25(OH)2D levels in the plasma could not be observed while 25-OH-D levels were increased. On the other hand, the administration of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) to the decompensated group caused a significant increase in the plasma levels of 1,25(OH)2D. Therefore, we suggest that the administration of 1 alpha-OH-D3 is useful for the treatment of bone disease induced by liver cirrhosis.     

Dietary phosphate deprivation increases renal synthesis and decreases renal catabolism of 1,25-dihydroxycholecalciferol in guinea pigs.

In guinea pigs, dietary phosphate deprivation decreases plasma phosphate concentration, increases plasma 1.25-dihydroxycholecalciferol [1,25-(OH)2D3] concentration and causes hypercalcemia concurrent with the maximal increase in plasma 1,25-(OH)2D3 levels. Our objective was to determine whether increased synthesis or decreased catabolism contributed to the elevation in plasma 1,25-(OH)2D3. Preliminary experiments using renal mitochondria from guinea pigs fed a control diet revealed that 23,25-dihydroxycholecalciferol [23,25-(OH)2D3], not 24,25-dihydroxycholecalciferol [24,25-(OH)2D3], was the reciprocal side-chain metabolite to 1,25-(OH)2D3 in this species. An assay employing guinea pig renal mitochondria was used to measure the renal synthesis of 1,25-(OH)2D3 and 23,25-(OH)2D3 from [3H]25-OH-D3. These metabolites were unequivocally identified by combinations of HPLC, ultraviolet spectrophotometry and mass spectrometry. This renal mitochondrial assay was subsequently used to investigate the effect of dietary phosphate deprivation on guinea pig vitamin D metabolism. Within 1 wk the rate of synthesis of 1,25-(OH)2D3 was maximal in phosphate-deprived guinea pigs. This rate was significantly (P less than 0.005) higher than that achieved in same-day control guinea pigs. Conversely, within 1 d the synthesis of 23,25-(OH)2D3 was significantly (P less than 0.005) decreased in phosphate-deprived guinea pigs. Similarly, the rate of 1,25-(OH)2D3 metabolism was decreased within 1 d of dietary phosphate deprivation and was at a minimum within 1 wk. This rate was significantly (P less than 0.005) less than that attained in same-day control guinea pigs. These results suggest that both increased synthesis and decreased metabolism of 1,25-(OH)2D3 contribute to the plasma 1,25-(OH)2D3 elevation that occurs in response to dietary phosphate deprivation.     

Celiac disease is not increased in women with hip fractures and low vitamin D levels

Objective

Celiac disease is associated with decreased bone density; however, the risk of fractures in celiac disease patients is unclear. We compared the prevalence of celiac disease between a group of women with hip fractures and a group of women undergoing elective joint replacement surgery and the association between celiac disease and vitamin D levels.

Methods

Two hundred eight community dwelling and postmenopausal women were recruited from Boston, MA (n=81) and Baltimore, MD (n=127). We measured tissue transglutaminase IgA by ELISA to diagnose celiac disease and 25-hydroxyvitamin D (25(OH)D) levels by radioimmunoassay in both women with hip fractures (n=157) and a control group (n=51) of total hip replacement subjects from Boston. Subjects were excluded if they took any medications or had medical conditions that might affect bone.

Results

Median serum 25(OH)D levels were significantly lower (p< 0.0001) in the hip fracture cohorts compared to the elective joint replacement cohort (14.1 ng/ml vs. 21.3 ng/ml, respectively). There were no differences in the percentage of subjects with a positive tissue transglutaminase in the women with hip fractures versus the control group (1.91% vs. 1.96%, respectively).

Conclusion

Vitamin D levels are markedly reduced in women with hip fractures, however hip fracture patients did not show a higher percentage of positive tissue transglutaminase levels compared with controls. These data suggest that routine testing for celiac disease among hip fracture patients may not be necessary in the absence of clinical signs and symptoms, although data from larger studies among hip fracture subjects are needed.     

Changes in the concentrations of vitamin D and its metabolites in the plasma of healthy subjects orally given physiological doses of vitamin D2 by multivitamin or vitamin D preparations

Changes in the concentrations of vitamin D and its metabolites in plasma of healthy subjects orally given physiological doses of vitamin D2 by multivitamin or vitamin D liquid preparations were determined and the bioavailability of vitamin D was studied. Separative assay on the D2 and D3 compounds of vitamin D, 25-hydroxyvitamin D (25-OH-D), 24R,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] was performed in plasma of eight healthy male volunteers. When the concentrations of vitamin D and its metabolites in plasma of volunteers were assayed after daily oral administration of 400 IU of vitamin D2 in a form of multivitamin tablet for 1 week, the variations of vitamin D3 and its metabolites in plasma levels were very small. In contrast, the concentrations of 25-OH-D2 and 1,25(OH)2D2 slightly increased after the administration, while neither vitamin D2 nor 24,25(OH)2D2 was detected. A single dose of 4,000 IU of vitamin D2 was orally given to the volunteers in a form of a vitamin D liquid preparation and the hourly variations were observed during 24 h. These concentrations of vitamin D2, 25-OH-D2, and 1,25(OH)2D2 were slightly higher than those of the repeated doses. The result suggests that even the high dose of 4,000 IU has little effect on the plasma levels of vitamin D2 and its metabolites by a single dose, indicating a low risk for hypervitaminosis D.     

Relation of serum albumin concentration to death rate in nursing home men

Serum albumin was measured in 126 men (average age 70.6; range 40 to 96) of a Veterans Administration Nursing Home, and was correlated with other items in an extensive clinical data base, including death or survival during the year after the analysis. The reason for institutionalization was chronic neurologic disease or other disabling physical condition in 63 men (group A), and psychiatric disorder in 63 men (group B). In group A, the proportions of men with albumin less than 3.5, 3.5-4.0, and greater than 4.0 g/dl were 6%, 37%, and 57%, respectively. In this group, the serum albumin level was significantly (p less than 0.05) correlated with death rate, hemoglobin, hematocrit, serum cholesterol, and serum lactic dehydrogenase. The death rate in group A during the year after the albumin analysis was 25%. For the patients with albumin level less than 3.5, 3.5-4.0, and greater than 4.0 g/dl, the death rates were 50%, 43%, and 11% respectively (p less than 0.01 for comparison of the former two groups with the latter). The subgroup with albumin 3.5-4.0 g/dl represented only 37% of the men in group A, but accounted for 63% of the group's deaths. In group B, serum albumin level was not significantly correlated with any other clinical variable. Death rate during the year after the albumin analysis was only 2% in group B, and did not correlate with the albumin level. These data indicate that, in nonpsychiatric Nursing Home men, the desirable level for the serum albumin concentration is higher than 3.5 g/dl.     

All-trans retinoic acid antagonizes the action of calciferol and its active metabolite, 1,25-dihydroxycholecalciferol, in rats

An antagonistic interaction between retinol and calciferol has been established. However, the mechanism by which this antagonism occurs is unclear. One possibility is that retinol affects the metabolism of calciferol. To investigate this hypothesis, retinol- and calciferol-depleted rats were given various amounts of ergocalciferol, cholecalciferol, 1alpha,25-dihydroxycholecalciferol [1,25(OH)2D3], or 24,24-difluoro-1alpha,25-dihydroxycholecalciferol [24-F2-1,25(OH)2D3] in combination with various amounts of retinyl acetate or all-trans retinoic acid (ATRA) in a series of studies. Rats administered 1720 or 3440 microg retinyl acetate once every 3 d for 33 d in combination with 25.8 ng ergocalciferol or 25 ng cholecalciferol every 3 d had lower serum calcium and greater serum phosphorus concentrations than rats fed 0 or 11.4 mug retinyl acetate every 3 d. In addition, rats fed 400 microg ATRA/d in combination with 25.8 ng ergocalciferol every 3 d, 25 ng cholecalciferol every 3 d, 2-5 ng 1,25(OH)2D3/d, or 0.5-1 ng 24-F2-1,25(OH)2D3/d had significantly lower serum calcium and higher serum phosphorus concentrations than rats not given ATRA in the diet. Therefore, both retinyl acetate and ATRA are able to antagonize the action of ergocalciferol and cholecalciferol in vivo. Additionally, ATRA antagonizes the in vivo action of 1,25(OH)2D3 and an analog, 24-F2-1,25(OH)2D3, that cannot be 24-hydroxylated. Together, these results suggest that retinol does not antagonize the action of calciferol by altering the metabolism of calciferol or 1,25(OH)2D3, but does so by another mechanism.     

老年妇女PTH分泌异常及1，25（OH）2D3的疗效观察

目的 研究老年妇女甲状旁腺激素的分泌变化以及维生素1，25(OH)2D3的疗效。方法测定20例年轻妇女(25～35岁)和20例老年妇女(70～78岁)血清PTH浓度，用RIA方法测定使用1，25(OH)2D3前后VFH的变化。使用RIA方法测定血清1，25(OH)2D和25(OH)D的血清浓度。结果 血清PTH浓度随增龄而升高，使用1，25(OH)2D3后，两组的PTH水平均下降。结论 1，25(OH)2D3能减少老年妇女PTH分泌的异常增加。     

Plasma 1,25-(OH)2-vitamin D concentrations and net intestinal calcium, phosphate, and magnesium absorption in humans.

We evaluated the relationship between plasma concentrations of the renal hormone 1,25-(OH)2-vitamin D and net intestinal absorption of Ca, PO4, and Mg in vitamin D-replete patients eating similar diets, who had undetectable, normal or elevated plasma 1,25-(OH)2-D levels, Net intestinal Ca absorption was positively correlated to plasma 1,25-(OH)2-D concentrations: percentage dietary Ca absorbed = 10 + 0.17 x plasma total 1,25-(OH)2-3, pmole/liter, r = + 0.58; P less than 0.001. By contrast, there was no significant correlation between PO4 or Mg absorption and plasma 1,25-(OH)2-D concentrations. Moreover, significant quantities of PO4 and Mg were absorbed in the absence of detectable plasma 1,25-(OH)2-D. We conclude that net intestinal Ca absorption is critically dependent upon the availability of the renal hormone 1,25-(OH)2-D in vitamin D-replete humans when dietary Ca intake is normal. By contrast, other factors must play a dominant role in regulating net intestinal PO4 and Mg absorption.     

Seasonal changes in calcitropic hormones in Israeli men

Seasonal changes in calcitropic hormones might be expected, being that dietary calcium intake may differ with fluctuations in climate and temperature, and vitamin D is diet- and sunlight-dependent. While there are studies on elderly subjects, prospective data on younger men is limited. The objective of this study was to clarify possible seasonal changes in homeostatic regulators of calcium in Israeli men aged 25–64 years. The study was a prospective follow-up analysis of data collected during June–August 1995 and 1996 (summer) and January–March 1995 and 1996 (winter). Subjects were ninety-five industrial male employees with and without occupational lead exposure. The main outcome measures were summer and winter serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), and 1,25-dihydroxyvitamin D (calcitriol). Summer and winter values of PTH were similar (38.2 and 39.8ng/l, respectively). 25-OH-D levels were significantly higher in summer (32.8ng/ml) than in winter (25.4ng/ml) after controlling for possible confounders (p<0.0001). Calcitriol levels were significantly higher in summer (79.1pmol/l) than in winter (73.5pmol/l) in univariate analyses, but not after controlling for possible confounders. We conclude that healthy men show considerable seasonal changes in 25-OH-D levels even in Israel, a relatively sunnycountry all the year round. Summer values of 25-OH-D, were 35% higher than in winter. These fluctuations should be taken into account during evaluation of pathological conditions and in research. Given an adequate diet and vitamin D status there are no seasonal variations in PTH or in calcitriol levels.     

Fortified malted milk drinks containing low-dose ergocalciferol and cholecalciferol do not differ in their capacity to raise serum 25-hydroxyvitamin D concentrations in healthy men and women not exposed to UV-B

Uncertainty remains regarding the efficacy of low intakes of ergocalciferol (vitamin D2 or D2) and cholecalciferol (vitamin D3 or D3) provided in food to increase serum 25-hydroxy-vitamin D (25-OH-D) metabolite concentrations when UV-B exposure is low. We recruited 40 healthy men and women into a double-blind, parallel design, randomized controlled trial. Participants received placebo or 1 of 4 experimental treatments (D2 or D3 at 5 or 10 μg/d) supplied as a malted milk drink for 4 wk during a period of minimal UV-B exposure in the UK. The primary outcome was a change in serum 25-OH-D2 and 25-OH-D3 concentrations measured by ultra-performance liquid chromatography tandem MS. The secondary outcomes were changes in concentrations of plasma parathyroid hormone and serum calcium (Ca(2+)). Baseline concentrations (geometric mean ± SD) of 25-OH-D2, 25-OH-D3, and total 25-OH-D were 3 ± 4, 32 ± 22, and 37 ± 22 nmol/L, respectively. Both D2- and D3-fortified drinks resulted in dose-dependent increases (P < 0.001) in their respective 25-OH metabolites that did not significantly differ in size. Increments from baseline compared with the placebo group following 5 and 10 μg/d of D2 were (mean ± SEM) 9.4 ± 2.5 and 17.8 ± 2.4 nmol/L for 25-OH-D2 and following 5 and 10 μg/d of D3 were 15.1 ± 4.7 and 22.9 ± 4.6 nmol/L for 25-OH-D3, respectively. There was no difference between D2 and D3 groups in the incremental AUC of their respective metabolites. These findings suggest that D2 and D3 are equipotent in increasing 25-OH-D in healthy men and women with negligible UV-B exposure.     

Serum 25-hydroxyvitamin D is a predictor of serum 1,25-dihydroxyvitamin D in overweight and obese patients

Recent research suggests that 1,25-dihydroxyvitamin D [1,25(OH)(2)D], a steroid hormone that regulates calcium homeostasis, may also play a role in the development and progression of cancer, multiple sclerosis, cardiovascular, and other diseases. Decreased serum 1,25(OH)(2)D concentrations are often observed in overweight and obese patients. However, little is known about the factors that may influence 1,25(OH)(2)D renal synthesis, because it is generally accepted that serum 1,25(OH)(2)D concentration is strictly regulated by parathyroid hormone and serum concentrations of calcium and phosphorus. In this study, the associations among serum 1,25(OH)(2)D, serum 25-hydroxyvitamin D [25(OH)D], and body composition were analyzed in 1779 patients with excess body weight registered in a Metabolic and Medical Lifestyle Management Clinic in Oslo, Norway. According to our results, serum 25(OH)D, adiposity, age, season of blood sampling, and gender directly influence serum 1,25(OH)(2)D (r = 0.33; P < 0.001), with serum 25(OH)D being the strongest predictor for serum 1,25(OH)(2)D. The 1,25(OH)(2)D concentrations were 25.4 pmol/L (95% Cl: 19.3-31.5; P < 0.001) lower in the lowest 25(OH)D quartile to compared with highest quartile. A seasonal variation was observed for both vitamin D metabolites. Thus, our results suggest that in patients with excess body weight, serum 1,25(OH)(2)D concentrations were associated with 25(OH)D and varied during the year. Therefore, it may also be valuable to measure both serum 25(OH)D and 1,25(OH)(2)D for the evaluation of vitamin D status in overweight and obese persons.