Vitamin D receptor (VDR) knockout mice reveal VDR-independent regulation of intestinal calcium absorption and ECaC2 and calbindin D9k mRNA

To study the role of calbindin D(9k) (CaBP) and epithelial calcium channel ECaC2 in intestinal calcium (Ca) absorption, vitamin D receptor knockout (KO) and wild-type (WT) mice were fed either 0.5% Ca or a 2.0% Ca rescue diet starting at 21 d of age. Ca absorption and parameters involved in this process were measured at 60 or 90 d of age. Compared with WT, KO mice fed the 0.5% Ca diet had higher plasma parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], and lower plasma Ca and insulin-like growth factor-I (IGF-I). Duodenal Ca absorption (% Ca absorbed) in KO mice was reduced 71% relative to WT mice and was associated with 55% lower CaBP mRNA, 47% lower CaBP protein and 95% lower ECaC2 mRNA levels. Compared with WT mice, the percentage of Ca absorbed in KO mice fed the 0.5% Ca diet was inappropriately low for the level of duodenal CaBP. The 2% Ca rescue diet normalized plasma Ca, prevented osteomalacia, increased growth and plasma IGF-I levels, but did not normalize plasma PTH or 1,25(OH)(2)D(3) in KO mice. In addition, the relationship between CaBP protein and the percentage of Ca absorbed was normalized, whereas ECaC2 mRNA fell to near zero. Our data demonstrate that higher CaBP levels do not ensure high rates of duodenal Ca absorption and that transcellular Ca absorption can occur even when ECaC2 gene expression is very low. In addition, our data suggest that the 2% Ca diet promotes a vitamin D receptor-independent anabolic effect on bone formation and calcium absorption, leading to improved calcium balance even in the presence of high PTH levels.     

Dietary short-chain fructooligosaccharides increase calbindin-D9k levels only in the large intestine in rats independent of dietary calcium deficiency or serum 1,25 dihydroxy vitamin D levels

Dietary short-chain fructooligosaccharides (Sc-FOS) increase mucosal calbindin-D9k (CaBP) levels in the large intestine whereas levels in the small intestine are decreased in rats. In the present study, we investigated the mechanism by which Sc-FOS induce this increase in CaBP in the large intestine by measuring intestinal CaBP levels in rats fed normal and calcium-deficient diets. Dietary groups included a calcium-containing (0.5%) diet with or without Sc-FOS (100 g/kg diet) and a calcium-deficient (abt. 0.01%) diet with or without Sc-FOS (100 g/kg diet). The rats were fed these diets for 10 days following which they were killed and the intestine removed for collection of the entire mucosa which was divided into four segments, i.e., proximal and distal segments of the small intestine, the cecum and the colorectum. Mucosal CaBP and plasma calcium (Ca), 1,25-dihydroxycholecalciferol (1,25(OH)2D3), 25-hydroxycholecalciferol (25(OH)D3), parathyroid hormone (PTH) and calcitonin levels were measured. Feeding of calcium deficient diet resulted in an increase in CaBP levels in the small intestine, but did not influence levels in the large intestine. Moreover, a significant positive correlation between plasma 1,25(OH)2D3 and CaBP levels in the case of both small intestinal segments (proximal, r = 0.77012, p < 0.00007; distal, r = 0.75056, p < 0.00014) was observed, but not in the case of the large intestinal segments. Sc-FOS increased CaBP levels in the large intestine. These results suggest that the large intestinal CaBP levels do not change in response to dietary calcium conditions and are not regulated by circulating 1,25(OH)2D3 indicating that the effect of Sc-FOS on CaBP levels in the large intestine is independent of the action of 1,25(OH)2D3.     

Effects of vitamin D on calcium regulation in vitamin-D-deficient pigs given a phytate-phosphorus diet

1. Vitamin-D-deficient pigs were fed on a phytate-phosphorus diet and treated with vitamin D3 (+D) to examine the time-course of adaptative changes in plasma minerals, vitamin D metabolites, parathyroid hormone (PTH) and calcium balance and intestinal Ca-binding protein (CaBP). 2. The 5-week vitamin D repletion (25 micrograms cholecalciferol/kg diet) regimen restored plasma Ca, P and alkaline phosphatase (EC 3.1.3.1) to normal, decreased PTH and markedly and rapidly increased plasma 25-hydroxycholecalciferol (25-OHD, sevenfold after 4 d) and 1,25-dihydroxycholecalciferol (1, 25(OH)2D3, 1.8-fold after 4 d). 3. CaBP concentrations were markedly elevated all along the digestive tract, especially in the distal regions. 4. Ca absorption and retention were enhanced (fourfold and sixfold respectively) by the +D diet. 5. The improved Ca absorption, coupled with increased CaBP and 1,25(OH)2D3 levels, suggest that vitamin D metabolism in phytate-P-fed pigs is sensitive to the depressed Ca availability due to phytate feeding. It also indicates that CaBP may play an important role in the adaptation of Ca absorption. 6. Persistent hypercalciuria indicates that mineral metabolism was still affected by the phytate nature of the dietary P in spite of the vitamin D treatment.     

Effects of 3 diets with various calcium contents on 24-h energy expenditure, fat oxidation, and adipose tissue message RNA expression of lipid metabolism-related proteins

BACKGROUND: Evidence from molecular and animal research and epidemiologic investigations indicates that calcium intake may be inversely related to body weight, possibly through alterations in 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] metabolism. OBJECTIVE: We tested whether energy and substrate metabolism and adipose tissue enzyme messenger RNA (mRNA) expression can be altered by dietary calcium intake in healthy, nonobese, human volunteers consuming an isocaloric diet. DESIGN: Twelve healthy men [age: 28 +/- 2 y; body mass index (BMI; in kg/m(2)): 25.2 +/- 06] received 3 isocaloric diets [high calcium (1259 +/- 9 mg/d), high dairy (high/high); high calcium (1259 +/- 9 mg/d), low dairy (high/low); and low calcium (349 +/- 8 mg/d), low dairy (low/low)] in a randomized crossover design. At the end of the 7-d dietary periods, 24-h energy expenditure and substrate metabolism were measured, and fat biopsy specimens were obtained to determine mRNA expression in genes involved in the lipolytic and lipogenic pathways. RESULTS: The 24-h energy expenditure was 11.8 +/- 0.3, 11.6 +/- 0.3, and 11.7 +/- 0.3 MJ/24 h in the high/high, high/low, and low/low conditions, respectively. Fat oxidation in these conditions was 108 +/- 7, 105 +/- 9, and 100 +/- 6 g/24 h. These differences were not statistically significant. mRNA concentrations of UCP2, FAS, GPDH2, HSL, and PPARG did not differ significantly. Serum 1,25(OH)(2)D(3) concentrations changed from 175 +/- 16 to 138 +/- 15, 181 +/- 23 to 159 +/- 19, and 164 +/- 13 to 198 +/- 19 pmol/L in the high/high, high/low, and low/low conditions, respectively, and was significantly different between the high/high and low/low conditions (P < 0.05). CONCLUSION: Altering the dietary calcium content for 7 d does not influence substrate metabolism, energy metabolism, or gene expression in proteins related to fat metabolism, despite significant changes in 1,25(OH)(2)D(3) concentrations.     

Gastrointestinal absorption of lead in chicks: involvement of the cholecalciferol endocrine system

The role of dietary calcium and phosphorus in modifying the intestinal absorption of lead and also the effect of lead ingestion on the metabolism of cholecalciferol were studied in chicks. The efficiency of absorption of 203Pb and 47Ca was increased when the animals were fed a low calcium diet and treated with cholecalciferol. The synthesis of the vitamin D-induced calcium-binding protein (CaBP) was correspondingly increased. When the chicks were depleted of vitamin D and repleted with 1,25-dihydroxycholecalciferol [1,25(OH)2D3] as their only source of the vitamin, the absorption of both 47Ca and 203Pb was unaffected by dietary calcium levels, and no change in CaBP levels occurred. Low dietary intake of phosphorus resulted in an increase in 47Ca and 203Pb absorption and in CaBP synthesis when the animals were treated with cholecalciferol. However, when the birds were repleted with 1,25(OH)2D3, the intestinal absorption of 47Ca and of 203Pb was increased, as well as the intestinal CaBP levels. Intracardial injection of increasing doses of 1,25(OH)2D3 to rachitic chicks resulted in a concomitant increase in 203Pb absorption in a manner that correlated with the degree of synthesis of CaBP. Ingestion of lead by the chicks was found to impair growth and renal production of 1,25(OH)2D3, resulting in lowered circulating and intestinal content of the hydroxylated metabolites of cholecalciferol.     

Moderate cholecalciferol supplementation depresses intestinal calcium absorption in growing dogs

Hormonal regulation of calcium (Ca) absorption was investigated in a cholecalciferol (vitamin D(3))-supplemented group (hVitD) vs. a control group (cVitD) of growing Great Danes (100 vs. 12.5 micro g vitamin D(3)/kg diet). Although Ca intakes did not differ, fractional Ca absorption was significantly lower in the hVitD group than in the cVitD group. There were no differences in plasma concentrations of Ca, inorganic phosphate, parathyroid hormone, growth hormone or insulin-like growth factor I between groups. Plasma 25-hydroxycholecalciferol [25(OH)D(3)] concentrations were maintained in the hVitD dogs at the same levels as in the cVitD dogs due to increased turnover of 25(OH)D(3) into 24,25-dihydroxycholecalciferol [24,25(OH)(2)D(3)] and 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)]. In hVitD dogs, the greater plasma 24,25(OH)(2)D(3) concentration and the enhanced metabolic clearance rate (MCR) of 1,25(OH)(2)D(3) indicated upregulated 24-hydroxylase activity. The increased MCR of 1,25(OH)(2)D(3) decreased plasma 1,25(OH)(2)D(3) concentrations. In hVitD dogs, the greater production rate of 1,25(OH)(2)D(3) was consistent with the 12.9-fold greater renal 1alpha-hydroxylase gene expression compared with cVitD dogs and compensated to a certain extent for the accelerated MCR of 1,25(OH)(2)D(3). The moderately decreased plasma 1,25(OH)(2)D(3) concentration can only partially explain the decreased Ca absorption in the hVitD dogs. Intestinal vitamin D receptor concentrations did not differ between groups and did not account for the decreased Ca absorption. We suggest that 24,25(OH)(2)D(3) may downregulate Ca absorption.     

Serum metabolite profiles and target tissue gene expression define the effect of cholecalciferol intake on calcium metabolism in rats and mice

We studied the effect of cholecalciferol (VD3) intake on VD3 status and markers of calcium (Ca) homeostasis in mice and rats. Serum 25 hydroxycholecalciferol (25OH-VD3) concentrations were increased in animals fed diets containing 400-20,000 international units (IU) VD3/kg (37 nmol.L(-1).1000 IU VD3(-1)), but body weight, serum Ca, and duodenal gene expression were not altered. High-VD3 intake decreased serum 1, 25-dihydroxycholecalciferol [1,25(OH)2-VD3] and renal 25 hydroxycholecalciferol-1alphahydroxylase (CYP27B1) mRNA, suggesting that rodents tolerate high-VD3 intake by suppressing the activity of the VD3 endocrine system. Serum 25OH-VD3 declined when animals were fed diets containing 1000 to 25 IU VD3/kg (9-11 wk, inflection at 200 IU/kg, 4-fold steeper slope below this). Neither body weight nor serum Ca were influenced by low-VD3 intake. However, mice fed the 25-IU/kg diet had lower serum 1,25(OH)2-VD3, duodenal calbindin D9k mRNA, bone mineral density, and renal 25 hydroxycholecalciferol-24 hydroxylase mRNA, whereas renal CYP27B1 mRNA was elevated when rodents were fed < 200 IU VD3/kg. These data reveal a stress on VD3 and Ca metabolism at low dietary VD3 intake. Dietary Ca restriction (0.25 vs. 0.5%, 9 wk) increased serum 1,25(OH)2-VD3 and was 30% greater in rats fed a 10,000-IU VD3/kg diet. High-VD3 intake did not prevent Ca restriction-induced bone loss. Our data show that modeling human VD3 status requires lower intake than the current NRC rodent requirement (1000-IU/kg diet). Also, although rodents are very tolerant of high-VD3 intake, it cannot compensate for moderate Ca restriction.     

上皮钙通道基因在维生素D受体和Calbindin-D28k双基因敲除鼠中的变化

目的研究上皮钙通道TRPV5和TRPV6基因与维生素D受体(VDR)和钙结合基因Calbindin-D28k的关系,以及肾钙的重吸收减少是否与TRPV5和TRPV6基因表达减少有关。方法制备VDR和CaBP-D28k双基因敲除小鼠,普通和高钙食物喂养下,检测野生型鼠(WT),CaBP-D28(-/-),VDR(-/-),和VDR(-/-)/CaBP-D28k(-/-)鼠的体重、摄食量及血尿参数值,用实时RT-PCR的方法检测各种鼠肾脏TRPV5和TRPV6的mRNA水平。结果普通饮食下,双基因敲除小鼠尿钙的分泌和血清甲状旁腺激素水平更高。TRPV5和TRPV6两者的表达在CaBP-D28k敲除鼠中均无变化,而在VDR敲除鼠和双基因敲除鼠中下调的幅度相当。高钙饮食下,VDR及双基因敲除小鼠的血离子钙水平正常。所有小鼠这两个基因的表达普遍降低,而在VDR和双基因敲除鼠中的表达更低。结论这些结果证实了上皮钙通道基因受钙和维生素D的调节,CaBP-D28k的缺失对两者无影响。肾钙的重吸收减少与TRPV5和TRPV6基因表达无明显关系。     

Calcium and cholecalciferol: effects of small supplements in normal men

The effect of small calcium and vitamin D supplements on mineral metabolism in normal persons is unclear. To investigate the biochemical response to these medications, we administered 1000 mg Ca and 25 micrograms cholecalciferol per day or a placebo to 92 normal men for 1 y. The Ca and cholecalciferol were tolerated well. 25-Hydroxycholecalciferol [25-(OH)D] and 24,25-dihydroxycholecalciferol [24,25-(OH)2D] levels rose in treated subjects; there was no definite change in 1,25-(OH)2D concentrations. The average difference in 25-(OH)D levels between treated and untreated subjects was 30 nmol/L at 1 y. Fasting serum Ca, alkaline phosphatase, creatinine, and parathyroid hormone levels and the fasting urinary excretion of Ca, phosphorus and cAMP, were not affected. However, 24-h urinary Ca excretion was higher in the supplemented group (3.5 +/- 1.9 vs 4.7 +/- 1.7 mmol/d, p = 0.006). Serum P concentrations were slightly higher in the supplemented group at 1 y. In normal men small calcium and cholecalciferol supplements are safe, provide adequate vitamin D nutrition and apparently increase net gastrointestinal Ca absorption.     

Ovariectomy, dietary zinc, and bone metabolism in retired breeder rats

Bone mineral turnover was studied in sham and ovariectomized (ovax) retired breeder rats after 16 wk of dietary treatment. Rats were fed either a commercial rat diet (CRD) containing high calcium and cholecalciferol or egg-white diets (EWD) containing 2 g Ca/kg, 1,25-(OH)2cholecalciferol (5 micrograms/kg), and either 10 or 200 mg zinc/kg. In rats fed EWD, high Zn enhanced femoral Zn deposition and concentration but did not affect serum Ca levels, bone mineral content (BMC), or turnover. Serum Ca levels and BMC were greater in sham rats and there was a gain in femoral Ca and phosphorus compared with the loss of these minerals in ovax rats. In CRD-fed ovax rats, values for these variables were similar to those of CRD-fed shams and there was no bone mineral loss. These data suggest that ovarian function may be a prerequisite for the beneficial effects of diets containing 1,25-(OH)2cholecalciferol and low Ca on bone metabolism.     

Dietary calcium and phosphate restriction in guinea-pigs during pregnancy: fetal mineralization induces maternal hypocalcaemia despite increased 1 alpha,25-dihydroxycholecalciferol concentrations

Guinea-pig fetuses at term are mineralized to a degree comparable with human fetuses, which makes the guinea-pig an attractive animal model to study maternal-fetal interactions with regard to Ca and phosphate (P) homeostasis. We studied non-pregnant and pregnant (day 57) vitamin D-replete guinea-pigs, fed either a normal guinea-pig chow with 9.6 g Ca/kg and 4.9 g P/kg or a study diet with 2 g Ca/kg and 1 g P/kg (low-Ca-P diet) for 7-8 weeks. Both pregnancy and the low-Ca-P diet decreased plasma concentrations of 25-hydroxycholecalciferol (25(OH)D3), but increased total and free 1 alpha,25-dihydroxycholecalciferol (1,25(OH)2D3), strongly suggesting an additive stimulation of 1 alpha-hydroxylase activity. Maternal and fetal 25(OH)D3 and 1,25(OH)2D3 levels were highly correlated (r 0.82 and 0.92 respectively, P < 0.001). Dual-energy absorption X-ray absorptiometry (DXA) showed that both pregnancy and the low-Ca-P diet decreased bone mineral density (BMD) of the maternal femur, particularly at the distal metaphysis. Despite higher 1,25(OH)2D3 concentrations and lower BMD, pregnant animals on the low-Ca-P diet were hypocalcaemic; blood Ca2+ levels were inversely correlated with the number of fetuses in this group (r -0.93, P < 0.001). Fetal growth as well as mineralization (assessed by whole-body and femoral DXA, bone histomorphometry and plasma-bone osteocalcin measurements) were unaltered in the low-Ca-P group. In conclusion, fetal mineralization proceeds normally but induces maternal hypocalcaemia in guinea-pigs with dietary restriction of Ca and P.     

Bone mineral content in girls perinatally infected with HIV

BACKGROUND: Early diagnostic efforts and advances in multidrug therapy have considerably prolonged the survival time of children infected perinatally with HIV. Despite these advances, few studies have addressed calcium status and bone growth in HIV-infected children. OBJECTIVE: Our objective was to examine the effect of HIV infection on calcium status and bone growth in children. DESIGN: We measured calcitropic hormones, urinary calcium excretion, bone mineral content, and body composition in 19 young girls aged 9.2 +/- 2.6 y (range: 5.9-15.2 y) who were infected perinatally with HIV. RESULTS: Serum concentrations of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and parathyroid hormone concentrations were elevated above normal ranges in 25% and 12% of these girls, respectively. Urinary calcium excretion normalized for creatinine excretion was also elevated (Ca/Cr >0.18) in 17% of these children despite suboptimal calcium intakes (679 +/- 437 mg/d). Total-body bone mineral content, measured with the use of dual-energy X-ray absorptiometry, averaged 845.1 +/- 279.0 g and was on average 2.7 z scores below age- and race-matched values reported in non-HIV-infected healthy girls. Significant positive correlations were found between an indirect marker of bone resorption in urine (N:-telopeptide) and 1,25(OH)2D (P < 0.02, r2 = 0.586, n = 9), and between serum N-telopeptide and total alkaline phosphatase (P < 0.001, r2 = 0.541, n = 17), suggesting that calcium insufficiency may be increasing bone resorption in this group. CONCLUSIONS: Young girls with HIV infection had low bone mass and evidence of calcium insufficiency. Nutritional counseling of children with HIV infection should emphasize adequate calcium intakes because of the importance of this age period in bone mineral acquisition.     

Vitamin D metabolism and calbindin (calcium-binding protein) in aged laying hens

Calbindin (calcium-binding protein) concentration, vitamin D metabolism and shell quality were investigated in young (7- to 9-mo-old) and aged (19- to 21-mo-old) laying hens consuming normal or low levels of calcium (Ca). Although egg weight and percent of cracked eggs were higher and egg production and shell density (mg/cm2) were lower (significantly, P less than 0.01) in aged hens, shell weight, plasma Ca and duodenal and egg shell gland calbindin were similar to those of young hens. Dietary Ca restriction reduced shell weight, shell density and structural bone and plasma Ca in both the young and aged birds. The production of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its concentration in the plasma were higher in hens fed low dietary levels of Ca than in hens fed normal Ca levels only in the younger hens. However, a slightly higher production of 1,25(OH)2D3 and concentration of duodenal calbindin were also observed in severely Ca-restricted (1.4% Ca for 19 d) aged hens than in the younger hens. The results suggest that the aged hen loses its ability to adapt to changes in Ca intake or needs through mechanisms involving modulation of vitamin D metabolism.     

Effects of sodium bicarbonate and 1,25-dihydroxy-cholecalciferol on calcium and phosphorus balances in the rat

Metabolic balance studies were undertaken to determine whether sodium bicarbonate (NaHCO3) supplements (4.5 mmol/day) altered 7-day cumulative calcium (Ca) phosphorus (P) balances in growing rats consuming either a basal diet providing 0.6% Ca and 0.3% P, or this diet plus 1,25-dihydroxycholecalciferol [40 ng 1,25(OH)2D3/day]. Feeding bicarbonate lowered urinary Ca but raised fecal Ca so that Ca balance became less positive. However, 1,25(OH)2D3 increased net absorption of Ca and P to the same degree when given to control rats and rats consuming bicarbonate. Nevertheless, bicarbonate-fed rats had lower net Ca absorption than controls, even when treated with high doses of 1,25(OH)2D3. Changes in net Ca absorption induced by bicarbonate may occur at a point in the gut distal to the duodenum since duodenal 45Ca absorption was decreased by bicarbonate feeding. The present results show that bicarbonate consumption depressed net Ca absorption in the rat. The effect appears to be independent of changes in 1,25(OH)2D3 metabolism because it is manifest in animals receiving high doses of 1,25(OH)2D3, which stimulate alimentary Ca absorption maximally, and because bicarbonate-fed rats are able to respond normally to exogenous 1,25(OH)2D3 by increasing their net absorption of Ca and P. In view of this demonstration that NaHCO3 supplements elevate fecal Ca loss in the rat, it is suggested that studies should be undertaken to determine whether bicarbonate exerts similar adverse effects on Ca balance in humans.     

Biological activity of the three mono-beta-D-glucopyranosides of 1,25-dihydroxycholecalciferol

The biological activity of the three mono-beta-D-glucopyranosides (mono-glucosides) of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] synthesized chemically has been studied in chicks and Japanese quails. While the 1- and the 3-glucoside showed no or only little effect on serum calcium, bone weight, calcium binding protein (CaBP) or calcium deposition in the egg shell, the 25-glucoside was found to be more than half as active as the aglycone 1,25(OH)2D3. The bioactivity of this glucoside parallels a higher binding constant to the intestinal 1,25(OH)2D3 receptor compared to those of the two other glucosides.     

Insulin-like growth factor-I stimulates renal 1, 25-dihydroxycholecalciferol synthesis in old rats fed a low calcium diet

The adaptive increase in renal proximal tubule 25-hydroxyvitamin D-alpha-hydroxylase activity (1-OHase) during dietary calcium restriction is mediated by an increase in parathyroid hormone (PTH) and is inhibited by aging. Recent studies in mature (3-4 mo) rats demonstrated that insulin-like growth factor-I (IGF-I) restored stimulation of renal 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)] production by low phosphorus diet (LPD), another major stimulus of 1-OHase. These studies were designed to determine whether IGF-I stimulates 1-OHase during low calcium intake in old rats. Male rats were fed a normal calcium diet (NCD, 6 g Ca/kg diet) or low calcium diet (LCD, 0.2 g Ca/kg diet) for 14 d, and recombinant human IGF-I [rhIGF-I, 1.4 mg/(24h 160 kg body wt)] or vehicle was administrated via miniosmotic pump for 72 h before killing. In 4-mo-old male Sprague-Dawley rats, LCD increased in vitro renal 1-OHase activity in the presence but not in the absence of rhIGF-I. LCD increased in vitro1-OHase activity in young (1-mo-old) but not old (24-mo-old) male Fischer 344 rats. RhIGF-I increased 1-OHase activity in 24 mo-old rats fed LCD to levels that were not different from those in 1-mo-old rats fed LCD. The results indicate that the adaptive increase in 1-OHase activity due to a LCD is lost by 4 mo in rats and can be restored by pharmacologic doses of rhIGF-I.     

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.     

Efficacy of several vitamin D compounds in the prevention of tibial dyschondroplasia in broiler chickens

Studies were conducted to evaluate several cholecalciferol (D3 metabolites: 1,25-dihydroxycholecalciferol [1,25-(OH)2D3], 1,24R,25-trihydroxycholecalciferol [1,24R,25-(OH)3D3], 1 alpha-hydroxy-cholecalciferol (1 alpha-OHD3), 24R,25-dihydroxycholecalciferol [24R,25-(OH)2D3], 1,25-dihydroxy-26,27 hexadeuterium cholecalciferol (1,25-(OH)2-26,27[2H]6D3) and 1,25-dihydroxy-24R-fluorocholecalciferol [1,25-(OH)2-24R-FD3] for their activity in preventing the development of tibial dyschondroplasia in broilers. The basal diet used is low in calcium, high in phosphorus and chlorine and is known to promote a high incidence of tibial dyschondroplasia. The chicks received ultraviolet radiation from fluorescent lights in addition to 1100 ICU/kg (27.5 micrograms/kg) of D3 in the basal diet. Supplementation of the diet with 10 micrograms/kg of all the metabolites except 24R,25-(OH)2D3 significantly lowered the incidence and severity of tibial dyschondroplasia and increased bone ash when compared to birds receiving the basal diet. None of the active D3 metabolites was effective when fed at 0.1 or 1.0 micrograms/kg of diet. Two active compounds tested [1,25-(OH)2D3 and 1,24R,25-(OH)3D3] at 5 micrograms/kg of diet were effective in reducing either the incidence or severity of tibial dyschondroplasia.