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Search for: limit 10 to yr="2004 -Current" [Limit not valid in DARE; records were retained]
Results: 40

Database: EBM Reviews - Cochrane Database of Systematic Reviews <2005 to March 2014>, EBM Reviews - ACP Journal Club
<1991 to April 2014>, EBM Reviews - Database of Abstracts of Reviews of Effects <1st Quarter 2014>, EBM Reviews -
Cochrane Central Register of Controlled Trials <April 2014>, EBM Reviews - Cochrane Methodology Register <3rd Quarter
2012>, EBM Reviews - Health Technology Assessment <2nd Quarter 2014>, EBM Reviews - NHS Economic Evaluation Database
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1    vitamin D.mp. [mp=ti, ot, ab, tx, kw, ct, sh, hw] (3253)
2    Deficiency.mp. [mp=ti, ot, ab, tx, kw, ct, sh, hw] (7826)
3    treatment.mp. [mp=ti, ot, ab, tx, kw, ct, sh, hw] (348946)
4    response.mp. [mp=ti, ot, ab, tx, kw, ct, sh, hw] (110848)
5    outcome$.mp. [mp=ti, ot, ab, tx, kw, ct, sh, hw] (202127)
6    cholecalciferol.mp. [mp=ti, ot, ab, tx, kw, ct, sh, hw] (640)
7    1 or 6 (3399)
8    4 or 5 (276759)
9    2 and 3 and 7 and 8 (264)
10    limit 9 to humans [Limit not valid in CDSR,ACP Journal Club,DARE,CCTR,CLCMR; records were retained] (264)
11    limit 10 to yr="2004 -Current" [Limit not valid in DARE; records were retained] (238)

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7.
Vitamin D supplementation for prevention of mortality in adults.
Bjelakovic, Goran.  Gluud, Lotte Lise.  Nikolova, Dimitrinka.  Whitfield, Kate.  Wetterslev, Jorn.  Simonetti, Rosa G.
Bjelakovic, Marija.  Gluud, Christian.
EBM Reviews - Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews. 1, 2014.
[Systematic Review]
AN: 00075320-100000000-06086
Background
Available evidence on the effects of vitamin D on mortality has been inconclusive. In a recent systematic review, we
found evidence that vitamin D(subscript 3) may decrease mortality in mostly elderly women. The present systematic review
updates and reassesses the benefits and harms of vitamin D supplementation used in primary and secondary prophylaxis of
mortality.
Objectives
To assess the beneficial and harmful effects of vitamin D supplementation for prevention of mortality in healthy adults
and adults in a stable phase of disease.
Search methods
We searched The Cochrane LibraryMEDLINE, EMBASE, LILACS, the Science Citation Index-Expanded and Conference Proceedings
Citation Index-Science (all up to February 2012). We checked references of included trials and pharmaceutical companies
for unidentified relevant trials.
Selection criteria
Randomised trials that compared any type of vitamin D in any dose with any duration and route of administration versus
placebo or no intervention in adult participants. Participants could have been recruited from the general population or
from patients diagnosed with a disease in a stable phase. Vitamin D could have been administered as supplemental vitamin
D (vitamin D(subscript 3) (cholecalciferol) or vitamin D(subscript 2) (ergocalciferol)) or as an active form of vitamin
D (1[alpha]-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)).
Data collection and analysis
Six review authors extracted data independently. Random-effects and fixed-effect meta-analyses were conducted. For
dichotomous outcomes, we calculated the risk ratios (RRs). To account for trials with zero events, we performed
meta-analyses of dichotomous data using risk differences (RDs) and empirical continuity corrections. We used published
data and data obtained by contacting trial authors.
Main results
We identified 159 randomised clinical trials. Ninety-four trials reported no mortality, and nine trials reported
mortality but did not report in which intervention group the mortality occurred. Accordingly, 56 randomised trials with
95,286 participants provided usable data on mortality. The age of participants ranged from 18 to 107 years. Most trials
included women older than 70 years. The mean proportion of women was 77%. Forty-eight of the trials randomly assigned
94,491 healthy participants. Of these, four trials included healthy volunteers, nine trials included postmenopausal
women and 35 trials included older people living on their own or in institutional care. The remaining eight trials
randomly assigned 795 participants with neurological, cardiovascular, respiratory or rheumatoid diseases. Vitamin D was
administered for a weighted mean of 4.4 years. More than half of the trials had a low risk of bias. All trials were
conducted in high-income countries. Forty-five trials (80%) reported the baseline vitamin D status of participants based
on serum 25-hydroxyvitamin D levels. Participants in 19 trials had vitamin D adequacy (at or above 20 ng/mL).
Participants in the remaining 26 trials had vitamin D insufficiency (less than 20 ng/mL).
Vitamin D decreased mortality in all 56 trials analysed together (5,920/47,472 (12.5%) vs 6,077/47,814 (12.7%); RR 0.97
(95% confidence interval (CI) 0.94 to 0.99); P = 0.02; I(superscript 2) = 0%). More than 8% of participants dropped out.
'Worst-best case' and 'best-worst case' scenario analyses demonstrated that vitamin D could be associated with a
dramatic increase or decrease in mortality. When different forms of vitamin D were assessed in separate analyses, only
vitamin D(subscript 3) decreased mortality (4,153/37,817 (11.0%) vs 4,340/38,110 (11.4%); RR 0.94 (95% CI 0.91 to 0.98);
P = 0.002; I(superscript 2) = 0%; 75,927 participants; 38 trials). Vitamin D(subscript 2)alfacalcidol and calcitriol did
not significantly affect mortality. A subgroup analysis of trials at high risk of bias suggested that vitamin
D(subscript 2) may even increase mortality, but this finding could be due to random errors. Trial sequential analysis
supported our finding regarding vitamin D(subscript 3)with the cumulative Z-score breaking the trial sequential
monitoring boundary for benefit, corresponding to 150 people treated over five years to prevent one additional death. We
did not observe any statistically significant differences in the effect of vitamin D on mortality in subgroup analyses
of trials at low risk of bias compared with trials at high risk of bias; of trials using placebo compared with trials
using no intervention in the control group; of trials with no risk of industry bias compared with trials with risk of
industry bias; of trials assessing primary prevention compared with trials assessing secondary prevention; of trials
including participants with vitamin D level below 20 ng/mL at entry compared with trials including participants with
vitamin D levels equal to or greater than 20 ng/mL at entry; of trials including ambulatory participants compared with
trials including institutionalised participants; of trials using concomitant calcium supplementation compared with
trials without calcium; of trials using a dose below 800 IU per day compared with trials using doses above 800 IU per
day; and of trials including only women compared with trials including both sexes or only men. Vitamin D(subscript 3)
statistically significantly decreased cancer mortality (RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I(superscript 2) = 0%;
44,492 participants; 4 trials). Vitamin D(subscript 3) combined with calcium increased the risk of nephrolithiasis (RR
1.17 (95% CI 1.02 to 1.34); P = 0.02; I(superscript 2) = 0%; 42,876 participants; 4 trials). Alfacalcidol and calcitriol
increased the risk of hypercalcaemia (RR 3.18 (95% CI 1.17 to 8.68); P = 0.02; I(superscript 2) = 17%; 710 participants;
3 trials).
Authors' conclusions
Vitamin D(subscript 3) seemed to decrease mortality in elderly people living independently or in institutional care.
Vitamin D(subscript 2)alfacalcidol and calcitriol had no statistically significant beneficial effects on mortality.
Vitamin D(subscript 3) combined with calcium increased nephrolithiasis. Both alfacalcidol and calcitriol increased
hypercalcaemia. Because of risks of attrition bias originating from substantial dropout of participants and of outcome
reporting bias due to a number of trials not reporting on mortality, as well as a number of other weaknesses in our
evidence, further placebo-controlled randomised trials seem warranted.
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13.
Vitamin D supplementation in infancy for improving bone density.
Winzenberg, Tania M.  Shaw, Kelly A.  van der Mei, AF Ingrid.  Jones, Graeme.
EBM Reviews - Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews. 7, 2013.
[Protocol]
AN: 00075320-100000000-09035
This is the protocol for a review and there is no abstract. The objectives are as follows:
To determine the effectiveness of vitamin D supplementation of infants for improving bone mineral density in infancy,
childhood or adulthood.
To determine if any effect of vitamin D supplementation varies by baseline vitamin D status, sex, or the type or dose of
vitamin D given.
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24.
Vitamin D supplementation for cystic fibrosis.
Ferguson, Janet H.  Chang, Anne B.
EBM Reviews - Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews. 4, 2012.
[Systematic Review]
AN: 00075320-100000000-05950
Background
Cystic fibrosis (CF) is a genetic disorder with multiorgan effects. In a subgroup with pancreatic insufficiency
malabsorption of the fat soluble vitamins (A, D, E, K) may occur. Vitamin D is involved in calcium homeostasis and bone
mineralisation and may have extraskeletal effects. This review examines the evidence for vitamin D supplementation in
CF.
Objectives
To assess the effects of vitamin D supplementation on the frequency of vitamin D deficiency, respiratory outcomes and
vitamin D toxicity in the CF population.
Search methods
We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from
comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference
proceedings.
Selection criteria
Randomised and quasi-randomised controlled trials of vitamin D supplementation compared to placebo in the CF population
regardless of exocrine pancreatic function.
Data collection and analysis
Both authors independently assessed the 'risk of bias' of each included trial and extracted outcome data (from published
trial information) for assessment of bone mineralization, growth and nutritional status, frequency of vitamin D
deficiency, respiratory status, quality of life and adverse events.
Main results
Three studies are included, although only data from two were available (41 adults and children with CF). One of these
studies compared supplemental 800 international units (IU) vitamin D and placebo for 12 months in 30 osteopenic
pancreatic insufficient adults; both groups continued 900 IU vitamin D daily. The other (abstract only) compared
supplemental 1g calcium alone, 1600 IU vitamin D alone, 1600 IU vitamin D and 1g calcium and placebo in a double-blind
randomised cross-over trial; only 11 children (vitamin D and placebo groups) after six-months supplementation are
included; inclusion criteria, pancreatic sufficiency or disease status of participants are not defined. There were no
significant differences in primary or secondary outcomes in either study. The studies are not directly comparable due to
differences in supplementation, outcome reporting and possibly participant characteristics (eg severity of lung disease,
growth and nutrition, pancreatic sufficiency). There were no adverse events in either study. The third study (abstract
only) compared daily calcitriol (0.25 or 0.5 micrograms) with placebo in pancreatic insufficient children and young
adults, only pre-intervention data were available.
Authors' conclusions
There is no evidence of benefit or harm in the limited number of small-sized published trials. Adherence to relevant CF
guidelines on vitamin D should be considered until further evidence is available.
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28.
Vitamin D for the treatment of chronic painful conditions in adults.
Straube, Sebastian.  Derry, Sheena.  Moore, Andrew R.  McQuay, Henry J.
EBM Reviews - Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews. 8, 2012.
[Systematic Review]
AN: 00075320-100000000-06376
Background
Vitamin D is produced in the skin after sun-light exposure and can also be obtained through food. Vitamin D deficiency
has recently been linked with a range of diseases including chronic pain. Observational and circumstantial evidence
suggests that there may be a role for vitamin D deficiency in the aetiology of chronic pain conditions.
Objectives
To assess the efficacy and adverse events of vitamin D supplementation in chronic painful conditions.
Search methods
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to September 2009. This
was supplemented by searching the reference lists of retrieved articles, textbooks and reviews.
Selection criteria
Studies were included if they were randomised double blind trials of vitamin D supplementation compared with placebo or
with active comparators for the treatment of chronic pain conditions in adults.
Data collection and analysis
Two review authors independently selected the studies for inclusion, assessed methodological quality, and extracted
data. Pooled analysis was not undertaken due to paucity and heterogeneity of data.
Main results
Four studies, with a total of 294 participants, were included. The studies were heterogeneous with regard to study
quality, the chronic painful conditions that were investigated, and the outcome measures reported. Only one study
reported a beneficial effect, the others found no benefit of vitamin D over placebo in treating chronic pain.
Authors' conclusions
The evidence base for the use of vitamin D for chronic pain in adults is poor at present. This is due to low quality and
insufficient randomised controlled trials in this area of research.
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43.
Vitamin D supplementation for improving bone mineral density in children.
Winzenberg, Tania M.  Powell, Sandi.  Shaw, Kelly A.  Jones, Graeme.
EBM Reviews - Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews. 10, 2010.
[Systematic Review]
AN: 00075320-100000000-05680
Background
Results of randomised controlled trials (RCTs) of vitamin D supplementation to improve bone density in children are
inconsistent.
Objectives
To determine the effectiveness of vitamin D supplementation for improving bone mineral density in children, whether any
effect varies by sex, age or pubertal stage, the type or dose of vitamin D given or baseline vitamin D status, and if
effects persist after cessation of supplementation.
Search strategy
We searched the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2009), MEDLINE (1966 to present),
EMBASE (1980 to present), CINAHL (1982 to present), AMED (1985 to present) and ISI Web of Science (1945 to present) on 9
August 2009, and we handsearched key journal conference abstracts.
Selection criteria
Placebo-controlled RCTs of vitamin D supplementation for at least three months in healthy children and adolescents (aged
from one month to < 20 years) with bone density outcomes.
Data collection and analysis
Two authors screened references for inclusion, assessed risk of bias, and extracted data. We conducted meta-analyses and
calculated standardised mean differences (SMD) of the percent change from baseline in outcomes in treatment and control
groups. We performed subgroup analyses by sex, pubertal stage, dose of vitamin D and baseline serum vitamin D and
considered these as well as compliance and allocation concealment as possible sources of heterogeneity.
Main results
We included six RCTs (343 participants receiving placebo and 541 receiving vitamin D) for meta-analyses. Vitamin D
supplementation had no statistically significant effects on total body bone mineral content (BMC), hip bone mineral
density (BMD) or forearm BMD. There was a trend to a small effect on lumbar spine BMD (SMD 0.15, 95% CI -0.01 to 0.31, P
= 0.07). There were no differences in effects between high and low serum vitamin D studies at any site though there was
a trend towards a larger effect with low vitamin D for total body BMC (P = 0.09 for difference). In low serum vitamin D
studies, significant effects on total body BMC and lumbar spine BMD were approximately equivalent to a 2.6% and 1.7 %
percentage point greater change from baseline in the supplemented group.
Authors' conclusions
These results do not support vitamin D supplementation to improve bone density in healthy children with normal vitamin D
levels, but suggest that supplementation of deficient children may be clinically useful. Further RCTs in deficient
children are needed to confirm this.
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46.
Vitamin D supplementation for preventing infections in children less than five years of age.
Yakoob, Yawar Mohammad.  Bhutta, Zulfiqar A.
EBM Reviews - Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews. 11, 2010.
[Protocol]
AN: 00075320-100000000-07267
This is the protocol for a review and there is no abstract. The objectives are as follows:
To evaluate the role of vitamin D supplementation for the prevention of infectious illnesses (pneumonia, TB, malaria,
and diarrhoea) in children under five years of age.
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52.
Vitamin D compounds for people with chronic kidney disease not requiring dialysis.
Palmer, Suetonia C.  McGregor, David O.  Craig, Jonathan C.  Elder, Grahame.  Macaskill, Petra.  Strippoli, FM Giovanni.

EBM Reviews - Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews. 4, 2009.
[Systematic Review]
AN: 00075320-100000000-06669
Background
Vitamin D compounds are used to suppress elevated serum parathyroid hormone (PTH) in people with chronic kidney disease
(CKD).
Objectives
To assess the efficacy of vitamin D therapy on biochemical, bone, cardiovascular, and mortality outcomes in people with
CKD and not requiring dialysis.
Search strategy
We searched The Cochrane Renal Group's specialised register, Cochrane's Central Register of Controlled Trials (CENTRAL),
MEDLINE, EMBASE, and reference lists of retrieved articles.
Selection criteria
Randomised controlled trials (RCTs) comparing different forms, schedules, or routes of administration of vitamin D
compounds for people with CKD not requiring dialysis were included. Vitamin D compounds were defined as established
(calcitriol, alfacalcidol, 24,25(OH)(subscript 2)vitamin D(subscript 3)) or newer (doxercalciferol, maxacalcitol,
paricalcitol, falecalcitriol) vitamin D compounds.
Data collection and analysis
Data were extracted by two authors. Statistical analyses were performed using the random effects model. Results were
summarized as risk ratio (RR) for dichotomous outcomes or mean differences (MD) for continuous outcomes with 95%
confidence intervals (CI).
Main results
Sixteen studies (894 patients) were included. No formulation, route, or schedule of vitamin D compound was found to
alter the mortality risk or need for dialysis. Vitamin D compounds significantly lowered serum PTH (4 studies, 153
patients: MD -49.34 pg/mL, 95% CI -85.70 to -12.97 (-5.6 pmol/L, 95% CI -9.77 to -1.48)) and were more likely to reduce
serum PTH > 30% from baseline value (264 patients: RR 7.87, 95% CI 4.87 to 12.73). Vitamin D treatment was associated
with increased end of treatment serum phosphorus (3 studies, 140 patients: MD 0.37 mg/dL, 95% CI 0.09, 0.66 (0.12
mmol/L, 95% CI 0.03, 0.21)) and serum calcium (5 studies, 184 patients: MD 0.20 mg/dL, 95% CI 0.17 to 0.23 (0.05 mmol/L,
95% CI 0.04 to 0.06)). Few data were available comparing intermittent with daily vitamin D administration, or other
schedules of dosing.
Authors' conclusions
There are not sufficient data to determine the effect of vitamin D compounds on mortality and cardiovascular outcomes in
people with CKD not requiring dialysis. While vitamin D compounds reduce serum PTH (49.3 pg/mL (5.6 pmol/L)) compared
with placebo, the relative clinical benefits of PTH lowering versus treatment-related increases in serum phosphorus and
calcium remain to be understood.
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53.
Vitamin D supplementation for prevention of cancer in adults.
Bjelakovic, Goran.  Gluud, Lotte Lise.  Nikolova, Dimitrinka.  Whitfield, Kate.  Wetterslev, Jorn.  Gluud, Christian.
EBM Reviews - Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews. 4, 2009.
[Protocol]
AN: 00075320-100000000-06085
This is the protocol for a review and there is no abstract. The objectives are as follows:
To assess the beneficial and harmful effects of vitamin D supplementation for prevention of cancer in adults.
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55.
Interventions for the prevention of nutritional rickets in term born children.
Lerch, Christian.  Meissner, Thomas.
EBM Reviews - Cochrane Database of Systematic Reviews Cochrane Database of Systematic Reviews. 4, 2009.
[Systematic Review]
AN: 00075320-100000000-04806
Background
Nutritional rickets is a disease of growing children leading to bone deformities, bone pain, convulsions or delayed
motor development. Today, high-incidence of nutritional rickets is mainly found in low-income countries.
Objectives
To assess the effects of various interventions on the prevention of nutritional rickets in term born children.
Search strategy
Studies were obtained from computerised searches of The Cochrane Library, MEDLINE, EMBASE, LILACS and reference lists of
relevant articles. We contacted authors of studies or reviews to obtain further studies.
Selection criteria
Studies were included if they were randomised controlled clinical trials, controlled clinical trials or prospective
cohort studies comparing any intervention for the prevention of nutritional rickets in term born children with placebo
or no intervention. Minimum duration of the intervention was three months for children under 12 months or six months for
children over 12 months.
Data collection and analysis
Two authors independently extracted data and assessed study quality. Authors of studies were contacted to obtain missing
information.
Main results
Four studies enrolled approximately 1700 participants. Trials lasted between nine months to two years. Three studies
were randomised controlled trials, two of which showed a cluster randomised design; one trial probably was a controlled
trial with researcher controlled group assignment. In children up to three years of age in Turkey, Vitamin D compared to
no intervention showed a relative risk of 0.04 (95% confidence interval (CI) 0 to 0.71). Despite a marked
non-compliance, a Chinese trial in children up to three years of age comparing a combined intervention of
supplementation of vitamin D, calcium and nutritional counselling showed a relative risk of 0.76 (95% CI 0.61 to 0.95)
compared to no intervention. In two studies conducted in older children in China and in France no rickets occurred in
both the intervention and control group.
Authors' conclusions
There a only few studies on the prevention of nutritional rickets in term born children. Until new data become
available, it appears sound to offer preventive measures (vitamin D or calcium) to groups of high risk, like infants and
toddlers; children living in Africa, Asia or the Middle East or migrated children from these regions into areas where
rickets is not frequent. Due to a marked clinical heterogeneity and the scarcity of data, the main and adverse effects
of preventive measures against nutritional rickets should be investigated in different countries, different age groups
and in children of different ethnic origin.
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61.
Review: Vitamin D with calcium reduces fractures in adults
Ott, Susan M. MD.
EBM Reviews - ACP Journal Club ACP Journal Club.  v156(6):JC6-7, June, 2012.
[Therapeutics]
AN: 00021607-201206000-00006
Question:
What are the benefits and harms of vitamin D supplementation, with or without calcium, in adults?
Review scope:
Included studies compared oral vitamin D, with or without calcium, with placebo or no supplementation in healthy adults
(< 20% had major chronic disease) or in ambulatory adults >= 65 years of age who did not have cancer (but may have had
other diseases). Studies that included pregnant women only, measured vitamin D status only during pregnancy, compared
vitamin D dosages without a control group that did not receive vitamin D, used synthetic vitamin D analogues, or had
follow-up < 1 month were excluded. Outcomes were cancer, fracture, and adverse events.
Review methods:
MEDLINE and Cochrane Central Register of Controlled Trials (to Jul 2011) were searched for English-language, randomized,
controlled trials (RCTs). Eligible articles from a broader search done in 2009 were also included. 63 RCTs met the
selection criteria. 18 of these RCTs (n = 104 959, mean age 53 to 85 y, 24% to 100% women) reported cancer and fracture
outcomes; vitamin D doses ranged from 300 IU/d to 1100 IU/d. Of the 18 RCTs, 4 were of good quality, 9 were of fair
quality, and 5 were of poor quality. Mean follow-up ranged from 7 months to 7 years.
Main results:
Meta-analyses were not done for the 3 trials (n = 40 147) that provided data for cancer outcomes. Of 4 comparisons, 1 (n
= 734) found a reduction in cancer with vitamin D plus calcium compared with placebo; the results of the other 3
comparisons were not statistically significant. The findings for fracture are in the . 1 RCT found an increase in renal
and urinary tract stones with vitamin D plus calcium (hazard ratio 1.2, 95% CI 1.0 to 1.3 for both outcomes), but there
were too few data to assess other adverse events.
Conclusions:
Oral vitamin D with-but not without-calcium reduces fracture risk in adults. Limited data are available to evaluate the
effect of vitamin D on cancer or adverse events.
Institution
University of Washington, Seattle, Washington, USA
Reviewed Source
Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of
cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med.
2011;155:827-38.
Commentary
A 2011 report by the Institute of Medicine reviewed evidence for diseases that could be caused by vitamin D deficiency
and found that oral vitamin D, with added calcium, but not without it, had skeletal benefits . These conclusions were
influenced by a 2009 meta-analysis by Chung and colleagues . In this update by the same team of investigators, which
focuses exclusively on fractures and cancer, only a few new RCTs were added to the meta-analysis, but these have not
changed any of the original conclusions. Moreover, another RCT of an annual injection of vitamin D showed increased risk
for hip fracture, strengthening the conclusion that vitamin D alone probably does not reduce fracture risk .
The 2011 review by Chung and colleagues has some limitations. The investigators included only studies of breast,
prostate, and colon cancer, thereby excluding the Cohort Consortium Vitamin D Pooling Project , which confirmed previous
reports of increased risk for pancreatic cancer in patients with higher levels of vitamin D. Also, the authors separated
studies according to calcium supplementation. A complementary analysis by Tang and colleagues assessed calcium with or
without vitamin D . Both analyses found that combined treatment reduced fractures. The analysis by Tang and colleagues
found a reduction in calcium-only studies , but the analysis by Chung and colleagues did not find a benefit with vitamin
D-only studies. Thus, it is possible that calcium alone plays the major role in preventing fractures. Finally, by not
including more recent observational vitamin D studies, the review omitted a report from the Women's Health Initiative,
which found a lower risk for fracture in black women with low vitamin D levels-the reverse of the findings in white
women . Therefore, vitamin D results cannot be generalized to all races.
In this still-controversial area, it is refreshing to see a report based on evidence, not opinion or hope. The benefits
of vitamin D with calcium are modest, even for fracture reduction, and are found mainly in elderly, institutionalized
patients. More studies are needed; fortunately, several large randomized trials are in progress.
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62.
Review: Cholecalciferol (vitamin D(subscript 3)) reduces mortality in adults; other forms of vitamin D do not
Murff, Harvey J. MD, MPH.
EBM Reviews - ACP Journal Club ACP Journal Club.  v155(5):JC5-4, November, 2011.
[Therapeutics]
AN: 00021607-201111000-00003
Questions:
Does vitamin D reduce mortality in adults? What are the harms?
Review scope:
Included studies compared supplemental vitamin D (cholecalciferol [vitamin D(subscript 3)] or ergocalciferol [vitamin
D(subscript 2)]) or active forms of vitamin D (alfacalcidol or calcitriol), alone or combined with calcium, with placebo
or no intervention in adults >= 18 years of age who were healthy or had stable disease or vitamin D deficiency. Trials
that enrolled patients with secondary-induced osteoporosis or cancer or women who were pregnant or lactating were
excluded. Primary outcomes were all-cause mortality and adverse events. Other outcomes included cardiovascular (CV) and
cancer mortality.
Review methods:
MEDLINE, EMBASE/Excerpta Medica, Cochrane Library, LILACS, Science Citation Index Expanded, and Conference Proceedings
Citation Index-Science (all to Jan 2011); ongoing trial databases; and reference lists were searched for randomized
controlled trials (RCTs). Investigators, experts, and manufacturers of vitamin D were contacted. 144 RCTs (n = 108 496)
met the selection criteria: 84 did not report any deaths, 10 reported mortality for all groups combined, and 50 reported
mortality by treatment group and were included in meta-analyses. Of those 50 RCTs (n = 94 148, mean age 74 y, 79%
women), 26 had low risk for bias. 38 used placebo control, and 12 used no control intervention; 32 included a vitamin D
plus calcium intervention group.
Main results:
Meta-analysis showed that use of any vitamin D reduced all-cause mortality more than placebo or no intervention .
Meta-analysis by type of vitamin D showed that cholecalciferol reduced all-cause but not CV or cancer mortality;
ergocalciferol, alfacalcidol, and calcitriol did not reduce all-cause mortality . Active forms of vitamin D increased
risk for hypercalcemia (3 RCTs, n = 710, relative risk increase [RRI] 218%, 95% CI 17 to 768), and cholecalciferol plus
calcium increased risk for nephrolithiasis (4 RCTs, n = 42 876, RRI 17%, CI 2 to 34) more than placebo or no
intervention; vitamin D did not increase risk for other reported adverse events.
Conclusion:
Cholecalciferol (vitamin D(subscript 3)) reduces mortality in adults more than placebo or no treatment; other forms of
vitamin D do not.
Institution
Vanderbilt University, Nashville, Tennessee, USA
Reviewed Source
Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane
Database Syst Rev. 2011;(7):CD007470.
Commentary
Adequate levels of vitamin D are important for bone health. Inconsistent data suggesting a beneficial role of vitamin D
on nonskeletal health outcomes have, however, led to aggressive supplementation. The Institute of Medicine (IOM)
concluded that the prevalence of vitamin D deficiency in the USA has often been overestimated, and a serum
25-hydroxyvitamin D level of 20 ng/mL (50 nmol/L) should be adequate for >= 97.5% of the population .
To address questions about the efficacy of vitamin D for nonskeletal outcomes, the meta-analysis by Bjelakovic and
colleagues included RCTs of vitamin D supplementation that also captured data on secondary outcomes, including all-cause
mortality. The results are similar to an earlier meta-analysis, which found that vitamin D supplementation reduced the
risk for all-cause mortality (relative risk reduction 7%, CI 1% to 13%) , although only 2 of the included studies
evaluated ergocalciferol (vitamin D(subscript 2)). Bjelakovic and colleagues included RCTs evaluating the effect of
several forms of vitamin D, including 12 that used ergocalciferol, and questioned the presumed equivalence of different
forms of vitamin D. Animal and human studies have, in fact, shown that cholecalciferol is more potent for raising serum
25-hydroxyvitamin D levels than ergocalciferol .
Providers should be concerned about vitamin D levels in their patients because supplementation can have beneficial
effects on bone health and may lower the risk for mortality in some individuals. The IOM report should reassure
providers that blood levels of 25-hydroxyvitamin D >= 20 ng/mL are probably sufficient for most patients, and the
results of the meta-analysis by Bjelakovic and colleagues should encourage providers to consider cholecalciferol
(vitamin D(subscript 3)) as their preferred choice for vitamin D supplementation.
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63.
Review: Oral vitamin D prevents nonvertebral and hip fractures in a dose-dependent manner in patients >= 65 years of age

Denman, Michael MD, FRCP.
EBM Reviews - ACP Journal Club ACP Journal Club.  v151(2):JC2-8, August, 2009.
[Therapeutics]
AN: 00021607-200908000-00006
Question:
In patients >= 65 years of age, does oral vitamin D prevent nonvertebral and hip fractures?
Review scope:
Included studies evaluated oral vitamin D supplementation and reported >= 1 fracture in patients with mean age >= 65
years; studies had to be double-blind and have >= 1 year of follow-up. Exclusion criteria included uncontrolled,
observational, or animal studies; and studies of patients with organ transplantation or stroke, and those taking
steroids or treatment for Parkinson disease. Outcomes were first or repeated nonvertebral fracture or hip fracture.
Review methods:
MEDLINE and Cochrane Controlled Trials Register (1960 to Aug 2008), EMBASE/Excerpta Medica (1991 to Aug 2008), reference
lists, and abstracts from the American Society of Bone and Mineral Research (1995 to 2007) were searched, and experts
were contacted for randomized controlled trials (RCTs). 12 high-quality RCTs (n = 42 279, mean age 78 y, 89% women) met
the selection criteria.
Main results:
Meta-analysis showed that vitamin D doses > 400 IU/d (range 482 to 770 IU/d) reduced nonvertebral and hip fractures but
vitamin D doses <= 400 IU/d (range 340 to 380 IU/d) did not differ from placebo or calcium supplementation alone for
nonvertebral or hip fractures ().
Conclusion:
Oral vitamin D prevents nonvertebral and hip fractures in a dose-dependent manner in patients >= 65 years of age.
Institution
Northwick Park Hospital; Harrow, England, UK
Reviewed Source
Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose
dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169:551-61.
Commentary
The value of oral vitamin D supplements in preventing nonvertebral fractures in older patients has remained unresolved
because of conflicting study findings. The meticulous study by Bischoff-Ferrari and colleagues clarifies many reasons
for the differing conclusions. They identify the supplemental vitamin D dose as the most important factor and emphasize
that only studies that assess serum 25-hydroxyvitamin D concentrations can be considered reliable. This point applies
equally to clinical practice. Malabsorption or poor adherence can be detected by this simple precaution. The overall
conclusion is that 400 IU is the minimum daily dose likely to benefit individuals >= 65 years of age. The main clinical
implication is that vitamin D supplementation is a rational means of reducing risk for nonvertebral fractures in this
age group.
The findings strongly suggest that it is more effective and economical to prescribe cholecalciferol than ergocalciferol.
Although adequate supplementation reduced incidence of nonvertebral fractures, the overall reduction was not dramatic,
and other preventive measures should be considered. However, identifying which other forms of treatment might complement
vitamin D supplementation is difficult. The authors point out that patient heterogeneity in reported RCTs makes it
difficult to assess the value of calcium prescribed with vitamin D supplements. It is more difficult to assess the value
of simultaneously prescribing such antiosteoporosis drugs as bisphosphonates. Further, the analysis included persons
living independently and in institutions, making it difficult to determine the extent to which increased physical
activity might reduce the need for vitamin D supplementation.
Another issue not addressed is the age at which vitamin D supplementation should be considered. Indeed, there is a
paucity of information about the skeletal effects of vitamin D deficiency in younger age groups . The importance of this
is emphasized by reports of an increasing incidence of vitamin D insufficiency, especially in economically disadvantaged
individuals .
Accruing evidence exists that vitamin D contributes to many forms of host immunity to infection , accounting for the
immunodeficiency in individuals with vitamin D deficiency . The deleterious effects of vitamin D deficiency on other
disorders, including cancer and hypertension, also merit further study.
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64.
Review: Calcium supplementation, with or without vitamin D, prevents osteoporotic fractures in people >= 50 years of age

EBM Reviews - ACP Journal Club ACP Journal Club.  v148(2):41, March/April, 2008.
[Therapeutics]
AN: 00021607-200803000-00015
Question:
In patients >= 50 years of age, does calcium supplementation, with or without vitamin D, prevent osteoporotic fractures?
Methods:
Data sources
MEDLINE, EMBASE/Excerpta Medica, Current Contents, CINAHL, Database of Abstracts of Reviews of Effects, Cochrane Central
Register of Controlled Trials, and Cochrane Database of Systematic Reviews (all to January 2007); clinical trials
repositories; resource Web sites; conference abstracts; review articles; and bibliographies of primary studies.
Study selection and assessment
Published or unpublished randomized controlled trials (RCTs) in any language that compared the effects of calcium, with
or without vitamin D, with placebo on fractures or bone mineral density (BMD) in patients >= 50 years of age. Exclusion
criteria were use of dietary calcium as an intervention, use of calcium as part of a nutritional supplementation regimen
or combined with other treatment, secondary osteoporosis, and use of vitamin D without calcium. 29 studies met the
selection criteria (n = 63 897, mean age 68 y, 92% women, median baseline risk for fracture 16%). Mean duration of
treatment was 3.5 years. Dosage thresholds were set at 1200 mg/d for calcium and 800 IU/d for vitamin D. Quality
assessment of individual studies was based on a 4-item checklist (reporting of randomization method, allocation
concealment, blinding of outcome assessment, and completeness of follow-up).
Outcomes
Fracture of any site, including hip, vertebra, and wrist; only the first fracture in a given patient was counted as an
event. Secondary outcome was percentage of change in BMD.
Main results:
Meta-analysis showed that calcium, with or without vitamin D, reduced risk for fractures more than placebo  and reduced
bone loss in the hip (difference in mean BMD 0.54%, 95% CI 0.35 to 0.73; 24 trials, n = 44 990) and spine (difference in
mean BMD 1.19%, CI 0.76 to 1.61; 24 trials, n = 3913).
Conclusion:
Calcium supplementation, with or without vitamin D, prevents osteoporotic fractures and reduces bone loss at the hip and
spine.
Reviewed Source
Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. Use of calcium or calcium in combination with vitamin D
supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet.
2007;370:657-66.
Commentary
The meta-analysis by Tang and colleagues shows that, compared with placebo, calcium supplements >= 1200 mg/d can reduce
fracture risk by up to 12% in men and women >= 50 years of age. Subgroup analyses showed that only those compliant with
calcium had reduced fracture risk. This finding may explain why recent trials using intention-to-treat analyses failed
to find an association between calcium and risk reduction . For clinicians, this finding highlights the importance of
promoting lifelong adherence to calcium for bone health.
These results are not generalizable to persons obtaining calcium from dietary sources. Such persons could have even
greater fracture reductions because of the micronutrients in dietary sources of calcium. Further, some evidence  shows
that long-term adherence to calcium supplementation is better if changes are made to diet rather than by taking pills.
An important issue not addressed in this meta-analysis is the role of vitamin D in fracture prevention; Tang and
colleagues found that adding vitamin D to calcium did not enhance treatment effect. This conclusion may seem surprising
because there is a close relation between calcium and vitamin D in maintaining bone homeostasis, and with increasing
age, calcium and vitamin D deficiency often coexist. Further, vitamin D deficiency is independently associated with
decreased muscle strength, and some  but not all summary data  demonstrate that vitamin D, without calcium, can reduce
falls. Thus, the physiologic rationale for using calcium and vitamin D for fracture prevention is persuasive. The lack
of an effect of vitamin D in the meta-analysis by Tang and colleagues could be explained by the low doses of vitamin D
in the included studies. Indeed, subgroup analyses found a greater treatment effect with increasing doses of vitamin D.
Until further studies are available, it seems reasonable for clinicians to prescribe vitamin D, in doses >= 800 IU, in
addition to calcium.
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66.
Review: Vitamin D supplementation decreases all-cause mortality in adults and older individuals
EBM Reviews - ACP Journal Club ACP Journal Club.  v148(2):30, March/April, 2008.
[Therapeutics]
AN: 00021607-200803000-00004
Question:
What is the effect of vitamin D supplementation on all-cause mortality?
Methods:
Data sources
PubMed, ISI Web of Science (Science Citation Index Expanded), EMBASE/Excerpta Medica, Cochrane Library, and
bibliographies of selected studies, reviews, or books (to November 2006).
Study selection and assessment
Principal published reports of randomized controlled trials (RCTs) that assessed the effects of vitamin D
supplementation (vitamin D(subscript 2) [ergocalciferol] or vitamin D(subscript 3) [cholecalciferol]), taken for any
condition, on all-cause mortality. Trials had to randomize participants on an individual (rather than cluster) basis and
include sufficient information to allow for calculation of relative risks and 95% CIs for all-cause mortality for
vitamin D supplementation vs placebo or control. Trials that evaluated treatment with 1[alpha]-hydroxyvitamin
D(subscript 3) (alfacalcidol), 1[alpha],25-dihydroxyvitamin D(subscript 3) (calcitriol), or other vitamin D analogues in
patients with advanced prostate cancer, chronic or end-stage renal disease, or those on renal dialysis were excluded. 17
RCTs and 1 quasi-RCT (n = 57 311, age range 33 to 106 y) met the inclusion criteria. Mean daily dose of vitamin D
(adjusted for trial size) was 528 IU. Mean follow-up (adjusted for study size) was 5.7 years. Quality assessment of
individual trials was not reported.
Outcomes
All-cause mortality.
Main results:
4777 deaths occurred in the 18 trials. Meta-analysis of all trials showed that use of vitamin D supplements decreased
the risk for all-cause mortality . Meta-analysis of the 9 trials with sufficient power showed similar results .
Conclusion:
Vitamin D supplementation reduces all-cause mortality in adults and older individuals.
Reviewed Source
Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials.
Arch Intern Med. 2007;167:1730-7.
Commentary
Vitamin D insufficiency, defined as biochemical evidence of deficiency without clinical signs or symptoms, corresponds
to serum 25-hydroxyvitamin D levels of approximately < 20 to 30 ng/mL and is highly prevalent, affecting 25% to 70% of
patients, depending on the subpopulation and season of year . Achieving adequate blood levels is clinically important
because vitamin D affects more than bone health, and insufficiency has been associated with increased risks for some
types of cancer, cardiovascular disease, hypertension, musculoskeletal pain, and type 2 diabetes.
The meta-analysis by Autier and Gandini pooled 18 trials of vitamin D supplementation among various study populations
with baseline vitamin D levels consistent with insufficiency. The study participants were followed for a mean 5.7 years
for all-cause mortality. Participants who received vitamin D supplementation had an 8% relative risk reduction and a
small absolute risk reduction, which translates to approximately 1 death prevented for every 150 persons receiving
supplementation. Because many persons are at risk, achieving adequate blood levels may have an important impact on both
morbidity and mortality.
Current guidelines recommend 5 to 15 minutes of sun exposure at least twice weekly to the face, arms, hands, or back
without sunscreen  and a daily vitamin D intake of 200 IU for persons <= 50 years, 400 IU for those 50 to 70 years, and
600 IU for those > 70 years . These recommendations may, however, be too conservative, and daily intakes ranging from
800 to 1000 IU or higher may be necessary to achieve 25-hydroxyvitamin D levels of 30 to 40 ng/mL. Because dietary
sources rich in vitamin D are limited to fatty fish and some fortified foods, use of a vitamin D-containing supplement
is a reasonable approach for patients who are at risk for, or have, vitamin D insufficiency.
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67.
Review: Vitamin D plus calcium, but not vitamin D alone, prevents osteoporotic fractures in older persons
EBM Reviews - ACP Journal Club ACP Journal Club.  v144(1):14, January/February, 2006.
[Therapeutics]
AN: 00021607-200601000-00017
Question:
In older persons, does supplementation with vitamin D or a vitamin D analogue, alone or in combination with calcium,
reduce the incidence of fractures?
Methods:
Data sources
10 databases, lists of conference abstracts, bibliographies of relevant studies, and contact with researchers in the
field.
Study selection and assessment
Randomized and quasi-randomized controlled trials (RCTs) that compared vitamin D or a vitamin D analogue (alone or in
combination with calcium) with placebo, no intervention, or calcium alone in postmenopausal women or men > 65 years of
age. Studies involving corticosteroid therapy were excluded.
Outcomes
New vertebral, hip, and other nonvertebral fractures and adverse events.
Main results:
38 RCTs met the selection criteria. Vitamin D alone did not prevent hip, vertebral, or any fracture more than placebo or
no treatment . Vitamin D plus calcium prevented hip and nonvertebral fractures more than placebo or no treatment, but
not more than calcium alone . The benefit was greater in persons who lived in institutions (i.e., frail elderly). No
difference in treatment effect was observed between persons with or without a history of osteoporotic fracture. Only a
few trials, most with small sample size, assessed the efficacy of vitamin D analogues. Vitamin D or its analogues
increased risk for hypercalcemia, especially the analogue calcitriol (relative risk 15, 95% CI 3 to 76, 3 trials). Risk
for gastrointestinal events or renal disease was not increased.
Conclusions:
In postmenopausal women and older men, vitamin D alone does not reduce risk for fracture more than placebo or no
treatment. Vitamin D plus calcium reduces risk for hip and nonvertebral fractures more than placebo or no treatment,
especially in older, frail persons living in institutions; however, vitamin D plus calcium is not more effective than
calcium alone.
Reviewed Source
Avenell A, Gillespie WJ, Gillespie LD, O'Connell DL. Vitamin D and vitamin D analogues for preventing fractures
associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev. 2005;(3):CD000227.
Commentary
It has long been known that calcium and vitamin D are important to bone, but it is uncertain whether vitamin D alone is
enough. Interestingly, calcium or vitamin D is recommended in all guidelines, either alone, combined, or in addition to
a bone-active drug.
Avenell and colleagues reviewed 38 trials assessing vitamin D and vitamin D analogues for prevention of fractures
associated with postmenopausal osteoporosis. The main finding was that vitamin D alone showed no statistically
significant reduction in hip fractures. A combination of vitamin D and calcium marginally reduced hip fractures by 19%.
However, this effect seems to be mainly restricted to persons living in institutional care. Lack of compliance was a
major issue in some of the studies, which may partially explain the negative findings. The risk for hypercalcemia was
elevated with the use of the more potent vitamin D analogue calcitriol, but not with vitamin D or [alpha]-calcidol.
The conclusion is that frail older persons confined to institutions may sustain fewer hip fractures and other
nonvertebral fractures if given vitamin D with calcium supplements. The evidence strongly supports calcium plus vitamin
D for fracture prevention in nursing homes or long-term care, in agreement with the recent meta-analysis by
Bischoff-Ferrari and colleagues , which concluded that an oral dose of vitamin D >= 700 IU/d is needed. The effect of
vitamin D alone in fracture prevention is still unclear, and no evidence exists of an advantage of vitamin D analogues
compared with vitamin D.
How should we interpret these data, since most guidelines recommend vitamin D and calcium? We should still advise our
patients to take vitamin D and calcium, until the reasons for negative findings in recent studies have been explored. At
least we know from the meta-analysis by Avenell and colleagues that the combination is valuable in institutionalized
patients, perhaps because of vitamin D deficiency, an issue that requires more study.
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68.
Vitamin D3, calcium, or both did not prevent secondary fractures in elderly people
EBM Reviews - ACP Journal Club ACP Journal Club.  v143(3):74, November/December, 2005.
[Therapeutics]
AN: 00021607-200511000-00020
Question:
In older persons with a previous low-trauma fracture, how do vitamin D(subscript 3), calcium, or both compare for
preventing secondary fractures?
Methods:
Design
Randomized placebo-controlled trial (Randomized Evaluation of Calcium Or Vitamin D [RECORD]).
Allocation
Concealed.
Blinding
Blinded ({patients, clinicians, data collectors}, and outcome assessors).
Follow-up period
24 to 62 months.
Setting
21 hospitals in the United Kingdom.
Patients
5292 patients >= 70 years of age (mean age 77 y, 85% women) who had a low-trauma, osteoporotic fracture (a fracture due
to a fall from no more than standing height, or radiologist-confirmed vertebral fracture) in the previous 10 years.
Exclusion criteria included bed or chair-bound before the fracture; cognitive impairment; cancer in the past 10 years
that could metastasize to bone; fracture associated with preexisting local bone abnormality; hypercalcemia; renal stone
in the past 10 years; life expectancy < 6 months; daily intake of > 200 IU vitamin D or > 500 mg calcium; intake in the
previous 5 years of fluoride, bisphosphonates, calcitonin, tibolone, hormone replacement therapy, selective
estrogen-receptor modulators, or any vitamin D(subscript 3) metabolite; and vitamin D(subscript 3) by injection in the
past year.
Intervention
Vitamin D(subscript 3), 800 IU taken as 2 tablets with meals (n = 1343); calcium, 1000 mg given as a carbonate (n =
1311); vitamin D(subscript 3) plus calcium (COMBO) (n = 1306); or placebo (n = 1332). Groups were combined to allow
comparisons between calcium and non-calcium-containing regimens (COMBO + calcium vs vitamin D(subscript 3) + placebo),
vitamin D(subscript 3) and non-vitamin D(subscript 3)-containing regimens (COMBO + vitamin D(subscript 3) vs calcium +
placebo), or COMBO and placebo.
Outcomes
All new low-trauma fractures. Secondary outcomes were all new fractures, radiographically confirmed fractures, hip
fractures, death, number of falls, and quality of life.
Patient follow-up
90% (intention-to-treat analysis)
Main results:
Of 698 patients (13%) who had a new low-trauma fracture, 183 (4%) had a hip fracture. New low-trauma fractures did not
differ between calcium and non-calcium-containing regimens . Results were similar between vitamin D(subscript 3) and
non-vitamin D(subscript 3)-containing regimens . COMBO and placebo groups did not differ for new low-trauma fractures .
Secondary outcomes did not differ among any group comparisons.
Conclusion:
In older persons with a previous low-trauma fracture, calcium, vitamin D(subscript 3), or both did not prevent secondary
fractures.
Reviewed Source
The RECORD Trial Group. Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people
(Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet. 2005;365:1621-8.
Commentary
See also Review: 700 to 800 IU/d of vitamin D reduces hip and nonvertebral fractures in older persons and Calcium and
vitamin D supplementation did not reduce fractures in women >= 70 years of age
The review by Bischoff-Ferrari and colleagues, the study by Porthouse and colleagues, and the RECORD trial examined
calcium and vitamin D supplementation for the prevention of fractures in older persons. The systematic review by
Bischoff-Ferrari and coworkers found that high-dose vitamin D (700 to 800 IU/d) combined with calcium (500 to 1200 mg/d)
reduced the risk for hip fractures by 26% (CI 12 to 39) and all nonvertebral fractures by 23% (CI 13 to 32). However,
the RECORD and Porthouse studies (which were not included in the Bischoff-Ferrari review) reported no benefit of
high-dose vitamin D and calcium for either secondary prevention of fractures or prevention of fractures in high-risk
patients of whom over half had previous fractures. Could differences in patient populations, study power, or adherence
to study drugs explain these seemingly discordant results?
The effect of vitamin D with or without calcium on fracture prevention may vary in different populations. Frail, elderly
persons and nursing home patients are at greater risk for falls and fractures than community-dwelling elderly persons.
This difference may in part be explained by vitamin D deficiency in persons who are often sunlight-deprived. Many of the
patients in the Bischoff-Ferrari meta-analysis were nursing-home residents. A Cochrane review that included 4 recent
studies (including the RECORD and Porthouse studies) found that vitamin D alone did not reduce fractures . However, when
vitamin D was given in combination with calcium, reductions occurred in hip and nonvertebral fractures but not in
vertebral fractures. Subgroup analysis suggested that this effect was restricted to elderly patients living in
institutions, with a reduction in fractures of 13% (CI 5 to 28). In both the RECORD and Porthouse studies, patients were
community-dwelling.
In the Porthouse and RECORD studies, power may not have been sufficient to show a clinically important difference,
especially between the vitamin D plus calcium and placebo groups. The RECORD trial was designed to have 80% power to
detect an absolute difference in fracture rates of 3% between treatment groups. The intervention groups were formed by
collapsing the 2 groups that received the specific intervention (calcium or vitamin D), and the control groups were
formed from the 2 groups that did not receive the intervention. The groups that received calcium with vitamin D only or
placebo were smaller and had only about 62% power to detect a 3% difference in fracture rate between these 2 groups. In
the study by Porthouse and colleagues, the authors could not exclude a reduction in risk < 30% for fractures with
vitamin D plus calcium. Meta-analyses in a Cochrane study  and the study by Bischoff-Ferrari and colleagues both found
reductions in risk for fractures < 30%.
Adherence to therapy and consequent vitamin D levels may have varied in these trials, resulting in differences in
biological effects. A meta-regression analysis in Bischoff-Ferrari showed a greater reduction in hip and nonvertebral
fractures with higher serum levels of 25-hydroxyvitamin D. 2 hip fracture studies that were included in the
Bischoff-Ferrari meta-analysis (Decalyos II  and Decalyos I ) reported exceptionally high rates of compliance with
treatment and placebo (95% in Decalyos II and 83% in Decalyos I). In contrast, compliance rates were 60% in the RECORD
trial, and 56.6% in the study by Porthouse and colleagues. For a subset of patients in the RECORD and Decalyos I
studies, baseline 25-hydroxyvitamin D levels were similar (15.2 ng/mL and 16 ng/mL, respectively). However, after 1 year
of treatment, the mean 25-hydroxyvitamin D levels in the Decalyos I treatment group increased to 42 ng/mL , while levels
in the RECORD study only increased to 24.8 ng/mL.
The review by Bischoff-Ferrari and colleagues and the Porthouse and RECORD studies suggest that calcium plus high-dose
vitamin D is effective for the prevention of hip and nonvertebral fractures in older persons, particularly those in
institutions. It is important to note that in the secondary prevention trials, which showed the effectiveness of
bisphosphonates, calcium and vitamin D were given to all participants . For patients with a previous low-impact
fracture, prevention should include a bisphosphonate in addition to calcium and vitamin D.
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69.
Calcium and vitamin D supplementation did not reduce fractures in women >= 70 years of age
EBM Reviews - ACP Journal Club ACP Journal Club.  v143(3):73, November/December, 2005.
[Therapeutics]
AN: 00021607-200511000-00019
Question:
Do calcium and vitamin D reduce the risk for fracture in at-risk community-dwelling older women?
Methods:
Design
Randomized controlled trial.
Allocation
Concealed.
Blinding
Unblinded.
Follow-up period
Median 25 months.
Setting
Nurse-led clinics in England, UK.
Patients
3454 women >= 70 years of age (mean age 77 y) with >= 1 risk factor for hip fracture (body weight < 58 kg, previous
fracture, maternal history of hip fracture, smoking, and poor to fair health). Exclusion criteria were calcium
supplementation > 500 mg/d, history of kidney or bladder stones, renal failure, hypercalcemia, cognitive impairment, or
life expectancy < 6 months.
Intervention
Information leaflet alone (n = 1993) or 6-month supply of calcium, 1000 mg and cholecalciferol (vitamin D) 800 IU daily,
taken as 2 tablets (Calcichew D, Forte, Hampshire, UK); lifestyle advice on how to reduce fracture risk; and an
information leaflet on prevention of falls and calcium and vitamin D intake (n = 1321).
Outcomes
Any fracture (excluding ribs, digits, face, and skull). Secondary outcomes were hip fracture, quality of life (12-item
Short Form Health Survey), death, hospital admissions and doctor visits, falls, and fear of falling. The study had 80%
power to detect a 34% reduction in fracture.
Patient follow-up
140 patients were excluded directly after randomization. 3314 patients (96%) were included in the intention-to-treat
analysis.
Main results:
During follow-up, 149 fractures were reported. Calcium and vitamin D supplementation did not reduce fractures . Groups
did not differ for quality of life, death, hospital admissions and doctor visits, and falls. The adjusted odds ratio for
falling was 0.99 (95% CI 0.8 to 1.20) at 6 months and 0.93 (CI 0.79 to 1.20) at 12 months.
Conclusion:
Supplementation with calcium and vitamin D for 2 years did not reduce the risk for fracture in at-risk
community-dwelling older women.
Reviewed Source
Porthouse J, Cockayne S, King C, et al. Randomised controlled trial of calcium and suplementation with cholecalciferol
(vitamin D(subscript 3)) for prevention of fractures in primary care. BMJ. 2005;330:1003.
Commentary
See also Review: 700 to 800 IU/d of vitamin D reduces hip and nonvertebral fractures in older persons and Vitamin
D(subscript 3), calcium, or both did not prevent secondary fractures in elderly people
The review by Bischoff-Ferrari and colleagues, the study by Porthouse and colleagues, and the RECORD trial examined
calcium and vitamin D supplementation for the prevention of fractures in older persons. The systematic review by
Bischoff-Ferrari and coworkers found that high-dose vitamin D (700 to 800 IU/d) combined with calcium (500 to 1200 mg/d)
reduced the risk for hip fractures by 26% (CI 12 to 39) and all nonvertebral fractures by 23% (CI 13 to 32). However,
the RECORD and Porthouse studies (which were not included in the Bischoff-Ferrari review) reported no benefit of
high-dose vitamin D and calcium for either secondary prevention of fractures or prevention of fractures in high-risk
patients of whom over half had previous fractures. Could differences in patient populations, study power, or adherence
to study drugs explain these seemingly discordant results?
The effect of vitamin D with or without calcium on fracture prevention may vary in different populations. Frail, elderly
persons and nursing home patients are at greater risk for falls and fractures than community-dwelling elderly persons.
This difference may in part be explained by vitamin D deficiency in persons who are often sunlight-deprived. Many of the
patients in the Bischoff-Ferrari meta-analysis were nursing-home residents. A Cochrane review that included 4 recent
studies (including the RECORD and Porthouse studies) found that vitamin D alone did not reduce fractures . However, when
vitamin D was given in combination with calcium, reductions occurred in hip and nonvertebral fractures but not in
vertebral fractures. Subgroup analysis suggested that this effect was restricted to elderly patients living in
institutions, with a reduction in fractures of 13% (CI 5 to 28). In both the RECORD and Porthouse studies, patients were
community-dwelling.
In the Porthouse and RECORD studies, power may not have been sufficient to show a clinically important difference,
especially between the vitamin D plus calcium and placebo groups. The RECORD trial was designed to have 80% power to
detect an absolute difference in fracture rates of 3% between treatment groups. The intervention groups were formed by
collapsing the 2 groups that received the specific intervention (calcium or vitamin D), and the control groups were
formed from the 2 groups that did not receive the intervention. The groups that received calcium with vitamin D only or
placebo were smaller and had only about 62% power to detect a 3% difference in fracture rate between these 2 groups. In
the study by Porthouse and colleagues, the authors could not exclude a reduction in risk < 30% for fractures with
vitamin D plus calcium. Meta-analyses in a Cochrane study  and the study by Bischoff-Ferrari and colleagues both found
reductions in risk for fractures < 30%.
Adherence to therapy and consequent vitamin D levels may have varied in these trials, resulting in differences in
biological effects. A meta-regression analysis in Bischoff-Ferrari showed a greater reduction in hip and nonvertebral
fractures with higher serum levels of 25-hydroxyvitamin D. 2 hip fracture studies that were included in the
Bischoff-Ferrari meta-analysis (Decalyos II  and Decalyos I ) reported exceptionally high rates of compliance with
treatment and placebo (95% in Decalyos II and 83% in Decalyos I). In contrast, compliance rates were 60% in the RECORD
trial, and 56.6% in the study by Porthouse and colleagues. For a subset of patients in the RECORD and Decalyos I
studies, baseline 25-hydroxyvitamin D levels were similar (15.2 ng/mL and 16 ng/mL, respectively). However, after 1 year
of treatment, the mean 25-hydroxyvitamin D levels in the Decalyos I treatment group increased to 42 ng/mL , while levels
in the RECORD study only increased to 24.8 ng/mL.
The review by Bischoff-Ferrari and colleagues and the Porthouse and RECORD studies suggest that calcium plus high-dose
vitamin D is effective for the prevention of hip and nonvertebral fractures in older persons, particularly those in
institutions. It is important to note that in the secondary prevention trials, which showed the effectiveness of
bisphosphonates, calcium and vitamin D were given to all participants . For patients with a previous low-impact
fracture, prevention should include a bisphosphonate in addition to calcium and vitamin D.
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70.
Review: 700 to 800 IU/d of vitamin D reduces hip and nonvertebral fractures in older persons
EBM Reviews - ACP Journal Club ACP Journal Club.  v143(3):72, November/December, 2005.
[Therapeutics]
AN: 00021607-200511000-00018
Question:
Does oral vitamin D supplementation prevent hip and any nonvertebral fractures in older persons?
Methods:
Data sources
MEDLINE and the Cochrane Controlled Trials Register (January 1960 to January 2005), EMBASE/Excerpta Medica (January 1991
to January 2005), experts in the field, reference lists of relevant studies, and abstracts presented at the American
Society for Bone and Mineral Research (1995 to 2004).
Study selection and assessment
Blinded randomized controlled trials (RCTs) of oral vitamin D supplementation (cholecalciferol or ergocalciferol) alone
or combined with calcium supplementation compared with placebo or calcium supplementation alone in participants >= 60
years of age, >= 1 fracture occurred in each trial, and follow-up was >= 1 year. Individual studies were assessed for
randomization procedure, concealment, blinding, and withdrawals.
Outcomes
First hip or nonvertebral fracture.
Main results:
7 RCTs (n = 9820, mean age 79 y, 68% women) met the selection criteria. 2 RCTs evaluated 400 IU/d of vitamin D, and 5
RCTs evaluated 700 to 800 IU/d. 4 RCTs included 500 to 1200 mg/d of calcium in the vitamin D intervention; in 2 RCTs the
mean calcium intake was 450 to 742 mg/d, and 1 RCT recommended a calcium intake of 800 mg/d through dairy products.
Treatment duration ranged from 12 to 60 months. Using random effects, pooling 3 RCTs of vitamin D at higher doses showed
reduced hip fracture, while pooling 2 RCTs using lower doses did not . Pooling of 5 RCTs with high doses of vitamin D
showed a reduction in any nonvertebral fracture, but not for 2 RCTs with low doses .
Conclusions:
Vitamin D at doses of 700 to 800 IU/d reduces hip and nonvertebral fractures in older persons. 400 IU/d of vitamin D
does not reduce fractures.
Reviewed Source
Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Fracture prevention with vitamin D supplementation: a meta-analysis of
randomized controlled trials. JAMA. 2005;293:2257-64.
Commentary
See also Calcium and vitamin D supplementation did not reduce fractures in women >= 70 years of age and Vitamin
D(subscript 3), calcium, or both did not prevent secondary fractures in elderly people
The review by Bischoff-Ferrari and colleagues, the study by Porthouse and colleagues, and the RECORD trial examined
calcium and vitamin D supplementation for the prevention of fractures in older persons. The systematic review by
Bischoff-Ferrari and coworkers found that high-dose vitamin D (700 to 800 IU/d) combined with calcium (500 to 1200 mg/d)
reduced the risk for hip fractures by 26% (CI 12 to 39) and all nonvertebral fractures by 23% (CI 13 to 32). However,
the RECORD and Porthouse studies (which were not included in the Bischoff-Ferrari review) reported no benefit of
high-dose vitamin D and calcium for either secondary prevention of fractures or prevention of fractures in high-risk
patients of whom over half had previous fractures. Could differences in patient populations, study power, or adherence
to study drugs explain these seemingly discordant results?
The effect of vitamin D with or without calcium on fracture prevention may vary in different populations. Frail, elderly
persons and nursing home patients are at greater risk for falls and fractures than community-dwelling elderly persons.
This difference may in part be explained by vitamin D deficiency in persons who are often sunlight-deprived. Many of the
patients in the Bischoff-Ferrari meta-analysis were nursing-home residents. A Cochrane review that included 4 recent
studies (including the RECORD and Porthouse studies) found that vitamin D alone did not reduce fractures . However, when
vitamin D was given in combination with calcium, reductions occurred in hip and nonvertebral fractures but not in
vertebral fractures. Subgroup analysis suggested that this effect was restricted to elderly patients living in
institutions, with a reduction in fractures of 13% (CI 5 to 28). In both the RECORD and Porthouse studies, patients were
community-dwelling.
In the Porthouse and RECORD studies, power may not have been sufficient to show a clinically important difference,
especially between the vitamin D plus calcium and placebo groups. The RECORD trial was designed to have 80% power to
detect an absolute difference in fracture rates of 3% between treatment groups. The intervention groups were formed by
collapsing the 2 groups that received the specific intervention (calcium or vitamin D), and the control groups were
formed from the 2 groups that did not receive the intervention. The groups that received calcium with vitamin D only or
placebo were smaller and had only about 62% power to detect a 3% difference in fracture rate between these 2 groups. In
the study by Porthouse and colleagues, the authors could not exclude a reduction in risk < 30% for fractures with
vitamin D plus calcium. Meta-analyses in a Cochrane study  and the study by Bischoff-Ferrari and colleagues both found
reductions in risk for fractures < 30%.
Adherence to therapy and consequent vitamin D levels may have varied in these trials, resulting in differences in
biological effects. A meta-regression analysis in Bischoff-Ferrari showed a greater reduction in hip and nonvertebral
fractures with higher serum levels of 25-hydroxyvitamin D. 2 hip fracture studies that were included in the
Bischoff-Ferrari meta-analysis (Decalyos II  and Decalyos I ) reported exceptionally high rates of compliance with
treatment and placebo (95% in Decalyos II and 83% in Decalyos I). In contrast, compliance rates were 60% in the RECORD
trial, and 56.6% in the study by Porthouse and colleagues. For a subset of patients in the RECORD and Decalyos I
studies, baseline 25-hydroxyvitamin D levels were similar (15.2 ng/mL and 16 ng/mL, respectively). However, after 1 year
of treatment, the mean 25-hydroxyvitamin D levels in the Decalyos I treatment group increased to 42 ng/mL , while levels
in the RECORD study only increased to 24.8 ng/mL.
The review by Bischoff-Ferrari and colleagues and the Porthouse and RECORD studies suggest that calcium plus high-dose
vitamin D is effective for the prevention of hip and nonvertebral fractures in older persons, particularly those in
institutions. It is important to note that in the secondary prevention trials, which showed the effectiveness of
bisphosphonates, calcium and vitamin D were given to all participants . For patients with a previous low-impact
fracture, prevention should include a bisphosphonate in addition to calcium and vitamin D.
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72.
Vitamin D treatment and mortality in chronic kidney disease:  a systematic review and meta-analysis (Structured
abstract).
Centre for Reviews and Dissemination.
EBM Reviews - Database of Abstracts of Reviews of Effects Database of Abstracts of Reviews of Effects. Issue 1, 2014.
[Miscellaneous]
AN: 00125498-100000000-35702
Institution
NHS Centre for Reviews and Dissemination. University of York, York, U.K..
Reviewed Source
Abstract and Commentary for: Duranton F, Rodriguez-Ortiz ME, Duny Y, Rodriguez M, Daures JP, Argiles A. Vitamin D
treatment and mortality in chronic kidney disease: a systematic review and meta-analysis. American Journal of
Nephrology. 2013;37(3):239-248.
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76.
Effects of vitamin D supplements on bone mineral density:  a systematic review and meta-analysis (Structured abstract).
Centre for Reviews and Dissemination.
EBM Reviews - Database of Abstracts of Reviews of Effects Database of Abstracts of Reviews of Effects. Issue 1, 2014.
[Miscellaneous]
AN: 00125498-100000000-38064
Institution
NHS Centre for Reviews and Dissemination. University of York, York, U.K..
Reviewed Source
Abstract and Commentary for:Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a
systematic review and meta-analysis. Lancet. 2013:.
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77.
Effectiveness and safety of vitamin D in relation to bone health (Structured abstract).
Centre for Reviews and Dissemination.
EBM Reviews - Database of Abstracts of Reviews of Effects Database of Abstracts of Reviews of Effects. Issue 1, 2014.
[Miscellaneous]
AN: 00125498-100000000-17241
Institution
NHS Centre for Reviews and Dissemination. University of York, York, U.K..
Reviewed Source
Abstract and Commentary for: Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D,
Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V. Effectiveness and safety of
vitamin D in relation to bone health. Title to be Checked, 2007:235.
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78.
Effect of vitamin D supplementation on muscle strength:  a systematic review and meta-analysis (Provisional abstract).
Centre for Reviews and Dissemination.
EBM Reviews - Database of Abstracts of Reviews of Effects Database of Abstracts of Reviews of Effects. Issue 1, 2014.
[Miscellaneous]
AN: 00125498-100000000-26435
Institution
NHS Centre for Reviews and Dissemination. University of York, York, U.K..
Reviewed Source
Abstract and Commentary for:Stockton KA, Mengersen K, Paratz JD, Kandiah D, Bennell KL. Effect of vitamin D
supplementation on muscle strength: a systematic review and meta-analysis. Osteoporosis International.
2011;22(3):859-871.
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79.
The effect of vitamin D on falls:  a systematic review and meta-analysis (Structured abstract).
Centre for Reviews and Dissemination.
EBM Reviews - Database of Abstracts of Reviews of Effects Database of Abstracts of Reviews of Effects. Issue 1, 2014.
[Miscellaneous]
AN: 00125498-100000000-28415
Institution
NHS Centre for Reviews and Dissemination. University of York, York, U.K..
Reviewed Source
Abstract and Commentary for:Murad MH, Elamin KB, Abu Elnour NO, Elamin MB, Alkatib AA, Fatourechi MM, Almandoz JP,
Mullan RJ, Lane MA, Liu H, Erwin PJ, Hensrud DD, Montori VM. The effect of vitamin D on falls: a systematic review and
meta-analysis. Journal of Clinical Endocrinology and Metabolism. 2011;96(10):2997-3006.
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81.
The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture:  a meta-analysis (Structured abstract).
Centre for Reviews and Dissemination.
EBM Reviews - Database of Abstracts of Reviews of Effects Database of Abstracts of Reviews of Effects. Issue 1, 2014.
[Miscellaneous]
AN: 00125498-100000000-12081
Institution
NHS Centre for Reviews and Dissemination. University of York, York, U.K..
Reviewed Source
Abstract and Commentary for:Jackson C, Gaugris S, Sen S S, Hosking D. The effect of cholecalciferol (vitamin D3) on the
risk of fall and fracture: a meta-analysis. QJM: an International Journal of Medicine. 2007;100(4):185-192.
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82.
A randomized, controlled trial of vitamin D supplementation upon musculoskeletal health in postmenarchal females.
Ward KA, Das G, Roberts SA, Berry JL, Adams JE, Rawer R, Mughal MZ
EBM Reviews - Cochrane Central Register of Controlled Trials The Journal of clinical endocrinology and metabolism.
95(10):4643-51, 2010 Oct.
[Journal Article.  Randomized Controlled Trial.  Research Support, Non-U.S. Gov't]
AN: CN-00763133  UPDATE
CONTEXT: There has been a resurgence of vitamin D deficiency rickets throughout the developed world, with infants and
adolescents being primarily affected. Adolescence is a crucial period for muscle and bone mineral accumulation.,
OBJECTIVE: The aim was to determine the effect of vitamin D supplementation on the adolescent musculoskeletal system.,
DESIGN AND SETTING: We conducted a community-based, double-blind, randomized controlled trial in a secondary school.,
PARTICIPANTS: Postmenarchal 12- to 14-yr-old females participated in the trial. Ninety-nine were screened, 73 were
included in randomized controlled trial, and 69 completed the trial. There were no adverse events.,  INTERVENTION: Four
doses of 150,000 IU vitamin D(2) (ergocalciferol) were given over 1 yr.,  MAIN OUTCOME MEASURES: Dual-energy x-ray
absorptiometry, peripheral quantitative computed tomography, and jumping mechanography were used.,  RESULTS: At
follow-up, 25-hydroxyvitamin D [25(OH)D] status was 56.0 +/- 8.9 nmol/liter in the intervention group and 15.8 +/- 6.6
nmol/liter in controls. There were no effects of supplementation on bone; however, for muscle function, efficiency of
movement improved in the vitamin D-treated group. There was an interaction between baseline 25(OH)D concentration and
response to vitamin D supplementation for muscle jump velocity.,  CONCLUSIONS: Despite improvements in 25(OH)D status,
treatment with vitamin D(2) was not shown to increase mineral accretion, bone geometry or strength, muscle force, or
power. There were greater increases in jump velocity in girls with the lowest baseline 25(OH)D concentrations. Lack of
effect of intervention after the period of peak mineral and muscle mass accretion suggests that earlier action is
required.
Institution
Medical Research Council Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
[log in to unmask]
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88.
DO IT Trial: Vitamin D Outcomes and Interventions in Toddlers - a TARGet Kids! randomized controlled trial.
Maguire JL, Birken CS, Loeb MB, Mamdani M, Thorpe K, Hoch JS, Mazzulli T, Borkhoff CM, Macarthur C, Parkin PC, Abdullah
K, Anderson L, Carsley S, Chen Y, D'Ascanio M, Katz-Lavigne M, Kavikondala K, Lee GJ, Omand J, Persaud N, van den Heuvel
M, Zabih W, Baker J, Barozzino T, Bonifacio J, Campbell D, Cheema S, Chisamore B, Danayan K, Das P, Derocher MB, Do A,
Dorey M, Freeman S, Fung K, Guiang C, Handford C, Hatch H, Jacobson S, Kiran T, Knowles H, Kwok B, Lakhoo S,
Lam-Antoniades M, Lau E, Leung F-H, Loo J, Mahmoud S, Moodie R, Morinis J, Naymark S, Neelands P, Owen J, Peer M,
Perlmutar M, Pinto A, Porepa M, Ramji N, Rosenthal A, Saunderson J, Saxena R, Sgro M, Shepherd S, Smiltnieks B, Taylor
C, Weisdors T, Wijayasinghe S, Wong P, Ying E, Young E
EBM Reviews - Cochrane Central Register of Controlled Trials BMC pediatrics.  14(1):2014.
[Journal: Article]
AN: CN-00981663  NEW
Background: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An
increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of
anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin
D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of
early childhood. The objectives of this study are: 1) to compare the effect of 'high dose' (2000 IU/day) vs. 'standard
dose' (400 IU/day) vitamin D supplementation in achieving reductions in laboratory confirmed URTI and asthma
exacerbations during the winter in preschool-aged Canadian children; and 2) to assess the effect of 'high dose' vitamin
D supplementation on vitamin D serum levels and specific viruses that cause URTI.Methods/Design: This study is a
pragmatic randomized controlled trial. Over 4 successive winters we will recruit 750 healthy children 1-5 years of age.
Participating physicians are part of a primary healthcare research network called TARGet Kids!. Children will be
randomized to the 'standard dose' or 'high dose' oral supplemental vitamin D for a minimum of 4 months (200 children per
group). Parents will obtain a nasal swab from their child with each URTI, report the number of asthma exacerbations and
complete symptom checklists. Unscheduled physician visits for URTIs and asthma exacerbations will be recorded. By May, a
blood sample will be drawn to determine vitamin D serum levels. The primary analysis will be a comparison of URTI rate
between study groups using a Poisson regression model. Secondary analyses will compare vitamin D serum levels, asthma
exacerbations and the frequency of specific viral agents between groups.Discussion: Identifying whether vitamin D
supplementation of preschoolers can reduce wintertime viral URTIs and asthma exacerbations and what dose is optimal may
reduce population wide morbidity and associated health care and societal costs. This information will assist in
determining practice and health policy recommendations related to vitamin D supplementation in healthy Canadian
preschoolers.  2014 Maguire et al.; licensee BioMed Central Ltd.
Institution
J.L. Maguire, The Applied Health Research Centre, Li Ka Shing Knowledge Inst. of St. Michael's Hospital, University of
Toronto, Toronto, ON, Canada. E-mail: [log in to unmask]
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103.
Corelation of symptoms with vitamin D deficiency and symptom response to cholecalciferol treatment: A randomized
controlled trial.
Arvold DS, Odean MJ, Dornfeld MP, Regal RR, Arvold JG, Karwoski GC, Mast DJ, Sanford PB, Sjoberg RJ
EBM Reviews - Cochrane Central Register of Controlled Trials Endocrine practice.  15(3):203-12, 2009.
[Journal: Article]
AN: CN-00754033  UPDATE
Objective: To examine the association of symptoms with vitamin D deficiency and symptom response to cholecalciferol
treatment in a randomized, double-blind, placebo-controlled trial. Methods: Adult primary care patients in Duluth,
Minnesota, were screened for vitamin D deficiency in February 2007. Participants completed questionnaires pertaining to
a variety of symptoms, vitamin D intake, and selected medical conditions. Patients with mild to moderate vitamin D
deficiency (25-hydroxyvitamin D [25(OH)D], 10-25 ng/mL) participated in a randomized controlled trial (RCT) of vitamin D
replacement and its effect on symptoms. Participants were randomly assigned to receive 50 000 units of cholecalciferol
(vitamin D3) weekly or placebo for 8 weeks. Patients with severe vitamin D deficiency (25[OH]D <10 ng/mL) were treated
in an unblinded fashion, and symptoms were reevaluated post treatment. Results: A total of 610 patients underwent
initial screening, and 100 patients with mild to moderate vitamin D deficiency participated in the RCT. Thirty-eight
severely deficient patients were treated in an unblinded fashion. On initial screening, 46.2% of participants were
deficient in vitamin D. Self-reported vitamin D supplementation, milk intake, celiac disease, gastric bypass, and
chronic pancreatitis were predictive of vitamin D status. Severely deficient participants reported increased
musculoskeletal symptoms, depression (including seasonal), and higher (worse) scores on a fibromyalgia assessment
questionnaire. In the RCT, the treated group showed significant improvement in fibromyalgia assessment scores (P =
0.03), whereas the placebotreated participants did not. Severely deficient patients did not show symptom improvement
over the 8-week trial period or when followed up 1 year later. Conclusions: Compared with participants in the placebo
group, patients in the treatment group showed mild short-term improvement in the overall fibromyalgia impact score, but
did not show significant improvement in most musculoskeletal symptoms or in activities of daily living.  2009 AACE.
Institution
D. S. Arvold, St. Luke's Internal Medicine Associates, 1001 East Superior Street, Suite L401, Duluth, MN 55802. E-mail:
[log in to unmask]
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104.
Comparison of oral versus injectable vitamin-D for the treatment of nutritional vitamin-D deficiency rickets.
Billoo AG, Murtaza G, Memon MA, Khaskheli SA, Iqbal K, Rao MH
EBM Reviews - Cochrane Central Register of Controlled Trials Journal of the College of Physicians and Surgeons--Pakistan
: JCPSP.  19(7):428-31, 2009.
[Journal: Article]
AN: CN-00754291  UPDATE
Objective: To assess the safety and acceptability of a single dose of vitamin-D versus the efficacy of injectable
Vitamin-D versus oral vitamin-D. Study Design: Case control. Place and Duration of Study: It was carried out at the
Department of Paediatrics, Kharadar General Hospital, Karachi, from August 2003 to April 2004. Methodology: Children of
the age of 6 months to 3 years with clinical, biochemical and radiological evidence of vitamin-D deficiency rickets were
included. The history, clinical examination, complete blood picture, serum calcium. Phosphorus, alkaline phosphatase and
X-ray of wrist joint were done. The children were divided into two groups A and B. Group A was given oral vitamin-D and
group B was given intramuscular injection of vitamin-D on the first day and then they were followed for two more visits
at 30 and 90 days with clinical, biochemical and radiological examinations to assess the outcome. Results: There were 50
confirmed cases of rickets in each group. The mean age was 10.9+5.1 months and 14.7+8.1 months in group A and B
respectively. In these children, clinical features were weakness, difficulty in walking, frontal bossing, ribcage
deformity and widening of wrist were seen. After one dose of vitamin-D (cholecalciferol), there was appreciable gain of
weight and height and raised levels of alkaline phosphatase became normal during follow-up. Radiological florid rickets
and non-florid rickets in both groups healed clinically during follow-up period. Oral and injectable forms of vitamin-D
(cholecalciferol) were effective but injectable form was shown to be statistically significant. There were no
undesirable side effects and both forms of treatment were well-tolerated.
Institution
A. G. Billoo, Hill Park, 3-A, Justice Inamullah Road, Karachi, Pakistan. E-mail: [log in to unmask]
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108.
The response of elderly veterans to daily vitamin D3 supplementation of 2,000 IU: a pilot efficacy study.
Cherniack EP, Florez HJ, Hollis BW, Roos BA, Troen BR, Levis S
EBM Reviews - Cochrane Central Register of Controlled Trials Journal of the American Geriatrics Society.  59(2):286-90,
2011 Feb.
[Comparative Study.  Journal Article.  Randomized Controlled Trial.  Research Support, U.S. Gov't, Non-P.H.S]
AN: CN-00778365  UPDATE
OBJECTIVES: To determine the prevalence of hypovitaminosis D (serum 25-hydroxyvitamin D<32 ng/mL; HVD) in a population
of elderly veterans and conduct a preliminary assessment of the efficacy of supplementation with cholecalciferol in
correcting HVD.,  DESIGN: Randomized, double-blind, placebo-controlled clinical trial.,  SETTING: Geriatric clinic at
the Bruce W. Carter Veterans Affairs Medical Center, Miami, Florida.,  PARTICIPANTS: Veterans aged 70 and older.,
INTERVENTION: Oral cholecalciferol 2,000 IU daily or placebo for 6 months.,  MEASUREMENTS: Serum calcium,
25-hydroxyvitamin D, parathyroid hormone, and 24-hour urinary calcium.,  RESULTS: Of the 34 participants who completed
the study, 62% had HVD at baseline. In the treatment group, mean serum 25-hydroxyvitamin D level rose from 28.4+/-7.9
ng/mL at baseline to 42.7+/-10.5 ng/mL at the end of the trial, but levels remained less than 32 ng/mL in three of 17
(18%) of the participants. In the placebo group, the baseline level of 27.7+/-8.3 ng/mL remained unchanged (28.8+/-8.7
ng/mL). Supplementation did not alter serum or urinary calcium levels and did not result in any adverse events.,
CONCLUSION: These initial observations suggest that, in older veterans, cholecalciferol 2,000 IU daily for 6 months is
generally safe and corrects HVD in most but not all individuals.
Institution
Geriatrics Institute, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Miami Miller
School of Medicine, Miami, Florida, USA. [log in to unmask]
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109.
Vitamin D(3) is more potent than vitamin D(2) in humans.
Heaney RP, Recker RR, Grote J, Horst RL, Armas LA
EBM Reviews - Cochrane Central Register of Controlled Trials Journal of clinical endocrinology and metabolism.
96(3):E447-52, 2011 Mar.
[Comparative Study.  Journal Article.  Randomized Controlled Trial.  Research Support, Non-U.S. Gov't]
AN: CN-00780035  UPDATE
BACKGROUND: Current unitage for the calciferols suggests that equimolar quantities of vitamins D(2) (D2) and D(3) (D3)
are biologically equivalent. Published studies yield mixed results.,  OBJECTIVE: The aim of the study was to compare the
potencies of D2 and D3.,  DESIGN: The trial used a single-blind, randomized design in 33 healthy adults. Calciferols
were dosed at 50,000 IU/wk for 12 wk. Principal outcome variables were area under the curve for incremental total
25-hydroxyvitamin D [25(OH)D] and change in calciferol content of sc fat.,  RESULTS: Incremental mean (sd) 25(OH)D area
under the curve at 12 wk was 1366 ng [middle dot] d/ml (516) for the D2-treated group and 2136 (606) for the D3 (P <
0.001). Mean (sd) steady-state 25(OH)D increments showed similar differences: 24 ng/ml for D2 (10.3) and 45 ng/ml (16.2)
for D3 (P <0.001). Subcutaneous fat content of D2 rose by 50 [mu]g/kg in the D2-treated group, and D3 content rose by
104 [mu]g/kg in the D3-treated group. Total calciferol in fat rose by only 33 ng/kg in the D2-treated, whereas it rose
by 104 [mu]g/kg in the D3-treated group. Extrapolating to total body fat D3, storage amounted to just 17% of the
administered dose.,  CONCLUSION: D3 is approximately 87% more potent in raising and maintaining serum 25(OH)D
concentrations and produces 2- to 3-fold greater storage of vitamin D than does equimolar D2. For neither was there
evidence of sequestration in fat, as had been postulated for doses in this range. Given its greater potency and lower
cost, D3 should be the preferred treatment option when correcting vitamin D deficiency.
Institution
Creighton University, 601 North 30th Street, Suite 4841, Omaha, Nebraska 68131, USA. [log in to unmask]
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110.
Effect of calcium and vitamin D supplementation on bone mineral density in women aged 65-71 years: a 3-year randomized
population-based trial (OSTPRE-FPS).
Karkkainen M, Tuppurainen M, Salovaara K, Sandini L, Rikkonen T, Sirola J, Honkanen R, Jurvelin J, Alhava E, Kroger H
EBM Reviews - Cochrane Central Register of Controlled Trials Osteoporosis international.  21(12):2047-55, 2010 Dec.
[Journal Article.  Randomized Controlled Trial.  Research Support, Non-U.S. Gov't]
AN: CN-00781524  UPDATE
SUMMARY: The Osteoporosis Risk Factor and Prevention-Fracture Prevention Study (OSTPRE-FPS) was a randomized
population-based open trial (n = 593). The supplementation group (n = 287) received daily cholecalciferol 800 IU +
calcium 1,000 mg for 3 years while the control group (n = 306) received neither supplementation nor placebo. Daily
vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women.,
INTRODUCTION: vitamin D deficiency is common in the elderly, and vitamin D levels are associated with low bone mineral
density (BMD). The working hypothesis was that vitamin D and calcium supplementation could prevent bone loss in
ambulatory postmenopausal women.,  METHODS: the OSTPRE-FPS was a randomized population-based open trial with a 3-year
follow-up in 3,432 women (aged 66 to 71 years). A randomly selected subsample of 593 subjects underwent BMD
measurements. The supplementation group (n = 287) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years
while the control group (n = 306) received neither supplementation nor placebo.,  RESULTS: in the intention-to-treat
analysis, total body BMD (n = 362) increased significantly more in the intervention group than in the control group
(0.84% vs. 0.19%, p = 0.011). The BMD change differences at the lumbar spine (p = 0.372), femoral neck (p = 0.188),
trochanter (p = 0.085), and total proximal femur (p = 0.070) were statistically nonsignificant. Analyses in compliant
women (>= 80% of use) resulted in stronger and statistically significant effects at the total body and femoral regions.,
CONCLUSION: daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory
postmenopausal women with adequate nutritional calcium intake.
Institution
Bone and Cartilage Research Unit, Mediteknia Building, University of Kuopio, P.O. Box 1627, 70211, Kuopio, Finland.
[log in to unmask]
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114.
A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: no advantage of loading doses
over daily supplementation.
Papaioannou A, Kennedy CC, Giangregorio L, Ioannidis G, Pritchard J, Hanley DA, Farrauto L, DeBeer J, Adachi JD
EBM Reviews - Cochrane Central Register of Controlled Trials BMC musculoskeletal disorders.  Vol.12, pp.135, 2011.
[Journal Article.  Multicenter Study.  Randomized Controlled Trial.  Research Support, Non-U.S. Gov't]
AN: CN-00799189  UPDATE
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.
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117.
Short-term effects of high-dose oral vitamin D3 in critically ill vitamin D deficient patients: a randomized,
double-blind, placebo-controlled pilot study.
Amrein K, Sourij H, Wagner G, Holl A, Pieber TR, Smolle KH, Stojakovic T, Schnedl C, Dobnig H
EBM Reviews - Cochrane Central Register of Controlled Trials Critical care (London, England).  15(2):R104, 2011.
[Journal Article.  Randomized Controlled Trial]
AN: CN-00801014  UPDATE
INTRODUCTION: Vitamin D deficiency is encountered frequently in critically ill patients and might be harmful. Current
nutrition guidelines recommend very low vitamin D doses. The objective of this trial was to evaluate the safety and
efficacy of a single oral high-dose vitamin D3 supplementation in an intensive care setting over a one-week observation
period.,  METHODS: This was a randomized, double-blind, placebo-controlled pilot study in a medical ICU at a tertiary
care university center in Graz, Austria. Twenty-five patients (mean age 62 +/- 16 yrs) with vitamin D deficiency
[25-hydroxyvitamin D (25(OH)D) <= 20 ng/ml] and an expected stay in the ICU >48 hours were included and randomly
received either 540,000 IU (corresponding to 13.5 mg) of cholecalciferol (VITD) dissolved in 45 ml herbal oil or matched
placebo (PBO) orally or via feeding tube.,  RESULTS: The mean serum 25(OH)D increase in the intervention group was 25
ng/ml (range 1-47 ng/ml). The highest 25(OH)D level reached was 64 ng/ml, while two patients showed a small (7 ng/ml) or
no response (1 ng/ml). Hypercalcemia or hypercalciuria did not occur in any patient. From day 0 to day 7, total serum
calcium levels increased by 0.10 (PBO) and 0.15 mmol/L (VITD; P < 0.05 for both), while ionized calcium levels increased
by 0.11 (PBO) and 0.05 mmol/L (VITD; P < 0.05 for both). Parathyroid hormone levels decreased by 19 and 28 pg/ml (PBO
and VITD, ns) over the seven days, while 1,25(OH)D showed a transient significant increase in the VITD group only.,
CONCLUSIONS: This pilot study shows that a single oral ultra-high dose of cholecalciferol corrects vitamin D deficiency
within 2 days in most patients without causing adverse effects like hypercalcemia or hypercalciuria. Further research is
needed to confirm our results and establish whether vitamin D supplementation can affect the clinical outcome of vitamin
D deficient critically ill patients. EUDRACT NUMBER: 2009-012080-34 GERMAN CLINICAL TRIALS REGISTER (DRKS):
DRKS00000750.
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123.
Manifestations of severe vitamin D deficiency in adolescents: effects of intramuscular injection of a megadose of
cholecalciferol.
Soliman AT, Adel A, Wagdy M, Alali M, Aziz Bedair EM
EBM Reviews - Cochrane Central Register of Controlled Trials Journal of tropical pediatrics.  57(4):303-6, 2011 Aug.
[Journal Article.  Randomized Controlled Trial]
AN: CN-00813465  UPDATE
We recorded the manifestations of severe vitamin D deficiency (VDD) in 40 adolescents before and 3 and 6 months after
treatment with a mega dose of cholecalciferol (10 000 IU kg(-1), max 600 000 IU). Significant improvement of symptoms
related to VDD was reported in 34/40. Three months after the injection, serus calcium, phosphate, alkaline phosphatase
and parathormone were normal in all adolescents with VDD with 25-hydroxyvitamin D (25OHD) level = or >20 ng ml(-1).
After 6 months, the majority had 25OHD level <20 ng ml(-1). Two patterns of radiological changes have been recorded with
complete healing achieved in all patients after a year of therapy. A mega dose of cholecalciferol is an effective
therapy for treatment of VDD in adolescents for 3 months but not for 6 months. Radiographs of the ends of long bones are
still valuable tool for diagnosis and follow-up of these patients.
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127.
Short-term effects on bone turnover markers of a single high dose of oral vitamin D₃.
Rossini M, Gatti D, Viapiana O, Fracassi E, Idolazzi L, Zanoni S, Adami S
EBM Reviews - Cochrane Central Register of Controlled Trials Journal of clinical endocrinology and metabolism.
97(4):E622-6, 2012 Apr.
[Controlled Clinical Trial.  Journal Article.  Research Support, Non-U.S. Gov't]
AN: CN-00832292  UPDATE
CONTEXT: Vitamin D deficiency is often treated or prevented by high intermittent doses of vitamin D to achieve a better
treatment adherence, but treatment outcomes were contradictory, and even a transient increase in fracture and fall risk
was reported.,  OBJECTIVE: The objective of the study was to investigate the short-term effects on bone turnover markers
of a single bolus of vitamin D₃.,  DESIGN, SETTING, PATIENTS, AND INTERVENTION: Twelve elderly subjects (eight women,
four men; mean age 76 +/- 3 yr) were given a single oral bolus of 600,000 IU vitamin D₃. Blood samples were taken at
baseline and 1, 3, 7, 14, 30, 60, and 90 d after vitamin D₃ administration. Twenty-four subjects served as controls.,
MAIN OUTCOME MEASURES: Changes in serum levels of 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D, PTH,
C-terminal-telopeptides of type I collagen, cross-linked N-telopeptide of type I collagen (sNTX), osteocalcin, and
bone-specific alkaline phosphatase.,  RESULTS: No relevant changes in 25OHD and bone turnover markers were observed in
the controls. In treated subjects, serum 25OHD attained a peak increment to 67.1 +/- 17.1 ng/ml (P < 0.001) at d 3.
Subsequently it slowly decreased to 35.2 +/- 5.8 ng/ml (P <0.01 vs. a baseline value of 21.7 +/- 5.6 ng/ml). Mean serum
PTH concentration decreased by 25-50% and serum 1,25-dihydroxyvitamin D rose by 25-50%. Serum CTX and sNTX rose
significantly at d 1 (P < 0.01), they attained a peak increment greater than 50% at d 3, and they subsequently decreased
almost back to baseline values at d 90. Serum osteocalcin slightly rose within the first 3 d and then declined by d 60.
No changes were observed in serum bone-specific alkaline phosphatase.,  CONCLUSIONS: Our results indicate that the use
of large doses of vitamin D may be associated with acute increases in C-terminal-telopeptides of type I collagen and
sNTX, which may explain the negative clinical results obtained by using intermittent high doses of vitamin D to treat or
prevent vitamin D deficiency.
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129.
Therapeutic effects of calcium & vitamin D supplementation in women with PCOS.
Firouzabadi Rd, Aflatoonian A, Modarresi S, Sekhavat L, MohammadTaheri S
EBM Reviews - Cochrane Central Register of Controlled Trials Complementary therapies in clinical practice.  18(2):85-8,
2012 May.
[Journal Article.  Randomized Controlled Trial]
AN: CN-00834785  UPDATE
OBJECTIVE: To evaluate the efficacy of calcium & vitamin D supplementation in infertile women suffering from
polycystic ovary syndrome (PCOS), and to assess levels of 25-hydroxy vitamin D in these patients.,  METHODS: In a case
control study, 100 infertile PCOS women based on a randomly divided into two groups. Group I (n = 50) were treated with
metformin 1500 mg/day, and group II (n = 50) treated with metformin 1500 mg/day plus Calcium 1000 mg/day and Vitamin D
100000 IU/month for 6 months. Patients were followed by transvaginal sonography at first, 3 and 6 months later for
evaluating dominant follicle. BMI, menstrual regularity, follicle diameter, pregnancy, serum 25-OH-vitamin D level were
matured and compared in two groups.,  RESULTS: BMI decreased almost significantly (25.49 +/- 1.88 vs 26.28 +/- 2.15, p:
0.054) in group II. A better improvement was gained in regulating menstrual abnormalities (70% vs 58%, p: 0.211),
follicle maturation (28% vs 22%, p: 0.698), and infertility (18% vs 12%, p: 0.401) in group II compared with group I,
but these results were not statistically significant. Eighty three percent of all the PCOS patients showed vitamin D
deficiency while 35% were severely deficient. The serum 25-OH-vitamin D mean levels were 13.38 +/- 6.48 ng/ml. Vitamin D
deficiency was recompensed in 74% of the PCOS patients who had taken calcium & vitamin D supplementation. There was
no correlation between BMI and 25-OH-VD before and after the treatment (p >= 0.01).,  CONCLUSION: This study showed the
positive effects of calcium & vitamin D supplementation on weight loss, follicle maturation, menstrual regularity,
and improvement of hyperandrogenism, in infertile women with PCOS.
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138.
Factors predicting vitamin D response variation in non-Hispanic white postmenopausal women.
Zhao LJ, Zhou Y, Bu F, Travers-Gustafson D, Ye A, Xu X, Hamm L, Gorsage DM, Fang X, Deng HW, Recker RR, Lappe JM
EBM Reviews - Cochrane Central Register of Controlled Trials Journal of clinical endocrinology and metabolism.
97(8):2699-705, 2012 Aug.
[Journal Article.  Randomized Controlled Trial.  Research Support, N.I.H., Extramural.  Research Support, Non-U.S.
Gov't]
AN: CN-00854148  UPDATE
OBJECTIVE: It is well documented that there is wide variation in the response of serum 25-hydroxyvitamin D [25(OH)D] to
a given dose of vitamin D supplementation. Understanding factors affecting the response variation is important for
identifying subjects who are susceptible to vitamin D deficiency or toxicity. This study aimed to evaluate potential
predictors for vitamin D response variation.,  DESIGN AND PARTICIPANTS: A total of 1179 non-Hispanic white
postmenopausal women were enrolled into a 4-yr calcium and vitamin D (1100 IU/d) clinical trial. Among them, serum
25(OH)D level of 1063 subjects were measured at both baseline and after 12 months treatment. Vitamin D response was
computed for these 1063 subjects as the difference in levels of serum 25(OH)D concentration at the end of a 12-month
vitamin D treatment compared with baseline. Stepwise linear regression was used to identify predictors of vitamin D
response variation.,  RESULTS: Increase in vitamin D intake, baseline serum 25(OH)D level, baseline blood collection
season, baseline serum calcium level, and baseline body mass index were predictors of vitamin D response variation.
These five factors explained 46.8% of the vitamin D response variation in the 1063 subjects. The first three factors
[increase in vitamin D intake, baseline serum 25(OH)D level, baseline blood collection season] remained as predictors in
the 392 subjects with trial vitamin D supplementation. For the first time, our study indicated that season is an
important prediction factor for vitamin D response variation. Subjects who started vitamin D treatment in a cold season
(autumn and winter) achieved a significantly higher serum 25(OH)D increase than those started in a hot season (summer)
(P < 0.001).,  CONCLUSION: Our study suggests that the increase in vitamin D supplementation, baseline serum 25(OH)D
level, and the season when initiating the vitamin D supplementation can partially predict vitamin D response variation
in non-Hispanic postmenopausal women.
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139.
Narrowband ultraviolet B three times per week is more effective in treating vitamin D deficiency than 1600 IU oral
vitamin D3 per day: a randomized clinical trial
Bogh MK, Gullstrand J, Svensson A, Ljunggren B, Dorkhan M
EBM Reviews - Cochrane Central Register of Controlled Trials British journal of dermatology.  167(3):625-30, 2012.
[Comparative Study.  Journal Article.  Randomized Controlled Trial]
AN: CN-00856434  UPDATE
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145.
Vitamin D supplementation in the management of knee osteoarthritis: study protocol for a randomized controlled trial.
Cao Y, Jones G, Cicuttini F, Winzenberg T, Wluka A, Sharman J, Nguo K, Ding C
EBM Reviews - Cochrane Central Register of Controlled Trials Trials.  Vol.13, pp.131, 2012.
[Journal Article.  Randomized Controlled Trial.  Research Support, Non-U.S. Gov't]
AN: CN-00864727  UPDATE
BACKGROUND: Osteoarthritis (OA) is a common health issue worldwide in the aging population who are also commonly
deficient in vitamin D. Our previous study suggested that higher serum 25-(OH)D levels were associated with reduced knee
cartilage loss, implying that vitamin D supplementation may prevent the progression of knee OA. The aim of the VItamin D
Effects on OA (VIDEO) study is to compare, over a 2- year period, the effects of vitamin D supplementation versus
placebo on knee structural changes, knee pain, and lower limb muscle strength in patients with symptomatic knee OA.,
METHODS/DESIGN: Randomised, placebo-controlled, and double-blind clinical trial aiming to recruit 400 subjects (200 from
Tasmania and 200 from Victoria) with both symptomatic knee OA and vitamin D deficiency (serum [25-(OH)D] level of >12.5
nmol/liter and <60 nmol/liter). Participants will be randomly allocated to vitamin D supplementation (50,000 IU
compounded vitamin D3 capsule monthly) or identical inert placebo group for 2 years. The primary endpoint is loss of
knee cartilage volume measured by magnetic resonance imaging (MRI) and Western Ontario and McMaster Universities Index
of OA (WOMAC) knee pain score. The secondary endpoints will be other knee structural changes, and lower limb muscle
strength. Several other outcome measures including core muscle images and central blood pressure will be recorded.
Linear and logistic regression will be used to compare changes between groups using univariable and multivariable
modeling analyses. Both intention to treat and per protocol analyses will be utilized.,  DISCUSSION: The trial is
designed to test if vitamin D supplementation will reduce loss of knee cartilage volume, prevent the progression of
other knee structural abnormalities, reduce knee pain and strengthen lower limb muscle strength, thus modify disease
progression in knee OA.,  TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand
Clinical Trials Registry: ACTRN12610000495022.
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147.
Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or
cholecalciferol: implications for treatment and prophylaxis.
Cipriani C, Romagnoli E, Pepe J, Russo S, Carlucci L, Piemonte S, Nieddu L, McMahon DJ, Singh R, Minisola S
EBM Reviews - Cochrane Central Register of Controlled Trials Journal of clinical endocrinology and metabolism.
98(7):2709-15, 2013 Jul.
[Comparative Study.  Journal Article.  Randomized Controlled Trial]
AN: CN-00876374  UPDATE
CONTEXT: We previously showed that a single high dose of oral (po) cholecalciferol (D₃) sharply increases serum
25-hydroxyvitamin D [25(OH)D].,  OBJECTIVE: We evaluated the long-term bioavailability and metabolism of a single po or
intramuscular (im) high dose of ergocalciferol (D₂) or D₃.,  DESIGN: This was a prospective intervention study.,
SETTING: The study was conducted in an ambulatory care setting.,  PATIENTS: Participants were 24 subjects with
hypovitaminosis D.,  INTERVENTIONS: A single dose of 600,000 IU of po or im D₂ or D₃ was administered.,  MAIN
OUTCOME MEASURES: Serum 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)₂D] were measured at baseline and at days 30, 60,
90, and 120 by RIA. Serum 1,25(OH)₂D₂, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], 24,25-hydroxyvitamin D₂
[24,25(OH)D₂], and 24,25-hydroxyvitamin D₃ [24,25(OH)D₃] were measured by liquid chromatography-tandem mass
spectrometry in a subgroup of patients receiving the po formulations.,  RESULTS: The areas under the curve of 25(OH)D
after D₃ were significantly higher than those after D₂ (P < .0001). Serum 25(OH)D basal difference significantly
increased at day 30 with po D₂ and D₃ (P < .01 and P < .0001) and up to day 90 with po D₃ (P < .01). The im
formulations produced a slow increased, and values peaked at day 120 relative to the other time points (P < .0001). We
found a decrease in 1,25(OH)₂D at day 30 (P < .05) and up to day 120 (P < .001) and an increase in 1,25(OH)₂D₂ at
day 30 (P < .01) and up to day 120 (P < .01) after po D₂. Oral D₂ and D₃ produced increases in 24,25(OH)D₂ and
24,25(OH)D₃, respectively, at day 30 (P < .001).,  CONCLUSIONS: A po dose of 600,000 IU of D₂ or D₃ is initially
more effective in increasing serum 25(OH)D than the equivalent im dose and is rapidly metabolized. Our RIA assay for
1,25(OH)₂D may not recognize 1,25(OH)₂D₂.
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