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Originalien

Orthopde Haiting Wu1 Qingjiang Pang2


DOI 10.1007/s00132-017-3446-y 1
Department of Spine Surgery, Ningbo No. 2 Hospital, Ningbo, China
2
Department of Orthopaedics Center, Ningbo No. 2 Hospital, Ningbo, China
Springer Medizin Verlag GmbH 2017

The eect of vitamin D and


calcium supplementation on falls
in older adults
A systematic review and meta-analysis

Introduction on falls is inconsistent, it is necessary to results. The reference lists from arti-
establish whether vitamin D supplemen- cles identied in the database searches
Older adults have a high risk of falls tation has a benecial eect on falls in were examined to identify potentially
[1]. Each year, one in three community- older adults. relevant investigations. Manual searches
dwelling individuals aged 65 and older In addition, maintaining calcium in- complemented the number of potential
experiences at least one fall, and this take has long been recommended in older articles. After removing duplicated arti-
percentage increases with age [2]. Fall- individuals to treat and prevent osteo- cles, each title and abstract for potential
related fractures and injuries are a se- porosis [9, 10]. Vitamin D combined inclusion was screened by two reviewers
rious problem aecting quality of life with calcium supplementation aects cal- independently. Studies that reported
and are a major cause of hospitalization cium homeostasis and increases muscle odds ratios (ORs) and 95% condence
and death in older persons [3]. There- strength. These benets translate into intervals (CIs) or cross-table data were
fore, safe, feasible, eective, and cost- a reduction in falls. Therefore, we hy- included. If the article was potentially
eective primary prevention measures pothesized that the eect of vitamin D eligible for inclusion, the full text was
are needed to reduce falls in older men supplemented with calcium on the reduc- examined by two independent reviewers.
and women. Multifactorial approaches, tion in falls may be dierent compared to Any disagreement in study selection and
such as medical and occupational therapy vitamin D supplementation alone. Above data collection was discussed by the two
assessments or adjustments in medica- all, we conducted a meta-analysis to eval- reviewers. A total of 26 studies were
tions, behavioral instructions, and exer- uate the eect of vitamin D, administered found to t the criteria.
cise programs reduce falls. However, they either alone or in combination with cal- Meta-analysis needs to meet the fol-
are expensive, take considerable time to cium, on falls in older adults. lowing criteria: Considerring any type of
implement, and are strongly dependent falls, including recurrent (falls 2 over
on the compliance of subjects. Vita- Methods the study period) and injurious falls. Falls
min D deciency is common in the el- were dened as unintentionally coming
derly [4, 5]. Many studies have demon- Data sources and searches to rest on the ground, oor, or other
strated an association between vitamin D lower level. Older adults (mean age 60
deciency and falls. Vitamin D supple- We systematically searched literature years) dwelling both inside and outside of
mentation has been shown to improve databases including PubMed and the hospital. We included only double-blind
muscle strength, function, and balance Cochrane Library through December RCTs that studied any type of vitamin D.
[6]. There is a meta-analysis in healthy 2016 by using the following search
subjects supporting the benecial eects terms: (randomized controlled trial Abbreviations
of vitamin D supplementation on falls [7]. OR controlled clinical trial OR random RCT Randomized controlled trial
Nevertheless, there is also a review sug- allocation) AND (vitamin D OR chole-
gesting that the evidence that vitamin D calciferol OR hydroxycholecalciferol OR OD Odds ratio
supplementation improves physical per- calcifediol OR ergocalciferol OR calcid- CI Condence interval
formance in older people is insucient iol OR 25-hydroxyvitamin D OR 1, 25-
MD Mean deviation
[8], and several randomized, controlled dihydroxyvitamin D OR calcitriol OR
trials demonstrated that vitamin D did alfacalcidol OR paricalcitol OR calcium) VD2 Vitamin D2
not reduce the number of falls. Therefore, AND fall. Search terms were used in var- VD3 Vitamin D3
since the potential eect of vitamin D ious combinations to maximize search

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Originalien

16,146 were assigned to control groups


(. Table 1). The mean age SD of partic-
Articles identified in Articles identified in
PubMed (n=471) Cochrane Library (n=17) ipants in these studies varied from 67 2
to 92 6 years. Study sizes ranged from
64 to 9440 participants, with the dura-
tion of follow-up ranging from 1 month
Articles screened Irrelevant articles to 60 months. The evaluated dose of
(n=488) excluded (n=455) vitamin D ranged from 200 IU/day VD2
to 1000 IU/day VD2; in 11 of the 26
studies the dosage was 800 IU/day, six
Full-text articles assessed Articles excluded with studies used a total dosage ranging
(n=33) no data (n=7) from 300,000 IU/36 months VD2 to
600,000 IU/6 months VD2. In the stud-
ies conducted by Bischo-Ferrari et al.
Studies included in the [7, 11, 12], Grant et al. [13], Burleigh
meta-analysis (n=26) et al. [14], Flicker et al. [15], Prince et al.
[16], Pfeifer et al. [17], Krkkinen et al.
[18], Neelemaat et al. [19], Berggren et al.
Fig. 1 8 Flow diagram of the stepwise selection of relevant studies [20], Larsen et al. [21], Harwood et al.
[22], and Chapuy et al. [23], vitamin D
Case reports and series of course were of analysis (I2 > 50%), otherwise a xed- was supplemented in combination with
course excluded. We also excluded re- eect model was applied for the meta- calcium in older adults. Other studies
views focussing solely on specialist pop- analysis. Together with I2 values, 95% were supplemented with vitamin D2 or
ulations (Parkinsons disease, e.g. stroke, condence intervals (CI) were calculated D3 alone.
Alzheimers disease, myasthenia gravis) for each I2 value. Tests for overall eect In the study conducted by Grant et al.
in order to increase homogeneity. (Z score) were regarded signicant at [13], participants were randomly allo-
P < 0.05. cated to four equal groups and assigned
Data extraction We conducted subgroup analysis to two tablets with meals daily consisting
determine whether study conclusions of 800 IU vitamin D3, 1000 mg calcium
Two review authors working indepen- were aected by the type of vitamin D- (given as carbonate), vitamin D3 (800 IU)
dently and in parallel assessed the full raising intervention (D2 vs. D3) or combined with calcium (1000 mg), or
texts of included studies. The following calcium co-administration status (vita- placebo. In group 1, participants received
characteristics of each study were ex- min D vs. vitamin D + calcium). To vitamin D and calcium. In group 2,
tracted: rst author, year, sample size, provide a comparison between outcomes participants received vitamin D alone.
mean age, treatment, vitamin D dose reported by the studies, odds ratios and Since the participants were dierent in
(IU/day), and study duration. associated 95% condence intervals were the two groups, we regarded the two
performed from each study and graphs groups as two independent studies. In
Denitions created using Review Manager 5.3. OR the study conducted by Broe et al. [31],
values under 1.00 were associated with vitamin D was supplemented in dierent
Our primary outcome measure was the a decreased risk for falls as a result of doses; again, we regarded the two groups
relative risk of having at least one fall the vitamin D-raising intervention. as two independent studies.
among older individuals receiving vita- All studies included were examined
min D compared with those not receiv- Results for heterogeneity; the heterogeneity of
ing vitamin D. Falls were recorded by the all studies was determined to be low: P <
nurses or the patients themselves in a fall Characteristics of included studies 0.001, I2 = 79% for vitamin D2, P = 0.130,
diary. I2 = 42% for vitamin D3, and P = 0.030,
Our literature search identied 488 I2 = 46% for vitamin D plus calcium. Ac-
Data analysis records, 33 of which were reviewed as cordingly, a random-eect model and a
full-text articles for inclusion. After fur- xed-eect model were applied for fur-
The heterogeneity of results between ther exclusions based on our selection ther meta-analysis.
studies was determined by I2. For I2, criteria, 26 provided sucient informa-
values of 25% to <50% were considered tion for data extraction and were deemed Main outcomes
low heterogeneity, 50% to <75% mod- suitable for our nal analysis (. Fig. 1).
erate, and 75% highly heterogeneous. In total, these randomized controlled tri- The eects of vitamin D2 supplementa-
A random-eect model was used when als included 32,686 older adults; 16,540 tion on falls in the studies included are
there was heterogeneity in the meta- received vitamin D intervention and shown in . Fig. 2. We found no signi-

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Abstract Zusammenfassung

cant association between vitamin D2 and Orthopde DOI 10.1007/s00132-017-3446-y


a reduction in the risk of falls (OR for Springer Medizin Verlag GmbH 2017
the risk of suering at least one fall, 0.77;
95% CI, 0.581.03; I2 = 79%; . Fig. 2). H. Wu Q. Pang
The eects of vitamin D3 supplemen- The eect of vitamin D and calcium supplementation on falls in
tation on falls in the studies included are older adults . A systematic review and meta-analysis
shown in . Fig. 3. We found no signi-
cant association between vitamin D3 and Abstract
a reduction in the risk of falls (OR for Objectives. A number of studies have vitamin D supplementation, while 16,146
hypothesized that vitamin D is a potential were assigned to control groups. The meta-
the risk of suering at least one fall, 1.08;
factor in the prevention of falls in the analysis showed that combined vitamin D plus
95% CI, 0.981.20; I2 = 42%; . Fig. 3). elderly; however, the eect of vitamin D is calcium supplementation has a signicant
The eects of vitamin D combined still inconsistent and not quantitative. We eect on the reduction in the risk of falls (OR
with calcium supplementation on falls conducted this meta-analysis to assess the for the risk of suering at least one fall, 0.87;
for the included studies are shown in eect of vitamin D on falls among elderly 95% CI, 0.800.94). However, no signicant
individuals. association between vitamin D2 or D3 and a
. Fig. 4. We found a signicant associa-
Methods. The PubMed and Cochrane Library reduction in the risk of falls was found (OR,
tion between vitamin D combined with databases were searched from the earliest 0.77; 95% CI, 0.581.03 for vitamin D2, and
calcium supplementation and a reduc- possible year up to December 2016. Two OR, 1.08; 95% CI, 0.981.20 for vitamin D3).
tion in the risk of falls (OR for the risk authors working independently reviewed the Conclusions. Combined calcium plus
of suering at least one fall, 0.87; 95% trials, and odds ratios (ORs) were calculated vitamin D supplementation is statistically
using a xed-eect or random-eect model signicantly associated with a reduction in fall
CI, 0.800.94; I2 = 46%; . Fig. 4).
by Review Manager 5.3. We included only risks across various populations.
For the eight RCTs comparing vi- double-blind randomized, controlled trials
tamin D with controls, individual and (RCTs) of vitamin D in elderly populations that Keywords
pooled mean dierences for the eight examined fall results. Vitamin D Calcium 25-Hydroxyvitamin D 1,
outcome measures are shown in . Fig. 5. Results. A total of 26 articles were included 25-Dihydroxyvitamin D Fall risk Elderly
According to . Fig. 5, vitamin D treat- in which 16,540 elderly individuals received
ment signicantly increased the pooled
mean values for serum 25-hydroxyvita-
Einuss der Vitamin-D- und Kalziumsupplementierung auf Strze
min D compared with control treatment
(MD, 10.04; 95% CI, 1.5318.55; I2 =
bei lteren Erwachsenen. Eine systematische bersicht und
100%). Metaanalyse
Among the three RCTs, vitamin D Zusammenfassung
treatment signicantly increased the Zielsetzung. In zahlreichen Studien wurde erhielten und 16.146 Personen Kontrollgrup-
pooled mean values for serum 1, 25-hy- spekuliert, dass Vitamin D ein potenzieller pen zugeteilt waren. Wie die Metaanalyse
droxyvitamin D compared with control Faktor in der Sturzprvention bei lteren ergab, hat die kombinierte Vitamin-D- und
treatment (MD, 7.23; 95% CI, 0.2114.25; Menschen ist. Der Eekt ist jedoch weiterhin Kalziumsupplementierung einen signikan-
widersprchlich und nicht quantiziert. In ten Eekt auf die Reduktion des Sturzrisikos
I2 = 89%; . Fig. 6). der vorliegenden Metaanalyse haben wir den (OR fr das Risiko, mindestens einen Sturz
Einuss von Vitamin D auf Strze bei lteren zu erleiden 0,87; 95%-Kondenzintervall
Discussion Menschen untersucht. [KI] 0,800,94). Dagegen fand sich keine
Methoden. Die Datenbanken PubMed und signikante Assoziation zwischen Vitamin D2
We conducted a meta-analysis to evaluate Cochrane Library wurden vom frhesten oder D3 und einer Reduktion des Sturzrisikos
erfassten Jahr bis Dezember 2016 durchsucht. (fr Vitamin D2: OR 0,77; 95%-KI 0,581,03; fr
the best available research evidence re- Vitamin D3: OR 1,08; 95%-KI 0,981,20).
Zwei Autoren sichteten unabhngig die
garding the eect of vitamin D on falls. Studien. Unter Anwendung von Review Schlussfolgerungen. Die kombinierte
This meta-analysis included 26 articles Manager 5.3 wurden mit einem Fixed-eects- Vitamin-D- und Kalziumsupplementierung
with 16,540 elderly individuals treated oder Random-eects-Modell Odds Ratios (OR) ist ber verschiedene Populationen hinweg
with dierent vitamin D analogues for berechnet. Einschluss in die Analyse fanden statistisch signikant mit einer Reduktion des
nur doppelblinde, randomisierte, kontrollierte Sturzrisikos assoziiert.
2 months up to 3 years. In all of these
Studien (RCT), in denen Vitamin D in
trials, the method of fall ascertainment Populationen lterer Menschen eingesetzt Schlsselwrter
and fall denitions were specied. Par- und Sturzergebnisse ausgewertet wurden. Vitamin D Kalzium 25-Hydroxyvitamin D
ticipants included healthy individuals liv- Ergebnisse. Insgesamt wurden 26 Beitrge 1,25-Dihydroxyvitamin D Sturzrisiko ltere
ing in the community, as well as hospital eingeschlossen, in denen 16.540 ltere Menschen
Menschen eine Vitamin-D-Supplementierung
inpatients. Evidence suggested that a re-
duction in the risk of falls depends on the
type of vitamin D supplementation. We
found a statistically signicant reduction
in the risk of falls in the sub-analyses of
vitamin D combined with calcium sup-

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Originalien

Table 1 Characteristics of the studies included in the meta-analysis


First author Year Falls/total Age Study Treatment
Experiment Control duration Experiment Control
(months)

Graafmans et al. [24] 1996 62/177 65/177 83 6 7 400 IU/day VD3 Placebo
Pfeifer et al. [25] 2000 11/74 19/74 75 0.5 12 1200 mg Ca+800 IU 1200 mg/Day Ca
VD3/Day
Chapuy et al. [23] 2002 251/393 118/190 85 7 24 1200 mg Ca+800 IU Placebo
VD3/Day
Bischo et al. [26] 2003 14/62 18/60 85 7 3 1200 mg Ca+800 IU 1200 mg/Day Ca
VD3/Day
Latham et al. [8] 2003 64/108 60/114 79 2 6 300,000 IU VD3 Placebo
Trivedi et al. [27] 2003 254/1027 261/1011 75 5 60 100,000 IU/4 Months VD3 Placebo
Dhesi et al. [28] 2004 11/70 14/69 77 6 6 600,000 IU VD2 Placebo
Harwood et al. [22] 2004 7/29 13/35 81 (6792) 12 1000 mg Ca+800 IU Control
VD3/Day
Grant et al. [13] 2005 161/1306 196/1332 77 6 45 1000 mg Ca+800 IU Placebo
VD3/Day
219/1343 196/1332 77 6 45 1000 mg/Day Ca Placebo
185/1311 196/1332 77 6 45 800 IU/Day VD3 Placebo
Flicker et al. [15] 2005 170/313 185/312 83 8 24 600 mg Ca+1000 IU 600 mg/Day Ca
VD2/Day
Larsen et al. [21] 2005 466/2491 403/2116 74 (65103) 42 1000 mg Ca+400 IU Control
VD3/Day
Sato et al. [29] 2005 11/48 33/48 74 4 24 1000 IU/Day VD2 Placebo
Bischo et al. [12] 2006 107/219 124/226 71 5 36 500 mg Ca+700 IU Placebo
VD3/Day
Bischo et al. [11] 2006 6/33 8/31 86 6 3 600 mg Ca+400 IU 600 mg/Day Ca
VD3/Day
Law et al. [30] 2006 770/1762 833/1955 85 10 1100 IU/day VD2 Control
Broe et al. [31] 2007 15/26 11/25 92 6 5 200 IU/day VD2 Placebo
15/25 11/25 88 5 5 400 IU/day VD2 Placebo
15/25 11/25 89 5 5 600 IU/day VD2 Placebo
5/23 11/25 89 5 5 800 IU/day VD2 Placebo
Burleigh et al. [14] 2007 36/100 45/103 83 7 1 1200 mg Ca+800 IU 1200 mg/Day Ca
VD3/Day
Smith et al. [32] 2007 2544/4727 2577/4713 79 3 36 300,000 IU VD2 Placebo
Berggren et al. [20] 2008 44/102 55/97 82 6 12 1000 mg Ca+800 IU Control
VD/Day
Prince et al. [16] 2008 80/151 95/151 77 5 12 1000 mg Ca+1000 IU 1000 mg/Day Ca
VD2/Day
Pfeifer et al. [17] 2009 49/122 75/120 77 4 20 1000 mg Ca+800 IU 1000 mg/Day Ca
VD3/Day
Krkkinen et al. [18] 2010 812/1566 833/1573 67 2 36 1000 mg Ca+800 IU Placebo
VD3/Day
Sanders et al. [33] 2010 837/1131 769/1125 76 4 3660 500,000 IU/Year VD3 Placebo
Witham et al. [34] 2010 2/53 5/52 79 6 5 100,000 IU/4 Weeks VD2 Placebo
Glendenning et al. [35] 2012 102/353 89/333 77 4 9 150,000 IU/3 Months VD3 Placebo
Neelemaat et al. [19] 2012 10/100 24/104 75 10 3 864 mg Ca+600 IU Placebo
VD3/Day

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Fig. 2 8 Correlation between vitamin D2 and falls in the meta-analysis

Fig. 3 8 Correlation between vitamin D3 and falls in the meta-analysis

plementation on the risk of falls. The injection of 300,000 IU vitamin D2 had falls. According to previous studies and
pooled results found a statistically signif- no eect in preventing falls when com- meta-analyses, the combination of cal-
icant 6% reduction in the risk of falling pared with placebo [32]. What is more, cium with vitamin D is important for
with vitamin D combined with calcium Sanders et al. even found a contrast- fall prevention [38]. An earlier study by
compared with the control group. How- ing result: the participants receiving an- Bischo et al. reported a 49% reduction
ever, there is no signicant association nual high-dose oral cholecalciferol expe- in falls during a 3-month intervention
between vitamin D2 or D3 supplemen- rienced 15% more falls than the placebo with 800 IU vitamin D and 1200 mg
tation and falls. group [33]. In line with these studies, calcium [26]. A meta-analysis showed
Although vitamin D is used to prevent no signicant association between vita- that vitamin D and calcium supplemen-
falls, the current evidence for an eect min D2 or D3 supplementation and falls tation reduced the falls risk by 21%
of supplementary vitamin D alone on was found in this meta-analysis. How- [39]. Calcium intake is signicantly
fall outcomes is limited and conicting. ever, our results indicate that a vitamin D lower in developing countries due to
There continues to be evidence suggest- supplement is able to signicantly in- the decient use of dairy products. Vi-
ing that vitamin D alone has no eect on crease serum 25-hydroxyvitamin D and tamin D together with calcium is the
reducing the risk of falls. In the study serum 1, 25-dihydroxyvitaminDlevels in recommended combination for achiev-
conducted by Latham et al., the vita- the elderly. Previous studies also showed ing health benets. Increasing calcium
min D intervention was given in a single that serum 25-hydroxyvitamin D levels intake either by dietary sources or sup-
oral dose. Patients received 300,000 IU are associated with quadriceps strength plements has benecial eects on bone
vitamin D3. However, there was no ef- and balance. density. Specically, a single interven-
fect of vitamin D3 supplementation on Older people are recommended to tion with vitamin D plus calcium over
physical function in older people, even take at least 10001200 mg/day of cal- a 3-month period reduced the risk of
in those patients with low 25-OH-D lev- cium to treat and prevent osteoporosis falling by 49% and signicantly improved
els [36]. The largest population-based, [37]. There is increasing evidence to musculoskeletal function compared with
randomized, double blind, placebo-con- suggest that vitamin D combined with calcium alone in older adults [26]. Sim-
trolled trial found that an annual i. m. calcium produces a benecial eect on ilarly, vitamin D plus calcium compared

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Originalien

Fig. 4 8 Correlation between vitamin D combined with calcium and falls in the meta-analysis

Fig. 5 8 Forest plot comparing the eect of vitamin D on 25-hydroxyvitamin D

with calcium alone improved quadriceps min D work together synergistically on Safety
strength by 8% and decreased body sway the bone, and the results of our meta-
by 9% within 2 months in elderly women analysis support their combined use to Although quantitative safety data of vita-
[25]. It is well known that vitamin D reduce fall risk. min D supplementation in humans has
promotes calcium absorption and helps not been reported denitively, a number
to maintain adequate serum calcium of studies have found no adverse side
concentrations to enable normal bone eects in humans. In fact, the majority
mineralization. Thus, calcium and vita- of these studies indicate that vitamin D

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Fig. 6 8 Forest plot comparing the eect of vitamin D on 1, 25-dihydroxyvitamin D

is safe. The optimal dose of vitamin D 12. Bischo-Ferrari HA, Orav EJ, Dawson-Hughes B
Compliance with ethical (2006) Eect of cholecalciferol plus calcium on
is currently not conclusive: most studies guidelines falling in ambulatory older men and women: a 3-
advise taking 800 IU of vitamin D daily year randomized controlled trial. Arch Intern Med
for the maximum benet. The consump- 166:424430
Conict of interest. H. Wu and Q. Pang declare that 13. Grant AM, Avenell A, Campbell MK, McDonald
tion of vitamin D in dosages as high as they have no competing interests. AM, MacLennan GS, McPherson GC, Anderson
1000 IU/day was not found to have any FH, Cooper C, Francis RM, Donaldson C, Gillespie
This article does not contain any studies with human WJ, Robinson CM, Torgerson DJ, Group RT (2005)
side eects in humans. Along with deter- participants or animals performed by any of the au- Oral vitamin D3 and calcium for secondary
mining an optimal dose, the long-term thors. prevention of low-trauma fractures in elderly
safety of vitamin D supplementation in people (Randomised Evaluation of Calcium Or
older adults needs to be assessed. vitamin D, RECORD): a randomised placebo-
controlled trial. Lancet 365:16211628
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