Rev. bras. ortop. vol.51 número2

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w w w . r b o . o r g . b r

Updating

article

For

the

first

fracture

to

be

the

last

Bernardo

Stolnicki

a,∗

,

Lindomar

Guimarães

Oliveira

a,b

a_{Osteometabolic}_Diseases_Sector,_Orthopedics_Service,_Hospital_Federal_de_Ipanema,_Rio_de_Janeiro,_RJ,_Brazil

b_Department_of_Orthopedics_and_{Traumatology,}_Hospital_das_Clínicas,_Universidade_Federal_de_Goiás,_Goiânia,_GO,_Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received30March2015

Accepted31March2015

Availableonline1February2016

Keywords:

Osteoporosis

Fractures,bone

Osteoporoticfractures

a

b

s

t

r

a

c

t

Increasedlongevityhasmadeprogressioninthenumberoffracturesincreasingly

signifi-cant.Becausehipfracturesgiverisetohighmorbidityandmortalityratesandhavehigh

treatmentcosts,theiroccurrenceisthemostimportantmarkerofeffectivenessinrelation

toosteoporosistreatment.Incountriesandsystemsthat,especiallyoverthelastdecade,

havebeeninvestinginthepreventionofosteoporosisanditsconsequences,thenumberof

hipfractureshasbeendecreasing.Whatthesecountrieshaveincommonissecondary

pre-ventionoffractures,i.e.toavoidsubsequentfractures.Giventhathalfofthepatientswho

presenthipfractureshavehadapreviousfractureandthatthetreatmentsavailablehave

proventobeextremelyefficientfordecreasingsubsequentfractures,agoodproportionof

hipfracturesarepreventable.Itiswithinthisscenariothatorthopedistsplayaleadingrole.

Ltda.Allrightsreserved.

Para

que

a

primeira

fratura

seja

a

última

Palavras-chave:

Osteoporose

Fraturasósseas

Fraturasporosteoporose

r

e

s

u

m

o

Oaumentodalongevidadefazcomqueaprogressãodonúmerodefraturassejacadavez

maisexpressiva.Aocorrênciadafraturadoquadril,pelasuaaltataxademortalidadee

morbidadeepeloaltocustodetratamento,éomaisimportantemarcadordaefetividade

notratamentodaosteoporose.Empaísesesistemasque,especialmentenaúltimadécada,

vêminvestindonaprevenc¸ãodaosteoporoseedesuasconsequências,onúmerode

frat-urasdoquadrilvemdiminuindo.Oqueelestêmemcomuméaprevenc¸ãosecundáriade

fraturas,ouseja,evitarafraturaseguinte.Vistoquemetadedospacientesquetiveramuma

fraturadoquadrilteveumafraturapréviaequeostratamentosdisponíveisprovaramser

extremamenteeficientesparadiminuirfraturassubsequentes,boapartedasfraturasde

quadriléevitável.Énessecenárioqueoortopedistadesempenhaumpapelpreponderante.

Ltda.Todososdireitosreservados.

∗ _{Corresponding}_author_.

E-mail:stolnick@hotmail.com(B.Stolnicki).

http://dx.doi.org/10.1016/j.rboe.2016.01.005

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Introduction

Osteoporosisisdefined asa bonedisease characterizedby

impairment of bone resistance, which predisposes toward

increasedriskoffractures.1,2

Fractures due to bone fragility are the greatest clinical

expressionofthisdisease.

FracturesduetofragilityaredefinedbytheWorldHealth

Organizationas“fracturescausedbytraumathatwould be

insufficienttofracturenormalboneandwhichresultsfrom

reducedresistancetocompressionortorsion”.3

From a clinical point of view, these fractures can be

defined asresulting from minimal trauma, such asfalling

fromastandingpositionorlessthanthis,orbyunidentified

trauma.Fracturesduetofragilitytypicallyincludevertebral,

proximalfemoral(hip), distalradialand proximal humeral

fractures.4

Fracturesduetofragilityare thestrongestindicatorora

riskoffuturefractures.Patientswhohavehadafractureat

anysitepresentapproximatelytwicetheriskofhavinga

frac-tureinthefuture,incomparisonwithindividualswhohave

neverhadsuchinjuries.Patientswithfracturesdueto

low-energytraumatothewrist,hip,proximalhumerusorankle

present ariskoffuture fracturesthat isalmost fourtimes

greater.Patientswithavertebralfracturewillhavenew

verte-bralfractureswithinthenextthreeyears,andmanywillhave

themwithinthefirstoftheseyears.5–7

Patientswithvertebralfracturespresentariskofhaving

similarinjuriesinthefuturethatisalmostfivetimeshigher,

andariskofhavinghipfracturesandothernon-vertebral

frac-turesthatistwiceashigh.Patientswhosufferwristfractures

presentarelativeriskofhavinghipfracturesinthefuturethat

isalmosttwiceashigh.5–7

Secondaryfracturesoccurrapidlyafterthefirstfracture.

Theriskofsubsequentfracturesseemstobehigherjustafter

afracture,especiallyinthefirstyear.5–7

Patientswhohavesufferedahipfractureformagroupat

higherriskofhavingfracturesinthefuture.Theyneedtobe

prioritizedforassessmentandforstartingtreatments,soas

toavoidothersecondaryfractures.8–10

Contrarytowhatmightbeimagined, thesepatientscan

benefitgreatlyfromtreatment.11,12

Initiativesforavoidingsecondary (subsequent) fractures

shouldbeofferedtoallmenandwomenovertheageof50

years who have had fractures due to fragility, since these

fracturesmayprecedehipfracturesinacycleinwhichone

fractureleadstoanother,ina“cascade”offractures.13–15

Aninitialfractureduetofragilityissufficientfor

request-inganevaluationthatincludesmeasurementofbonemineral

density,withevaluationoftheriskoffractures,andfor

start-ingthetreatmentifthereisnoformalcontraindication.16,17

Studieswiththehighestlevelofevidencehaveshownthat

osteoporosiscanbetreated,thusdiminishingthelikelihood

offracturesinthefuture.17

Around50%ofallcasesofhopfractureareconcentrated

in16%ofthepostmenopausalfemalepopulation,with

histo-riesoffractures.Therefore,secondarypreventionpresentsan

opportunityforinterventioninaroundhalfofallhipfracture

patients.18,19

The

impact

of

fractures

due

to

fragility

In Brazil, the number of people affected by fractures due

fragilityreaches10millionandtheexpenditureontreating

and caringforthesecaseswithintheNational Health

Sys-tem (SUS)ishigh.In2010alone, aroundR$81 millionwas

spentwithinSUSonattendingtopatientswithosteoporosis

andwhohadsufferedfallsandfractures.20

Ithasbeenestimatedthatthenumberofhipfracturesper

yearinBrazil,whichwasaround121,700in2010,willreach

160,000by2050.21,22

ArecentstudyconductedbytheMayoClinicshowedthat

between2000and2011,therewere4.9millionhospital

admis-sionsduetoosteoporoticfractures,2.9millionduetoacute

myocardialinfarction(AMI),threemillionduetostrokeand

700,000duetobreastcancer.Osteoporoticfracturesaccounted

formorethan40%ofthehospitaladmissionsamongthese

fourtypesofadmission,andforthelengthofhospitalstay.

Thehospitalcostwasgreaterforosteoporoticfractures(US$

5.1billion)thanforAMI(US$4.3billion),stroke(US$3billion)

orbreastcancer(US$0.5billion).23

Drug

treatments

Drugsfortreatingosteoporosiscanbedividedintotwogroups:

(1) inhibitors of bone reabsorption, which work through

blockingtheactionofosteoclasts.Theseconsistof

bisphos-phonates, selective estrogen receptor modulators (SERMs),

calcitonin, estrogen and denosumab and (2) activators of

boneformation,whichworkasanabolicagents,thus

increas-ingbonemetabolism,withpredominanceofboneformation

throughstimulationofosteoblasts.Thesecomprise

parathy-roid hormone (PTH),teriparatide(which issimilar toPTH),

growth hormone (GH) and active metabolitesofvitamin D

(alphacalcidolandcalcitriol).

Strontiumranelatepresents adoublemodeofaction,in

thatitbothinhibitsreabsorptionandstimulatesbone

forma-tion.

Bisphosphonatesreduceoccurrencesofvertebraland

non-vertebral fractures by 40–50%. They are indicated both for

womenandformen,andincasesofsecondaryosteoporosis

inducedthroughcorticoids.24,25

Theyareavailableinoralandinjectableformsinvarious

frequenciesofdosage:daily,weekly,monthly,three-monthly

andannualuse.

RaloxifeneistheSERMmostusedforpreventingand

treat-ingosteoporosis.Overathree-yearevaluationonwomenwith

osteoporosis,therewasanincreaseinbonemineraldensity

inthespineandfemoralneck,withareductionintheriskof

vertebralfractures.26,27

Calcitonin isavailable in as a nasal spray or in

subcu-taneous form for daily use. It gives rise to a reductionin

occurrences of vertebral fractures in 36% of the patients,

butwithoutanyreductioninhipfracturesoranysignificant

changeineitherbonemineraldensityorbonemetabolism.28

Estrogenreplacementtherapyisindicatedforpreventive

(3)

option need to be discussed between the patient and her

gynecologist.29

Denosumabisamonoclonalantibodythathasbeenfound

toreducethe incidenceofnewvertebral fracturesand hip

fracturesinpostmenopausalwomenwhoareathighriskof

sufferingfractures.Itsconvenientformofdosage(asingle

sub-cutaneousapplicationeverysixmonths)facilitatesadherence

tothetreatment.30

TheactivemetabolitesofvitaminD(calcitrioland

alpha-calcidol)increasecalciumabsorption.Theymayhaveadirect

effecton bone cells and may alsoreduce theincidence of

fractures.ActivederivativesofvitaminDhavebeenindicated

foruse amongdebilitatedelderly peoplewithosteoporosis

whoare reclusiveand havelittleexposuretothe sun,ata

doseof0.5mcg/day.However,theresultsrelatingtofracture

preventionarenotuniform.Alphacalcidolmaydiminishthe

myopathyconsequenttoaging.31,32

Teriparatide (PTH) has an anabolic effect. It stimulates

bonereabsorptionandformation,actsonthecoupling

mecha-nismofboneremodeling,promoteslargegainsofbonemass,

diminishestheriskofvertebralandnon-vertebralfractures

and increasesthe bonemassofvertebrae, femursand the

wholebody.Itsuseissafeandwelltolerated,bothformen

andforwomen.Itisindicatedincasesofsevereosteoporosis

withfractures:ithasamajoreffectonosteoporosisinduced

duetocorticoidsandtheeffectspersistforsixmonthsafter

withdrawal.Recentstudieshaveshownthatitcanbeusedfor

twoyears.Beyondthatpoint,thetherapycancontinuewith

bisphosphonatesordenosumab.33,34

Strontiumranelateactsbothtoinhibitreabsorptionandto

stimulateboneformation.Ithasbeenshowntobeeffective

forreducingtheoccurrencesofvertebral,non-vertebraland

hipfractures.35–37

Physical

activity,

calcium

and

vitamin

D

Peakmaturationoftheskeletonisattainedbetweentheages

of20and30years.Withadequatenutritionandthenormal

levelsofphysicalactivityavailabletoeveryone,higherlevels

ofbonemasscanbeattained.Thisformsacalciumreserve

bankfromwhichthedepositswillbespentduringtheperiod

ofaging,thusdelayingorimpedingosteoporosis,especiallyin

women.Duringgrowth,theskeletongainsbonehelpsto

main-tainthebonemassthathasbeenacquiredand,duringthe

agingprocess,thisdiminishesthelosses,maintainsmuscle

tonusandaidsindiminishingthenumberoffalls.38,39

Allpatientspresentingboneloss,orwhoarepotentiallyat

riskoflosses,shouldbecounseledtoincludecalciumand

vita-minDintheirdiets,orassupplements.Calciumabsorption

decreaseswithage. Around75%ofthecalciumingestedby

childrenisabsorbed,whileonly30–50%isabsorbedinadults.

VitaminDactivatescalciumabsorptionintheintestineandit

needstobesupplementedinelderly,sedentaryorhospitalized

individuals.40

Gaps

in

treatment

Despite substantial evidencethat previous occurrenceof a

fracture resultsin increasedrisk ofa subsequent fracture,

fewerthan30% ofpostmenopausalwomenandfewerthan

10%ofmenwithpreviousfracturesaretreated.41,42

Independentoftheavailabilityofmedicationsthatreduce

the risk of repeated fractures by 25–70%, the majority of

patients with incidental osteoporotic fractures are neither

investigatednortreated.43,44

Currentpracticeshavetheresultthat80%ofpatientswith

fracturesduetofragilityareneitherevaluatednortreatedfor

osteoporosisorforpreventionoffallssoastoreducethefuture

incidenceoffractures.Theconsequenceofthisgapin

treat-mentsisthatverymanyfracturesoccurbutcouldhavebeen

avoided.Theseareanafflictionamongelderlypeopleandcost

millionsofdollarsaroundtheworld.45,46

Secondary

prevention

Treatments that are started early on, aftera primary

frac-ture,maydiminishrecurrentfractureratesbybetween30and

60%.47,48

Anti-osteoporosis treatment implemented after repair

treatmentforahipfracturecausedbyminimaltraumahas

beencorrelatedwithareducedrateofnewclinicalfractures

andwithlowermortalityandlongersurvival.12,49–51

Patientswhohavesufferedahipfracturearethegroupat

highestriskofsubsequentfractures.Priorityneedstobegiven

tostartingtheirtreatment,inordertoavoidsecondary

frac-tures.Contrarytocommonassumptions,thesepatientsmay

benefitgreatlyfromthistreatment.

Several studies have shown that persistence with and

adherence to osteoporosistreatment ispoor, and that this

resultsinless-than-idealeffectiveness(underrealtreatment

conditions).Non-adherentpatientshavebeenfoundtohave

morecomorbidities,bemorefrailandhavehigherhealthcare

expenditure.13,52–54

Foreachenvironmentreported,afractureliaisonservice

(FLS)isthemosteffectivetool.TheFLSisaservicededicatedto

treatingpatientssubsequenttofracturesduetofragility.This

isperhapstheonlyeffectivemeansforachievingachange

in the current panorama. Thisapproach creates a

contin-uumofcareandmakesitpossibletosurmountthegapsin

investigation and interventionsubsequent tofractures and

theunnecessarilyhighincidenceoffracturesthereafter.

TheFLSinGlasgowhasalreadyattendedmorethana

mil-lionpeoplesincetheturnofthecentury.Acost-effectiveness

analysishasshown thatforevery10,000patientsattended

through the FLS, in comparison with ordinary attendance

intheUnitedKingdom,18casesoffractureswere avoided,

including11casesofhipfracture,withsavingsequivalentto

33,600dollars.55,56

The Healthy Bones program run by the health

insur-ancecompanyKaiserPermanenteisthebiggestprogramfor

preventing fracturesduetofragilityintheworld.Itis

con-ductedbyorthopedistsandishighlyfocusedonreducingthe

incidenceoffracturesby20%overafive-yearperiod.The

pro-grambeganwithhipfracturesaloneand,asitseffectiveness

becameproven,moreresourceswereinjected,suchthatitnow

actsinrelationtobothsecondaryandprimaryprevention.In

(4)

elevenmedicalcentersinsouthernCalifornia,thehipfracture

reductionratehadsurpassed40%.57–59

Prevrefrat

–

the

Brazilian

experience

Prevrefrat(ProgramadePrevenc¸ãoaRefraturas,i.e.repeated

fracturepreventionprogram)isaservicedestinedfor

treat-ingpatientswhohavehadfracturescausedbylow-intensity

traumasuchasfallingfromastandingposition,consequent

toosteoporosis.

Ithasbeeninoperationforalmostfouryearsand,since

2013,ithasbeenaworldwidereferencepointforprevention

ofnewfractures.

Throughitscoordinator,Prevrefrathasdisseminateda

phi-losophyofsecondaryfracturepreventionandhasdecisively

helpedinimplementingotherservicesthroughoutBrazil.

PrevrefratisoneofthemostrespectedFLSintheworld,

andisclassifiedasagoldstandard,asdemonstratedinFig.1.

Methodology

of

Prevrefrat

Thefirstconsultationconsistsofabriefinterviewtoascertain

whetherthecasefitswithintheprogram.Thenextstepisto

registertheindividualswithintheprogram,throughgathering

datarelatingtotheirmedicalhistory,theirlifestylehabitsand

thefracturethatoccurred.

Afterthis,lateralradiographsofthefractureandofthe

dor-salandlumbarspineareproduced,andbonedensitometryis

measured.

Laboratorytestsarerequested:calcium,creatinine,25(OH)

vitaminDand PTH,andpossiblyothersifneeded.Another

consultationisscheduled,onaveragefourweekslater,inorder

toassessthetests.

If a secondarycause isdetected,the patient isreferred

tootherspecialists.Incasesofosteopeniaorprimary

osteo-porosis,andifthereisnocontraindication,anannualvenous

infusionofzoledronicacidisadministered,ordenosumabis

appliedsubcutaneouslyifthecreatinineclearanceislessthan

35.

SupplementationofcalciumandvitaminDisalsoapplied,

inaccordancewiththecriteriaestablishedthroughthe

inter-nationalguidelines.

Atthephysician’sdiscretion,aDVDcontaining14exercises

tobeperformedathomeisprovided.Thenextconsultationis

scheduledforthreeweeksafterwards,onaverage.Inthefirst

year, theconsultationstakeplace everythreemonthsand,

afterthis,theybecomehalf-yearly.

IntheclinicalprofileforPrevrefrat,injectabledrugsthatare

administeredonceayearorhalf-yearly(suppliedbythe

Fed-eralHospitalofIpanema)arespecified.Thisisbecauseofthe

extremelylowdegreeofadherencetooraldrugs:morethan

70%ofsuchpatientsdonotcompleteoneyearoftreatment.

Pooradherencehasadecisivenegativeinfluenceonthe

out-comewithregardtoavoidanceofnewfractures.Theseverity

ofourpatients’clinicalconditiondoesnotallowuseofdrugs

withthisprofileoflowadherence.

StudiespresentedattheInternationalOsteoporosis

Foun-dationWorldCongressof2014demonstratedadherencerates

of100%amongpatientswithhipfracturesand85%among

thosewithnon-hipfractures.

Theresultsthatfollowprovethatthisoptioniscorrectand

effective.

Results

from

Prevrefrat

Overaperiodofthreeyearsandtenmonths,450patientswere

followedupand12casesoffracturesoccurred.Noneofthese

(5)

werehip fractures.Inother words,therate ofreductionof

subsequentfractureswasmorethan97%.

Ethical

dimension

of

secondary

prevention

of

fractures

Olderpatientsusuallypresentwiththeirfirstfractureatan

emergencyservice,orgotoanorthopedistwhohastheskills

andexpertisetomanagetheacuteconditionandrepairthe

fracture. However,thereisanadditionaldimension:

know-ingthatthefractureoccurredinanindividualwithlowbone

resistanceidentifiesthispersonaspresentinghigherriskof

futurefractures.Studies withthe highestlevel ofevidence

haveshownthatosteoporosiscanbemanagedtodiminishthe

likelihoodoffuturefractures.Thedataclearlydemonstrate

thatahighproportionofsecondaryfracturescanbeavoided

throughappropriatemanagementandthataninitialfracture

duetofragilityisreasonenoughtoaskforacomplete

eval-uation,includingmeasurementofbonemineraldensityand

evaluationoftherisk,andisenoughforstartingtreatment.

Itmightbearguedthatinmanycases,neitherthe

ortho-pedistnor theemergency physicianistheidealperson for

startingthisinvestigationandtreatment.However,thisdoes

notabsolvethemfromtheresponsibilityforensuringthatthe

patientorthepatient’sfamilyisfullyawareoftheriskandfor

referringthepatientforappropriateevaluationandfollow-up.

Theunderlying bone fragility and the increased risk of

fractures can be managed subsequently by orthopedists,

endocrinologists, rheumatologists, geriatricians and other

healthcareprofessionals,alongwithcollaborationfrom

pro-fessionalsinvolvedintherehabilitationprocess.

Thedataaresufficientlyconvincingtocharacterize

appro-priatereferralasanobligationtodothe rightthing, i.e.to

providethewayforwardtothebestresult.Anyconduct

dif-feringfromthiswillcertainlybebelowtheacceptableethical

andclinicalstandards.60

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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1. Osteoporosisprevention,diagnosis,andtherapy.NIH ConsensStatement.2000;17(1):1–45.

2. NIHConsensusDevelopmentPanelonOsteoporosis Prevention.Diagnosisandtherapy.Osteoporosisprevention, diagnosis,andtherapy.JAMA.2001;285(6):785–95.

3. Guidelinesforpreclinicalevaluationandclinicaltrialsin osteoporosis.Geneva:WorldHealthOrganization;1998.

4. BrownJP,JosseRG.Clinicalpracticeguidelinesforthe diagnosisandmanagementofosteoporosisinCanada.CMAJ. 2002;16710Suppl:S1–34.

5. JohnellO,KanisJA,OdénA,SernboI,Redlund-JohnellI, PettersonC,etal.Fractureriskfollowinganosteoporotic fracture.OsteoporosInt.2004;15(3):175–9.

6. LauritzenJB,LundB.Riskofhipfractureafterosteoporosis fractures.451womenwithfractureoflumbarspine,

olecranon,kneeorankle.ActaOrthopScand. 1993;64(3):297–300.

7.DreinhöferKE,FéronJM,HerreraA,HubeR,JohnellO,Lidgren L,etal.Orthopaedicsurgeonsandfragilityfractures.Asurvey bytheBoneandJointDecadeandtheInternational

OsteoporosisFoundation.JBoneJointSurgBr. 2004;86(7):958–61.

8.LönnroosE,KautiainenH,KarppiP,HartikainenS,KivirantaI, SulkavaR.Incidenceofsecondhipfractures.A

population-basedstudy.OsteoporosInt.2007;18(9):1279–85.

9.NymarkT,LauritsenJM,OvesenO,RöckND,JeuneB.Short time-framefromfirsttosecondhipfractureintheFunen CountyHipFractureStudy.OsteoporosInt.2006;17(9):1353–7.

10.LawrenceTM,WennR,BoultonCT,MoranCG.Age-specific incidenceoffirstandsecondfracturesofthehip.JBoneJoint SurgBr.2010;92(2):258–61.

11.BlackDM,DelmasPD,EastellR,ReidIR,BoonenS,CauleyJA, etal.;HorizonPivotalFractureTrial.Once-yearlyzoledronic acidfortreatmentofpostmenopausalosteoporosis.NEnglJ Med.2007;356(18):1809–22.

12.LylesKW,Colón-EmericCS,MagazinerJS,AdachiJD,Pieper CF,MautalenC,etal.;HORIZONRecurrentFractureTrial. Zoledronicacidandclinicalfracturesandmortalityafterhip fracture.NEnglJMed.2007;357(18):1799–809.

13.PortL,CenterJ,BriffaNK,NguyenT,CummingR,EismanJ. Osteoporoticfracture:missedopportunityforintervention. OsteoporosInt.2003;14(9):780–4.

14.EdwardsBJ,BuntaAD,SimonelliC,BolanderM,Fitzpatrick LA.Priorfracturesarecommoninpatientswithsubsequent hipfractures.ClinOrthopRelatRes.2007;461:226–30.

15.KlotzbuecherCM,RossPD,LandsmanPB,AbbottTA3rd, BergerM.Patientswithpriorfractureshaveanincreasedrisk offuturefractures:asummaryoftheliteratureandstatistical synthesis.JBoneMinerRes.2000;15(4):721–39.

16.KanisJA,JohnellO,DeLaetC,JohanssonH,OdenA,DelmasP, etal.Ameta-analysisofpreviousfractureandsubsequent fracturerisk.Bone.2004;35(2):375–82.

17.CranneyA,GuyattG,GriffithL,WellsG,TugwellP,RosenC, etal.Meta-analysesoftherapiesforpostmenopausal osteoporosis.IX:summaryofmeta-analysesoftherapiesfor postmenopausalosteoporosis.EndocrRev.2002;23(4):570–8.

18.BritishOrthopaedicAssociation.Thecareofpatientswith

fragilityfracture;2007.Availablefrom:http://www.fractures.

com/pdf/BOA-BGS-Blue-Book.pdf.

19.DepartmentofHealthinEngland.PreventionPackagefor

OlderPeople.Availablefrom:http://www.dh.gov.uk/en/

Publicationsandstatistics/Publications/DH103146.

20.Prevenc¸ãoàosteoporosedevecomec¸arnainfância.Available

from:http://portalsaude.saude.gov.br/index.php/cidadao/

principal/saude-em-dia/mais-sobre-saude-em-dia. 21.PinheiroMM,ReisNetoET,MachadoFS,OmuraF,YangJH,

SzejnfeldJ,etal.Riskfactorsforosteoporoticfracturesand lowbonedensityinpreandpostmenopausalwomen.Rev SaudePublica.2010;44(3):479–85.

22.MartiniLA,MouraEC,SantosLC,MaltaDC,PinheiroMM. Prevalênciadediagnósticoautorreferidodeosteoporose, Brasil,2006.RevSaudePublica.2009;43Suppl2:107–16.

23.SingerA,ExuzidesA,SpanglerL,O’MalleyC,ColbyC, JohnstonK,etal.Burdenofillnessforosteoporoticfractures comparedwithotherseriousdiseasesamong

postmenopausalwomenintheUnitedStates.MayoClinProc. 2015;90(1):53–62.

24.BlackDM,ThompsonDE,BauerDC,EnsrudK,MuslinerT, HochbergMC,etal.FractureInterventionTrial.Fracturerisk reductionwithalendronateinwomenwithosteoporosis:the FractureInterventionTrial.FITResearchGroup.JClin EndocrinolMetab.2000;85(11):4118–24.

(6)

andnonvertebralfracturesinwomenwithpostmenopausal osteoporosis:arandomizedcontrolledtrial.VertebralEfficacy WithRisedronateTherapy(VERT)StudyGroup.JAMA. 1999;282(14):1344–52.

26.JohnstonCCJr,BjarnasonNH,CohenFJ,ShahA,LindsayR, MitlakBH,etal.Long-termeffectsofraloxifeneonbone mineraldensity,boneturnover,andserumlipidlevelsin earlypostmenopausalwomen:three-yeardatafrom2 double-blind,randomized,placebo-controlledtrials.Arch InternMed.2000;160(22):3444–50.

27.EttingerB,BlackDM,MitlakBH,KnickerbockerRK,Nickelsen T,GenantHK,etal.Reductionofvertebralfractureriskin postmenopausalwomenwithosteoporosistreatedwith raloxifene:resultsfroma3-yearrandomizedclinicaltrial. MultipleOutcomesofRaloxifeneEvaluation(More) Investigators.JAMA.1999;282(7):637–45.

28.ChesnutCH3rd,SilvermanS,AndrianoK,GenantH,Gimona A,HarrisS,etal.Arandomizedtrialofnasalspraysalmon calcitonininpostmenopausalwomenwithestablished osteoporosis:thepreventrecurrenceofosteoporoticfractures study.ProofStudyGroup.AmJMed.2000;109(4):267–76.

29.TheWritingGroupforthePEPI.Effectsofhormonetherapy onbonemineraldensity:resultsfromthepostmenopausal estrogen/progestininterventions(PEPI)trial.JAMA. 1996;276(17):1389–96.

30.BoonenS,AdachiJD,ManZ,CummingsSR,LippunerK, TörringO,etal.Treatmentwithdenosumabreducesthe incidenceofnewvertebralandhipfracturesin

postmenopausalwomenathighrisk.JClinEndocrinolMetab. 2011;96(6):1727–36.

31.EastellR.Treatmentofpostmenopausalosteoporosis.NEnglJ Med.1998;338(11):736–46.

32.GuarnieroR,OliveiraLG.Osteoporose:atualizac¸ãono diagnósticoeprincípiosbásicosparaotratamento.RevBras Ortop.2004;39(9):477–85.

33.NeerRM,ArnaudCD,ZanchettaJR,PrinceR,GaichGA, ReginsterJY,etal.Effectofparathyroidhormone(1–34)on fracturesandbonemineraldensityinpostmenopausal womenwithosteoporosis.NEnglJMed.2001;344(19):1434–41.

34.LaneNE,SanchezS,ModinGW,GenantHK,PieriniE,Arnaud CD.Bonemasscontinuestoincreaseatthehipafter parathyroidhormonetreatmentisdiscontinuedin

glucocorticoid-inducedosteoporosis:resultsofarandomized controlledclinicaltrial.JBoneMinerRes.2000;15(5):944–51.

35.ReginsterJY,SpectorT,BadurskiJ.Ashort-termrun-instudy cansignificantlycontributetoincreasingthequalityof long-termosteoporosistrials.Thestrontiumranelatephase IIIprogram.OteoporosInt.2002;13Suppl1:S30.

36.MeunierPJ,RouxC,OrtolaniS.Strontiumranelatereduces thevertebralfractureriskinwomenwithpostmenopausal osteoporosis.OsteoporosInt.2002;13Suppl1:045.

37.ReginsterJY.Strontiumranelatereducestheriskofhip fractureinwomenwithpostmenopausalosteoporosis. OsteoporosInt.2002;13Suppl1:014.

38.BaileyDA,McKayHA,MirwaldRL,CrockerPR,FaulknerRA.A six-yearlongitudinalstudyoftherelationshipofphysical activitytobonemineralaccrualingrowingchildren:the universityofSaskatchewanbonemineralaccrualstudy.J BoneMinerRes.1999;14(10):1672–9.

39.PlaplerPG,RoccoJCP.Osteoporoseeexercícios.ActaOrtop Bras.1998;6(1):49–54.

40.NationalOsteoporosisFoundation(NOF).Osteoporosis PreventionStrategies.OsteoporosisClinicalUpdates.1996.

41.Brianc¸onD,deGaudemarJB,ForestierR.Managementof osteoporosisinwomenwithperipheralosteoporoticfractures after50yearsofage:astudyofpractices.JointBoneSpine. 2004;71(2):128–30.

42.McCloskeyE,deTakatsD,OrgeeJ.Characteristicsassociated withnon-persistenceduringdailytherapy.Experiencefrom theplacebowingofacommunitybasedclinicaltrial.JBone MinerRes.2005;20Suppl1:S282.

43.KleerekoperM,GoldDT.Osteoporosispreventionand management:anevidence-basedreview.ClinObstetGynecol. 2008;51(3):556–63.

44.GiangregorioL,PapaioannouA,CranneyA,ZytarukN,Adachi JD.Fragilityfracturesandtheosteoporosiscaregap:an internationalphenomenon.SeminArthritisRheum. 2006;35(5):293–305.

45.HoovenF,GehlbachSH,PekowP,BertoneE,BenjaminE. Follow-uptreatmentforosteoporosisafterfracture. OsteoporosInt.2005;16(3):296–301.

46.PengEW,ElniketyS,HatrickNC.Preventingfragilityhip fractureinhighriskgroups:anopportunitymissed.Postgrad MedJ.2006;82(970):528–31.

47.SmithMG,DunkowP,LangDM.Treatmentofosteoporosis: missedopportunitiesinthehospitalfractureclinic.AnnR CollSurgEngl.2004;86(5):344–6.

48.VaileJ,SullivanL,BennettC,BleaselJ.FirstFractureProject: addressingtheosteoporosiscaregap.InternMedJ. 2007;37(10):717–20.

49.BollandMJ,GreyAB,GambleGD,ReidIR.Effectof

osteoporosistreatmentonmortality:ameta-analysis.JClin EndocrinolMetab.2010;95(3):1174–81.

50.BeaupreLA,MorrishDW,HanleyDA,MaksymowychWP,Bell NR,JubyAG,etal.Oralbisphosphonatesareassociatedwith reducedmortalityafterhipfracture.OsteoporosInt. 2011;22(3):983–91.

51.SambrookPN,CameronID,ChenJS,MarchLM,SimpsonJM, CummingRG,etal.Oralbisphosphonatesareassociatedwith reducedmortalityinfrailolderpeople:aprospectivefive-year study.OsteoporosInt.2011;22(9):2551–6.

52.KothawalaP,BadamgaravE,RyuS,MillerRM,HalbertRJ. Systematicreviewandmeta-analysisofreal-worldadherence todrugtherapyforosteoporosis.MayoClinProc.

2007;82(12):1493–501.

53.CramerJA,GoldDT,SilvermanSL,LewieckiEM.Asystematic reviewofpersistenceandcompliancewithbisphosphonates forosteoporosis.OsteoporosInt.2007;18(8):1023–31.

54.HopmanWM,BergerC,JosephL,TowheedT,PriorJC, AnastassiadesT,etal.Health-relatedqualityoflifein Canadianadolescentsandyoungadults:normativedata usingtheSF-36.CanJPublicHealth.2009;100(6):449–52.

55.McLellanAR,GallacherSJ,FraserM,McQuillianC.The fractureliaisonservice:successofaprogramforthe evaluationandmanagementofpatientswithosteoporotic fracture.OsteoporosInt.2003;14(12):1028–34.

56.McLellanAR,WolowaczSE,ZimovetzEA,BeardSM,LockS, McCrinkL,etal.Fractureliaisonservicesfortheevaluation andmanagementofpatientswithosteoporoticfracture:a cost-effectivenessevaluationbasedondatacollectedover8 yearsofserviceprovision.OsteoporosInt.2011;22(7):2083–98.

57.DellR.FracturepreventioninKaiserPermanentSouthern California.OsteoporosInt.2011;22Suppl3:457–60.

58.DellRM,GreeneD,AndersonD,WilliamsK.Osteoporosis diseasemanagement:whateveryorthopaedicsurgeon shouldknow.JBoneJointSurgAm.2009;91Suppl6:79–86.

59.DellR,GreeneD,SchelkunSR,WilliamsK.Osteoporosis diseasemanagement:theroleoftheorthopaedicsurgeon.J BoneJointSurgAm.2008;90Suppl4:188–94.