w w w . r b o . o r g . b r
Original
Article
Associations
of
vitamin
D
deficiency
with
postoperative
gait
and
mortality
among
patients
with
fractures
of
the
proximal
femur
夽
David
Nicoletti
Gumieiro
∗,
Gilberto
José
Cac¸ão
Pereira,
Marcos
Ferreira
Minicucci,
Carlos
Eduardo
Inácio
Ricciardi,
Erick
Ribeiro
Damasceno,
Bruno
Schiavoni
Funayama
HipSurgeryGroup,DisciplineofOrthopedicsandTraumatology,DepartmentofSurgeryandOrthopedics,BotucatuMedicalSchool, UniversidadeEstadualPaulista(UNESP),Botucatu,SP,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received23April2014
Accepted4May2014
Availableonline1April2015
Keywords:
VitaminD
Mortality Gait
Femoralfractures
a
b
s
t
r
a
c
t
Objective:ToassesswhetherserumvitaminDconcentrationisassociatedwithgait
sta-tusandmortalityamongpatientswithfracturesoftheproximalfemur,sixmonthsafter
sufferingthefracture.
Methods:Consecutivepatientsaged≥65yearswithfracturesoftheproximalfemur,who
wereadmittedtotheorthopedicsandtraumatologywardofourservicebetweenJanuaryand
December2011,wereprospectivelyevaluated.Clinical,radiological,epidemiologicaland
laboratoryanalyseswereperformed,includingvitaminD.Thepatientsunderwentsurgery
andwerefollowedupasoutpatients,withreturnvisits15,30,60and180daysafterdischarge,
atwhichtheoutcomesofgaitandmortalitywereevaluated.
Results:Eighty-eightpatientswereevaluated.Twoofthemwereexcludedbecausethey
pre-sentedoncologicalfractures.Thus,86patientsofmeanage80.2±7.3yearswerestudied.
InrelationtoserumvitaminD,themeanwas27.8±14.5ng/mL,and33.7%ofthepatients
presenteddeficiencyofthisvitamin.Inrelationtogait,univariateandmultivariate
logis-ticregressionshowedthatvitaminDdeficiencywasnotassociatedwithgaitrecovery,even
afteradjustmentforgender,ageandtypeoffracture(OR:1.463;95%CI:0.524–4.088;p=0.469).
Regardingmortality, CoxregressionanalysisshowedthatvitaminDdeficiency wasnot
relatedtoitsoccurrencewithinsixmonths,eveninmultivariateanalysis(HR:0.627;95%CI:
0.180–2.191;p=0.465).
Conclusion: SerumvitaminDconcentrationwasnotrelatedtogaitstatusand/ormortality
amongpatientswithfracturesoftheproximalfemur,sixmonthsaftersufferingthefracture.
©2015SociedadeBrasileiradeOrtopediaeTraumatologia.PublishedbyElsevierEditora
Ltda.Allrightsreserved.
夽
WorkdevelopedintheHipSurgeryGroup,DepartmentofSurgeryandOrthopedics,BotucatuMedicalSchool,UniversidadeEstadual
Paulista(UNESP),Botucatu,SP,Brazil.
∗ Correspondingauthor.
E-mail:gumieiroort@hotmail.com(D.N.Gumieiro).
http://dx.doi.org/10.1016/j.rboe.2015.03.008
Associac¸ão
da
deficiência
de
vitamina
D
com
mortalidade
e
marcha
pós-operatória
em
paciente
com
fratura
de
fêmur
proximal
Palavraschave:
VitaminaD
Mortalidade Marcha
Fraturasdofêmur
r
e
s
u
m
o
Objetivo:Avaliarseaconcentrac¸ãoséricadevitaminaDestáassociadaaostatusdemarcha
eàmortalidadeempacientescomfraturadefêmurproximalseismesesapósafratura.
Métodos: Avaliadosprospectivamentepacientesconsecutivoscomfraturadefêmur
proxi-mal,comidade≥65anos,internadosnaenfermariadeortopediaetraumatologiadoservic¸o,
entrejaneiroadezembrode2011.Foramfeitasanálisesclínica,radiológica,epidemiológica
elaboratorial,incluindovitaminaD.Foramsubmetidosàcirurgiaeacompanhados
ambu-latorialmenteemretornos15,30,60e180diasapósaalta,quandoforamavaliadosos
desfechosdemarchaemortalidade.
Resultados: Avaliados88pacientes.Doisforamexcluídosporcausadefraturapatológica.
Oitentaeseispacientescomidademédiade80,2±7,3anosforamestudados.Emrelac¸ão
àvitaminaDséricaamédiafoide27,8±14,5ng/mLe33,7%dospacientesapresentavam
deficiênciadessavitamina.Emrelac¸ãoàmarcha,aanálisederegressãologísticaunie
mul-tivariadamostrouqueadeficiênciadevitaminaDnãoesteveassociadaasuarecuperac¸ão,
mesmoapósajusteporgênero,idadeetipodefratura(OR1,463;95%IC0,524-4,088;p=0,469).
Considerandoamortalidade,aanálisederegressãodeCoxmostrouqueadeficiênciade
vita-minaDtambémnãoesteverelacionadaàsuaocorrênciaemseismeses,mesmonaanálise
multivariada(HR0,627;95%IC0,180-2,191;p=0,465).
Conclusão:Aconcentrac¸ãodevitaminaDséricanãoesteverelacionadaaostatusdemarcha
e/ouàmortalidadeempacientecomfraturadefêmurproximalseismesesdepoisdela.
©2015SociedadeBrasileiradeOrtopediaeTraumatologia.PublicadoporElsevier
EditoraLtda.Todososdireitosreservados.
Introduction
Theincidenceoffracturesoftheproximalfemurhasincreased
overrecentdecadesandthereisanexpectationthatitwill
continuetoincreasebecauseoftheagingofthepopulation.1,2
Itisexpectedthatby2020,16.3% oftheAmerican
popula-tion and 25% ofthe Canadian population willbe over the
age of 65 years.2 This increase in the numbers of elderly
individuals willprobably give rise to higher incidenceand
prevalenceofdiseasesofthemusculoskeletalsystem, such
as fractures secondary to osteoporosis and osteoarthrosis.
AccordingtoThorngren,thenumberofcasesofhipfractures
amongpatientsovertheageof80yearshasdoubledoverthe
last20years.3AccordingtoHuetal.,41.5millioncasesofhip
fracturesoccuraroundtheworldandthisnumbermayreach
2.6millionin2025and4.5millionin2050.
Fractures secondary to bone fragility, especially those
occurringintheproximalfemur,havebeencorrelated with
significant reductionsinindependenceand increased
mor-bidityand mortality.5AccordingtoHoltetal.,6 only22%of
thepatientswho,beforethefractureoccurred,wereableto
walkwithoutsupportandunaccompaniedrecoverthislevel
ofindependencewithinthefirst120daysaftertheevent.This
lossofindependenceisevenmoreserious amongpatients
overtheageof95years:inthisgroup,only2%recovertheir
preoperativeabilitytowalkwithinthesameperiod.
Further-more,themortalityratesrelatingtofracturesoftheproximal
femurareveryhighandmayrangefrom14%to47%overthe
firstyearaftertheiroccurrence.All ofthesepoints
empha-sizetheimportanceofandinterestinrecoveringtheabilityto
walkandimprovingtheprognosis,forpatientswiththistype
offracture.6
Amongthemicronutrientsrelatingtotheriskoffallsand
fracturesamongelderlypeople,vitaminDcanbehighlighted.
Thisisaliposolublemicronutrientwithafunctionclassically
relatedtoincreasedintestinalabsorptionofcalcium,which
participates in active transportation ofthis ion in
entero-cytes.Italsoparticipatesinmobilizingcalciuminbones,in
the presenceofPTH,and inincreasingthe renal
reabsorp-tionofcalciuminthedistaltubule.7However,newfunctions
havenowbeenattributedtovitaminD.Studieshaveshown
that it has an importantrole inmodulating inflammatory
and immunologicalprocesses, andthatit mayhavea
rela-tionshipwithwoundhealingandwithalterationstomuscle
massandstrength.8,9HighervitaminDconcentrationshave
beencorrelatedwithlowerfallratesamongelderlypatients.
Consequently,thisdiminishestheriskofnewfractures.10
Theobjectives ofthis studywere toevaluatethe
demo-graphic, clinicaland biochemicalcharacteristicsofpatients
with and without vitaminD insufficiency and toascertain
whethertheserum concentrationofthisnutrientis
associ-atedwithwalkingstatusandwithmortalityamongpatients
withfractures ofthe proximalfemur, sixmonthsafterthe
occurrence.
Sample
and
methods
Thepresent study wasapprovedbyourinstitution’s ethics
committeeandallthepatientsorthepersonslegally
Consecutivepatientsofages≥65yearswithfracturesofthe
proximal femur who were hospitalized in the orthopedics
andtraumatologywardofourservicebetweenJanuaryand
December2011wereprospectivelyevaluated.Theexclusion
criterion was the presence of pathological fractures
(sec-ondarytoneoplasia).Allthe patientsunderwentasurgical
proceduretocorrectthefacture.
Onadmission,thepatients’demographicdatawere
reg-istered.Duringthefirst72hoursoftheirhospitalstay,blood
sampleswerecollected forlaboratorytests, including
mea-surement of serum 25(OH) vitamin D3. Data relating to
the type of fracture of the proximal femur (femoral neck,
intertrochantericor subtrochantericfracture),lengthofthe
waitingtime between hospitaladmission and surgery and
duration oftheoperationwere alsorecorded.Thepatients
werefollowedupforuptosixmonthsaftertheoccurrence
ofthefractureandwereassessedinrelationtopostoperative
walkingstatusandmortality.Theseassessmentsweremade
onthefirstdayafterthesurgicalprocedure,atthetimeof
hos-pitaldischargeandatreturnvisits15,30,60and180daysafter
discharge.Forpatientswhodiedbeforereaching180days,the
walkingstatusassessmentofthelastreturnvisitwastaken
intoconsideration.
VitaminDdeficiencywascharacterizedasaserum
concen-trationlowerthan20ng/mL.11Inrelationtowalkingstatus,
thepatientswereclassifiedaswalkers(whowerewalkingwith
orwithoutsupport=1)andnon-walkers(whowereunableto
walk=0).
Laboratoryassessment
Thebloodsamplescollectedoverthefirst72hoursafterthe
patient’sadmissionwereusedforlaboratorytests,including
thevitaminDlevels.
Toproduceahemogram,anautomatedmethodina
Coul-terSTKSauto-analyzerwasused,followedbyconfirmation
of the morphological findings, platelet counts,
leukome-tryand leukocytedifferentials,bymeansofaconventional
hematoscopymethod.Toassaythesodium,potassium,
mag-nesium,totalcalcium,glycemia,urea,creatinine,C-reactive
proteinandalbuminlevels,adrychemicalmethodwasused
(Ortho-ClinicalDiagnosticsVitros950®,Johnson&Johnson).
Prothrombintime(PT)andactivatedpartialthromboplastin
time(APTT)wereobtainedusingmanualmethods.
Determinationof25(OH)vitaminD3inserum
The concentrations of 25(OH) vitamin D3 in serum were
analyzedbymeans ofhigh-performanceliquid
chromatog-raphy (HPLC). Initially, 150L of serum was pipette into a
glassflask; 200Lofprecipitating reagentwere added and
themixturewasvortex-stirredfor30seconds.Followingthis,
400Lofextractionreagentwereaddedandthemixturewas
againvortex-stirredforanother30seconds.Itwasthen
cen-trifugedfor10minat13,000rpm.Thesupernatantwasthen
transferredtoanotherglassflask,evaporatedwithnitrogen,
resuspendedwith300Lofethanolandstirredforanother
minute. Following this, 20L were injected into the HPLC
apparatus.Afterrunningthisfor20min,thecolumnwasleft
tostabilizesothatanewreadingcouldbemade.
The equipment used was the isocratic HPLC with a
manual Rheodyne injector and a 20L loop. The
analy-sis was performed ina 4m silica column ofdimensions
125mm×4mm(KC3420RP;Immundiagnostik).The
ultravio-letwavelengthdetectorwassetat264nmandtheflowwasset
at0.75mL/min.Themobilephasewassuppliedbythe
manu-facturer(Immundiagnostik).Theinternalstandardusedwas
fromSigma–Aldrich(C9774)andthecontrolwasfrom
Chrom-systems(25[OH]vitaminD3serumcontrol,bi-levelI+II).The
testsensitivitywas2.5g/Landthecoefficientofvariationwas
<7%.12,13
Statisticalanalysis
Thedatawerepresentedasmeansandstandarddeviations
or as medians and 25th and 75th percentiles. The
categor-ical variables were analyzedby means of the 2 or Fisher
test.ThecontinuousvariableswereanalyzedusingStudent’s
ttestwhentheypresentedparametricdistributionorusing
theMann–Whitneytestwhentheypresentednonparametric
distribution. Toassess whether the 25(OH) vitaminD3
lev-els wereassociatedwithrecoveryoftheabilitytowalk180
daysafterthefracturing,weuseduniandmultivariate
logis-ticregression.Inordertoevaluatemortality,weusedtheCox
proportionalhazardsmodel.Inthemultivariateanalyses,the
variableswereadjustedaccordingtogender,ageandtypeof
fracture.Thesignificancelevelwastakentobe5%.
Results
Eighty-eightconsecutivepatientswithfracturesofthe
prox-imal femur were evaluated. Of these, two were excluded
becausetheirfractureswerepathological.Thus,86patients
of mean age 80.2±7.3 yearswere evaluated. Amongthese
patients, 77% were women, 70% presentedrecoveryof the
abilitytowalkand12.8%haddiedbythesixthmonthafter
thefractureevent.InrelationtoserumvitaminD,themean
concentrationwas27.8±14.5ng/mLand33.7%ofthepatients
presenteddeficienciesofthisvitamin.
Thedemographicandclinicaldataonthepatients
accord-ingtotheirserumvitaminDconcentrationsarepresentedin
Table1.Themajorityofthepatientshospitalizedpresented
transtrochantericfractures(55%)andfracturesofthefemoral
neck (38%).Thevitamin Dconcentration didnothave any
influenceonthetypeoffracture.Moreover,vitaminD
defi-ciencies did not present any associations with the clinical
and demographic data onthe patients evaluated (Table1).
ThebiochemicaldataarepresentedinTable2.Therewereno
differencesregardingthelaboratorytestresultsbetweenthe
groupswithandwithoutvitaminDdeficiencies.
In relationto walking, the uni and multivariate logistic
regressionanalysesshowedthatthevitaminDdeficienciesdid
nothaveanyassociationwithrecoveryoftheabilitytowalk
(OR1.212;95%CI0.451–3.252;p=0.703),evenafteradjustment
accordingtogender,ageandtypeoffracture(OR1.463;95%CI
0.524–4.088;p=0.469)(Table3).
With regard to mortality, the Cox regression analysis
showedthatthevitaminDdeficienciesalsodidnothaveany
Table1–Clinicalanddemographicvariablesofthepatientswithfracturesoftheproximalfemur,accordingtotheir serumvitaminDconcentration.
Variables SerumvitaminD(25OHvitD3) pvalue
≥20ng/mL(n=57) <20ng/mL(n=29)
Age(years) 79.8±6.7 81.0±8.3 0.475
Femalesex,n(%) 47(82.5) 19(65.5) 0.137
Preoperativehospitalstay(days) 6(4–8) 4(3–7.5) 0.091
Durationofoperation(min) 70(50–90) 65(50–90) 0.667
Typeoffracture,n(%) 0.590
Femoralneck 24(42) 9(31)
Transtrochanteric 29(51) 18(62)
Subtrochanteric 4(7) 2(7)
SAH,n(%) 37(64.9) 14(48.3) 0.210
DMtypeII,n(%) 14(24.6) 6(20.7) 0.895
Recoveryofabilitytowalk,n(%) 39(68.4) 21(72.4) 0.894
Death,n(%) 6(10.5) 5(17.2) 0.497
Table2–Laboratoryvariablesamongthepatientswithfracturesoftheproximalfemur,accordingtotheirserumvitamin Dconcentrations.
Variables SerumvitaminD(25OHvitD3) pvalue
≥20ng/mL(n=57) <20ng/mL(n=29)
Hematocrit(%) 34.5±6.2 34.0±7.5 0.755
Hemoglobin(g/L) 12.1(10.5–12.9) 11.9(9.6–13.4) 0.924
Platelets(×103/L) 206(157–258) 196(158–251) 0.756
Leukocytes(×103/L) 8.200(6.550–10.450) 7.700(5.750–9.750) 0.267
PT 1.05(1.0–1.13) 1.07(1.04–1.14) 0.217
APTT 1.06(0.93–1.18) 1.05(0.97–1.22) 0.689
CRP(mg/dL) 5.2(3.6–8.8) 4.6(3.0–17.8) 0.491
Sodium(mmoL/L) 138(136–141) 139(137–141) 0.745
Potassium(mmoL/L) 4.1(3.9–4.4) 4.2(3.7–4.7) 0.701
Magnesium(mg/dL) 2.0(1.8–2.1) 1.9(1.7–2.1) 0.498
Totalcalcium(mg/dL) 8.78±0.58 8.72±0.61 0.625
Urea(mg/dL) 52(36–72) 58(39–75) 0.698
Creatinine(mg/dL) 0.80(0.70–1.11) 0.80(0.65–1.05) 0.528
Glycemia(mg/dL) 119(95–150) 128(97–146) 0.827
Albumin(g/dL) 3.22±0.49 3.16±0.50 0.585
months(HR0.565;95%CI0.172–1.853;p=0.346),eveninthe multivariateanalysis(HR0.627;95%CI0.180–2.191;p=0.465) (Table4).
Discussion
Theincreaseinthesizeoftheelderlypopulationhasbeen
accompaniedbythepresenceofeventssuchasfracturesof
the proximal femur. After fractures have occurred, loss of
independence,particularlywithregardtoreturningtothe
pre-fracturewalkingstatus,isafrequentcomplicationthatoften
bringsdevastatingconsequencesforpatientsandtheir
care-giversinrelationtoqualityoflife.6Mortalitymayalsooccur.
Thus,itbecomesimportanttoidentifyfactorsthatmightbe
associatedwithrecoveryoftheabilitytowalkorwith
mor-tality.Ithasbeensuggestedthatthemicronutrientvitamin
Dhaspotentialeffectsonmusclestrengthandinrelationto
mortality. Thus,the present study compared demographic,
clinical and biochemical parameters in patients with and
withoutvitaminDdeficiencies.Inaddition,theserum
vita-minDconcentrationswereanalyzedaspotentialpredictors
ofrecoveryoftheabilitytowalkoraspredictorsof
mortal-ity.
Table3–Logisticregressionforpredictingrecoveryoftheabilitytowalkamongpatientswithfracturesoftheproximal femur.
Oddsratio 95%CI p
VitaminD<20ng/mL 1.212 0.451–3.252 0.703
VitaminD<20ng/mLa 1.439 0.515–4.023 0.488
VitaminD<20ng/mLb 1.463 0.524–4.088 0.469
a Adjustedforgenderandage.
Table4–Coxregressionsforpredictingmortalityamongpatientswithfracturesoftheproximalfemur.
Hazardratio 95%CI p
VitaminD<20ng/mL 0.565 0.172–1.853 0.346
VitaminD<20ng/mLa 0.639 0.189–2.163 0.471
VitaminD<20ng/mLb 0.627 0.180–2.191 0.465
a Adjustedforgenderandage.
b Adjustedforgender,ageandtypeoffracture.
WithregardtovitaminDdeficiency,patients presenting
concentrations lower than 20ng/mL were compared with
thosewhoseconcentrationswerehigherthanthis.Thetwo
groups presentedthe same demographic, clinical and
bio-chemical characteristics. In fact, it is not known whether
theseconcentrationsare sufficientfornon-classicalactions
ofvitaminD.Thereisnoconsensusintheliteratureregarding
whatthenormalserum vitaminDconcentrationwould be,
ofinrelationtothelevelsthatwouldcharacterizedeficiency
andinsufficiencyofthismicronutrient.14Thesevalueshave
always been based onthe relationship between vitaminD
concentrationsanddisordersinvolvingcalciumhomeostasis
andfractureoccurrences.Withregard tothenewfunctions
described,thevitaminDconcentrationthatissufficientfor
actionatthesedifferentsiteshasnotyetbeenestablished.
InCanada,theInternationalOsteoporosisFoundationhas
recommendedthattheserumvitaminDconcentrationshould
begreaterthan30ng/mL.15,16Ontheotherhand,theInstitute
ofMedicineoftheAmerican NationalAcademieshas
char-acterizedvitaminDdeficiencyasserumconcentrationlower
than12ng/mLandvitaminDinsufficiencyasconcentrations
between12and20ng/mL.17
Inrelationtorecoveryoftheabilitytowalk,Cooperstated
thatfracturesarerelatedtoapermanentincapacityrateof
30%withregardtoactivitiesofdailylivingandan
incapac-ityrateof40%withregardtowalkingindependently.18Larson
etal.19observedthefunctionalrecoveryofpatientswith
frac-turesoftheproximalfemur,among607patients.Amongthese
participants,446hadbeenabletowalkindependently
with-outsupportbeforethesurgeryand80%werefoundtohave
recoveredtheirpreoperativewalkingstatusoneyearafterthe
surgery.Ekstrometal.20foundthatonly55%ofthepatients
withfracturesoftheproximalfemurrecoveredtheir
preoper-ativewalkingstatus,while66%recoveredtheirpreoperative
performancelevelwithregardtoactivitiesofdailyliving.We
putforwardthe hypothesisthat theserum vitaminD
con-centrationmightinfluencethispostoperativewalkingstatus.
Thiswasbasedonthefunctionsmostrecentlyattributedto
vitaminD. Classically, vitamin Dhas been correlated with
maintenanceofcalciumhomeostasis,butithasrecentlyalso
beencorrelatedwithmusclecontractionthroughintracellular
calciumuptakeanddifferentiationofmyoblasts.Thiswould
diminishtheincidenceoffallsandconsequentlythenumber
offractures.10Inpatientswithfractures,thiswouldincrease
thechanceofachievingbetterpostoperativewalkingstatus.
Inourstudy,theserumvitaminDconcentrationdidnotshow
anycorrelationwiththepostoperativewalkingstatus,evenin
thecorrectedanalysis.
Withregardtomortality,theadventforsurgicalfixationof
fracturesoftheproximalfemurreducedthis.However,since
then,it hasremained stableat25–30%.21 Inour study,the
ratewas12.8%withinsixmonths.Therelationshipbetween
serumvitaminDconcentrationandmortalityhasbeenlittle
studied.Somestudieshaveshownthat lowserum
concen-tration is associated with higher mortality in the general
population and amongelderly people.22–27 Ina study with
morethan 180,000 participants,Saliba etal.28 showed that
the riskofdeathduetoall causes wassignificantlyhigher
among patients with low serum vitamin D concentration
(lowerthan50nmoL/L).Inpatientsinwhomthe
concentra-tionsarelowerthan30nmoL/L(deficiency),thisriskbecomes
doubled.Thomasetal.showedthatadequatevitaminDlevels
reducedmortalityduetoallcausesanddueto
cardiovascu-larcausesby75%and69%,respectively,amongpatientswith
metabolicsyndrome.29
Intheliterature,wefoundfewstudiesthatevaluatedthe
serumvitaminDconcentrationandmortalityamongpatients
withfracturesoftheproximalfemur.Inastudythatincluded
562 patientsover the age of70 yearswith thesefractures,
Madsenetal.30concludedthatPTHandserumcalciumwere
significantly associated with mortality, but not vitamin D
concentration.Likewise,inourstudy,serumvitaminD
con-centrationsdidnotshowanyassociationwithmortalitysix
months after the occurrence of fractures of the proximal
femur.
Conclusion
Inconclusion,inourstudy,serumvitaminDconcentrations
didnothaveanycorrelationwithwalkingstatusorwith
mor-talityamongpatientswithfracturesoftheproximalfemur,six
monthsaftertheevent.Thefindingsfromthisstudy
empha-sizethatthereisaneedforfurtherstudiesthatmightidentify
factorspredictiveofcomplicationssubsequenttofracturesof
theproximalfemur.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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e
s
1.KimSM,MoonYW,LimSJ,YoonBK,MinYK,LeeDY,etal.
2. DunbarMJ,HowardA,BogochER,ParviziJ,KrederHJ. Orthopaedicsin2020:predictorsofmusculoskeletalneed.J BoneJointSurgAm.2009;91(9):2276–86.
3. ThorngrenKG.Fracturesinolderpersons.DisabilRehabil. 1994;16(3):119–26.
4. HuF,JiangC,ShenJ,TangP,WangY.Preoperativepredictors formortalityfollowinghipfracturesurgery:asystematic reviewandmeta-analysis.Injury.2012;43(6):676–85.
5. HartholtKA,OudshoornC,ZielinskiSM,BurgersPT, PannemanMJ,vanBeeckEF,etal.Theepidemicofhip fractures:areweontherighttrack?PLoSOne. 2011;6(7):e22227.
6. HoltG,SmithR,DuncanK,HutchisonJD,GregoriA.Outcome aftersurgeryforthetreatmentofhipfractureinthe extremelyelderly.JBoneJointSurgAm.2008;90(9): 1899–905.
7. HouwingRH,RozendaalM,Wouters-WesselingW,Beulens JW,BuskensE,HaalboomJR.Arandomised,double-blind assessmentoftheeffectofnutritionalsupplementationon thepreventionofpressureulcersinhip-fracturepatients. ClinNutr.2003;22(4):401–5.
8. HengstermannS,FischerA,Steinhagen-ThiessenE,SchulzRJ. Nutritionstatusandpressureulcer:whatweneedfor nutritionscreening.JPENJParenterEnteralNutr. 2007;31(4):288–94.
9. PattersonBM,CornellCN,CarboneB,LevineB,ChapmanD. Proteindepletionandmetabolicstressinelderlypatients whohaveafractureofthehip.JBoneJointSurgAm. 1992;74(2):251–60.
10.PedrosaMA,CastroML.RoleofvitaminDinthe neuro-muscularfunction.ArqBrasEndocrinolMetabol. 2005;49(4):495–502.
11.HolickMF.VitaminDdeficiency.NEnglJMed. 2007;357(3):266–81.
12.MerkeJ,RitzE,SchettlerG.Newviewpointsontheroleof vitaminD.Currentknowledgeandoutlook.DtschMed Wochenschr.1986;111(9):345–9.
13.WichertsIS,vanSchoorNM,BoekeAJ,VisserM,DeegDJ,Smit J,etal.VitaminDstatuspredictsphysicalperformanceand itsdeclineinolderpersons.JClinEndocrinolMetab. 2007;92(6):2058–65.
14.PattonCM,PowellAP,PatelAA.VitaminDinorthopaedics.J AmAcadOrthopSurg.2012;20(3):123–9.
15.HanleyDA,CranneyA,JonesG,WhitingSJ,LeslieWD. GuidelinesCommitteeoftheScientificAdvisoryCouncilof OsteoporosisCanada.VitaminDinadulthealthanddisease: areviewandguidelinestatementfromOsteoporosisCanada (summary).CMAJ.2010;182(12):1315–9.
16.Dawson-HughesB,MithalA,BonjourJP,BoonenS,Burckhardt P,FuleihanGE,etal.IOFpositionstatement:vitaminD recommendationsforolderadults.OsteoporosInt. 2010;21(7):1151–4.
17.RossCA,TaylorCL,YaktineAL,DelValleHB.Consensus report:dietaryreferenceintakesforcalciumandvitaminD. WashingtonDC:InstituteofMedicineoftheNational Academies;2010.
18.CooperC.Thecripplingconsequencesoffracturesandtheir impactonqualityoflife.AmJMed.1997;103(2A):12S–7S.
19.LarssonS,FribergS,HanssonLI.Trochantericfractures. Mobility,complications,andmortalityin607casestreated withthesliding-screwtechnique.ClinOrthopRelatRes. 1990;(260):232–41.
20.EkströmW,MiedelR,PonzerS,HedströmM,SamnegårdE, TidermarkJ.Qualityoflifeafterastabletrochantericfracture –aprospectivecohortstudyon148patients.JOrthop Trauma.2009;23(1):39–44.
21.AbrahamsenB,vanStaaT,ArielyR,OlsonM,CooperC. Excessmortalityfollowinghipfracture:asystematic epidemiologicalreview.OsteoporosInt.2009;20(10):1633–50.
22.VisserM,DeegDJ,PutsMT,SeidellJC,LipsP.Lowserum concentrationsof25-hydroxyvitaminDinolderpersonsand theriskofnursinghomeadmission.AmJClinNutr. 2006;84(3):616–22.
23.GindeAA,ScraggR,SchwartzRS,CamargoCAJr.Prospective studyofserum25-hydroxyvitaminDlevel,cardiovascular diseasemortality,andall-causemortalityinolderU.S.adults. JAmGeriatrSoc.2009;57(9):1595–603.
24.FiscellaK,FranksP.VitaminD,race,andcardiovascular mortality:findingsfromanationalUSsample.AnnFamMed. 2010;8(1):11–8.
25.VirtanenJK,NurmiT,VoutilainenS,MursuJ,TuomainenTP. Associationofserum25-hydroxyvitaminDwiththeriskof deathinageneralolderpopulationinFinland.EurJNutr. 2011;50(5):305–12.
26.FordES,ZhaoG,TsaiJ,LiC.VitaminDandall-causemortality amongadultsinUSA:findingsfromtheNationalHealthand NutritionExaminationSurveyLinkedMortalityStudy.IntJ Epidemiol.2011;40(4):998–1005.
27.FreedmanDM,LookerAC,ChangSC,GraubardBI.Prospective studyofserumvitaminDandcancermortalityintheUnited States.JNatlCancerInst.2007;99(21):1594–602.
28.SalibaW,BarnettO,RennertHS,RennertG.Theriskof all-causemortalityisinverselyrelatedtoserum25(OH)D levels.JClinEndocrinolMetab.2012;97(8):2792–8.
29.ThomasGN,HartaighB,BoschJA,PilzS,LoerbroksA,Kleber ME,etal.VitaminDlevelspredictall-causeand
cardiovasculardiseasemortalityinsubjectswiththe metabolicsyndrome:theLudwigshafenRiskand CardiovascularHealth(Luric)Study.DiabetesCare. 2012;35(5):1158–64.
