The synergistic effects of vitamin D and estradiol deficiency on metabolic syndrome in Chinese postmenopausal women.

OBJECTIVE: Recent studies show that vitamin D (VitD) deficiency is associated with metabolic syndrome (MetS). Current evidence suggests that estrogen and VitD have similar physiological functions and potentially interact with bone health. We investigated the association between estradiol (E2) and 25-hydroxyvitamin-D [25(OH)D] with MetS and its components in Chinese postmenopausal women. METHODS: In this cross-sectional study, we examined 616 postmenopausal women (aged 49-86 y) from southern China who were not taking estrogen and VitD/calcium supplements. At the end of data collection, serum E2 and 25(OH)D were measured for each participant. MetS was defined according to the 2006 International Diabetes Federation standard. RESULTS: There was a positive correlation between 25(OH)D and E2. Higher 25(OH)D was associated with a favorable lipid profile, blood pressure, and glucose level. E2 was negatively associated with cholesterol, triglycerides, and blood pressure. The odds ratio for MetS was 2.19 (95% CI, 1.19-4.01, P value for trend=0.009) for deficient compared with sufficient women after multivariable adjustment. This association remained unchanged after further adjusting for E2 levels. After stratified analysis by VitD status, low E2 increased MetS risk in women with VitD deficiency (odds ratio = 3.49, 95% CI, 1.45-8.05 for the lowest vs the highest tertile). CONCLUSIONS: These results suggest a synergistic role of VitD and E2 deficiency in MetS in Chinese postmenopausal women.

Vitamin D, bone metabolism and fracture risk.

Insufficient serum levels of 25OH vitamin D (25OHD) is a risk factor for osteoporosis. A new paradigm has emerged with the locally synthesized 1,25(OH)2D within osteoblasts and osteoclasts as the essential pathway for the effects of 25OHD in regulating bone remodeling via direct or indirect activation of the specific receptor VDR. Vitamin D has positive effects on fracture risk but these results have been consistently observed whenever daily doses were above 800 UI/d administered to compliant patients together with adequate calcium supplementation and with an achieved biological target of serum 25OHD levels above 30 ng/mL.

Tratamiento doble con calcifediol asociado a paricalcitol y biomarcadores de riesgo cardiovascular en hemodiálisis / Double treatment with paricalcitol-associated calcifediol and cardiovascular risk biomarkers in haemodialysis

Introducción: El déficit de 25-hidroxivitamina D (25OHD) asociado a un hiperparatiroidismo secundario son hallazgos frecuentes en pacientes con enfermedad renal crónica (ERC) en hemodiálisis (HD). Estos hechos se asocian con un incremento de la morbimortalidad de origen cardiovascular (CV). Niveles séricos adecuados de 25OHD, así como el uso de activadores selectivos del receptor de vitamina D (AsRVD), han demostrado tener efectos beneficiosos sobre el metabolismo óseo-mineral y el riesgo CV de manera independiente. Actualmente aún existe controversia respecto al tipo de suplementación que precisan los pacientes con ERC en HD. Objetivo: El objetivo de nuestro estudio fue evaluar si existe beneficio alguno en el tratamiento combinado de 25OHD, calcifediol oral y AsRVD, paricalcitol oral sobre el metabolismo óseo-mineral y marcadores inflamatorios, respecto al tratamiento único con cada uno de ellos, en un grupo de pacientes de HD. Material y métodos: Realizamos un estudio prospectivo de 6 meses de duración sobre 26 pacientes de nuestra (..) (AU)

Background: The deficit of 25-hydroxyvitamin D (25OHD) associated with secondary hyperparathyroidism (SHPT) are frequent findings in patients with chronic kidney disease (CKD) on hemodialysis (HD). These events are associated with increased morbidity and mortality of cardiovascular (CV). 25OHD adequate serum levels as well as the use of selective activators of the vitamin D receptor (AsRVD) have been shown to have beneficial effects on bone metabolism and mineral and cardiovascular risk independently. Currently there is still controversy regarding the type of supplementation needed by patients with CKD on HD. Aims: The aim of our study was to evaluate whether there is benefit in combination therapy with 25OHD, calcifediol and a AsRVD, oral paricalcitol on bone-mineral metabolism and inflammatory markers, compared to single treatment with each of them in a group HD patients. Material and methods: A prospective study of 6 months, over 26 patients in our HD unit. We randomized patients into two groups: group 1 (G1) received oral paricalcitol treatment at doses of 1mcg/day. Group 2 (G2) was treated with 1 ampoule calcifediol/wk (0.266mg/wk=16.000U) orally. After 3 months of treatment, was added (..) (AU)

Longitudinal vitamin D status in pregnancy and the risk of pre-eclampsia.

OBJECTIVE: Whether vitamin D deficiency in pregnancy is a cause of pre-eclampsia remains controversial. Most previous studies to date have assessed exposure at only one time-point in pregnancy. We assessed longitudinal vitamin D status during pregnancy and the risk of pre-eclampsia. DESIGN: Prospective cohort study. SETTING: Seventeen urban obstetric hospitals, Canada. POPULATION: Pregnant women who were participants in a trial of vitamin C and E supplementation for the prevention of pre-eclampsia. Canadian participants who consented to participate in a biobank with plasma specimens available at the baseline visit were included (n = 697). METHODS: Maternal plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured at 12-18 and 24-26 weeks of gestation using chemiluminescence immunoassay. MAIN OUTCOME MEASURES: Pre-eclampsia. RESULTS: Of the women, 39% were vitamin D deficient (25(OH)D <50 nmol/l). A strong positive correlation was observed in maternal 25(OH)D concentrations between the two gestational age windows (r = 0.69, P < 0.0001). Mean maternal 25(OH)D concentrations at 24-26 weeks of gestation were significantly lower in women who subsequently developed pre-eclampsia compared with those who did not (mean ± SD: 48.9 ± 16.8 versus 57.0 ± 19.1 nmol/l, P = 0.03). Women with 25(OH)D < 50 nmol/l at 24-26 weeks gestation experienced an increased risk of pre-eclampsia (adjusted odds ratio 3.24, 95% confidence interval 1.37-7.69), whereas the association was not statistically significant for maternal 25(OH)D level at 12-18 weeks of gestation. CONCLUSIONS: Lower maternal 25(OH)D levels at late mid-trimester were associated with an increased risk of pre-eclampsia.

Vitamin D, race, and cardiovascular mortality: findings from a national US sample.

PURPOSE: Findings are conflicting about the relationship between vitamin D levels and cardiovascular mortality. We wanted to determine the contribution of vitamin D levels to black-white disparities in cardiovascular mortality. METHODS: We examined the association of serum 25(OH)D levels with cardiovascular mortality and its contribution to elevated risk among blacks through a retrospective cohort using baseline data from the third National Health and Nutrition Examination Survey 1988-1994 and cause-specific mortality through 2001 using the National Death Index. Using piecewise Poisson regression models, we examined the risk of cardiovascular death (coronary heart disease, heart failure, and stroke) by sample 25(OH)D quartile, adjusting for cardiovascular risk factors, and compared models of adjusted race-related cardiovascular mortality with and without further adjustment for 25(OH)D levels. RESULTS: Participants with 25(OH)D levels in the lowest quartile (mean = 13.9 ng/mL) compared with those in the 3 higher quartiles (mean = 21.6, 28.4, and 41.6 ng/mL) had higher adjusted risk of cardiovascular death (incident rate ratio [IRR] = 1.40; 95% confidence interval [CI], 1.16-1.70). The higher age- and sex-adjusted cardiovascular mortality observed in blacks vs whites (IRR = 1.38; 95% CI, 1.13-1.70) was attenuated (IRR = 1.14; 95% CI, 0.91-1.44) by adjustment for 25(OH)D levels and fully eliminated with further adjustment for income (IRR=1.01; 95% CI, 0.82-1.24). CONCLUSIONS: Low serum levels of 25(OH)D are associated with increased cardiovascular mortality in a nationally representative US sample. Black-white differences in 25(OH)D levels may contribute to excess cardiovascular mortality in blacks. Interventional trials among persons with low vitamin D levels are needed to determine whether oral supplementation improves cardiovascular outcomes.

Vitamin D insufficiency and health outcomes over 5 y in older women.

BACKGROUND: Vitamin D insufficiency was shown to be associated with adverse musculoskeletal and nonskeletal outcomes in numerous observational studies. However, some studies did not control for confounding factors such as age or seasonal variation of 25-hydroxyvitamin D [25(OH)D]. OBJECTIVE: We sought to determine the effect of vitamin D status on health outcomes. DESIGN: Healthy community-dwelling women (n = 1471) with a mean age of 74 y were followed in a 5-y trial of calcium supplementation. 25(OH)D was measured at baseline in all women. Skeletal and nonskeletal outcomes were evaluated according to seasonally adjusted vitamin D status at baseline. RESULTS: Fifty percent of women had a seasonally adjusted 25(OH)D concentration <50 nmol/L. These women were significantly older, heavier, and less physically active and had more comorbidities than women with a seasonally adjusted 25(OH)D concentration > or =50 nmol/L. Women with a seasonally adjusted 25(OH)D concentration <50 nmol/L had an increased incidence of stroke and cardiovascular events that did not persist after adjustment for between-group differences in age or comorbidities. Women with a seasonally adjusted 25(OH)D concentration <50 nmol/L were not at increased risk of adverse consequences for any musculoskeletal outcome, including fracture, falls, bone density, or grip strength or any nonskeletal outcomes, including death, myocardial infarction, cancer, heart failure, diabetes, or adverse changes in blood pressure, weight, body composition, cholesterol, or glucose. CONCLUSIONS: Vitamin D insufficiency is more common in older, frailer women. Community-dwelling older women with a seasonally adjusted 25(OH)D concentration <50 nmol/L were not at risk of adverse outcomes over 5 y after control for comorbidities. Randomized placebo-controlled trials are needed to determine whether vitamin D supplementation in individuals with vitamin D insufficiency influences health outcomes. This trial was registered at www.anzctr.org.au as ACTRN 012605000242628.

Highest prevalence of vitamin D inadequacy in institutionalized women compared with noninstitutionalized women: a case-control study.

The reduced capacity of older skin to synthesize vitamin D(3) under the influence of ultraviolet light makes older persons at risk of vitamin D deficiency. The risk could even be increased in institutionalized persons owing to their lower sunshine exposure. It has been reported that an inadequate vitamin D level is associated with secondary hyperparathyroidism, increased bone turnover, and bone loss, which increase fracture risk. The objective of this study was to assess the prevalence of inadequate serum vitamin D levels in institutionalized, postmenopausal, osteoporotic women. Assessment of 25-hydroxyvitamin D [25(OH)D] was performed in 445 institutionalized, osteoporotic women from nine countries (Australia, Belgium, France, Germany, Hungary, Italy, Poland, Spain and UK). For each institutionalized woman, three age-matched, noninstitutionalized, osteoporotic controls were also included. Four cutoffs of 25(OH)D inadequacy were fixed: less than 80, less than 75, less than 50 and less than 30 nmol/l. Mean age was 79.7 years (standard deviation [SD] = 5.8) for the institutionalized women and 79.5 years (SD = 5.5) for the noninstitutionalized women (p = 0.45). Significantly fewer institutionalized women received vitamin D supplements (13.2 vs 24.0%; p < 0.0001). In women without vitamin D supplements, the level of 25(OH)D was significantly lower in institutionalized women (56.9 [SD = 23.9] nmol/l) compared with noninstitutionalized women (63.2 [SD = 22.0] nmol/l; p < 0.0001). In institutionalized women (without vitamin D supplements), the prevalence of 25(OH)D inadequacy was 10.4, 41.2, 80.3 and 84.2% when considering cutoffs of 80, 75, 50 and 30 nmol/l, respectively. In the control group, the prevalence was 2.7, 22.9, 74.4 and 81.7%, respectively. The prevalence of vitamin D inadequacy was significantly higher in institutionalized women when considering the 75, 50 and 30 nmol/l cutoffs but not when considering the 80 nmol/l cutoff. This study highlights a high prevalence of vitamin D inadequacy in institutionalized, osteoporotic women. Compared with age-matched osteoporotic controls, the prevalence of severe vitamin D inadequacy was substantially more important in institutionalized women. We believe that a greater awareness of the importance of vitamin D inadequacy is needed in order to address this public health problem.

Prospective study of predictors of vitamin D status and cancer incidence and mortality in men.

BACKGROUND: Vitamin D has potent anticancer properties, especially against digestive-system cancers. Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure. Here, we considered multiple determinants of vitamin D exposure (dietary and supplementary vitamin D, skin pigmentation, adiposity, geographic residence, and leisure-time physical activity-to estimate sunlight exposure) in relation to cancer risk in the Health Professionals Follow-Up Study. METHODS: Among 1095 men of this cohort, we quantified the relation of these six determinants to plasma 25-hydroxy-vitamin D [25(OH)D] level by use of a multiple linear regression model. We used results from the model to compute a predicted 25(OH)D level for each of 47,800 men in the cohort based on these characteristics. We then prospectively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models. RESULTS: From 1986 through January 31, 2000, we documented 4286 incident cancers (excluding organ-confined prostate cancer and nonmelanoma skin cancer) and 2025 deaths from cancer. From multivariable models, an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17% reduction in total cancer incidence (multivariable relative risk [RR] = 0.83, 95% confidence interval [CI] = 0.74 to 0.92), a 29% reduction in total cancer mortality (RR = 0.71, 95% CI = 0.60 to 0.83), and a 45% reduction in digestive-system cancer mortality (RR = 0.55, 95% CI = 0.41 to 0.74). The absolute annual rate of total cancer was 758 per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men for the top decile; these respective rates were 326 per 100,000 and 277 per 100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for digestive-system cancer mortality. Results were similar when we controlled further for body mass index or physical activity level. CONCLUSIONS: Low levels of vitamin D may be associated with increased cancer incidence and mortality in men, particularly for digestive-system cancers. The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day.

Long-term nutritional and metabolic consequences of pancreaticoduodenectomy in children.

BACKGROUND: The long-term nutritional and metabolic consequences of pancreaticoduodenectomy in children are unknown. METHODS: Five children were evaluated in a clinical research center 2.5 to 10 years after pancreaticoduodenectomy to assess their nutritional status based on patterns of growth and to assess their gastrointestinal function. Investigation included vitamin levels, a bentiromide study, and serum immunoreactive trypsinogen levels to evaluate pancreatic function and a d-xylose absorption and a radionuclide gastric emptying scan for intestinal absorption and motility. RESULTS: Children were able to grow after pancreaticoduodenectomy. Three remained in low percentile groups for height/weight ratio, and two were near or above normal. Low normal levels of the fat-soluble vitamins were present. Very low levels of pancreatic function were found based on the bentiromide and trypsinogen studies, whereas intestinal absorption of d-xylose was normal except for one patient with extremely rapid gastric emptying. CONCLUSIONS: After pancreaticoduodenectomy children can grow and develop normally if given adequate levels of oral pancreatic supplements to replace the severely decreased level of endogenous pancreatic enzymes after operation. Routine supplementation of the fat-soluble vitamins should be considered.

Severe vitamin D deficiency in Auckland.

AIMS: To study the presentation of severe vitamin D deficiency in Auckland and to determine if appropriate therapy was given. METHODS: Retrospective review of records of patients with very low plasma 25 hydroxyvitamin D concentrations (< or = 12.5 nmol/L or 5 micrograms/L). RESULTS: Fifty cases were identified over a two year period. 28 subjects had recognised risk factors for vitamin D deficiency (such as gastrointestinal disease or greatly reduced food intake). The majority of the other 22 subjects were elderly residents of rest homes or private hospitals. Low body weight and reduced mobility were common features of both groups. Increased plasma alkaline phosphatase activity and hypocalcaemia were the most frequent biochemical findings. Appropriate treatment with high dose calciferol had been given to only 28% of the subjects. CONCLUSIONS: Severe vitamin D deficiency does occur in Auckland despite its low latitude. Low body weight, reduced mobility and lack of sun exposure are particular risk factors. Appropriate therapy is cheap, safe and effective but many patients with severe vitamin D deficiency are being managed suboptimally.

Serum 25-hydroxyvitamin D concentrations in sudden infant death syndrome.

Among the many theories put forth to explain sudden infant death syndrome (SIDS) is a theory of vitamin D deficiency. 25-Hydroxyvitamin D (25-OHD) serum concentrations were measured in 31 SIDS and 24 postmortem control infants. 25-OHD was 19.0 +/- 7.9 mg/ml in SIDS, 16.9 +/- 5.2 ng/ml in acute death control infants, and 11.9 +/- 4.4 ng/ml in in-hospital deaths. For four "near miss" infants the mean serum 25-OHD concentration was 21.1 +/- 4.1 ng/ml. The mean serum 25-OHD concentration of 39 living premature or small-for-gestational-age infants at 3 months of age was 26 +/- 9.9. Serum calcium and serum copper concentrations were also the same in SIDS and control infants. Parathyroid hormone was measured in ten and was detectable in five SIDS infants. These data eliminate a simple vitamin D deficiency or a 25-OHD deficiency as a significant contribution to the pathophysiology of SIDS.

Osteomalacia due to 1alpha,25-dihydroxycholecalciferol deficiency. Association with a giant cell tumor of bone.

Oncogenic osteomalacia is a syndrome in which unexplained osteomalacia remits after resection of a coexisting mesenchymal tumor. We have investigated the mechanism by which a giant cell tumor of bone caused biopsy-proved osteomalacia in a 42-yr-old woman. The biochemical abnormalities were: hypophosphatemia; decreased renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate; negative calcium and phosphorus balance; hyperaminoaciduria; and subnormal calcemic response to exogenously administered parathyroid hormone. Malabsorption, hypophosphatasia, fluorosis, and acidosis were excluded as causes of the osteomalacia. Serum 25-hydroxycholecalciferol was normal (27+/-1 ng/ml). However, the serum concentration of 1alpha,25-dihydroxycholecalciferol was low (1.6+/-0.1 ng/100 ml). Oral administration of physiological amounts of 1alpha,25-dihydroxycholecalciferol resulted in resolution of the biochemical abnormalities of the syndrome and healing of the bone pathology. We suggest that tumor-induced inhibition of 1alpha,25-dihydroxycholecalciferol synthesis caused the osteomalacia. The causal role of the tumor was proved by demonstrating that resection was accompanied by roentgenographic evidence of bone healing and maintenance of normal serum phosphorus; renal tubular maximum for the reabsorption of phosphate; calcium and phosphorus balance; aminoaciduria; and calcemic response to exogenous parathyroid hormone.

Vitamin-D deficiency in the osteomalacia of chronic renal failure.

The plasma level of 25-hydroxy-vitamin D (25-OHD) has been measured and the histological appearances of bone examined in 22 patients with stable chronic renal failure. The results show that osteomalacia occurred only in those patients with relatively low levels of 25-OHD. It is concluded that the osteomalacia of chronic renal failure results from a lack of 25-hydroxy-vitamin D3 superimposed on an existing deficiency of 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3) rather than from lack of 1,25-(OH)2D3 alone.

1,25-Dihydroxycholecalciferol deficiency: the probable cause of hypocalcemia and metabolic bone disease in pseudohypoparathyroidism.

Pseudohypoparathyroidism (PsH) is a genetic disease characterized by hypocalcemia, hyperphosphatemia, and metabolic unresponsiveness to parathyroid hormone (PTH). The administration of PTH elicits neither a significant rise in serum calcium (calcemic response) nor a decrease in the renal tubule reabsorption of phosphorus (phosphaturic response). The diminished phosphaturic response is due to an inability of PTH to generate cyclic AMP in renal tubule cells. We investigated the question of whether hypocalcemia and deficient calcemic response to PTH are due to a similar cyclic AMP defect in bone or to an acquired vitamin D deficiency. Four patients were studied. The active form of vitamin D (1,25-dihydroxycholecalciferol) was measured in 3 and was low. Treatment with vitamin D2 restored the serum calcium and the calcemic response to PTH to normal without changing the impaired renal response. Bone biopsy was performed in 2 patients and showed morphologic evidence of increased osteoclastic activity and osteomalacia. The data indicate that the hypocalcemia and bone disease in PsH are due to active vitamin D deficiency, possibly resulting from the genetic renal lesion.