© The Au ho 2017. Published by Ox o d Uni e si y P ess on behal o The Ge on ological Socie y o Ame ica. 1239
Jou nals o Ge on ology: Medical Sciences
ci e as: J Ge on ol A Biol Sci Med Sci, 2017, Vol. 72, No. 9, 1239–1245
doi:10.1093/ge ona/glx044
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Resea ch A icle
A 2-Yea Follow-Up A e a 2-Yea RCT wi h Vi amin D
and Exe cise: E ec s on Falls, Inju ious Falls and Physical
Func ioning Among Olde Women
Ki s i Uusi-Rasi,1 Radhika Pa il,1 Saija Ka inkan a,1 Pekka Kannus,1,2
Ka iTokola,1 Ch is elLambe g-Alla d ,3 and Ha iSie änen1
1The UKK Ins i u e o Heal h P omo ion Resea ch, Tampe e, Finland. 2Depa men o O hopaedics and T auma Su ge y, Tampe e
Uni e si y Hospi al, Tampe e Medical School, Uni e si y o Tampe e, Tampe e, Finland. 3Depa men o Food and En i onmen al Sciences,
Uni e si y o Helsinki, Helsinki, Finland.
Add ess co espondence o Ki s i Uusi-Rasi, PhD, The UKK Ins i u e o Heal h P omo ion Resea ch, P.O. Box 30, FI-33501 Tampe e, Finland.
E-mail: [email p o ec ed]
Recei ed No embe 9, 2016; Edi o ial Decision Da e Feb ua y 28, 2017
Decision Edi o : S ephen K i che sky, PhD
Abs ac
Backg ound: Bo h exe cise and i amin D a e ecommended means o p e en alls among olde adul s, bu hei combined e ec s on all-
induced inju ies a e sca cely s udied.
Me hods: A 2-yea ollow-up o a p e ious 2-yea andomized con olled ial wi h i amin D and exe cise (Ex) o 409 olde home-dwelling
women using a ac o ial 2 × 2 design (D−Ex−, D+Ex−, D−Ex+, D+Ex+). Besides mon hly all dia ies, emo al neck bone mine al densi y ( n-BMD),
and physical unc ioning we e assessed a 1 and 2 yea s a e he in e en ion.
Resul s: A e he in e en ion, S-25OHD concen a ions declined o baseline le els in bo h supplemen g oups. The g oups did no di e o
change in n-BMD o physical unc ioning, excep o leg ex enso muscle s eng h, which emained abou 10% g ea e in he exe cise g oups
compa ed wi h he e e ence g oup (D−Ex−). The e we e no be ween-g oup di e ences in he a e o all alls, bu medically a ended inju ious
alls educed in D+Ex− and D−Ex+ g oups compa ed wi h D−Ex−. Howe e , all o me ea men g oups had less medically a ended inju ed
alle s, HRs (95% CI) being 0.62 (0.39–1.00) o D+Ex−, 0.46 (0.28–0.76) o D−Ex+, and 0.55 (0.34–0.88) o D+Ex+, compa ed wi h D−Ex−.
Conclusions: Exe cise-induced bene i s in physical unc ioning pa ly emained 2yea s a e cessa ion o supe ised aining. Al hough he e
was no di e ence in he a e o all alls, o me exe cise g oups con inued o ha e lowe a e o medically a ended inju ed alle s compa ed
wi h e e en s e en 2yea s a e he in e en ion. Vi amin D wi hou exe cise was associa ed wi h less inju ious alls wi h no di e ence in
physical unc ioning.
Keywo ds: Physical unc ioning—Inju ious alls—Vi amin D—Exe cise
In oduc ion
The numbe o olde people will inc ease o e he nex decades,
accompanied wi h inc eased numbe o alls and all- ela ed inju-
ies, and e ec i e means o p e en ing alls and subsequen con-
sequences a e needed. Many isk ac o s o alls and all-induced
inju ies a e ela ed o physical inac i i y and low unc ional abili y
(e.g. mobili y limi a ions, educed lowe limb muscle s eng h, and
balance de ici ), and also o bone agili y in case o ac u es. Also
slow p ocessing speed in he abili y o eac o pe u ba ion may
explain inc eased isk o inju ious alls (1). All hese can be modi ied
by exe cise (2,3). The e is e idence om andomized con olled i-
als and sys ema ic e iews and me a-analyses ha egula s eng h
and balance aining can educe he isk o alling in communi y-
dwelling olde adul s by 15–50% (4–6). Vi amin D de iciency has
also been shown o be associa ed wi h lowe physical unc ioning
and g ea e isk o alls and ac u es in olde people (7–9). Howe e ,
ecen andomized con olled ial (RCTs) wi h high i amin D doses
ha e shown ei he no bene i (10) o e en ha m ul e ec s on lowe
ex emi y physical unc ioning, alls and ac u es (11,12). No did
a ecen RCT o exe cise and i amin D show any syne gic e ec on
alls in olde women (13).
Cu en ly, bo h exe cise and i amin D supplemen a ion a e ec-
ommended o p e en ion o alls among olde adul s. In pa icula ,
exe cise including s eng h and balance aining has been shown
o educe alls and inju ious alls, bu he esul s a e ye inconsis -
en (14–16). The e is also some e idence ha bene i s may las , a
leas o some ex en , a e cessa ion o he in e en ion as long as
he aining induced physical pe o mance is main ained (17). So a ,
only ew s udies ha e e alua ed a e o alls o inju ious alls once
he exe cise aining is s opped (17–20), bu i seems ha he isk o
inju ious alls emains educed e en a e cessa ion o he supe ised
exe cise aining (19). To ou knowledge, he e a e no ollow-ups
a e ceasing i amin D supplemen a ion.
P e iously, we showed ha supe ised exe cise aining educed
medically a ended inju ious alls among home-dwelling olde
women, while he a e o all alls was a ec ed by nei he exe cise
no i amin D in e en ion. Exe cise also imp o ed physical unc-
ioning, while i amin D did no (13). The aim o his p e-planned
2-yea ollow-up o he DEX ial was o assess whe he he ben-
e i s o mul imodal supe ised exe cise aining in educing alls and
medically a ended inju ious alls pe sis a e ceasing he aining.
In pa icula , we examined he esidual e ec s o he in e en ion on
alls, all-induced inju ies and physical unc ioning o up o 2-yea
a e comple ion o he in e en ion.
Me hods
T ialDesign
This s udy is a 2-yea ollow-up o he 2-yea double-blind, placebo-
con olled i amin D and open exe cise DEX ial (NCT00986466).
The pe iod o supe ised exe cise and i amin D/placebo supplemen-
a ion deno es he in e en ion pe iod (0–24mon hs) (21). The sub-
sequen 2-yea pe iod a e he in e en ion (24–48mon hs) deno es
he ollow-up pe iod, which is epo ed he e.
Pa icipan s
Ini ially, 409 home-dwelling 70-80-yea -old women we e andomly
assigned o one o ou g oups: (a) i amin D 20µg/day (800 IU)
and exe cise (D+Ex+) (b) placebo and exe cise (D−Ex+) (c) i amin D
20µg/day wi hou exe cise (D+Ex−), and (d) placebo wi hou exe -
cise (D−Ex−). The in e en ion esul s ha e been epo ed p e iously
(13,22). O he 370 women who comple ed he in e en ion, 15
we e unable o unwilling o con inue wi h he ollow-up. Fi e mo e
women wi hd ew du ing he ollow-up pe iod (Figu e1).
The s udy p o ocol was app o ed by he E hics Commi ee o
he Pi kanmaa Hospi al Dis ic , Finland (R09090). Each pa ici-
pan p o ided he w i en in o med consen p io o andomiza ion.
The exe cise aining p og am has been desc ibed p e iously
(21). B ie ly, exe cise consis ed o supe ised g oup aining classes
wo imes a week o he i s yea , and once a week o he second
yea o he in e en ion. The aining p og am was p og essi e and
consis ed o s eng h, balance, agili y, and mobili y aining, bo h in
he exe cise hall and gymnasium. Pa icipan s in he non-exe cising
g oup we e asked o main ain hei p e-s udy le el o physical ac i -
i y du ing he in e en ion. All pa icipan s ecei ed a bookle o
home exe cise aining a e he in e en ion.
Da a Collec ion
The numbe o alls was ob ained om p ospec i e all dia ies
e u ned mon hly ia mail, and de ails o each egis e ed all we e
asce ained o e elephone h oughou he 48-mon h s udy pe iod.
A all was de ined “an unexpec ed e en in which he pa icipan
comes o es on he g ound, loo o lowe le el.” (23) Inju ious alls
we e classi ied as mino inju ious alls and medically a ended inju i-
ous alls, he la e being hose o which pa icipan s sough medi-
cal ca e (nu se, physician, o hospi al) and included inju ies such as
b uises, ab asions, con usions, sp ains, ac u es, and head inju ies.
This classi ica ion con o ms wi h ha p oposed by Schwenk e al.
(24). The Pegasos pa ien medical eco ds o he Ci y o Tampe e
we e sea ched o all pa icipan s’ u iliza ion o heal hca e se ices
due o inciden alls du ing he ollow-up pe iod, o ind possibly
un epo ed all inju ies o which medical a en ion was sough .
Du ing ollow-up, all measu emen s we e done yea ly (a 36 and
48mon hs om baseline). Die a y in ake o calcium and i amin D
we e assessed wi h a alida ed ood equency ques ionnai e (25).
In addi ion o heigh and weigh , body composi ion and a eal bone
mine al densi y ( n-BMD) o he le emo al neck was assessed using
dual-ene gy X- ay abso p iome y (DXA, Luna P odigy Ad ance,
GE Luna , Madison. WI) (26).
Physical unc ioning was assessed by he Sho Physical
Pe o mance Ba e y (SPPB) (27), which comp ised s a ic balance, 4
m no mal walking speed and i e- ime chai s and es s, and by he
Timed up and go (TUG) es (28). Dynamic balance was assessed using
backwa ds walking (29). Maximal isome ic leg-ex enso s eng h
a a knee angle 110° was measu ed by a s ain gauge dynamome e
(Tam on, Tampe e, Finland). The Communi y Heal hy Ac i i ies
Model P og am o Senio s (CHAMPS) physical ac i i y ques ion-
nai e o olde adul s was used o moni o changes in physical ac i i y.
In addi ion, each pa icipan eco ded he daily s eps wi h a pedom-
e e (Om on HJ-112-E) o e he en i e 48-mon h pe iod.
Analysis o 25-Hyd oxy-Vi aminD
Fas ing se um 25-hyd oxy- i amin D (S-25OHD) was measu ed ial
wi h a manual OCTEIA immunoenzymome ic assay (IDS, Boldon,
UK) du ing he in e en ion, and wi h an au oma ed IDS-iSYS analyze
(IDS) du ing he ollow-up. Rep oducibili y was ensu ed by adhe -
ing o he Vi amin D Ex e nal Quali y Assessmen Scheme, DEQAS
(deqas.kmpd.co.uk). In e assay a ia ion was a oided by measu ing
all samples om he same pa icipan s in he same se ies. Acco ding
o he manu ac u e he esul s om he wo assays co ela e e y well
( =0.99). The eg ession equa ion be ween he wo me hods ende ed
a posi i e o nega i e bias o 1–3nmol/L be ween 50–80nmol/L.
S a is ical Analysis
All da a we e analyzed on an in en ion- o- ea basis (ITT). Changes
om baseline o he end o he in e en ion (0–24mon hs) ha e been
epo ed p e iously (13). He e we epo changes du ing he ollow-up
pe iod (24–48mon hs). Incidence a es o alls we e calcula ed as he
o al numbe o alls di ided by he ime o e which alls we e moni-
o ed (100 pe son-yea s) in each g oup. Nega i e binomial eg ession
was used o es ima e incidence a e a ios (IRR) o alls and inju ious
alls, and Cox- eg ession models o calcula ing haza d a ios (HR)
o alle s and inju ed alle s in each g oup, wi h he D−Ex− g oup
as e e ence. Only HR was analyzed o he en i e 48-mon h pe iod,
modeling he ime o i s all (i.e. becoming a alle ).
Fo physical unc ioning and BMD, be ween-g oup di e ences
(24–48mon hs) we e es ima ed by linea mixed models o no mally
1240 Jou nals o Ge on ology: MEDICAL SCIENCES, 2017, Vol. 72, No. 9
dis ibu ed ou comes ( n-BMD, walking speed and isome ic mus-
cle s eng h), and gene alized linea mixed models (GLMM) o
non-no mally dis ibu ed ou comes (TUG, backwa ds walking and
chai s and) using possible con ounding ac o s (e.g. age, heigh and
weigh ) as co a ia es. These me hods allowed he inco po a ion o
incomple e longi udinal da a in o he analysis.
Resul s
Follow-up measu emen s a 48mon hs we e done o 350 pa icipan s
(85.6% o he o iginal sample; he main eason o discon inua ion
was poo heal h). Desc ip i e cha ac e is ics a baseline (0mon hs) a e
gi en in Table1, he e we e no be ween-g oup di e ences in n-BMD
o physical unc ioning. Die a y in ake o calcium and i amin D we e
adequa ely main ained h oughou he s udy, he mean (SD) daily cal-
cium in ake was 1098 (378) mg and i amin D in ake 10.4 (3.9) µg a
baseline, and 1182 (387) mg and 11.6 (4.9) µg a he end o he ollow-
up (48mon hs), espec i ely. A e he in e en ion, S-25OHD concen-
a ions s a ed o decline owa ds baseline le els in bo h supplemen
g oups; mean S-25OHD being 72.5 (18.5) nmol/L a 48mon hs (see
Supplemen a y Figu e1) showing no di e ence be ween he o me
i amin D supplemen ed g oups and he placebo g oups (p=.15).
Falls and Inju iousFalls
O 635 alls in 226 alle s, 356 alls (56%) esul ed in inju ies. O
hese 356 inju ious alls, 116 (33%) we e a ended medically. The e
was no signi ican di e ence be ween g oups o he a e o all alls
o mino inju ious alls, bu less medically a ended inju ious alls
occu ed in he D+Ex− and D−Ex+ g oups compa ed wi h he e e -
ence g oup (D−Ex−) (Table2). All o me ea men g oups had less
medically a ended inju ed alle s HR (95% CI) being 0.62 (0.39–
1.00) o D+Ex−, 0.46 (0.28–0.76) o D−Ex+, and 0.55 (0.34–0.88)
o D+Ex+, when compa ed wi h D−Ex− (see Supplemen a y Figu e2).
Femo al Neck BMD and Physical Func ioning
Absolu e baseline alues a he end o he in e en ion (24mon hs)
and pe cen age changes du ing ollow-up (36 and 48mon hs) a e
gi en in Table3. Femo al neck BMD declined sligh ly in all g oups
du ing he ollow-up pe iod (Table3).
A e he end o he in e en ion, physical unc ioning showed
gene al decline du ing he 2-yea ollow-up wi h no be ween-g oup
di e ences in changes indica ing ha he achie ed mean ea men
e ec s compa ed wi h he e e ence g oup we e la gely main ained
(Table 3). The e we e no signi ican changes in no mal walking
speed o chai s and ime, no did any o he in e en ion g oups
di e om D−Ex−. The TUG es ime inc eased indica ing educed
pe o mance in all g oups excep o D−Ex+, in which i emained
unchanged. Isome ic leg ex enso muscle s eng h declined signi i-
can ly in he o me exe cise g oups bu was main ained in he non-
exe cise s. S ill, a he end o he ollow-up he maximal isome ic
leg ex enso s eng h was signi ican ly g ea e in he o me exe cise
g oups, mean di e ence being 10% o D+Ex+ and 8% o D−Ex+
compa ed wi h D−Ex−. Change in p opo ion o he women able o
do backwa ds walking es was simila in all g oups, indica ing ha
Figu e1. T ial p o ile.
Jou nals o Ge on ology: MEDICAL SCIENCES, 2017, Vol. 72, No. 9 1241
he o me exe cise g oups had main ained he bene i compa ed
wi h D−Ex− (Table3, and Supplemen a y Figu e3).
Habi ual physical ac i i y declined sligh ly. The equency o
mode a e-in ensi y physical ac i i y (CHAMPS) declined in all ou
g oups om he baseline mean o 6.7 (5.0) o 5.2 (4.3) h/week being
simila in all g oups a he end o he ollow-up (p=.79). Mean num-
be o daily s eps also educed by abou 400 s eps om he baseline
mean o abou 6,000 wi h no be ween-g oup di e ences (p=.77).
Discussion
This 2-yea ollow-up o he 2-yea DEX ial showed no be ween-
g oup di e ences in alls o alle s in gene al, bu esul s we e di -
e en o medically a ended inju ious alls. Du ing he ollow-up,
bo h D+Ex− and D−Ex+ had signi ican ly less medically a ended
inju ious alls compa ed wi h D−Ex−. Howe e , in all in e en ion
g oups, including D+Ex−, he e we e less medically a ended inju ed
alle s compa ed wi h D−Ex−, in spi e o he inding ha D+Ex− did
no di e om D−Ex− in physical unc ioning ei he du ing he
in e en ion o ollow-up and physical unc ioning declined also in
he exe cise g oups a e ceasing he supe ised aining. Wi hou
i amin D supplemen a ion, also S-25OHD concen a ions declined
owa ds baseline le els in bo h supplemen ed g oups, while he e
was no signi ican change in mean concen a ions in he o me pla-
cebo g oups.
Femo al neck BMD declined h oughou he 4-yea s udy pe iod
in all g oups. Nei he i amin D no exe cise could p e en bone
loss, al hough i s a e educed sligh ly du ing he 2-yea in e en ion.
The amoun o bone loss was simila o p e ious s udies showing less
han 1% annual bone loss among olde women (30). Hansen e al.
showed ha e en high dose cholecalci e ol did no meaning ully
a ec BMD sugges ing ha la ge inc eases in calcium abso p ion a e
needed o inc ease BMD (10). Also he in ensi y o mechanical load-
ing which may esul in inc eased BMD needs likely o be g ea e
han he aining gi en in his s udy (17,18).
A he end o he 2-yea ollow-up, some o he exe cise-induced
gain in physical unc ioning was main ained; he o me exe cise s
con inued o ha e be e balance han he e e ence g oup. Also,
abou a hal o aining-induced gains in isome ic muscle s eng h
emained ill he end o he ollow-up. O he es s o physical unc-
ioning showed sligh decline in all g oups and be ween-g oup di -
e ences achie ed du ing he in e en ion we e mos ly main ained.
Howe e , be e physical unc ioning canno explain he ewe medi-
cally a ended inju ious alls seen in D+Ex−, because his g oup did
no di e om he e e ence g oup ei he du ing he in e en ion o
ollow-up.
Table2. Ra e o Falls pe 100 Pe son-Yea s in Each S udy G oup Du ing he 2-Yea Follow-Up (24–48mon hs), and Incidence Ra e Ra ios
(IRR) (95% CI) o Falls and Inju ious Falls and Haza d Ra io (HR) (95% CI) Fo Falle s and Inju ed Falle s
Ou come D−Ex−D+Ex−D−Ex+D+Ex+
Falls, all 103.0 81.5 84.2 97.1
Mino inju ious alls 29.4 20.1 20.0 24.3
Medically a ended inju ious alls 23.8 10.6 10.6 21.4
Falls wi h ac u es 4.0 3.0 2.9 5.1
IRR
All alls 1 0.78 (0.53–1.14) 0.80 (0.55–1.18) 0.88 (0.60–1.28)
Mino inju ious alls 1 0.66 (0.38–1.13) 0.68 (0.39–1.16) 0.79 (0.47–1.33)
Medically a ended inju ious alls 1 0.45 (0.23–0.87) 0.44 (0.23–0.86) 0.84 (0.48–1.50)
HR
All alle s 1 0.86 (0.63–1.19) 1.01 (0.74–1.39) 0.99 (0.72–1.38)
Medically a ended inju ed alle s 1 0.62 (0.39–1.00) 0.46 (0.28–0.76) 0.55 (0.34–0.88)
No e: D−Ex−=placebo; D+Ex−=20µg i amin D daily; D−Ex+=placebo + exe cise; D+Ex+=20µg i amin D daily + exe cise.
Table1. Desc ip i e G oup Cha ac e is ics (mean, SD) a he Baseline o he 2-Yea In e en ion (0mon hs)
Cha ac e is ic
D−Ex−
N=102
D+Ex−
N=102
D−Ex+
N=103
D+Ex+
N=102
Age, yea s 73.8 (3.1) 74.1 (3.0) 74.8 (2.9) 74.1 (2.9)
Heigh , cm 160.7 (5.4) 159.2 (5.8) 159.4 (6.1) 159.7 (5.9)
Weigh , kg 72.0 (12.4) 73.0 (13.1) 70·9 (10·6) 73·2 (10·5)
Fa , % 41.1 (6.7) 42.0 (7.2) 41.3 (6.4) 42.8 (5.3)
Calcium in ake, mg/day 1,040 (345) 1,125 (420) 1,119 (346) 1,109 (385)
Vi amin D in ake, µg/day 10.2 (4.1) 10.9 (4.2) 10.3 (3.6) 10.4 (3.9)
S-25(OH)D, nmol/L 67.6 (18.8) 65.8 (17.1) 69.5 (18.0) 65.5 (17.5)
Cogni i e s a us, MMSE sco e (0–30)* 28.5 (1.7) 28.3 (1.4) 28.2 (1.4) 28.3 (1.5)
SPPB, ange 10.6 (3–12) 10.7 (1–12) 10.9 (7–12) 10.8 (5–12)
ADL sco e (6–36)†6.7 (1.6) 7.0 (2.2) 6.8 (1.9) 6.9 (1.8)
IADL sco e (8–48)†9.8 (2.7) 10.7 (4.9) 9.9 (3.8) 10.3 (4.0)
Di icul ies ou doo mobili y, n (%) 18 (17.6) 19 (18.6) 17 (16.5) 17 (16.7)
No es: ADL=Ac i i ies o daily li ing; D−Ex−=placebo; D+Ex− =20µg i amin D daily; D−Ex+=placebo + exe cise; D−Ex+=20µg i amin D daily + exe cise;
MMSE=Mini Men al S a e Examina ion; IADL=Ins umen al ac i i ies o daily li ing; SPPB=Sho physical pe o mance ba e y.
*Highe sco e indica es be e unc ioning.
†Lowe sco e indica es be e unc ioning.
1242 Jou nals o Ge on ology: MEDICAL SCIENCES, 2017, Vol. 72, No. 9
Exe cise-induced imp o emen s in lowe ex emi y unc ion, mobil-
i y, and balance can educe he se e i y o alls (5,14), bu no consis -
en ly (16,31). Ne e heless, o main ained bene i s i is c ucial ha he
imp o emen s a e no los . P e iously i has been shown ha gains in
balance induced s eng h and balance aining can be pa ly main ained
by weekly low-in ensi y Tai Chi aining (32), and e en ligh in ensi y
home-based weigh -bea ing exe cise aining may educe alls and inju-
ious alls compa ed wi h con ols (17,33). In ou p e ious ollow-up
o an exe cise in e en ion ial, physical pe o mance was pa ly main-
ained in a combina ion aining g oup, while mos o he bene i s dis-
appea ed in he pu e esis ance o balance aining g oups (18). E en
5yea s la e he combina ion aining g oup had signi ican ly less medi-
cally a ended inju ious alls. Howe e , physical pe o mance was no
measu ed, and i is no known whe he di e ences in muscle s eng h o
balance s ill exis ed and accoun ed o he obse ed e ec (19).
In his s udy, habi ual physical ac i i y es ima ed as daily s eps,
o ime spen in mode a e physical ac i i y was consis en wi h he
gene al olde Finnish popula ion (34). Habi ual physical ac i i y
es ima ed by pedome e s and ques ionnai es (CHAMPS) declined
o e ime in all g oups. Du ing he in e en ion, he exe cise s we e
mo e physically ac i e (by abou he amoun o supe ised aining;
1–2h pe week) han he non-exe cise s, bu a e cessa ion o he
aining, he exe cise s’ physical ac i i y e u ned o he le el o hei
con ol coun e pa s.
Vi amin D has been posi i ely associa ed wi h be e musculo-
skele al heal h and physical unc ioning, and ewe ac u es (35,36).
Howe e , he e is also e idence ha i amin D has no e ec , o may
e en be ha m ul in e ms o alls o ac u es (10–12). Recen ly,
Hansen e  al. (10) ound ha compa ed wi h placebo, high-dose
cholecalci e ol did no ansla e o be e physical unc ioning o
ewe alls. Simila ly, Bischo -Fe a i e al. (11) ound ha mon hly
high-dose i amin D ea men did no imp o e physical unc ion-
ing and was associa ed wi h inc eased isk o alls compa ed wi h
24,000 IU gi en mon hly (a dose co esponding o 800 IU/day).
Only a ew s udies ha e e alua ed e ec s o bo h i amin D and
exe cise on physical unc ioning (37), and none o hese s udies had
a ollow-up a e he in e en ion, no epo ed alls. These esul s
indica ed no e ec o i amin D supplemen a ion on muscle s eng h
Table3. Baseline Values (SD) and Mean Changes (95% CI) O e Time in BMD and Physical Func ioning in Each S udy G oup (The Righ mos
Column, pb, Shows he Signi icance o Di e ence in Changes Compa ed wi h D−Ex−)
Ou come
Absolu e Baseline
Value, Mean (SD)
Change a 24
Mon hs, %
pa Compa ed
wi h D−Ex−
Change a 36
Mon hs, %
Change a 48
Mon hs, %
pb o he O e all
G oup-Wise
Di e ence
Femo al neck BMD, g/cm2
D−Ex−0.872 (0.141) −1.4 (−2.1 o −0.7) −1.7 (−2.5 o −0.9) −2.6 (−3.5 o −1.8)
D+Ex−0.821 (0.107) −0.9 (−1.7 o −0.1) .017 −1.2 (−2.1 o −0.4) −2.7 (−3.6 o −1.8) .34
D−Ex+0.848 (0.115) −1.1 (−1.8 o −0.4) .012 −1.9 (−2.7 o −1.1) −2.1 (−3.1 o −1.3) .93
D+Ex+0.875 (0.134) −1.1 (−1.8 o −0.5) .041 −2.4 (−3.1 o −1.6) −3.2 (−4.1 o −2.4) .35
No mal walking speed, m/s
D−Ex−1.04 (0.21) −2.8 (−5.7 o 0.0) −4.2 (−7.3 o −1.1) −5.1 (−8.2 o −2.1)
D+Ex−1.00 (0.21) −3.5 (−6.6 o −0.5) .72 −5.0 (−8.2 o −1.7 −4.9 (−8.2 o −1.5) .61
D−Ex+1.01 (0.19) −1.8 (−4.8 o 1.2) .007 −0.7 (−3.9 o 2.6) −0.5 (−3.7 o 2.8) .11
D+Ex+1.03 (0.20) −2.1 (−5.0 o 0.7) .46 −4.7 (−7.9 o −1.7) −3.9 (−7.0 o −0.8) .98
Chai s and ime, s
D−Ex−12.6 (2.4) −0.8 (−4.2 o 2.7) −1.7 (−5.3 o 1.9) −0.7 (−4.6 o 3.3)
D+Ex−12.6 (3.3) −4.5 (−8.0 o −0.9) .46 −3.3 (−6.9 o 0.4) −3.9 (−8.0 o 0.2) .58
D−Ex+12.5 (2.8) −7.4 (−11.0 o −3.8) .027 −5.9 (−9.6 o −2.3) −6.9 (−10.9 o −2.8) .95
D+Ex+12.4 (2.5) −7.7 (−11.2 o −4.3) .054 −5.5 (−9.1 o −1.9) −5.2 (−9.2 o −1.2) .19
TUG ime, s
D−Ex−9.31 (2.07) −0.5 (−3.9 o 2.9) 4.6 (1.2 o 8.0) 8.7 (4.7 o 12.7)
D+Ex−9.73 (6.44) 2.5 (−0.9 o 5.8) .011 7.2 (3.9 o 10.5) 7.4 (3.4 o 11.4) .21
D−Ex+8.93 (1.94) 1.9 (−1.7 o 5.5) .19 4.4 (0.8 o 8.0) 1.9 (−2.4 o 6.2) .002
D+Ex+8.89 (1.64) −1.4 (−4.9 o 2.1) .63 4.3 (0.7 o 7.8) 5.0 (0.8 o 9.2) .62
Muscle s eng h, N/kg
D−Ex−23.1 (6.1) 1.4 (−3.2 o 6.1) 0.6 (−4.2 o5.5) 2.3 (−2.5 o 7.2)
D+Ex−23.4 (7.7) 3.0 (−1.5 o 7.4) .10 3.4 (−1.4 o 8.3) 2.0 (−2.9 o 6.9) .68
D−Ex+23.6 (6.0) 16.7 (12.3 o 21.2) <.001 12.3 (7.7 o 16.9) 10.2 (5.7 o 14.9) .003
D+Ex+22.2 (6.6) 17.3 (12.7 o 21.9) <.001 12.7 (7.9 o 17.5) 12.4 (7.5 o 17.3) .007
Backwa ds walking,
p opo ion o hose able o
do 6.1 m, %
A baseline A 24mon hs A 36mon hs A 48mon hs
D−Ex−42.2 50.0 48.3 48.1
D+Ex−30.4 40.5 .68 43.9 45.9 .34
D−Ex+45.1 72.7 .001 65.9 61.7 .32
D+Ex+51.0 78.0 .026 71.6 73.8 .56
No es: D−Ex−=placebo; D+Ex−=20µg i amin D daily; D−Ex+=placebo + exe cise; D+Ex+=20µg i amin D daily + exe cise.
aBased on analysis o co a iance (ANCOVA).
bp alue o he o e all g oup-wise di e ence om he end o in e en ion (24mon hs) o 48mon hs. Based on Gene alized Linea Mixed Models (GLMM) o
Linea Mixed Models (LMM).
Jou nals o Ge on ology: MEDICAL SCIENCES, 2017, Vol. 72, No. 9 1243

o unc ion ollowing exe cise. This is in acco dance wi h he DEX
ial, which showed ha i amin D in e en ion wi h o wi hou exe -
cise had no e ec on physical unc ioning o alls compa ed wi h he
e e ence g oup du ing he in e en ion. Howe e , du ing ollow-up
D+Ex− had 55% less medically a ended inju ious alls and nea ly
40% less medically a ended inju ed alle s han he e e ence g oup.
One explana ion could be ha i amin D con e ed a delayed p e-
en i e e ec on se e e alls h ough an unknown mechanism. The e
was no co esponding e ec on physical unc ioning, which declined
simila ly in bo h non-exe cise g oups wi h o wi hou i amin
D.Fu he mo e, hough he achie ed bene i in physical unc ioning
was pa ly main ained a e cessa ion o aining, i declined in bo h
exe cise g oups, and exe cise s wi h i amin D did no di e om
exe cise s wi hou i amin D.Also, S-25OHD conce a ions e u ned
o baseline le els in bo h supplemen ed g oups wi h no signi ican
di e ence compa ed wi h he e e ence g oup. These indings do no
suppo he delayed bene i o i amin D concen a ions on alls.
A majo s eng h o his s udy is he long 2-yea ollow-up a e
he 2-yea in e en ion. The d op-ou a e was low; only 15 women
(4%) o he o iginal coho who comple ed he in e en ion we e no
willing o con inue in he ollow-up, and i e mo e discon inued a e
he i s ollow-up yea mainly due o declined heal h s a us. Physical
unc ioning was objec i ely measu ed, and alls we e assessed wi h
p ospec i e and con olled mon hly all dia ies, ee o ecall bias,
o e he en i e 48mon hs. Medical eco ds we e sc u inized o con-
i ming sel - epo ed medically a ended inju ious alls. Vi amin D
concen a ions we e also assessed annually du ing he ollow-up in
win e when concen a ions a e expec ed o be a hei lowes le els.
A limi a ion was ha de ailed in o ma ion on pa icipan s’ physical
ac i i y in he ou s udy g oups was no a ailable du ing he ollow-
up. Ou s udy did no include olde men o ins i u ionalized pe sons,
and he esul s can only be gene alized o olde home-dwelling women.
Also, he s udy was powe ed o alls, and esul s ega ding inju ious
alls o alle s should be in e p e ed cau iously, hough a e consis -
en wi h cu en li e a u e (14,19). Vi amin D supplemen a ion may
be mo e e ec i e among people wi h i amin D insu iciency. In his
s udy, despi e he decline in i amin D concen a ions a e s opping
supplemen a ion, pa icipan s s ill had adequa e i amin D s a us (38).
In conclusion, exe cise-induced bene i s in physical unc ioning
pa ly emained 2yea s a e cessa ion o supe ised exe cise ain-
ing. Al hough he e was no di e ence in he a e o all alls, o me
exe cise g oups had less medically a ended inju ed alle s compa ed
wi h e e en s e en 2yea s a e he in e en ion. Vi amin D wi hou
exe cise was also associa ed wi h less inju ious alls wi h no co e-
sponding di e ence in physical unc ioning.
In he absence o a s uc u ed exe cise aining p og am, aining
e ec s a e likely o educe wi h ime, as do habi ual physical ac i i y.
T aining p og ams ocusing on balance and esis ance aining and
adequa e i amin D in ake should be an in eg al pa o daily li e in
olde adul s o p e en ing inju ious alls.
Supplemen a y Ma e ial
Supplemen a y da a is a ailable a The Jou nals o Ge on ology,
Se ies A: Biomedical Sciences and Medical Sciences online
Funding
This wo k was suppo ed by he Academy o Finland (g an no. 131524);
Juho Vainio Founda ion, Helsinki, Finland; and Finnish Cul u al Founda ion,
Pi kanmaa Regional und, Finland.
Con lic o in e es
The au ho s decla e no con lic o in e es .
Re e ences
1. Welme AK, Rizzu o D, Laukka EJ, Johnell K, F a iglioni L. Cogni i e and
physical unc ion in ela ion o he isk o inju ious alls in olde adul s: a
popula ion-based s udy. J Ge on ol ABiol Sci Med Sci. 2016.
2. Ka inkan a S, Pii ola M, Sie änen H, Uusi-Rasi K, Kannus P. Physical
he apy app oaches o educe all and ac u e isk among olde adul s.
Na Re Endoc inol. 2010;6:396–407. doi:10.1038/n endo.2010.70.
3. Fe ucci L, Coope R, Sha dell M, Simonsick EM, Sch ack JA, Kuh D. Age-
Rela ed Change in Mobili y: Pe spec i es F om Li e Cou se Epidemiology
and Ge oscience. J Ge on ol A Biol Sci Med Sci. 2016;71:1184–1194.
doi:10.1093/ge ona/glw043.
4. Gillespie LD, Robe son MC, Gillespie WJ, e al. In e en ions o p e en -
ing alls in olde people li ing in he communi y. Coch ane Da abase Sys
Re . 2012;9:CD007146. doi:10.1002/14651858.
5. Pal anen M, Kannus P, Pii ola M, Niemi S, Pa kka i J, Jä inen M.
E ec i eness o he Chaos Falls Clinic in p e en ing alls and inju ies
o home-dwelling olde adul s: a andomised con olled ial. Inju y.
2014;45:265–271. doi:10.1016/j.inju y.2013.03.010.
6. She ing on C, Michale ZA, Fai hall N, e al. Exe cise o p e en alls in
olde adul s: an upda ed sys ema ic e iew and me a-analysis. B J Spo s
Med. 2016.
7. Bischo -Fe a i HA, Dawson-Hughes B, Wille WC, e  al. E ec o
i amin D on alls: a me a-analysis. JAMA. 2004;291:1999–2006.
doi:10.1001/jama.291.16.1999.
8. Bischo -Fe a i HA, Wille WC, O a EJ, e  al. A pooled analysis o
i amin D dose equi emen s o ac u e p e en ion. N Engl J Med.
2012;367:40–49. doi:10.1056/NEJMoa1109617.
9. P ei e M, Bege ow B, Minne HW, Suppan K, Fah lei ne -Pamme A,
Dobnig H. E ec s o a long- e m i amin D and calcium supplemen a-
ion on alls and pa ame e s o muscle unc ion in communi y-dwelling
olde indi iduals. Os eopo os In . 2009;20:315–322. doi:10.1007/
s00198-008-0662-7.
10. Hansen KE, Johnson RE, Chambe s KR, e  al. T ea men o i a-
min D insu iciency in pos menopausal women: a andomized clini-
cal ial. JAMA In e n Med. 2015;175:1612–1621. doi:10.1001/
jamain e nmed.2015.3874.
11. Bischo -Fe a i HA, Dawson-Hughes B, O a EJ, e  al. Mon hly high-
dose i amin D ea men o he p e en ion o unc ional decline: a and-
omized clinical ial. JAMA In e n Med. 2016;176:175–183. doi:10.1001/
jamain e nmed.2015.7148.
12. Sande s KM, S ua AL, Williamson EJ, e al. Annual high-dose o al i a-
min D and alls and ac u es in olde women: a andomized con olled
ial. JAMA. 2010;303:1815–1822. doi:10.1001/jama.2010.594.
13. Uusi-Rasi K, Pa il R, Ka inkan a S, e al. Exe cise and i amin D in all
p e en ion among olde women: a andomized clinical ial. JAMA In e n
Med. 2015;175:703–711. doi:10.1001/jamain e nmed.2015.0225.
14. El-Khou y F, Cassou B, Cha les MA, Da gen -Molina P. The e ec o all
p e en ion exe cise p og ammes on all induced inju ies in communi y
dwelling olde adul s: sys ema ic e iew and me a-analysis o andomised
con olled ials. BMJ. 2013;347: 6234. doi:10.1136/bmj. 6234.
15. F eibe ge E, Häbe le L, Spi duso WW, Zijls a GA. Long- e m e ec s o
h ee mul icomponen exe cise in e en ions on physical pe o mance and
all- ela ed psychological ou comes in communi y-dwelling olde adul s:
a andomized con olled ial. J Am Ge ia Soc. 2012;60:437–446.
doi:10.1111/j.1532-5415.2011.03859.x.
16. Gianoudis J, Bailey CA, Ebeling PR, e al. E ec s o a a ge ed mul imodal
exe cise p og am inco po a ing high-speed powe aining on alls and
ac u e isk ac o s in olde adul s: a communi y-based andomized con-
olled ial. J Bone Mine Res. 2014;29:182–191. doi:10.1002/jbm .2014.
17. Ko pelainen R, Keinänen-Kiukaanniemi S, Nieminen P, Heikkinen J,
Väänänen K, Ko pelainen J. Long- e m ou comes o exe cise: ollow-up
o a andomized ial in olde women wi h os eopenia. A ch In e n Med.
2010;170:1548–1556. doi:10.1001/a chin e nmed.2010.311.
1244 Jou nals o Ge on ology: MEDICAL SCIENCES, 2017, Vol. 72, No. 9
18. Ka inkan a S, Heinonen A, Sie änen H, Uusi-Rasi K, Fogelholm M,
Kannus P. Main enance o exe cise-induced bene i s in physical unc ion-
ing and bone among elde ly women. Os eopo os In . 2009;20:665–674.
doi:10.1007/s00198-008-0703-2.
19. Ka inkan a S, Kannus P, Uusi-Rasi K, Heinonen A, Sie änen H. Combined
esis ance and balance-jumping exe cise educes olde women’s inju ious
alls and ac u es: 5-yea ollow-up s udy. Age Ageing. 2015;44:784–789.
doi:10.1093/ageing/a 064.
20. Liu-Amb ose TY, Khan KM, Eng JJ, Gillies GL, Lo d SR, McKay HA.
The bene icial e ec s o g oup-based exe cises on all isk p o ile and
physical ac i i y pe sis 1yea pos in e en ion in olde women wi h low
bone mass: ollow-up a e wi hd awal o exe cise. J Am Ge ia Soc.
2005;53:1767–1773. doi:10.1111/j.1532-5415.2005.53525.x.
21. Uusi-Rasi K, Kannus P, Ka inkan a S, e  al. S udy p o ocol o p e-
en ion o alls: a andomized con olled ial o e ec s o i a-
min D and exe cise on alls p e en ion. BMC Ge ia . 2012;12:12.
doi:10.1186/1471-2318-12-12.
22. Pa il R, Ka inkan a S, Tokola K, Kannus P, Sie änen H, Uusi-Rasi K. E ec s
o i amin D and exe cise on he wellbeing o olde communi y-dwelling
women: a andomized con olled ial. Ge on ology. 2016;62:401–408.
doi:10.1159/000442441.
23. Lamb SE, Jø s ad-S ein EC, Haue K, Becke C; P e en ion o Falls
Ne wo k Eu ope and Ou comes Consensus G oup. De elopmen o a
common ou come da a se o all inju y p e en ion ials: he P e en ion
o Falls Ne wo k Eu ope consensus. J Am Ge ia Soc. 2005;53:1618–
1622. doi:10.1111/j.1532-5415.2005.53455.x.
24. Schwenk M, Lauen o h A, S ock C, e al. De ini ions and me hods o meas-
u ing and epo ing on inju ious alls in andomised con olled all p e-
en ion ials: a sys ema ic e iew. BMC Med Res Me hodol. 2012;12:50.
doi:10.1186/1471-2288-12-50.
25. Ou ila TA, Kä kkäinen MU, Lambe g-Alla d CJ. Vi amin D s a us a ec s
se um pa a hy oid ho mone concen a ions du ing win e in emale ado-
lescen s: associa ions wi h o ea m bone mine al densi y. Am J Clin Nu .
2001;74:206–210.
26. Uusi-Rasi K, Rauhio A, Kannus P, e al. Th ee-mon h weigh educ ion
does no comp omise bone s eng h in obese p emenopausal women.
Bone. 2010;46:1286–1293. doi:10.1016/j.bone.2009.10.013.
27. Gu alnik JM, Simonsick EM, Fe ucci L, e al. A sho physical pe o -
mance ba e y assessing lowe ex emi y unc ion: associa ion wi h sel -
epo ed disabili y and p edic ion o mo ali y and nu sing home admis-
sion. J Ge on ol. 1994;49:M85–M94.
28. Podsiadlo D, Richa dson S. The imed “Up & Go”: a es o basic unc ional
mobili y o ail elde ly pe sons. J Am Ge ia Soc. 1991;39:142–148.
29. Husu P, Suni J, Pasanen M, Miilunpalo S. Heal h- ela ed i ness es s as
p edic o s o di icul ies in long-dis ance walking among high- unc ioning
olde adul s. Aging Clin Exp Res. 2007;19:444–450.
30. Uusi-Rasi K, Sie änen H, Pasanen M, Oja P, Vuo i I. Main enance o
body weigh , physical ac i i y and calcium in ake helps p ese e bone
mass in elde ly women. Os eopo os In . 2001;12:373–379. doi:10.1007/
s001980170105.
31. Gill TM, Paho M, Gu alnik JM, e al.; LIFE S udy In es iga o s. E ec o
s uc u ed physical ac i i y on p e en ion o se ious all inju ies in adul s
aged 70-89: andomized clinical ial (LIFE S udy). BMJ. 2016;352:i245.
doi:10.1136/bmj.i245.
32. Wol son L, Whipple R, De by C, e al. Balance and s eng h aining in
olde adul s: in e en ion gains and Tai Chi main enance. J Am Ge ia
Soc. 1996;44:498–506.
33. Hwang HF, Chen SJ, Lee-Hsieh J, Chien DK, Chen CY, Lin MR. E ec s
o home-based Tai Chi and lowe ex emi y aining and sel -p ac ice
on alls and unc ional ou comes in olde alle s om he Eme gency
Depa men -A Randomized Con olled T ial. J Am Ge ia Soc.
2016;64:518–525. doi:10.1111/jgs.13952.
34. Husu P, Suni J, Vähä-Ypyä H, e  al. Objec i ely measu ed seden a y
beha io and physical ac i i y in a sample o Finnish adul s: a c oss-
sec ional s udy. BMC Public Heal h. 2016;16:920. doi:10.1186/
s12889-016-3591-y.
35. Bischo -Fe a i HA, Dawson-Hughes B, Pla z A, e al. E ec o high-dos-
age cholecalci e ol and ex ended physio he apy on complica ions a e hip
ac u e: a andomized con olled ial. A ch In e n Med. 2010;170:813–
820. doi:10.1001/a chin e nmed.2010.67.
36. Bischo -Fe a i HA, Die ich T, O a EJ, e al. Highe 25-hyd oxy i a-
min D concen a ions a e associa ed wi h be e lowe -ex emi y unc ion
in bo h ac i e and inac i e pe sons aged > o =60 y. Am J Clin Nu .
2004;80:752–758.
37. Minshull C, Bian LC, Rals on SH, Gleeson N. A sys ema ic e iew o
he ole o i amin d on neu omuscula emodelling ollowing exe -
cise and inju y. Calci Tissue In . 2016;98:426–437. doi:10.1007/
s00223-015-0099-x.
38. Lambe g-Alla d C, B us ad M, Meye HE, S eing imsdo i L. Vi amin D -
a sys ema ic li e a u e e iew o he 5 h edi ion o he No dic
Nu i ion Recommenda ions. Food Nu Res. 2013;57. doi:10.3402/ n .
57i0.22671.
Jou nals o Ge on ology: MEDICAL SCIENCES, 2017, Vol. 72, No. 9 1245