Vitamin D deficiency in northern Vietnam: Prevalence,risk factors and associations with bone mineral density

PurposeVitamin D deficiency has been linked to osteoporosis and also to the risk of cancer, autoimmune disorders and cardiovascular diseases. This study sought to determine the prevalence of, and risk factors for, vitamin D deficiency and its relationship with bone mineral density (BMD) in a Vietnamese population.MethodsThis cross-sectional study involved 269 women and 222 men aged 13–83 years, who were randomly selected from urban and rural areas in northern Vietnam. Serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and parathyroid hormone (PTH) were measured by electrochemiluminescence immunoassay. Vitamin D deficiency was defined as serum 25(OH)D levels below 20 ng/mL. BMD was measured by dual X-ray absorptiometry.ResultsThe prevalence of vitamin D deficiency in women was 30%, almost two-fold higher than in men (16%). Significant predictors of vitamin D deficiency in women were urban residency (p < 0.01) and age less than 30 years (p < 0.01), whereas use of contraceptive pills was protective (p < 0.01). In men, winter season was the only significant predictor of vitamin D deficiency (p < 0.01). In multiple linear regression analysis, serum levels of 25(OH)D were positively associated with BMD in both women (p < 0.001) and men (p < 0.001).ConclusionsThese data suggest that the prevalence of vitamin D deficiency is high in the Vietnamese population, and that part of this prevalence could be explained by low exposure to sunlight (urban residency and winter season). The high prevalence of vitamin D deficiency should raise the awareness of potentially important health issues such as osteoporosis within the Vietnamese society.     

Vitamin D deficiency in northern Vietnam: Prevalence,risk factors and associations with bone mineral density

PurposeVitamin D deficiency has been linked to osteoporosis and also to the risk of cancer, autoimmune disorders and cardiovascular diseases. This study sought to determine the prevalence of, and risk factors for, vitamin D deficiency and its relationship with bone mineral density (BMD) in a Vietnamese population.MethodsThis cross-sectional study involved 269 women and 222 men aged 13–83 years, who were randomly selected from urban and rural areas in northern Vietnam. Serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and parathyroid hormone (PTH) were measured by electrochemiluminescence immunoassay. Vitamin D deficiency was defined as serum 25(OH)D levels below 20 ng/mL. BMD was measured by dual X-ray absorptiometry.ResultsThe prevalence of vitamin D deficiency in women was 30%, almost two-fold higher than in men (16%). Significant predictors of vitamin D deficiency in women were urban residency (p < 0.01) and age less than 30 years (p < 0.01), whereas use of contraceptive pills was protective (p < 0.01). In men, winter season was the only significant predictor of vitamin D deficiency (p < 0.01). In multiple linear regression analysis, serum levels of 25(OH)D were positively associated with BMD in both women (p < 0.001) and men (p < 0.001).ConclusionsThese data suggest that the prevalence of vitamin D deficiency is high in the Vietnamese population, and that part of this prevalence could be explained by low exposure to sunlight (urban residency and winter season). The high prevalence of vitamin D deficiency should raise the awareness of potentially important health issues such as osteoporosis within the Vietnamese society.     

Strong relationship between vitamin D status and bone mineral density in anorexia nervosa

BackgroundAnorexia nervosa (AN) is associated with impaired bone health and low bone mineral density (BMD) as a consequence of an inadequate peak bone mass in adolescence and bone loss in young adulthood. The vitamin D status with its implications for bone health in patients affected by AN has only been examined previously in small studies.ObjectiveTo evaluate the prevalence of vitamin D deficiency and test the hypothesis that patients with AN and vitamin D deficiency might have worse bone metabolism and lower bone density as compared with AN with adequate vitamin D repletion.DesignWe analysed the vitamin D status and bone metabolism in a large cohort (n = 89) of untreated patients affected by AN, with amenorrhoea.ResultsVitamin D deficiency is widespread in untreated patients with AN: 16.9% had 25OH vitamin D levels below 12 ng/ml, 36% below 20 ng/ml and 58.4% below 30 ng/ml. PTH values were higher and BMD at both femoral sites were lower in patients with vitamin D < 20 ng/ml. Progressively higher values of BMD were observed by 4 ranks of 25 OH vitamin D values (severe deficiency: < 12 ng/ml, deficiency: ≥ 12 ng/ml and < 20 ng/ml, insufficiency: ≥ 20 and < 30 ng/ml and normal: ≥ 30 ng/ml). In patients with severe vitamin D deficiency BMD at the hip were significantly lower than that measured in groups with values over 20 ng/ml (p < 0.001 for trend). The level of significance did not change for values adjusted for BMI or body weight.ConclusionWe found a strong relationship between vitamin D status and hip BMD values with additional benefits for those with 25OHD levels above 20 ng/ml. Our results support the design of a randomized placebo-controlled clinical trial on the effect of vitamin D on BMD in patients with AN. The second point, whether 25OHD should be above 20 or 30 ng/ml remains a discussion point.     

Relationship between vitamin D deficiency and bone fragility in sickle cell disease: A cohort study of 56 adults

BackgroundRecent studies suggest that patients with sickle cell disease (SCD) have profound vitamin D (VD) deficiency. Limited data exist on the effect of VD deficiency on bone fragility in these patients.ObjectivesTo assess the prevalence of VD deficiency in adults with SCD and its consequences on bone metabolism and fragility.MethodsThis prospective study included 56 SCD adult patients (mean age 29.8 ± 9.5 years), in a clinically steady state. Clinical and laboratory data were recorded. Bone mineral density (BMD) was measured using dual X-ray absorptiometry. Fracture history, BMD, avascular osteonecrosis, H-shaped vertebra and markers of mineral metabolism were compared between two groups of patients presenting very low (≤ 6 ng/mL, n = 26) (group 1) and low (> 6 ng/mL, n = 26) (group 2) 25(OH)D concentration, respectively.ResultsMedian 25(OH)D concentration was 6 ng/mL. VD deficiency (25(OH)D < 10 ng/mL) was found in 42 out of 56 patients (75%) and secondary hyperparathyroidism in 40 (71.4%). History of fracture was documented in 17 patients (30.3%), osteopenia and/or osteoporosis in 39.6% of patients. Overall, patients of group 1 were more likely to have sustained a fracture (42.8%) compared to patients of group 2 (17.8%) (p = 0.04). These patients had also lower body mass index and significantly higher parathyroid hormone, C-terminal telopeptides of type I-collagen and bone-specific alkaline phosphatase serum levels. There was no difference between group for BMD, avascular osteonecrosis history, H-shaped vertebra, and disease severity markers.ConclusionThis study suggests that VD deficiency is a key feature in SCD-bone disease. It is highly prevalent and associated with hyperparathyroidism, bone resorption markers, and history of fracture. The optimal supplementation regimen remains to be determined.     

25-hydroxy vitamin D levels in healthy premenopausal women: Association with bone turnover markers and bone mineral density

BackgroundVitamin D deficiency is very common in elderly people while there are very few reports on its incidence, determinants and metabolic consequences in young subjects.ResultsIn 608 young healthy premenopausal women participating in the BONTURNO study, levels of 25-hydroxyvitamin D [25(OH)D] below 20 ng/ml were found in almost a third of the women. Its levels were inversely (P < 0.001) related with age and body mass index (BMI kg/m²) and directly with sunlight exposure during the summer time, and latitude: i.e. the higher the latitude over Italy, the higher the 25(OH)D level. In women on contraceptive pill the mean 25(OH)D level was significantly increased even when the data were adjusted for age, BMI and sun exposure.25(OH)D levels, adjusted for age and BMI, were significantly and positively related with serum C-telopeptide of type 1 collagen, serum phosphate and spine bone mineral density (BMD) and negatively with serum PTH, serum magnesium, serum bone alkaline phosphatase (bone AP).ConclusionVitamin D deficiency is rather common in young otherwise healthy Italian women and particularly among those living in the Southern part of the country. The most close determinants of vitamin D deficiency were BMI and sunlight exposure. Vitamin D insufficiency is associated with low spine BMD and increased bone AP even in young individuals.     

The associations of 25-hydroxyvitamin D levels,vitamin D binding protein gene polymorphisms,and race with risk of incident fracture-related hospitalization: Twenty-year follow-up in a bi-ethnic cohort (the ARIC Study)

BackgroundDeficient levels of 25-hydroxyvitamin D [25(OH)D] have been associated with increased fracture risk. Racial differences in fracture risk may be related to differences in bioavailable vitamin D due to single nucleotide polymorphism (SNP) variations in the vitamin D binding protein (DBP).MethodsWe measured 25(OH)D levels in 12,781 middle-aged White and Black participants [mean age 57 years (SD 5.7), 25% Black] in the ARIC Study who attended the second examination from 1990–1992. Participants were genotyped for two DBP SNPs (rs4588 and rs7041). Incident hospitalized fractures were measured by abstracting hospital records for ICD-9 codes. We used Cox proportional hazards models to evaluate the association between 25(OH)D levels and risk of fracture with adjustment for possible confounders. Interactions were tested by race and DBP genotype.ResultsThere were 1122 incident fracture-related hospitalizations including 267 hip fractures over a median of 19.6 years of follow-up. Participants with deficient 25(OH)D (< 20 ng/mL) had a higher risk of any fracture hospitalization [HR = 1.21 (95% CI 1.05–1.39)] and hospitalization for hip fracture [HR = 1.35 (1.02–1.79)]. No significant racial interaction was noted (p-interaction = 0.20 for any fracture; 0.74 for hip fracture). There was no independent association of rs4588 and rs7041 with fracture. However, there was a marginal interaction for 25(OH)D deficiency with rs7041 among Whites (p-interaction = 0.065). Whites with both 25(OH)D deficiency and the GG genotype [i.e. with predicted higher levels of DBP and lower bioavailable vitamin D] were at the greatest risk for any fracture [HR = 1.48 (1.10–2.00)] compared to Whites with the TT genotype and replete 25(OH)D (reference group).ConclusionsDeficient 25(OH)D levels are associated with higher incidence of hospitalized fractures. Marginal effects were seen in Whites for the DBP genotype associated with lower bioavailable vitamin D, but result inconclusive. Further investigation is needed to more directly evaluate the association between bioavailable vitamin D and fracture risk.     

Transient effectiveness of vitamin D2 therapy in pediatric cystic fibrosis patients

BackgroundThe effectiveness of current treatment recommendations for vitamin D insufficiency in children with CF is unknown. Therefore, we assessed the effectiveness of vitamin D₂ 50,000 IU once daily for 28 days for vitamin D insufficiency.MethodsRetrospective chart review of pediatric CF patients from 2006–2008. Vitamin D₂ 50,000 IU daily for 28 days was given to patients with 25-OHD < 30 ng/mL and repeat 25-OHD levels were obtained after completion of therapy.ResultsOne hundred forty-seven levels from 97 individuals were assessed. Success of treatment was 54% (n = 80/147). Seventeen of 39 patients (43%) followed for an additional 6–18 months were able to maintain levels of ≥ 30 ng/mL.ConclusionsVitamin D₂ 50,000 IU daily for 28 days was effective in correcting vitamin D insufficiency in approximately 50% of subjects. However, almost half of successfully treated patients were unable to maintain normal 25-OHD levels > 6 months after completion of therapy, implying that this effect is transient.     

Vitamin D inadequacy in French osteoporotic and osteopenic women

ObjectiveStudies have shown that low serum vitamin D levels are associated with secondary hyperparathyroidism, which decreases bone strength and increases fracture risk, most notably after 50 years of age. The objective of this study was to evaluate the vitamin D status of postmenopausal women in France.MethodsWe conducted a cross-sectional observational study of 1292 menopausal women with osteoporosis or osteopenia. The age range was 52–94 years. Serum 25-OH-vitamin D was assayed in each patient. Based on data in the literature, we used four 25-OH-D cutoffs to define vitamin D deficiency: 30, 50, 75, and 80 nmol/L (<12, <20, <30, and <32 ng/ml).ResultsMean serum 25-OH-D was 51.5 ± 26.1 nmol/L (about 20.6 ± 10.4 ng/ml). In the 343 (26.5%) patients taking supplemental vitamin D with or without supplemental calcium, the mean serum 25-OH-D level was significantly higher than in the other patients (65.0 ± 26.0 ng/ml vs. 46.6 ± 18.6 ng/ml; P < 0.001). In the subgroup not taking vitamin D supplements, the prevalence of vitamin D deficiency was 27.3%, 54.1%, 89.9%, and 93.2% with the 30, 50, 75, and 80 nmol/L cutoffs, respectively. The mean 25-OH-D level varied across seasons (P < 0.001), with the highest value being obtained in summer (53.4 ± 18.7 nmol/L; about 21.3 ± 7.5 ng/ml).ConclusionVitamin D deficiency is common among postmenopausal women with osteoporosis or osteopenia in France.     

Vitamin D status and common risk factors for bone fragility as determinants of quantitative ultrasound variables in a nationally representative population sample

Calcaneal quantitative ultrasound (QUS) can predict bone strength and fracture risk. Bone fragility has no single cause but results from a complex interplay of several etiologic or contributing factors. Vitamin D is essential for bone health even though it is still unclear how much of this vitamin is required to maintain bone strength and prevent fractures. Measurements of serum 25-hydroxyvitamin D [S-25(OH)D] have indicated a high prevalence of inadequate vitamin D status in a number of studies mostly based on selected study populations. The objective of this study was to examine the associations between S-25(OH)D, common risk factors for bone fragility, and QUS variables in a large unselected population sample.The study population consisted of 2736 men and 3299 women from a nationally representative population sample, aged 30 years or over. Information on lifestyle was elicited by means of interviews and questionnaires. Body fat mass was estimated using an impedance-meter. S-25(OH)D was measured by radioimmunoassay. Calcaneal QUS was performed on the Hologic Sahara apparatus recording broadband ultrasound attenuation (BUA) and speed of sound (SOS). The potential determinants of BUA and SOS were analysed using separate multiple linear regression models for men and women.S-25(OH)D proved to be an independent determinant of BUA (P < 0.0001 for men, P < 0.001 for women) and SOS (P < 0.0001 for men, P < 0.05 for women). BUA was also independently associated with age, height, weight, alcohol consumption, and postmenopausal status in women, and with weight, alcohol consumption, smoking and physical activity in men. All of the above variables, except for weight in women, were also found to be independent determinants of SOS in both men and women. A reverse association was found between S-25(OH)D and adiposity in spite of higher intakes of vitamin D in those with higher fat mass.In this unselected sample of men and women, vitamin D status, several lifestyle factors and physical characteristics proved to be significant determinants of BUA and SOS. Inadequate vitamin D status was common, and measures ensuring adequate intakes of vitamin D in the population thus deserve continued attention. Obesity should be taken into account in future assessments of vitamin D status in Finland as in other countries.     

Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of osteosclerotic bone metastasis

IntroductionBreast cancer metastases to bone are common in advanced stage disease. We have recently demonstrated that vitamin D deficiency enhances breast cancer growth in an osteolytic mouse model of breast cancer metastasis. In this study, we examined the effects of vitamin D deficiency on tumor growth in an osteosclerotic model of intra-skeletal breast cancer in mice.MethodsThe effects of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] on proliferation and apoptosis of MCF-7 breast cancer cells, and changes in the expression of genes within the vitamin D metabolic pathway (VDR, 1α- and 24-hydroxylase) were examined in vitro. MCF-7 breast cancer cells were injected intra-tibially into vitamin D deficient and vitamin D sufficient mice co-treated with and without osteoprotegerin (OPG). The development of tumor-related lesions was monitored via serial X-ray analysis. Tumor burden and indices of proliferation and apoptosis were determined by histology along with markers of bone turnover and serum intact PTH levels.ResultsIn vitro, MCF-7 cells expressed critical genes for vitamin D signalling and metabolism. Treatment with 1,25(OH)₂D₃ inhibited cell growth and proliferation, and increased apoptosis. In vivo, osteosclerotic lesions developed faster and were larger at endpoint in the tibiae of vitamin D deficient mice compared to vitamin D sufficient mice (1.49 ± 0.08 mm² versus 1.68 ± 0.15 mm², P < 0.05). Tumor area was increased by 55.8% in vitamin D deficient mice (0.81 ± 0.13 mm² versus 0.52 ± 0.11 mm² in vitamin D sufficient mice). OPG treatment inhibited bone turnover and caused an increase in PTH levels, while tumor burden was reduced by 90.4% in vitamin D sufficient mice and by 92.6% in vitamin D deficient mice. Tumor mitotic activity was increased in the tibiae of vitamin D deficient mice and apoptosis was decreased, consistent with faster growth.ConclusionVitamin D deficiency enhances both the growth of tumors and the tumor-induced osteosclerotic changes in the tibiae of mice following intratibial implantation of MCF-7 cells. Enhancement of tumor growth appears dependent on increased bone resorption rather than increased bone formation induced by these tumors.     

Vitamin D levels in 577 consecutive elective foot & ankle surgery patients

BackgroundVitamin D deficiency is a global concern impacting upon large communities and certain disease populations. It can adversely affect the outcome of orthopaedic operations. We aimed to perform an audit of the Vitamin D status of patients in two centres in the United Kingdom undergoing elective foot and ankle surgery.MethodsSerum 25-hydroxyvitamin-D (vitamin D) levels were obtained prospectively in 577 consecutive elective patients undergoing elective foot and ankle surgery between October 2014 and March 2017 (29 months). Variables including age, gender, ethnicity, location, season, month and procedure type were recorded.Results577 patients were included over the study period. 62.0% were female. Mean age was 53.2 (median 54.5, range 16.7–86.6). 300 patients were treated in Northampton and 277 in Leicester. The serum 25-hydroxyvitamin-D levels for the patient group were normally distributed. The mean was 52.3 nmol/L (SD 28.0; range 7.5–175) and the median 47.5 nmol/L. 21.7% were grossly deficient, 31.9% deficient, 28.9% insufficient and 17.5% within normal range. Age, gender and procedure type did not statistically affect vitamin D levels (p = 0.5, t-test). Ethnicity, location and Winter season did affect Vitamin D levels (p < 0.05). August was the most significant month with levels significantly higher than January, February, March, April, June, November and December (p < 0.05, one-way ANOVA).ConclusionsOnly 1 in 5.7 patients had a normal Vitamin D level and 1 in 4.6 were grossly deficient. Ethnicity and patient location significantly affected Vitamin D results. Summer months were noted to demonstrate significantly the highest levels and August the highest. We did not find that age or gender affected Vitamin D levels in our cohort.     

Clinical Effect of Preoperative 25-OH-Vitamin D3 Level in Liver Transplant Recipients

BackgroundVitamin D deficiency is common in patients with chronic liver disease and is associated with increased risk of infection and mortality. This study evaluated the effects of preoperative vitamin D levels on clinical outcomes after liver transplant.MethodsThis single-center retrospective study included liver transplant recipients from June to November 2017 who had preoperative 25-OH-vitamin D3 (25-OH-D3) data. Severe vitamin D deficiency, insufficiency, and normal levels were defined as serum 25-OH-D3 concentrations of < 10 ng/mL, 10 to 20 ng/mL, and ≥ 20 ng/mL, respectively. The primary outcome was length of hospital stay; secondary outcomes included the duration of normalization of inflammatory markers after liver transplant, new infection rates, rejection rates, length of intensive care unit stay, and mortality according to preoperative 25-OH-D3 levels.ResultsAmong 219 liver transplant recipients, 67.6% were vitamin D-deficient. The mean (standard deviation) 25-OH-D3 concentration was 17.8 (13.2) ng/mL, and 65 (29.7%) patients had levels < 10 ng/mL. Patients with lower mean 25-OH-D3 levels had significantly longer intensive care unit (13.8 [21.9] days vs 5.9 [12.3] days vs 2.7 [4.6] days, P < .001) and hospital (59.0 [66.0] days vs 42.0 [67.4] days vs 27.2 [17.1] days, P = .001) stays. The incidence of new infections was higher in the vitamin D deficiency group. (46.2% vs 28.9% vs 14.1%, P < .001). A higher Nutritional Risk Screening 2002 score (adjusted odds ratio, 1.77; 95% confidence interval [CI], 1.24-2.56; P = .002) and severe vitamin D deficiency (adjusted odds ratio, 3.43; 95% CI, 1.57-7.57; P = .002) were significant risk factors for poor outcome among patients who had been in the hospital for more than 43 days.ConclusionsVitamin D deficiency before liver transplant was associated with increased intensive care unit and hospital lengths of stay. Although several factors may influence the clinical outcomes of patients with liver transplant, low vitamin D3 was an independent risk factor.     

Impact of demographic,environmental, and lifestyle factors on vitamin D sufficiency in 9084 Japanese adults

BackgroundLittle is known about correlates of vitamin D status in Asian populations. In this study, we established the prevalence of vitamin D sufficiency in the Murakami region (latitude N38°13′) in Niigata, Japan, and examined demographic, environmental, and lifestyle factors that might be associated with vitamin D sufficiency, with the aim of clarifying the relative contributions of previously described determinants of vitamin D status as well as identifying new determinants in this Japanese population.MethodsThis study involved a cross-sectional analysis of baseline data obtained from a cohort study conducted in 2011–2013. Participants were 9084 individuals aged between 40 and 74 years who provided blood samples for the determination of plasma 25-hydroxyvitamin D [25(OH)D] concentrations. Lifestyle information was obtained from 8498 participants, with some missing values regarding different lifestyle factors. Multiple logistic regression analysis was used to obtain odds ratios for vitamin D sufficiency, which was defined as a plasma 25(OH)D concentration ≥ 75 nmol/L.ResultsThe prevalence of vitamin D sufficiency (i.e., plasma 25(OH)D concentration ≥ 75 nmol/L) was 9.1%, and significant associations were observed with male gender (P < 0.0001; OR = 2.37, 95% CI: 1.84–3.05), older age (P for trend < 0.0001), lower BMI (P for trend < 0.0001), higher METs score (P for trend = 0.0138), higher vitamin D intake (P for trend = 0.0467), summer season (P for trend < 0.0001), longer duration outdoors (P for trend = 0.0026), no sunscreen use (P = 0.0135; OR = 1.40, 95% CI: 1.07–1.82), higher salmon consumption (P for trend < 0.0001), higher alcohol consumption (P for trend < 0.0001), and lower coffee consumption (P for trend = 0.0025). Unlike other populations previously reported, vitamin D sufficiency was associated with older age.ConclusionsThe prevalence of vitamin D sufficiency (i.e., 25[OH]D ≥ 75 nmol/L) was low (9.1%) in this Japanese population. A number of demographic, environmental, and lifestyle factors are associated with vitamin D sufficiency, and thus lifestyle modification may present an opportunity to achieve vitamin D sufficiency.     

There is still a care gap in osteoporosis management for patients with rheumatoid arthritis

ObjectivesTo assess compliance rates with the current Canadian osteoporosis guidelines and whether the Fracture Risk Assessment Tool score in patients with rheumatoid arthritis correlated with the likelihood of receiving osteoporosis treatment and having a bone mineral density test.MethodsCharts of serial outpatients with rheumatoid arthritis were reviewed to collect bone mineral density test data and patients’ use of calcium, vitamin D, and osteoporosis treatment. Odds ratios (OR) were calculated to determine if a higher Fracture Risk Assessment Tool score increased the likelihood of osteoporosis treatment or having a bone mineral density test.ResultsUsing the Fracture Risk Assessment Tool, the 10-year risk of major osteoporotic fracture was high in 92 (12.5%), moderate in 216 (29.3%), and low in 429 (58.2%) patients. Compared to those at low risk, patients identified as high risk were more likely to receive osteoporosis treatment (OR 16.31, 95% CI 9.45–28.13, P < 0.001); calcium (OR 3.89, 95% CI 2.43–6.25, P < 0.001); vitamin D (OR 3.46, 95% CI 2.12–5.64, P < 0.001); and to have had a bone mineral density test (OR 10.22, 95% CI 5.50–18.96, P < 0.001). Among 124 patients currently taking prednisone, half (46.8%) were prescribed a bisphosphonate.ConclusionsAlthough compliance with current osteoporosis guidelines remains low among all patients with rheumatoid arthritis, higher risk patients were more likely to have a bone mineral density test and receive treatment for osteoporosis, as indicated by the clear dose response seen along the 10-year fracture risk from low to high-risk groups.     

Pharmacokinetics of oral vitamin D3 and calcifediol

AimLong-term pharmacokinetics after supplementation with vitamin D₃ or calcifediol (the 25-hydroxyvitamin D₃ metabolite) is not well studied. Additionally, it is unclear whether bolus doses of vitamin D₃ or calcifediol lead to 25(OH)D₃ plasma concentrations considered desirable for fracture prevention (30 ng/mL). We therefore investigated plasma pharmacokinetics of 25(OH)D₃ during different vitamin D₃ and calcifediol supplementation regimens.MethodsIn this seven-arm, randomized, double-blind, controlled parallel-group study, 35 healthy females aged 50–70 years (5 per group) received 20 μg calcifediol or vitaminD₃ daily, 140 μg calcifediol or vitaminD₃ weekly, for 15 weeks, or a single bolus of either 140 μg calcifediol, or vitaminD₃, or both. 25(OH)D₃ plasma concentrations were quantified using LC–MS/MS in 14 clinical visits among all participants.ResultsFor daily (weekly) dosing, the area under the concentration–time curve (AUC_0–24h), which is the measure for exposure, was 28% (67%) higher after the first dose of calcifediol than after the first dose of vitamin D₃. After 15 weeks, this difference was 123% (178%). All women in the daily and weekly calcifediol groups achieved 25(OH)D₃ concentrations > 30 ng/mL (mean, 16.8 days), but only 70% in the vitamin D₃ daily or weekly groups reached this concentration (mean, 68.4 days). A single dose of 140 μg calcifediol led to 117% higher 25(OH)D₃ AUC_0–96h values than 140 μg vitamin D₃, while the simultaneous intake of both did not further increase exposure.ConclusionsCalcifediol given daily, weekly, or as a single bolus is about 2–3 times more potent in increasing plasma 25(OH)D₃ concentrations than vitamin D₃. Plasma 25(OH)D₃ concentrations of 30 ng/mL were reached more rapidly and reliably with calcifediol.     

Hip fracture type: Important role of parathyroid hormone (PTH) response to hypovitaminosis D

ObjectiveTo investigate whether clinical and laboratory characteristics, including serum 25-hydroxyvitamin D (25(OH) D), PTH and parameters of mineral and bone metabolism, differ by hip fracture (HF) type.Patients and methodsWe studied prospectively 761 consecutively admitted older patients (mean age 82.3 + 8.8(SD) years; 74.9% women) with low trauma non-pathological HF. A detailed clinical examination was performed, haematologic, renal, liver and thyroid function tests, serum 25(OH)D, PTH, calcium, phosphate, magnesium, C-reactive protein (CRP) and cardiac troponin I (cTnI) measured. In a subset of 294 patients' markers of bone formation (serum osteocalcin, OC; bone specific alkaline phosphatase, BAP) and bone resorption (urinary deoxypyridinoline, DPD/Cr; N-terminal cross-linked telopeptide of type 1 collagen, NTx/Cr; both corrected to urinary creatinine, Cr) were also measured.ResultsIn the trochanteric compared to the cervical group, females were older than males and the prevalence of Parkinson's disease, mean haemoglobin and albumin levels were lower. Incidence and degree of myocardial injury (cTnl rise) and inflammatory reaction (CRP elevation) as well as length of hospital stay, need of institutionalisation or in-hospital mortality were similar in both groups. Hypovitaminosis D (25(OH)D < 50 mmol/L) was present in 77.8% of patients with cervical and in 82.1% with trochanteric HF, elevated PTH (> 6.8 pmol/L) in 30.2% and 41.3%, respectively. The associations between 25(OH)D, PTH, and parameters of mineral metabolism and bone turnover were site-specific. In multivariate analyses, PTH (both as a continuous or categorical variable) response to hypovitaminosis D was a strong independent predictor of HF type. Coexistence of vitamin D deficiency (25(OH) D< 25 nmol/L) and elevated PTH predicts trochanteric HF while blunted PTH response predicts cervical HF (OR = 3.5; 95% CI 1.5–80; p = 0.005). PTH response and phosphate status (above or below median level) correctly discriminated HF type in 73.8% of patients with vitamin D deficiency.ConclusionsHF type is significantly associated with PTH response to hypovitaminosis D and impaired phosphate homeostasis. We detected only minor differences between two main HF types with regard to a wide range of clinical and routine laboratory variables as well as short-term outcomes.     

Screening for celiac disease in patients with osteoporosis

ObjectiveWhether patients with osteoporosis should be screened for celiac disease is controversial. The objective of this study was to measure the prevalence of asymptomatic celiac disease in a cohort of patients with osteoporosis.MethodsWe studied 140 patients (133 postmenopausal women and 7 men) aged 40–75 years (mean age, 62.9 ± 9.4 years) with primary osteoporosis diagnosed by absorptiometry (spine or hip T-score <?2.5 SD). We routinely measured serum and urinary calcium, serum phosphate, alkaline phosphatase, 25-OH-vitamin D3, and IgG and IgA antigliadin antibodies. Patients with positive antigliadin antibody tests were tested for antitransglutaminase antibodies.ResultsA history of fractures were noted in 52 (37%) patients, with 57 peripheral and 54 vertebral fractures overall. Vitamin D deficiency was found in 60 (43%) patients. IgG antigliadin antibodies were positive in 11 (8%) patients, IgA antigliadin antibodies in 11 (8%) patients, and both antibodies in 4 (3%) patients. Antitransglutaminase antibodies were negative in all patients. No significant differences in laboratory test or absorptiometry results were found between patients with versus without IgA antigliadin antibodies. The T-score at the spine was nonsignificantly lower in patients with than without IgG antigliadin antibodies (?3.17 ± 0.49 and ?2.82 ± 0.77, P = 0.076).ConclusionWe found no excess risk of celiac disease in our cohort of patients with osteoporosis. Despite the small sample size, our results cast doubt on the need for celiac-disease screening in osteoporotic patients who have no gastrointestinal symptoms.     

Vitamin D metabolites and bone mineral density: The multi-ethnic study of atherosclerosis

Previous studies demonstrate associations of low 25-hydroxyvitamin D (25(OH)D) concentrations with low bone mineral density (BMD) and fractures, motivating widespread use of vitamin D supplements for bone health. However, previous studies have been limited to predominantly White populations despite differences in the distribution and metabolism of 25(OH)D by race/ethnicity. We determined associations of serum 25(OH)D, 24,25-dihydroxyvitamin D (24,25(OH₂)D₃), and parathyroid hormone (PTH) with BMD among 1773 adult participants in the Multi-Ethnic Study of Atherosclerosis (MESA) in a staggered cross-sectional study design. Vitamin D metabolites were measured using liquid chromatography-mass spectroscopy and PTH using a 2-site immunoassay from serum collected in 2000–2002. Volumetric trabecular lumbar BMD was measured from computed tomography scans performed in 2002–2005 expressed as g/cm³. We used linear regression and graphical methods to compare associations of vitamin D metabolite and PTH concentrations with BMD as the outcomes measure among White (n = 714), Black (n = 353), Chinese (n = 249), and Hispanic (n = 457) participants. Serum 25(OH)D and 24,25(OH₂)D₃ concentrations were highest among Whites and lowest among Blacks. BMD was greatest among Black participants. Higher serum 25(OH)D was only associated with higher BMD among Whites and Chinese participants (P-for-interaction = 0.054). Comparing the lowest category of 25(OH)D (< 20 ng/ml) to the highest (≥ 30 ng/ml), the adjusted mean difference in BMD was –8.1 g/cm³ (95% CI − 14.8, − 1.4) for Whites; − 10.2 g/cm³ (− 20.4, 0.0) for Chinese vs. 8.8 g/cm³ (− 2.8, 20.5) for Black and − 1.1 g/cm³ (− 8.3, 6.2) for Hispanic. Similar results were observed for serum 24,25(OH₂)D_3. Serum PTH was not associated with BMD. In a multi-ethnic population, associations of 25(OH)D with BMD were strongest among White and Chinese participants and null among Black and Hispanic participants. Further studies are needed to determine optimal biomarkers for bone health for multiple ethnic groups.     

Regulation of PTH secretion by 25-hydroxyvitamin D and ionized calcium depends on vitamin D status: A study in a large cohort of healthy subjects

IntroductionPrevious papers investigating vitamin D status have often outlined the significant relationships between serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD), but the influence of ionized calcium levels has not been concomitantly considered.DesignCross-sectional.Materials and methodsIn 1050 healthy men (547) and women (503), serum ionized calcium (iCa), creatinine (Cr), albumin, 25OHD, and PTH were measured. After conventional analysis, a regression tree was fitted on the data set.Results25OHD and PTH values showed significant opposite seasonal changes. 25OHD levels negatively correlated with PTH, which in turn negatively correlated with iCa. A regression tree was fitted to the whole data set using PTH as the response variable and 25OHD and iCa as covariates. PTH concentration depended on that of iCa only in subjects with 25OHD levels > 16.35 ng/mL, while for 25OHD <16.35 ng/mL it depended on 25OHD values.ConclusionsOur results indicated that PTH levels were highly conditioned by those of 25OHD in subjects with 25OHD values lower than 16.35 ng/mL and by those of iCa only for higher 25OHD concentration.