Vitamin D insufficiency defined by serum 25-hydroxyvitamin D and parathyroid hormone before and after oral vitamin D3 load in Japanese subjects

Vitamin D insufficiency is a risk for both skeletal and nonskeletal health. However, some ambiguity remains about threshold serum 25(OH)D for vitamin D insufficiency. To determine the threshold serum 25(OH)D to maintain normal calcium availability without elevation in serum parathyroid hormone (PTH) among Japanese subjects with various calcium intakes, we conducted a multicenter prospective open-labeled study. We recruited 107 ambulatory subjects without disorders affecting vitamin D metabolism to whom oral vitamin D₃ 800?IU/day for 4?weeks or 1,200?IU/day for 8?weeks was given. Serum 25(OH)D, PTH, calcium, phosphate, and magnesium were measured before and after vitamin D₃ supplementation. Calcium intake was assessed by questionnaires. When all the data were combined, serum 25(OH)D was negatively correlated with PTH. The cubic spline curve between serum 25(OH)D and PTH indicated PTH reached its plateau between 35 and 40?pg/ml at 25(OH)D between 25 and 30?ng/ml. Vitamin D₃ supplementation increased serum 25(OH)D and decreased PTH. Change in PTH correlated positively with baseline serum 25(OH)D. From the regression analyses, baseline serum 25(OH)D above 28?ng/ml corresponded to the threshold level without reduction in PTH after vitamin D₃ supplementation. In multivariate regression analyses, age but not calcium intake was a significant determinant of PTH. We concluded that a serum 25(OH)D level of 28?ng/ml was identified as a threshold for vitamin D insufficiency necessary to stabilize PTH to optimal levels.     

Vitamin D supplementation during pregnancy: Double‐blind,randomized clinical trial of safety and effectiveness

The need, safety, and effectiveness of vitamin D supplementation during pregnancy remain controversial. In this randomized, controlled trial, women with a singleton pregnancy at 12 to 16 weeks' gestation received 400, 2000, or 4000 IU of vitamin D₃ per day until delivery. The primary outcome was maternal/neonatal circulating 25‐hydroxyvitamin D [25(OH)D] concentration at delivery, with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25‐dihydroxyvitamin D₃ [1,25(OH)₂D₃] production. Of the 494 women enrolled, 350 women continued until delivery: Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different (p < 0.0001), and the percent who achieved sufficiency was significantly different by group, greatest in 4000‐IU group (p < 0.0001). The relative risk (RR) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000‐ and the 400‐IU groups (RR = 1.52, 95% CI 1.24–1.86), the 4000‐ and the 400‐IU groups (RR = 1.60, 95% CI 1.32–1.95) but not between the 4000‐ and. 2000‐IU groups (RR = 1.06, 95% CI 0.93–1.19). Circulating 25(OH)D had a direct influence on circulating 1,25(OH)₂D₃ concentrations throughout pregnancy (p < 0.0001), with maximal production of 1,25(OH)₂D₃ in all strata in the 4000‐IU group. There were no differences between groups on any safety measure. Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels. It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race, whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations, especially in African Americans. © 2011 American Society for Bone and Mineral Research     

Vitamin D and its Major Metabolites: Serum Levels after Graded Oral Dosing in Healthy Men

We determined the quantitative relationships between graded oral dosing with vitamin D₃, 25(OH)D₃, and 1,25(OH)₂D₃ for short treatment periods and changes in circulating levels of these substances. The subjects were 116 healthy men (mean age, 28 + 4 years, with usual milk consumption of 40.47 l/day and mean serum 25(OH)D of 67 + 25 nmol/l). They were distributed among nine open-label treatment groups: vitamin D₃ (25, 250 or 1250 mg/day for 8 weeks), 25(OH)D₃ (10, 20 or 50 mg/day for 4 weeks) and 1,25(OH)₂D₃ (0.5, 1.0 or 1.0 mg/day for 2 weeks). All treatment occurred between January 3 and April 3. We measured fasting serum calcium, parathyroid hormone, vitamin D₃, 25(OH)D and 1,25(OH)₂D immediately before and after treatment. In the three groups treated with vitamin D₃, mean values for circulating vitamin D₃ increased by 13, 137 and 883 nmol/l and serum 25(OH)D increased by 29, 146 and 643 nmol/l for the three dosage groups, respectively. Treatment with 25(OH)D₃ increased circulating 25(OH)D by 40, 76 and 206 nmol/l, respectively. Neither compound changed serum 1,25(OH)₂D levels. However, treatment with 1,25(OH)₂D₃ increased circulating 1,25(OH)₂D by 10, 46 and 60 pmol/l, respectively. Slopes calculated from these data allow the following estimates of mean treatment effects for typical dosage units in healthy 70-kg adults: an 8-week course of vitamin D₃ at 10 mg/day (400 IU/day) would raise serum vitamin D by 9 nmol/l and serum 25(OH)D by 11 nmol/l; a 4-week course of 25(OH)D₃ at 20 mg/day would raise serum 25(OH)D by 94 nmol/l; and a 2-week course of 1,25(OH)₂D₃ at 0.5 mg/day would raise serum 1,25(OH)₂D by 17 pmol/l. Received: 4 August 1997 / Accepted: 14 October 1997     

Standard multivitamin supplementation does not improve vitamin D insufficiency after burns

Children suffering severe burns develop progressive vitamin D deficiency because of inability of burned skin to produce normal quantities of vitamin D₃ and lack of vitamin D supplementation on discharge. Our study was designed to determine whether a daily supplement of a standard multivitamin tablet containing vitamin D₂ 400 IU (10 μg) for 6 months would raise serum levels of 25-hydroxyvitamin D [25(OH)D] to normal. We recruited eight burned children, ages 5–18, whose families were deemed reliable by the research staff. These children were given a daily multivitamin tablet in the hospital for 3 months in the presence of a member of the research staff and then given the remainder at home. At 6 months, the subjects returned for measurements of serum levels of 25(OH)D,1,25-dihydroxyvitamin D [1,25(OH)₂D], intact parathyroid hormone (iPTH), Ca, P, albumin, and total protein as well as bone mass by dual energy X-ray absorptiometry. Serum 25(OH)D levels were compared to a group of seven age-matched burned children studied at an earlier date without the vitamin supplement but with the same method of determination of 25(OH)D at 6 months post-burn. In addition, the chewable vitamins were analyzed for vitamin D₂ content by high performance liquid chromatography. Serum concentration of 25(OH)D was 21 ± 11(SD) ng/ml (sufficient range 30–100) with only one of the eight children having a value in the sufficient range. In comparison, the unsupplemented burn patients had mean serum 25(OH)D level of 16 ± 7, P = 0.33 versus supplemented. Serum levels of 1,25(OH)₂D, iPTH, Ca, P, albumin, and total protein were all normal in the supplemented group. Vitamin D₂ content of the chewable tablets after being saponified and extracted was 460 ± 20 IU. Bone mineral content of the total body and lumbar spine, as well as lumbar spine bone density, failed to increase as expected in the supplemented group. No correlations were found between serum 25(OH)D levels and age, length of stay, percent body surface area burn or third-degree burn. Supplementation of burned children with a standard multivitamin tablet stated to contain 400 IU of vitamin D₂ failed to correct the vitamin D insufficiency.     

Rapid correction of low vitamin D status in nursing home residents

Summary  This prospective study finds that ergocalciferol 50,000 IU three times weekly for four weeks effectively and safely corrects vitamin D inadequacy in nursing home residents. Introduction  Low vitamin D status is common among nursing home residents and contributes to bone loss, falls and fractures. The objective of this study was to evaluate the efficacy and safety of short course, high dose, oral vitamin D₂ (ergocalciferol) treatment. Methods  This prospective study included 63 nursing home residents. The 25 with low vitamin D status (serum 25(OH)D ≤ 25 ng/ml) received oral ergocalciferol 50,000 IU three times weekly for four weeks; the others received no change to their routine care. Serum total 25(OH)D, 25(OH)D₂, 25(OH)D₃, calcium, parathyroid hormone (PTH), bone turnover markers and neuro-cognitive assessments were obtained at baseline and four weeks. Results  Mean total 25(OH)D concentration increased (p < 0.0001) from 17.3 to 63.8 ng/ml in the treated group and remained unchanged in the comparison group. Serum 25(OH)D₃ remained stable in the comparison group, but declined (p < 0.0001) with D₂ treatment from 15.4 to 9.1 ng/ml. Serum PTH trended down in the treatment group (p = 0.06). No treatment-induced improvement in ambulation, cognition or behavior was observed. No hypercalcemia or other adverse effects were observed with ergocalciferol treatment. Conclusion  Four weeks of oral vitamin D₂ supplementation effectively and safely normalizes serum 25(OH)D in nursing home residents.     

Vitamin D3 Dose Requirement to Raise 25‐Hydroxyvitamin D to Desirable Levels in Adolescents: Results from a Randomized Controlled Trial

Several organizations issued recommendations on desirable serum 25‐hydroxy vitamin D [25(OH)D] levels and doses of vitamin D needed to achieve them. Trials allowing the formulation of evidence‐based recommendations in adolescents are scarce. We investigated the ability of two doses of vitamin D₃ in achieving recommended vitamin D levels in this age group. Post hoc analyses on data from a 1‐year double‐blind trial that randomized 336 Lebanese adolescents, aged 13 ± 2 years, to placebo, vitamin D₃ at 200 IU/day (low dose), or 2000 IU/day (high dose). Serum 25(OH)D level and proportions of children achieving levels ≥20 ng/mL and 30 ng/mL were determined. At baseline, mean 25(OH)D was 15 ± 7 ng/mL, 16.4 ± 7 ng/mL in boys, and 14 ± 8 ng/mL in girls, p = 0.003, with a level ≥20 ng/mL in 18% and ≥30 ng/mL in 5% of subjects. At 1 year, mean levels were 18.6 ± 6.6 ng/mL in the low‐dose group, 17.1 ± 6 ng/mL in girls, and 20.2 ± 7 ng/mL in boys, p = 0.01, and 36.3 ± 22.3 ng/mL in the high‐dose group, with no sex differences. 25(OH)D increased to ≥20 ng/mL in 34% of children in the low‐dose and 96% in the high‐dose group, being higher in boys in the low‐dose arm only; it remained ≥30 ng/mL in 4% of children in the low‐dose arm but increased to 64% in the high‐dose arm. Baseline 25(OH)D level, body mass index (BMI), and vitamin D dose assigned were the most significant predictors for reaching a 25(OH)D level ≥20 ng/mL and 30 ng/mL. A daily dose of 2000 IU raised 25(OH)D level ≥20 ng/mL in 96% of adolescents (98% boys versus 93% girls). Dose‐response studies are needed to determine in a definitive manner the daily allowance of vitamin D for Middle Eastern adolescents with a similar profile. © 2014 American Society for Bone and Mineral Research.     

Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: A 1‐year double‐blind RCT in postmenopausal women

Few year‐long vitamin D supplementation trials exist that match seasonal changes. The aim of this study was to determine whether daily oral vitamin D₃ at 400 IU or 1000 IU compared with placebo affects annual bone mineral density (BMD) change in postmenopausal women in a 1‐year double‐blind placebo controlled trial in Scotland. White women aged 60 to 70 years (n = 305) were randomized to one of two doses of vitamin D or placebo. All participants started simultaneously in January/February 2009, attending visits at bimonthly intervals with 265 (87%) women attending the final visit and an additional visit 1 month after treatment cessation. BMD (Lunar iDXA) and 1,25‐dihydroxyvitamin D[1,25(OH)₂D], N‐terminal propeptide of type 1 collagen [P1NP], C‐terminal telopeptide of type I collagen [CTX], and fibroblast growth factor‐23 [FGF23] were measured by immunoassay at the start and end of treatment. Circulating PTH, serum Ca, and total 25‐hydroxyvitamin D [25(OH)D] (latter by tandem mass spectrometry) were measured at each visit. Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group (0.05% ± 1.46%) compared with the 400 IU vitamin D or placebo groups (0.57% ± 1.33% and 0.60% ± 1.67%, respectively) (p < 0.05). Mean (± SD) baseline 25(OH)D was 33.8 ± 14.6 nmol/L; comparative 25(OH)D change for the placebo, 400 IU, and 1000 IU vitamin D groups was ?4.1 ± 11.5 nmol/L, +31.6 ± 19.8 nmol/L, and +42.6 ± 18.9 nmol/L, respectively. Treatment did not change markers of bone metabolism, except for a small reduction in PTH and an increase in serum calcium (latter with 1000 IU dose only). The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome, nor how much vitamin D is being stored. © 2013 American Society for Bone and Mineral Research.     

Vitamin D levels in post-menopausal Korean women with a distal radius fracture

IntroductionThe purpose of this study was to investigate serum levels of vitamin D in post-menopausal Korean women with a distal radius fracture (DRF) and to determine if there is any association between vitamin D levels and bone-related variables such as bone mineral densities (BMDs), serum parathyroid hormone (PTH) levels and several bone turnover markers.Materials and methodsThe data of 104 postmenopausal women surgically treated for a distal radius fracture (DRF group) and 107 age-matched control patients without a fracture (control group) were compared. Serum vitamin D levels (25-hydroxycholecalciferol, 25(OH)D₃) were compared between the groups with consideration of age and seasonal variations. BMDs, serum PTH and several bone turnover markers, including serum osteocalcin, C-telopeptide and urine N-telopeptide, were measured and analysed to find any association with vitamin D levels.ResultsThe mean 25(OH)D₃ level was significantly lower in the DRF group compared to the control group (p < 0.001). In particular, patients in their sixth and seventh deciles in the DRF group had significantly lower 25(OH)D₃ levels than patients in the control group (p = 0.001 and 0.013, respectively). When seasonal variation was considered, significant differences of 25(OH)D₃ levels were found between the groups in autumn and winter. Hip BMDs were significantly lower in the DRF group than in the control group, and there was a positive correlation between serum 25(OH)D₃ levels and hip BMDs. Bone turnover markers were not significantly different between the two groups, although serum PTH levels were marginally higher in the DRF group (p = 0.08).ConclusionsPost-menopausal Korean women with a DRF were found to have significantly lower serum vitamin D levels than the control group, and vitamin D levels were particularly lower in women in their sixth and seventh deciles who may be a good target group for prevention of future fractures. Future investigation should focus on determining whether vitamin D supplementation can be helpful in preventing future fractures in patients with a DRF.     

Relative effectiveness of vitamin D metabolites in increasing bone mineral solubility

Summary Weanling rats were given a vitamin D-deficient diet containing 1.4% calcium and 1.0% phosphorus. After 4 weeks these deficient animals were injected for 7 days with selected doses of one of the following vitamin D metabolites: 25(OH)D₃, 1,25(OH)₂D₃, 24,25(OH)₂D₃, 25,26(OH)₂D₃ or the ethanol vehicle. A vitamin D-replete group was placed on the same diet but injected with 50 IU of vitamin D₃ once a week for the entire 5-week period. By the use of a modified Ussing chamber [1], the measurements of calcium fluxes into and from the rat calvaria were possible. These data enabled the apparent mineral solubilities to be derived. After 5 weeks on this diet the vitamin D-deficient rats had low levels of serum calcium (1.41 mM) and decreased mineral solubility when compared to the vitamin D-replete group. The apparent solubility of the bone mineral increased toward the vitamin D-replete level in calvaria from vitamin D metabolite-treated rats. However, these changes did not directly reflect the alterations in the level of serum calcium. At any given dose level, 1,25(OH)₂D₃ was the most effective metabolite in increasing serum calcium. In fact, the high dose (250 pmoles/day) was hypercalcemic. Next in effectiveness was 25(OH)D₃. These two metabolites were equally effective in increasing mineral solubility. At a 10 times higher dose, the 24,25(OH)₂D₃ metabolite was able to normalize serum calcium and improve but not normalize mineral solubility. At the high dose (260 pmoles/day), the 25,26(OH)₂D₃ metabolite caused no effect on mineral solubility and minimal increases in serum calcium.     

Vitamin D for skeletal and non-skeletal health: What we should know

Vitamin D plays an essential role in regulating calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. Humans obtain vitamin D from sunlight exposure, dietary foods and supplements. There are two forms of vitamin D: vitamin D₃ and vitamin D₂. Vitamin D₃ is synthesized endogenously in the skin and found naturally in oily fish and cod liver oil. Vitamin D₂ is synthesized from ergosterol and found in yeast and mushrooms. Once vitamin D enters the circulation it is converted by 25-hydroxylase in the liver to 25-hydroxyvitamin D [25(OH)D], which is further converted by the 25-hydroxyvitamin D-1α-hydroxylase in the kidneys to the active form, 1,25-dihydroxyvitamin D [1,25(OH)₂D]. 1,25(OH)₂D binds to its nuclear vitamin D receptor to exert its physiologic functions. These functions include: promotion of intestinal calcium and phosphate absorption, renal tubular calcium reabsorption, and calcium mobilization from bone. The Endocrine Society's Clinical Practice Guideline defines vitamin D deficiency, insufficiency, and sufficiency as serum concentrations of 25(OH)D of <20 ng/mL, 21–29 ng/mL, and 30–100 ng/mL, respectively. Vitamin D deficiency is a major global public health problem in all age groups. It is estimated that 1 billion people worldwide have vitamin D deficiency or insufficiency. This pandemic of vitamin D deficiency and insufficiency is attributed to a modern lifestyle and environmental factors that restrict sunlight exposure, which is essential for endogenous synthesis of vitamin D in the skin. Vitamin D deficiency is the most common cause of rickets and osteomalacia, and can exacerbate osteoporosis. It is also associated with chronic musculoskeletal pain, muscle weakness, and an increased risk of falling. In addition, several observational studies observed the association between robust levels of serum 25(OH)D in the range of 40–60 ng/mL with decreased mortality and risk of development of several types of chronic diseases. Therefore, vitamin D-deficient patients should be treated with vitamin D₂ or vitamin D₃ supplementation to achieve an optimal level of serum 25(OH)D. Screening of vitamin D deficiency by measuring serum 25(OH)D is recommended in individuals at risk such as patients with diseases affecting vitamin D metabolism and absorption, osteoporosis, and older adults with a history of falls or nontraumatic fracture. It is important to know if a laboratory assay measures total 25(OH)D or only 25(OH)D₃. Using assays that measure only 25(OH)D₃ could underestimate total levels of 25(OH)D and may mislead physicians who treat patients with vitamin D₂ supplementation.     

Correction of preoperative vitamin D deficiency after Roux-en-Y gastric bypass surgery

BackgroundTo evaluate the adequacy of supplementation to correct preoperative vitamin D deficiency in adult patients during the year after Roux-en-Y gastric bypass (RYGB) surgery.MethodsThe medical records were reviewed and the preoperative and 12-month postoperative serum 25-hydroxyvitamin D [25(OH)D] levels were compared in patients who underwent RYGB from 2002 to 2004. The serum 25(OH)D levels were defined as being optimal (≥80 nmol/L), suboptimal (50–79 nmol/L), or deficient (<50 nmol/L). Patients with deficient 25(OH)D levels were prescribed 50,000 IU ergocalciferol weekly. The remaining patients averaged 710 IU supplemental vitamin D intake daily.ResultsThe mean patient age was 43.8 ± 10.7 years, and the mean preoperative body mass index was 51.8 ± 9.8 kg/m². Of the 95 patients with baseline and 12-month 25(OH)D levels, 89% were women. The mean preoperative 25(OH)D level was 49.7 ± 26.5 nmol/L; 34% had suboptimal 25(OH)D levels and 54% had deficient levels before surgery. Twelve months after surgery, those receiving 50,000 IU weekly (n = 40) had a mean 25(OH)D level of 69.2 ± 22.2 nmol/L; 63% had suboptimal and 8% deficient levels. Those taking 710 IU daily (n = 55) had a mean 25(OH)D level of 85.5 ± 33.0 nmol/L; 44% had suboptimal and 6% deficient levels.ConclusionVitamin D deficiency is prevalent in RYGB patients before surgery. The vitamin D status improved markedly after RYGB surgery with either 710 IU vitamin D daily or 50,000 IU weekly. Current supplementation practices do not appear to optimize the serum 25(OH)D levels and need to be more closely examined.     

Successful treatment of postsurgical hypoparathyroidism by intramuscular injection of vitamin D3 in a patient associated with malabsorption syndrome due to multiple abdominal surgeries

A 56-year-old patient with postsurgical hypothyroidism and hypoparathyroidism associated with gastrointestinal malabsorption syndrome was prescribed with l-thyroxine and 1α(OH)D₃ at a massive daily dosage of 600 and 39 μg, respectively. Although the patient became nearly euthyroid, she had been hypocalcemic, requiring frequent intravenous injection of calcium gluconate to prevent tetany. Because the serum level of 1,25(OH)₂D hardly increased after an oral intake of 21 μg 1α(OH)D₃, vitamin D₃ was administered intramuscularly. After stoss therapy (600,000 IU), the patient has been receiving 300,000 IU vitamin D₃ at intervals of 2–4 months so that she remained slightly hypocalcemic (7–8 mg/dl). At 1.5 years later, serum levels of 25(OH)D and 1,25(OH)₂D were maintained at about 60 ng/ml and 30–50 pg/ml, respectively, and renal function was maintained well. These data suggest that intramuscular injection of 300,000 IU vitamin D₃ at an interval of a few months to maintain a slightly increased serum level of 25(OH)D and a slightly decreased serum level of calcium is a safe and cost-effective treatment in such a parathyroid hormone-deficient hypoparathyroid patient with malabsorption syndrome.     

Meal conditions affect the absorption of supplemental vitamin D3 but not the plasma 25‐hydroxyvitamin D response to supplementation

It is sometimes assumed that dietary fat is required for vitamin D absorption, although the impact of different amounts of dietary fat on vitamin D absorption is not established. This study was conducted to determine whether the presence of a meal and the fat content of the meal influences vitamin D absorption or the 25‐hydroxyvitamin D [25(OH)D] response to supplemental vitamin D₃. Based on earlier studies in rats we postulated that absorption would be greatest in the low‐fat meal group. Sixty‐two healthy older men and women were randomly assigned to one of three meal groups: no meal, high‐fat meal, or low‐fat meal; each was given a monthly 50,000 IU vitamin D₃ supplement with the test breakfast meal (or after a fast for the no‐meal group) and followed for 90 days. Plasma vitamin D₃ was measured by liquid chromatography–mass spectroscopy (LC/MS) before and 12 hours after the first dose; plasma 25(OH)D was measured by radioimmunoassay at baseline and after 30 and 90 days. The mean 12‐hour increments in vitamin D₃, after adjusting for age and sex, were 200.9 nmol/L in the no‐meal group, 207.4 nmol/L in the high‐fat meal group, and 241.1 nmol/L in the low‐fat meal group (p = 0.038), with the increase in the low‐fat group being significantly greater than the increases in the other two groups. However, increments in 25(OH)D levels at 30 and 90 days did not differ significantly in the three groups. We conclude that absorption was increased when a 50,000 IU dose of vitamin D was taken with a low‐fat meal, compared with a high‐fat meal and no meal, but that the greater absorption did not result in higher plasma 25(OH)D levels in the low‐fat meal group.     

Effect of alendronate and vitamin D3 on fractional calcium absorption in a double‐blind,randomized, placebo‐controlled trial in postmenopausal osteoporotic women

Menopause and increasing age are associated with a decrease in calcium absorption that can contribute to the pathogenesis of osteoporosis. We hypothesized that alendronate plus vitamin D₃ (ALN + D) would increase fractional calcium absorption (FCA). In this randomized, double‐blind, placebo‐controlled multicenter clinical trial, 56 postmenopausal women with 25‐hydroxyvitamin D [25(OH)D] concentrations of 25 ng/mL or less and low bone mineral density (BMD) received 5 weekly doses of placebo or alendronate 70 mg plus vitamin D₃ 2800 IU (ALN + D). Calcium intake was stabilized to approximately 1200 mg/d prior to randomization. FCA was determined using a dual‐tracer stable‐calcium isotope method. FCA and 25(OH)D were similar between treatment groups at baseline (0.31 ± 0.12 ng/mL and 19.8 ± 4.7 ng/mL, respectively). After 1 month of treatment, subjects randomized to ALN + D experienced a significant least squares (LS) mean [95% confidence interval (CI)] increase in FCA [0.070 (0.042, 0.098)], whereas FCA did not change significantly in the placebo group [?0.016 (?0.044, 0.012)]. After ALN + D treatment, patients had higher 25(OH)D levels (LS mean difference 7.3 ng/mL, p < .001). The rise in serum 1,25‐dihydroxyvitamin D₃ (p < .02) and parathyroid hormone (p < .001) were greater in the ALN + D group than in placebo‐treated patients. ALN + D was associated with an increase in FCA of 0.07. To our knowledge, there is no other trial showing such a marked rise in calcium absorption owing to treatment with a bisphosphonate or owing to a small rise in 25(OH)D. This unique response of ALN + D is important for the treatment of osteoporosis, but the exact mechanism requires further study. © 2011 American Society for Bone and Mineral Research     

Vitamin D Supplementation Efficacy: Sleeve Gastrectomy Versus Gastric Bypass Surgery

Background

Vitamin D deficiency is common with bariatric surgery, and few prospective studies comparing different surgical procedures have evaluated appropriate vitamin D supplementation levels. Therefore, vitamin D₃ and calcium supplementation were evaluated following gastric bypass and sleeve gastrectomy.

Methods

Women consumed 2,000 international units (IU) of vitamin D₃ and 1,500 mg calcium citrate daily for 3 months following gastric bypass (n?=?11) and sleeve gastrectomy (n?=?12). Height, weight, body mass index (BMI), serum 25-hydroxyvitamin D [25(OH)D], and serum PTH concentrations were measured preoperatively and at 3 months. Wilcoxon signed rank analyses compared body weight parameters, serum 25(OH)D and PTH concentrations, and dietary intakes of vitamin D and calcium preoperatively and at 3 months. Vitamin D deficiency was defined as a serum 25(OH)D concentration <20 ng/mL (50 nmol/L).

Results

Vitamin D deficiency decreased from 60.6 % preoperatively to 26.1 % after 3 months (P?P?Conclusions Reduced food intake increased the risk of vitamin D deficiency following bariatric surgery. However, daily supplementation with 2,000 IU of vitamin D₃ and 1,500 mg calcium citrate significantly increased 25(OH)D concentrations and reduced the percent of women who were vitamin D deficient. Although serum 25(OH)D concentrations did not reach levels associated with detrimental health effects, several women remained vitamin D deficient and more aggressive supplementation may be indicated.     

Low utility of serum 25–hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3 in predicting peripheral Treg and Th17 cell counts in ESRD and renal transplant patients

BackgroundVitamin D has shown an immune-modulatory effect in different studies. Vitamin D stimulates Tregs and inhibits Th17 cells. The immune-modulatory role of vitamin D in chronic kidney disease (CKD) and renal transplant patients is unclear. We measured whether different serum levels of vitamin D were associated with an increased or decreased presence of lymphocyte subsets including Treg and Th17 cells in end-stage renal disease (ESRD) and renal transplant recipients.MethodsEighty-seven renal transplant recipients and 53 end-stage renal disease (ESRD) patients were enrolled in this study. The absolute counts of CD4 + and CD8 + T, CD16 + CD56 + NK, CD19 + B, CD4 + CD25 + CD127- Foxp3 + (Tregs), Helios + Tregs, CD38 + Tregs, and CD4 + CD17 + (Th17) cells were analyzed in peripheral blood in both patient groups. In addition, serum 25 (OH) D₃, 1, 25 (OH)₂ D₃, IL-6, IL-17, IL-23, and TGF-β₁ were measured. The association between lymphocyte subset counts and 1, 25 (OH)₂ D₃ or 25 (OH) D₃ was studied, as was the association between serum IL-6, IL-17, IL-23, or TGF-β₁ and 1,25 (OH)₂ D₃ or 25 (OH) D₃.ResultsSerum 25 (OH) D₃ and 1,25 (OH)₂ D₃ levels were not independently associated with peripheral CD4 + T, CD19 + B, CD16 + CD56 + NK, Treg, or Th17 cell counts. In contrast to serum 25 (OH) D₃, serum1, 25 (OH)₂ D₃ was positively associated with CD8 + T cells counts in renal transplant recipients.ConclusionOur findings indicate low utility of serum 25 (OH) D₃ and 1, 25 (OH)₂ D₃ levels in predicting a change in lymphocyte subset counts in ESRD and renal transplant patients.     

Clustering patients on the basis of their individual course of low back pain over a six month period

Background

There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients. The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels.

Methods

In this randomized controlled study, patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario, Canada. Participants were randomized to one of three loading dose groups: placebo; 50,000 IU vitamin D₂; or 100,000 IU D₂. Following a placebo/loading dose, all patients received a daily tablet of 1,000 IU vitamin D₃ for 90 days. Serum 25-hydroxy vitamin D (25-OHD) was measured at baseline, discharge from acute care (approximately 4-weeks), and 3-months.

Results

Sixty-five patients were enrolled in the study (44% male). An immediate rise in 25-OHD occurred in the 100,000 group, however there were no significant differences in 25-OHD between the placebo, 50,000 and 100,000 loading dose groups after 4-weeks (69.3, 84.5, 75.6 nmol/L, p = 0.15) and 3-months (86.7, 84.2, 73.3 nmol/L, p = 0.09), respectively. At the end of the study, approximately 75% of the placebo and 50,000 groups had reached the target therapeutic range (75 nmol/L), and 44% of the 100,000 group.

Conclusions

In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture, our findings suggest that starting with a lower daily dose of Vitamin D₃ achieved similar results as providing an additional large loading dose of Vitamin D₂. At the end of the study, all three groups were equally effective in attaining improvement in 25-OHD levels. Given that a daily dose of 1,000 IU vitamin D₃ (with or without a loading dose) resulted in at least 25% of patients having suboptimal vitamin D status, patients with acute hip fracture may benefit from a higher daily dose of vitamin D.

Trial registration

Clinical Trials # NCT00424619     

Comparison of the effects of vitamin D metabolites on collagen synthesis and resportion of fetal rat bone in organ culture

Summary We compared the effects of four vitamin D metabolites, 1α,25 dihydroxy vitamin D₃ (1α,25(OH)₂D₃), 1α hydroxy vitamin D₃ (1αOH D₃), 25 hydroxy vitamin D₃ (25 OH D₃), and 24R,25 dihydroxy vitamin D (24R,25(OH)₂D₃) on resorption and collagen synthesis in fetal rat bone maintained in organ culture. Resorption was quantitated by measuring the release of previously incorporated⁴⁵Ca from long bone shafts of 19-day fetal rats, and collagen synthesis was assessed by measuring the incorporation of³H-proline into collagenase digestible protein (CDP) in calvaria from 21-day fetal rats. All four compounds stimulated bone resorption and inhibited collagen synthesis, but 1α,25(OH)₂D₃ was approximately 1000 times more potent in both organ culture systems. Although the differences were small among the other three compounds, the order of potency was 1αOH D₃>25 OH D₃≧24R,25(OH)₂D₃. These results suggest that the receptor for 1α25(OH)₂D₃ in both bone resorbing and bone forming cells has similar affinities for several vitamin D metabolites.     

Evaluation and correction of low vitamin D status

Low vitamin D status, which is endemic due to inadequate oral intake combined with sun avoidance, contributes to musculoskeletal and other pathologies. Although controversial, it is increasingly recommended that serum 25-hydroxyvitamin D (25[OH]D) concentrations less than 30 ng/mL be considered suboptimal. Clinicians should appreciate that 25(OH)D measurements, like all quantitative laboratory tests, are subject to assay and biologic variability. Additionally, international standardized calibrators do not exist for 25(OH)D measurement. As such, a single 25(OH)D value of “30 ng/mL” may have substantial variability surrounding it, thereby making 25(OH)D levels of approximately 35 to 40 ng/mL a reasonable therapeutic goal to assure vitamin D adequacy. Achieving such levels often requires vitamin D supplementation. Vitamin D₃ (cholecalciferol) or D₂ (ergocalciferol) may be used; whether vitamin D₃ is more potent than vitamin D₂ in maintaining 25(OH)D is controversial.