Review Osteoporosis

19/11/2015
GmailDynaMedEMail:Osteoporosis
DaniloDeFranco<dadefranco@gmail.com>
DynaMedEMail:Osteoporosis
1mensaje
dadefranco@gmail.com<dadefranco@gmail.com>
Para:dadefranco@gmail.com
19denoviembrede2015,13:14
Osteoporosis
Osteoporosis
Updated2015Apr1509:16:00AM:reviewofscreeningforosteoporosis(JAMA2015Apr14)view
updateShowmoreupdates
vitaminK2supplementsmaynotreduceincidenceoffracturesbutmayincreaselumbarbonemineral
densityinpostmenopausalwomenwithosteoporosis(OsteoporosInt2015Mar)viewupdate
vitaminK2supplementsmaynotreduceincidenceoffracturesorimprovevertebralbonemineraldensity
inpostmenopausalwomenwithoutosteoporosis(OsteoporosInt2015Mar)viewupdate
RelatedSummaries:
Osteoporosiscausesandriskfactors
Bisphosphonatesfortreatmentandpreventionofosteoporosis
Hormonalreplacementtherapy(HRT)andosteoporosis
CalciumandvitaminDfortreatmentandpreventionofosteoporosis
PhysicianQualityReportingSystemQualityMeasures
GeneralInformation
Description:
generalizedskeletaldisordercharacterizedbycompromisedbonestrengthanddeteriorationofbone
quality,oftenleadingtofragilityfracture(2)
lowbonemassfrequentlyfound,butnotrequired,fordiagnosis
regardlessofbonemass,fragilityfracturenecessitatesdiagnosis
Definitions:
osteomalaciadefinedassofteningofbones,usuallyduetoseverelackofvitaminD(4)
osteopenia(preferredtermsare"lowbonemass"or"lowbonedensity")definedaslownormalbone
density,asdefinedbyTscorebetween1and2.5whendeterminedbylowestcalculationfromlumbar
spine(atleast2evaluablevertebrae),femoralneck,ortotalfemurTscore,notlowenoughtobe
osteoporosis (1,2)
osteoporosisdefinedasfragilityfractureorTscore2.5whendeterminedbylowestcalculationfrom
lumbarspine(atleast2evaluablevertebrae),femoralneck,ortotalfemurTscore(onethirdradiussite
maybeusedifeitherlumbarspineorfemurisnonevaluable)(1,2)
primaryosteoporosisisdeteriorationofbonemassunassociatedwithotherchronicillness,relatedto
https://mail.google.com/mail/u/0/?ui=2&ik=57a4354ead&view=pt&search=inbox&type=150fe2a25b1b4d8a&th=151212b463126d90
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aginganddecreasedgonadalfunction(bonelossacceleratedduringsixthdecadeoflifeor
perimenopausalperiodinwomen)(AmFamPhysician2001Mar163(5):897)
secondaryosteoporosisisdeteriorationofbonemassassociatedwithchronicconditionsthatcontribute
significantlytoacceleratedboneloss(AmFamPhysician2001Mar163(5):897)
severeosteoporosisdefinedasfragilityfractureorfracturesANDTscore2.5(1,2)
osteitisfibrosadefinedassofteninganddeformityofbones,usuallyduetocomplicationsof
hyperparathyroidism
fragility(lowimpact)fractureisfracturefromminortrauma(forinstance,fallfromstandingheightorless)
(1,2)
hightraumafractureisfracturefromhightrauma(forinstance,fromcaraccident)(1,2)
clinicalfracturefracturesuspectedfromsignsonclinicalexam(1,2)
Epidemiology
Whoismostaffected:
postmenopausalwomen(1,2)
persons65yearsold(1,2)
CaucasiansandpeopleofAsiandescent(1,2)
personswithsmallbodyframe(1,2)
Incidence/Prevalence:
prevalenceofosteoporosisinadultsaged50yearsinUnitedStates (1,2)
>10millionpersonsoverall
>33millionhavelowbonedensityathip
estimatedprevalenceofosteoporosis22million(21%)womenand5.5million(6%)meninEuropean
Union
basedon7.5millionadultsaged5084yearsinSwedenwhohadbonemineraldensity(BMD)data
atfemoralneckreportedaspartofthirdNationalHealthandNutritionExaminationSurvey
(NHANESIII)
prevalenceofosteoporosisacross27countriesofEuropeanUnionwascalculatedbyapplying
prevalenceofosteoporosisinSwedentopopulationdemographicineachcountryandassuming
thatmeanfemoralneckBMDissimilaracrossallcountriesatage50years
3.5millionincidencesoffragilityfracture(hip,vertebral,forearm,orotherfracture)estimatedin
EuropeanUnionin2010
ReferenceArchOsteoporos20138(12):136fulltext
prevalenceofosteoporosis37%inpostmenopausalwomen50yearsoldand7.8%inmen50years
oldinKoreain20082010
basedon3,849postmenopausalwomenand3,314menaged5090yearswhohadbonemineral
densitydatareportedaspartofKoreaNationalHealthandNutritionExaminationSurvey
(KNHANES)in20082010
ReferenceEndocrinolMetab(Seoul)2013Sep28(3):180fulltext
osteoporosisinmen
osteoporosisdetectedin20%30%of86menwithchronicobstructivepulmonarydisease,57%of
whomweretakingglucocorticoids
basedonretrospectivecohortstudy
ReferenceChest2002May121(5):1456fulltext
17.5%57.8%incidenceofosteoporosisfoundinmen>50yearsoldwithfractures
basedonretrospectivechartreviewof2,035men>50yearsoldwith2,142fractures,
including90menwithhipfractureand143menwithanklefracture
57.8%withhipfractureand17.5%withanklefracturehadosteoporosis
ReferenceJBoneJointSurgBr2008Jan90(1):72fulltext
EtiologyandPathogenesis
Causesandriskfactors:
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lifestylefactorslowcalciumintake,vitaminDdeficiency,excessvitaminAintake,inadequatephysical
activity,smoking,andalcoholabuse
geneticfactorsparentalhistoryofhipfracture,cysticfibrosis,hemochromatosis,variousgenetic
disordersandgenevariants,porphyria,osteogenesisimperfecta,hypophosphatasia
medicalconditions
endocrinedisordershyperparathyroidism,hypogonadalstates,anorexianervosa,diabetes
mellitus,Cushingsyndrome,excessthyroidhormone,endocrinetherapiesforcancer
gastrointestinaldisordersCeliacdisease,gastricbypass,Crohndisease,malabsorption,cirrhosis
hematologicdisordersmultiplemyeloma,thalassemia,leukemia,lymphoma,mastocytosis
rheumatologicandautoimmunedisordersrheumatoidarthritis,ankylosingspondylitis,systemic
lupuserythematosus
centralnervoussystemdisordersepilepsy,multiplesclerosis,Parkinsondisease
othermedicalconditionsHIVinfection,amyloidosis,chronicobstructivepulmonarydisease
(COPD),heartfailure,chronickidneydisease,hypercalciuria,weightloss,alcoholism,renaltubular
acidosis
medications
includinglongtermanticoagulation,hormonaltherapies,glucocorticosteroids,some
immunosuppressants,lithium,thiazolidinediones(glitazones),longtermprotonpumpinhibitoruse
highdosebutnotlowdoseinhaledsteroidsmaybeassociatedwithincreasedriskoffracturesin
elderlypersons(level2[midlevel]evidence)
seeOsteoporosiscausesandriskfactorsfordetails
Pathogenesis:
processofboneremodelingmaintainshealthybonemassthroughoutlife(1,3)
inhealthybone,boneresorption(osteoclastcells)isbalancedbyboneformation(osteoblastcells)
bonelossoccurswhenboneresorptionoutpacesboneformation,resultingindecreasedbone
massandincreasedriskoffracture
fractureresultsfromoverloadingofweakenedbones
inprimaryosteoporosis,bonelossresultsfromfactorsassociatedwithagingandsexsteroiddeficiency
(forinstance,decreasedcirculatinglevelsof17betaestradiolinmenopauseinhibitsboneresorption
withoutincreasingboneformation)(1,3)
insecondaryosteoporosis,bonelossresultsfromspecificcauses,suchas (1)
decreasedboneformationandreducedbonequalityandintegritywithglucocorticoids
antiproliferativeeffectonosteoblastcellswithalcohol
HistoryandPhysical
History:
Chiefconcern(CC):
usuallyasymptomaticuntilfracture(1)
maydetectwithincidentradiographicvertebralfracturesfoundduringimagingforotherclinicalindications
orduringscreeningimaginginhighriskpersons (2)
Historyofpresentillness(HPI):
certainfracturesappearmorelikelytobeduetoosteoporosis
fracturesmostlikelytobeduetoosteoporosisinclude
femoralneckfractures
pathologicfracturesofvertebrae
lumbarandthoracicvertebralfractures
distalradiusfractures
fractureslesslikelytobeduetoosteoporosisinclude
openproximalhumerusfractures
skullfractures
facialbonefractures
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ReferenceJClinEpidemiol2011Jan64(1):46,editorialcanbefoundinJClinEpidemiol2011
Jan64(1):45
askabout(1)
backpainandposturalchangewhichmayoccurwithvertebralfractures
dyspnea,constipation,abdominalpain,distention,reducedappetite,andearlysatietymaybe
relatedtolossofheightfromvertebralcollapse
Medicationhistory:
askaboutmedicationsthatincreaseriskforosteoporosis (2)
includinglongtermanticoagulation,hormonaltherapies,glucocorticosteroids,some
immunosuppressants,lithium,thiazolidinediones(glitazones),longtermprotonpumpinhibitoruse
highdosebutnotlowdoseinhaledsteroidsmaybeassociatedwithincreasedriskoffracturesin
elderlypersons(level2[midlevel]evidence)
Pastmedicalhistory(PMH):
askaboutmedicalconditionsthatincreaseriskforosteoporosisincluding(2)
endocrinedisordershyperparathyroidism,hypogonadalstates,anorexianervosa,diabetes
mellitus,Cushingsyndrome,excessthyroidhormone,endocrinetherapiesforcancer
gastrointestinaldisordersCeliacdisease,gastricbypass,Crohndisease,malabsorption,cirrhosis
hematologicdisordersmultiplemyeloma,thalassemia,leukemia,lymphoma,mastocytosis
rheumatologicandautoimmunedisordersrheumatoidarthritis,ankylosingspondylitis,systemic
lupuserythematosus
centralnervoussystemdisordersepilepsy,multiplesclerosis,Parkinsondisease
othermedicalconditionsHIVinfection,amyloidosis,chronicobstructivepulmonarydisease
(COPD),heartfailure,chronickidneydisease,hypercalciuria,weightloss,alcoholism,renaltubular
acidosis
Familyhistory(FH):
askabout(2)
geneticfactorsthatincreaseriskforosteoporosiscysticfibrosis,hemochromatosis,various
geneticdisordersandgenevariants,porphyria,osteogenesisimperfecta,hypophosphatasia
parentalhistoryofhipfracture
Socialhistory(SH):
askaboutlifestylefactorsthatincreaseriskforosteoporosisincluding(2)
alcoholuse
dietlowcalciumintake,vitaminDdeficiency,excessvitaminAintake
lowphysicalactivitylevel
smoking
Physical:
Generalphysical:
lowbodymassindexorweight<127pounds(57.6kg)isriskfactor(2)
assessfor
heightloss (1,2)
signsofhyperthyroidism(1,3,4) (suchastachycardia,weightloss,hypertension,goiter)
somephysicalfindingsareassociatedwithincreasedriskofosteoporosis
systematicreviewof14studiesofaccuracyorprecisionofphysicalexamfordiagnosing
osteopenia,osteoporosis,orspinalfracture
nosinglefindingsufficienttoruleinorruleoutosteoporosisorspinalfracturewithouttesting
findingswithincreasedlikelihoodofosteoporosisorspinalfracture
weight<51kg(112lbs)hadpositivelikelihoodratio7.3
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wallocciputdistance>0cmhadpositivelikelihoodratio4.6
ribpelvisdistance<2fingerbreadthshadpositivelikelihoodratio3.8
toothcount<20hadpositivelikelihoodratio3.4
ReferenceJAMA2004Dec15292(23):2890,commentarycanbefoundinEvidenceBased
Medicine2005JulAug10(4):123
Lungs:
evaluateforrestrictiveorobstructivelungdiseaseascomorbidcondition
Abdomen:
protuberantabdomenmayresultfromkyphosis (1,3)
Back:
dorsalkyphosis(abnormalcurvatureofthoracicspine)(1,3,4)
Extremities:
bonedeformitiesmayresultfromfractures (1,3)
Genitalexam:
assessfortesticularatrophy (4)
Diagnosis
Makingthediagnosis:
makeclinicaldiagnosisofosteoporosisinadultswithfragilityfracture,regardlessofanytestresults (1,2,
3)
ifnofragilityfracture
considerscreeningforosteoporosiswithbonemineraldensitytesting(usuallydualenergyxray
absorptiometry[DEXA]measurementatposterioranteriorspineand/orhip)in
allwomen65yearsold,andallmen70yearsold
postmenopausalwomen<65yearsold,perimenopausalwomen,andmenaged5069years
withclinicalriskfactorsforfracture
anyadultwithfractureafterage50years
anyadultwithcondition(suchasrheumatoidarthritis)oruseofmedication(suchas
glucocorticoids3months)associatedwithlowbonemassorboneloss
riskcalculators(FractureRiskAssessmentFRAX,QFracture2013RiskCalculator,Garvan
InstituteFractureRiskCalculator)predict10yearriskoffracture
osteoporosisdefinedasfragilityfractureorTscore2.5whendeterminedbylowestcalculationfrom
lumbarspine(atleast2evaluablevertebrae),femoralneck,ortotalfemurTscore
osteopenia(preferredtermsare"lowbonemass"or"lowbonedensity")definedaslownormalbone
density,asdefinedbyTscorebetween1and2.5whendeterminedbylowestcalculationfromlumbar
spine(atleast2evaluablevertebrae),femoralneck,ortotalfemurTscore,notlowenoughtobe
osteoporosis (1,2)
inchildren
diagnoseosteoporosisinchildrenwithzscore2plusclinicallysignificantfracturehistory(2
longbonefracturesbyage10yearsor3longbonefracturesbyage19years)(5)
1vertebralcompressionfracture(inabsenceoflocaldiseaseorhighimpacttrauma)inchildren
issuggestiveofosteoporosisandindicatesneedforbonemineraldensitytesting(5)
Differentialdiagnosis:
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seeCauses
homocystinuria/homocysteinemia
hyperparathyroidism
mastocytosis
multiplemyeloma
osteomalaciaandrenalosteodystrophy(adults)
rickets(children)
Pagetdiseaseofbone
scurvy
sicklecellanemia
osteitisfibrosacystica
bonetumors,suchasenchondromaandosteochondroma
Testingoverview:
bonemineraldensity(BMD)testingwithdualenergyxrayabsorptiometry(DEXA)
inadultsmeasureBMDathip(femoralneck,totalhip)andposterioranteriorspine,or33%radiusif
unabletousehipand/orspine
inchildrenposterioranteriorspineortotalbodylessheadpreferred
considervertebralfractureassessment(VFA)inwomen>70yearsold,men>80yearsold,patientswith
historicalheightloss>4cm(1.5inches),orpatientstakingchroniccorticosteroids
teststhatmaybeusefulinrulingoutsecondarycausesofbonelossinclude(2)
bloodtests
forallpatientswithosteoporosis
25hydroxyvitaminD
calcium
creatinine
thyroidstimulatinghormone(TSH)
forpatientswithsuspectedsecondarycauses
alkalinephosphatase(ALP)
phosphorus
parathyroidhormone(PTH)
completebloodcount
erythrocytesedimentationrate(ESR)orCreactiveprotein(CRP)
testosterone(men)orestradiol(women)
luteinizinghormone(LH),folliclestimulatinghormone(FSH),andprolactin
tissuetransglutaminaseantibody
serumproteinelectrophoresis
urinetests
24hoururinarycalciumexcretion
24hoururinaryfreecortisol,ifsuspectosteoporosisduetoglucocorticoidexcess
salivarycortisol
Clinicalpredictionrules:
clinicaldecisionrulesappearinaccurateforidentifyingosteoporosisinpatientswithrheumatoid
arthritis(level2[midlevel]evidence)
basedonderivationcohortstudywithoutvalidation
287patientsaged2272yearswithrheumatoidarthritis(RA)andcompletedataavailablefrom
OsloRAregisterwereevaluated
validationofpreviouslypublished3itemclinicaldecisionrulewasattemptedbutrulehadlimited
predictivevalue
62patients(21.6%)hadosteoporosis(Tscore2.5)atfemoralneckand/orspine
5itemclinicaldecisionrulederivedwith5criteria
highdiseaseactivitywithmeanCreactiveprotein(CRP)>20mg/Land/ormeanerythroyte
sedimentationrate(ESR)>20mm/hour
age>50yearsinwomenor>60yearsinmen
immobilitywithHealthAssessmentQuestionnaire(HAQ)score1.25
weight<60kg(132.3lbs)
currentuseofcorticosteroids
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fordetectionofosteoporosis,meeting3of5criteriahad
sensitivityof82%
specificityof45%
positivepredictivevalueof29%
negativepredictivevalueof90%
positivelikelihoodratioof1.49
negativelikelihoodratioof0.4
ReferenceAnnRheumDis2002Dec61(12):1085fulltext
Bloodtests:
Determiningsecondarycausesofosteoporosis:
considertestingallpatientswithosteoporosisforsecondarycauses(ICSIStrongrecommendation,Low
qualityevidence)(2)
initialtestingforallpatientswithoutpriorworkup(2,3)
25hydroxyvitaminD(25[OH]D)level
optimallevel30ng/mL(74.9nmol/L)
iflow(vitaminDdeficiency),mayindicateinadequateexposuretosunlight,inadequate
vitaminDintake,gastrointestinalmalabsorption,orceliacdisease
serumcalcium
iflow(hypocalcemia),mayindicatemalabsorptionorvitaminDdeficiency
ifelevated(hypercalcemia),mayindicatehyperparathyroidism
serumcreatinineelevatedcreatininesuggestsrenaldysfunction
thyroidstimulatinghormone(TSH)lowTSHmayindicatehyperthyroidism
furtherteststoconsider(2,3)
serumalkalinephosphatase,ifelevated,mayindicatePagetdiseaseofbone,prolonged
immobilization,acutefractures,osteomalacia,vitaminDdeficiency,gastrointestinal
malabsorption,hyperparathyroidism,orliverorbiliarydiseases
serumphosphorus
maybeelevatedinrenalfailure(acuteorchronic)
maybelowinhyperparathyroidismorosteomalacia
parathyroidhormonelevel(PTH),ifelevated,suggestshyperparathyroidism
completebloodcountmaysuggestbonemarrowmalignancyorinfiltrativeprocess(anemia,low
whitebloodcells,orlowplatelets)ormalabsorption(anemia,microcytosis,ormacrocytosis)
erythrocytesedimentationrate(ESR)orCreactiveprotein(CRP),ifelevated,mayindicate
inflammatoryprocessormonoclonalgammopathy
testosterone(totalandfree)inmenandestradiol(totalandbioavailable)inwomen,luteinizing
hormone(LH),folliclestimulatinghormone(FSH),and/orprolactin,iflow,mayindicate
hypogonadotropichypogonadism
freetestosteronelevelsinverselyassociatedwithbonemineraldensityinmen,butno
associationwithtotaltestosteronelevels
basedoncohortstudyof792menaged5185years
meantotalhipbonemineraldensity0.94g/cm2inmenwithfreetestosterone<146
pmol/L(4.2ng/dL)vs.0.97g/cm2inmenwithfreetestosterone146pmol/L(4.2
ng/dL)(p<0.01)
ReferenceJClinEndocrinolMetab2003Nov88(11):5240
antitissuetransglutaminaseantibody,ifconcernforceliacdisease
serumproteinelectrophoresis,monoclonalbandmayindicatemultiplemyeloma
1in20patientswithosteoporosismayhavemonoclonalgammopathyofundetermined
significanceormultiplemyeloma
799adults(685women)aged1994yearsnewlyreferredtoosteoporosiscenterwithsuspected
osteoporosiswereevaluated
366hadosteoporosis
serumMcomponentfoundin18patients(4.9%)withosteoporosisvs.9patients(2.2%)without
osteoporosis
multiplemyelomadiagnosedin3patients(0.8%)withosteoporosis
serumMcomponenthad17.6%positivepredictivevalueformultiplemyeloma
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monoclonalgammopathyofundeterminedsignificancediagnosedin13patients(3.6%)with
osteoporosisand8patients(2%)withnormalbonemineraldensityorosteopenia
ReferenceBMJ2005Apr9330(7495):818fulltext
Boneturnovermarkersfordiagnosingosteoporosis:
highboneturnoverhasbeenobservedinpatientswithosteoporosis,butcurrentlylittleconsensusonuse
ofserumboneturnovermarkerstodiagnoseosteoporosis (2)
serumboneturnovermarkers(BTMs)may,however,helpassessriskoffractureinpatientswith
osteoporosisorshowresponsetotherapy (1,3)
InternationalOsteoporosisFoundation(IOF)andInternationalFederationofClinicalChemistryand
LaboratoryMedicine(IFCC)bonemarkerstandardsworkinggrouprecommendationsonuseofbone
turnovermarkersinclinicalpractice
boneturnovermarkers,especiallyboneresorptionmarkers,mayhavesomeutilityforpredicting
fractureoutcomesandformonitoringtreatment
referencestandardsrecommendedforresearchonuseofboneturnovermarkers
useserumcollagentypeIcrosslinkedCtelopeptide(sCTX)asreferencestandardforbone
resorption
useserumprocollagentypeINterminalpropeptide(P1NP)asreferencestandardforbone
formation
collectsampleinEDTAtube,ifpossible
useautomatedanalyzers,ifavailable,butifnot,useELISAkit
ReferenceOsteoporosInt2011Feb22(2):391
elevatedlevelsofserumbonealkalinephosphataseandserumcollagentypeIcrosslinkedC
telopeptidemaybefoundinpatientswithosteoporosis(level2[midlevel]evidence)
basedonsystematicreviewwithwideconfidenceintervals
133cohortorcasecontrolstudiesevaluatinguseofboneturnovermarkerstoassessbonedensity
inpatientswithand/orwithoutosteoporosis
increasedlevelsofboneturnovermarkersinpatientswithosteoporosiscomparedtopatients
withoutosteoporosis
serumbonealkalinephosphatase(boneALP),meandifference7.76units/L(95%CI0.17
15.35units/L)inanalysisof7studieswith452patients
serumcollagentypeIcrosslinkedCtelopeptide(sCTX),meandifference523.7pmol/L
(95%CI134.6912.8pmol/L)inanalysisof4studieswith271patients
nosignificantdifferenceinserumosteocalcin(sOC)inanalysisof10studieswith660patientsor
urinarycollagentypeIcrosslinkedCtelopeptide(uNTX)inanalysisof2studieswith148patients
nosignificantdifferenceinsOCbetweenpatientswithosteoporosiswithandwithoutvertebral
fractureinanalysisof3studieswith235patients
nodataavailabletocalculatesensitivity,specificity,orpredictivevaluesforboneturnovermarkers
indiagnosisofosteoporosisorassessmentoffractureriskinosteoporosis
ReferenceJointBoneSpine2012Jan79(1):20
Urinestudies:
initialtestingtodeterminesecondarycausesinallpatientswithoutpriorworkupincludes24hoururine
calciumexcretion(2,3)
iflow,mayindicatestateofmalabsorption(suchaswithceliacdiseaseorpostgastricbypass),
vitaminDdeficiency,lowcalciumintake,oruseofthiazidediuretics
ifelevated,mayindicateidiopathichypercalciuria,primaryhyperparathyroidism,renalcalcium
leak,multiplemyeloma,metastaticcancerinvolvingbone,orhyperthyroidismbutalsocommonin
patientswithexcessivecalciumintake
additionaltestingmayinclude(2)
24hoururinaryfreecortisol,elevatedwithglucocorticoidexcess
urineproteinelectrophoresis,maycontainmonoclonallightchainswithmultiplemyeloma
Imagingstudies:
Dualenergyxrayabsorptiometry(DEXA):
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DEXAtestingindications:
InternationalSocietyforClinicalDensitometry/NationalOsteoporosisFoundation/InstituteforClinical
SystemsImprovement(ISCD/NOF/ICSI)recommendationsonbonemineraldensity(BMD)testingin
adultsrecommendsDEXAfor(1,2,6)
allwomen65yearsoldandallmen70yearsold
youngerpostmenopausalwomen,womeninmenopausaltransition,andmen<70yearsoldwith
clinicalriskfactorsforfracture(suchas,lowbodyweightorpriorfracture)
adultswithfragilityfracture
adultswithconditions(forexample,rheumatoidarthritis)ortakingmedications(forexample,
prednisone5mg/dayorequivalentglucocorticoidfor3months)associatedwithlowbonemass
orboneloss
anyoneconsideringmedicationforosteoporosis
anyonebeingtreatedforosteoporosis
anyonenotbeingtreatedbutinwhomevidenceofbonelosswouldleadtotreatment
womendiscontinuingestrogenwhomeetanyoftheseindications
BodysiteselectionforDEXA:
SystemsImprovement(ISCD/NOF/ICSI)recommendationsonbonemineraldensity(BMD)testingin
adults (1,2,6)
posterioranteriorspineandhipinallpatients
posterioranteriorspinemeasurement
useL1L4forposterioranteriorspine
usemaximumnumberofevaluablevertebraeandonlyexcludevertebraeifaffected
bylocalstructuralchangeorartifact
ifanynonevaluablevertebraeexcluded,useallremainingvertebraetoderiveT
score,unlessonlysinglevertebraremains,usedifferentvalidskeletalsite
excludeanatomicallyabnormalvertebraeifclearlyabnormalandnonassessable
withinresolutionofsystemor1Tscoredifferencebetweenabnormalvertebraeand
adjacentvertebrae
donotuselateralspinefordiagnosis
hipmeasurement
usefemoralneckortotalproximalfemur(ateitherhip),whicheverislowest
insufficientevidencetodetermineifmeanTscoresforbilateralhipBMDcanbe
usedfordiagnosis
meanhip(preferablytotalhip)BMDcanbeusedformonitoring
forearm(onethirdor33%radiusofnondominantforearm)BMDfordiagnosisonlyif
hipand/orspinecannotbemeasuredorinterpreted
patienthashyperparathyroidism
patientisoverweightlimitfordualenergyxrayabsorptiometry(DEXA)table
TscoreandZscoreclassification:
Tscoreusedinpostmenopausalwomenormen50yearsold(2)
Tscorenumberofstandarddeviationsaboveorbelowmeanforagenderandethnicitymatched
youngadulthealthypopulation
TscoreCalculation:
(measuredBMDyoungadultpopulationmeanBMD)/youngadultpopulationSD
bonemineraldensity(BMD)measuredbydualenergyxrayabsorptiometry(DEXA)
standarddeviation(SD)
classificationofTscorebasedonWorldHealthOrganization(WHO)internationalclassification
normalTscore1
lowbonemass(osteopenia)Tscore1to2.5
osteoporosisTscore2.5
severeorestablishedosteoporosisTscore2.5and1fractures
Zscoreusedinpremenopausalwomen,men50yearsold,andchildren(2)
Zscorenumberofstandarddeviationsaboveorbelowthemeanforgender,ethnicity,andage
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matchedhealthypopulation
ZscoreCalculation:
(measuredBMDagematchedpopulationmeanBMD)/agematchedpopulationSD
bonemineraldensity(BMD)measuredbydualenergyxrayabsorptiometry(DEXA)
standarddeviation(SD)
classificationbasedonInternationalSocietyforClinicalDensitometryratherthanWHO
classification
withinexpectedrangeforageZscore>2
lowbonemineraldensityforchronologicalage(belowexpectedrangeforage)Zscore2
cannotquantitativelycompareBMDorcalculateleastsignificantchangebetweenfacilitieswithoutcross
calibration(6)
DEXAinchildren:
InternationalSocietyforClinicalDensitometry/NationalOsteoporosisSociety(ISCD/NOS)
recommendationsonBMDtestinginchildren(5) ,NOS2004PDF)
osteoporosisshouldnotbediagnosedinchildrenbasedondensitometriccriteriaalone
DEXAassessmentindicatedforchildrenwithincreasedriskoffracture
donotperformDEXAonchildrenwhocannotbesafelyandappropriatelypositionedfortesting
performDEXAwhenchildrenexpectedtobenefitfrominterventiontoreducefractureriskandwhen
DEXAresultsexpectedtoinfluenceintervention
siteselection
lumbarspineforchildrenaged5years,or
wholebodyforchildrenaged3years
forearmandfemurmeasurementsarefeasibleforchildrenaged5years,butmethodology,
reproducibility,andreferencedataforthissitearelacking
considerimpactofgrowthdelayoninterpretationofresultsinchildrenaged5years
DEXAinterpretation
DEXApreferredmethodforassessingbonemineralcontent(BMC)andarealBMD(grams
ofmineralpersquarecentimeterscanned)
preferredsitesforperformingBMCandarealBMDmeasurementsareposterioranterior
spine(PA)andtotalbodylesshead(TBLH)butothersitesmaybeuseddependingon
clinicalneed
donotusehipforBMCandarealBMDbecauseofvariabilityinskeletaldevelopment
considersofttissuemeasuresinchildrenwithchronicconditionsassociatedwith
malnutritionormuscleandskeletaldisorders
612monthminimumintervalbetweenscans
adjustspineandTBLHBMCandarealBMDinchildrenwithshortstatureorgrowthdelay
(forspine,adjustusingeitherbonemineralapparentdensity[BMAD]orheightZscorefor
TBLH,adjustusingheightZscore)
appropriatereferencedatasetincludeshealthyrepresentativesofgeneralpopulationnormal
insizefortheirage
useZscoreforreportingBMDinchildren
classification(Zscore>2doesnotexcludepossibilityofskeletalfragilityandincreasedfracture
risk)
withinexpectedrangeforage,Zscore>2
lowbonemineraldensityforchronologicalage(belowexpectedrangeforage),Zscore2
osteoporosis,Zscore2andclinicallysignificantfracturehistory(2longbonefractures
byage10yearsor3longbonefracturesbyage19years)
Peripheraldualenergyxrayabsorptiometry(pDEXA):
peripheraldualenergyxrayabsorptiometry(pDEXA)isDEXAmeasurementofbonedensityofforearm,
finger,orheel(2)
SystemsImprovement(ISCD/NOF/ICSI)recommendationsonpDEXAinadults (1,2,6)
mayusevalidatedpDEXAdevicetoassessvertebralandglobalfragilityfractureriskin
menopausalwomen,butpredictiveperformanceofcentralDEXAandheelquantitativeultrasound
(QUS)better
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radiuspDEXAplusclinicalriskfactorsmaybeusedtoidentifypopulationatverylowfracture
probabilitywhomayrequirenofurtherdiagnosticevaluation
pDEXAofperipheralsitesnotappropriatefordiagnosisofosteoporosisuseonlyfemurneck,total
femur,lumbarspine,or33%radiusmeasuredbyDEXAorpDEXAdeviceswithvalidatedyoung
adultreferencedatabaseforWHOdiagnosticclassification
sufficientlyhighfractureprobabilitybyradiuspDEXAplusclinicalriskfactorscanbeusedto
initiatetreatment,ifcentralDEXAcannotbeperformed
donotusepDEXAtomonitorskeletaleffectsoftreatmentsforosteoporosis
Vertebralfractureassessment(VFA):
vertebralfractureassessment(VFA)densitometricspineimagingtodetectvertebralfractures (6)
VFAhaslessradiationexposurethanstandardspinexrays (2)
InternationalSocietyforClinicalDensitometry(ISCD)positionstatementonVFAwithDEXA(orlateral
spineradiography)inadults (6)
VFAindicatedforpatientswithTscore<1andatleastoneoffollowing
women70yearsoldormen80yearsold
historicalheightloss>4cm(1.5inches)
selfreportedbutundocumentedpriorvertebralfracture
prednisone5mg/dayorequivalentglucocorticoidfor3months
useGenantvisualsemiquantitativemethodfordiagnosingvertebralfracturewithVFAandinclude
assessmentofgrade/severity
confirmseverityofdeformityusingmorphometry,ifdesired
followVFAwithanotherimagingmodalityif
2mild(grade1)deformitieswithoutanymoderateorsevere(grade2or3)deformities
lesionsinvertebraethatcannotbeattributedtobenigncauses
vertebraldeformitiesinpatientwithknownhistoryofrelevantmalignancy
equivocalfractures
unidentifiablevertebraebetweenT7andL4
scleroticorlyticchanges,orfindingssuggestiveofconditionsotherthanosteoporosis
Quantitativeultrasound(QUS):
quantitativeultrasound(QUS)measuresspeedofsoundand/orbroadbandultrasoundattenuationatheel,
tibia,patella,orotherperipheralskeletalsites (1)
SystemsImprovement(ISCD/NOF/ICSI)recommendationsonBMDtestingusingQUSinadults (1,2,6)
BMDfromdifferentdevicescannotbedirectlycompared
TscoresfrommeasurementsotherthanDEXAatfemurneck,totalfemur,lumbarspine,or33%
radiuscannotbeusedaccordingtoWHOdiagnosticclassificationbecausetheyarenotequivalent
heelisonlyvalidatedskeletalsiteforclinicaluseinosteoporosismanagement
QUSinfractureprediction
validatedheelQUSdevicespredictfragilityfractureindependentlyofcentralDEXABMDin
postmenopausalwomen(hip,vertebral,andglobalfracturerisk)andinmenaged65years
(hipandallnonvertebralfractures)
discordantresultsbetweenheelQUSandcentralDEXAarecommon
heelQUSplusclinicalriskfactorsmaybeusedtoidentifypopulationatverylowfracture
probabilitywhomayrequirenofurtherdiagnosticevaluation
QUSintherapeuticdecisions
centralDEXAmeasurementsatspineandfemurpreferredfortherapeuticdecisionmaking
sufficientlyhighfractureprobabilitybyheelQUSplusclinicalriskfactorscanbeusedto
initiatetreatment,ifcentralDEXAcannotbeperformed
donotuseQUStomonitorskeletaleffectsoftreatmentsforosteoporosis
quantitativeultrasoundofcalcaneusmayhavelowtomoderatespecificityfordiagnosisof
osteoporosis(level2[midlevel]evidence)
basedonsystematicreviewlimitedbyclinicalheterogeneity
systematicreviewof6diagnosticstudiesevaluatingQUSofcalcaneusfordetectionof
osteoporosisin12,250adults
referencestandardwasDEXAwithcutoffTscore<2.5
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analysislimitedbyclinicalheterogeneityinQUSequipment(LunarAchilles,HologicSahara)and
QUScutoffTscoresfordetectionofosteoporosis
QUSofcalcaneusfordiagnosingosteoporosis
sensitivityranges64%100%in5studies,41%59%in1outlierstudy
specificityranges13%90%
ReferenceActaReumatolPort2011OctDec36(4):327fulltext
DynaMedcommentarysensitivityandspecificityrangesreportedfromTable3inarticlewhich
includesrangesforsubpopulationsanddifferentcomparators(spineDEXA,totalhipDEXA)rather
thananalyzingoptimumTscorethresholdderivedfromeacharticle(whichmayoverestimate
diagnosticaccuracy)toobtainresultsreportedinabstractanddiscussion
quantitativeheelultrasounddoesnotappeartohaveadequatesensitivityorspecificityfor
confirmingorrulingoutosteoporosisbasedonDEXA(level2[midlevel]evidence)
basedonsystematicreviewof25studieslimitedbyclinicalheterogeneity
quantitativeheelultrasoundwithTscorethresholdof1had79%sensitivityand58%specificity
foridentifyingindividualswithDEXAdeterminedTscore2.5athiporspine
ReferenceAnnInternMed2006Jun6144(11):832
calcanealquantitativeultrasoundmaybeanoptionfordiagnosisofosteoporosisinwomenaged
>65years
basedonsubgroupanalysisfromprospectivecohortstudy
5,934womenaged75yearswhotookpartinEPIDOScohortstudywereevaluatedatheelwith3
differentQUSdevices,usingDEXA(referencestandard)resultstodetermineQUSdevice
thresholds
QUSthresholdsweresettoidentifyosteoporosiswithboth90%sensitivity(lowlikelihood)and
specificity(highlikelihood)
GELunarAchilles,HologicSahara,andDMSUBIS5000systemsevaluatedinwomenaged>65
years
DiagnosticThresholdsforOsteoporosis:
Device
HighLikelihood
LowLikelihood
Heelstiffnessindex
Heelstiffnessindex>
GELunarAchilles
57%
78%
HologicSahara
Quantitativeindex59 Quantitativeindex>83
DMSUBIS5000
BUA55
BUA>62
Abbreviation:BUA,broadbandultrasoundattenuation.
diagnosticperformanceusingabovediagnosticthresholds
sensitivity89%
specificity87%
patientswithresultsbelowhighlikelihoodthresholdhaveahighprobabilityofhavingosteoporosis
andthosewithresultsabovelowlikelihoodthresholdhavelowprobabilityofhavingosteoporosis
patientswithresultsthatfallbetweenthresholdswarrantfurtherevaluation,forinstance,with
DEXA
ReferenceSaludPublicaMex200951Suppl1:S25fulltext
Quantitativecomputedtomographybasedabsorptiometry(QCT):
SystemsImprovement(ISCD/NOF/ICSI)recommendationsonBMDusingquantitativecomputed
tomography(QCT)andperipheralQCT(pQCT)testinginadults (1,2,6)
scanL1L3ifusingsingleslicedeviceorL1L2ifusingthreedimensional(3D)device
spinaltrabecularBMDmaypredictvertebralfracturesinpostmenopausalwomenwithsame
accuracyasanteriorposteriorspinalBMDbyDEXA
insufficientdatatorecommendspineQCTforhipfractureprediction
pQCTofforearmatultradistalradiuspredictship,butnotspine,fragilityfracturesin
postmenopausalwomen
sufficientlyhighfractureprobabilitybyspineQCTorradiuspQCTplusclinicalriskfactorscanbe
usedtoinitiatetreatment,ifcentralDEXAcannotbeperformed
trabecularBMDoflumbarspineQCTmaybeusedtomonitorage,disease,andtreatmentrelated
BMDchanges
trabecularBMDofultradistalradiuspQCTmaybeusedtomonitoragerelatedBMDchanges
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ISCDpositionstatementonBMDusingQCTandperipheralQCT(pQCT)testinginchildren(5)
nopreferredmethodforQCTinchildren
QCT,pQCT,andhighresolution(HR)pQCTmaybeusedclinicallyinchildrenifappropriate
referencedataandexpertiseareavailable
QCTprotocolsinchildrenusinggeneralcomputedtomography(CT)scannersrequireappropriate
exposurefactors,calibrationphantoms,andsoftwaretooptimizeresultsandminimizeradiation
exposure
QCTandpQCTassociatedwithgreaterradiationexposurethanDEXA(1,2)
Biomechanicalanalysisofcomputedtomography:
biomechanicalanalysisofcontrastenhancedcomputedtomographyenterographyidentifies
osteoporosisinpatientswithinflammatoryboweldisease(level1[likelyreliable]evidence)
basedonretrospectivediagnosticcohortstudy
136adults(medianage44years)withinflammatoryboweldiseaseandbodymassindex<30
kg/m2whohadcontrastenhancedcomputedtomography(CT)enterographyanddualenergyxray
absorptiometry(DXA)scanswithin30daysofeachotherwereassessed
5.1%hadosteoporosis(Tscore2.5)byDXA(referencestandard)
bonemineraldensity(BMD)estimatedfromCTenterographsbybiomechanicalCTanalysisat
femoralneck
diagnosticperformanceofbiomechanicalCTanalysisfordetectionofosteoporosis
sensitivity85.7%
specificity98.5%
positivepredictivevalue75%
negativepredictivevalue99.2%
positivelikelihoodratio57
negativelikelihoodratio0.15
ReferenceAmJGastroenterol2014Mar109(3):401fulltext
derivationofbiomechanicalCTanalysisforestimationofBMDcanbefoundinAnnNYAcadSci
2010Mar1192:57
Treatment
Treatmentoverview:
lifestylerecommendationsforallpatients
balanceddietwithadequatecalciumandvitaminDintake(ICSIStrongrecommendation,
Moderatequalityevidence)
regularweightbearingandmusclestrengtheningexercisetoimproveagility,strength,posture,and
balance,increasebonemineraldensity,andreduceriskoffallsandfractures(ICSIStrong
recommendation,Lowqualityevidence,level2[midlevel]evidence)
smokingcessation(ICSIStrongrecommendation,Moderatequalityevidence)
avoidexcessalcoholintake
medicationsrecommendedin
postmenopausalwomenandmen50yearsoldif
ICSIStrongrecommendation,
Hiporvertebralfracture
Moderatequalityevidence,
NNT1923forpreventionofany
(includingasymptomatic
EndocrineSocietyStrong
clinicalfracture(level1[likely
vertebralfracture)withoutmajor
recommendation,Moderate
reliable]evidence)*
trauma
qualityevidence
ICSIStrongrecommendation,
NNT4749forpreventionof
Osteoporosis(Tscore2.5)** EndocrineSocietyStrong
nonvertebralfractures(level1
recommendation,Lowquality
[likelyreliable]evidence)*
evidence
ICSIStrongrecommendation, NNT67forpreventionof
Osteopenia(Tscore1to
vertebralfractures(clinicalplus
EndocrineSocietyStrong
2.5)**andhighriskfor
radiographic)(level3[lacking
recommendation,Lowquality
fracture***
direct]evidence)*
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evidence
*numberneededtotreat(NNT)basedondatafromtrialsevaluatingbisphosphonates
**atfemoralneck,totalhip,orlumbarspinebydualenergyxrayabsorptiometry(DEXA)
***10yearrisk3%forhipfractureor20%formajorosteoporosisrelatedfractureusing
FractureRiskAssessment(FRAX)
patientstakinglongtermglucocorticoids(ICSIStrongrecommendation,Moderatequality
evidence,EndocrineSocietyStrongrecommendation,Lowqualityevidence)
menwithprostatecancerreceivingandrogendeprivationtherapywhohavehighriskoffracture
(EndocrineSocietyStrongrecommendation,Moderatequalityevidence)
bisphosphonatesareusualfirstlinechoicewhenpharmacologictherapyindicated
level1[likelyreliable]evidence
10mgorallyoncedaily*or70mg forpostmenopausalwomen,level
Alendronate
orallyonceweekly
3[lackingdirect]evidencefor
men
150mgorallyoncemonthlyor3 level2[midlevel]evidencefor
Ibandronate
mgIVevery3months
postmenopausalwomen
5mgoncedaily,35mgweekly,or level2[midlevel]evidencefor
Risedronate
150mgmonthly(orally)*
postmenopausalwomen
level1[likelyreliable]evidence
afterhipfracture,level2[mid
Zoledronicacid
5mgIVonceyearly
level]evidencefor
postmenopausalwomen
*5mgorallyoncedailyforsteroidinducedosteoporosis
parathyroidhormone134(teriparatide)20mcgsubcutaneouslyoncedailycanbefirstlinechoicefor
patientsathighestriskforfracture(ICSIStrongrecommendation,Highqualityevidence)
teriparatidemaybemoreeffectivethanalendronateforreducingnonvertebralfractures(NNT11)in
postmenopausalwomen(level2[midlevel]evidence)
teriparatidemaybemoreeffectivethanalendronateforreducingclinicalvertebralfractures(NNT
42)incorticosteroidinducedosteoporosis(level2[midlevel]evidence)
otherlicensedmedicationsforosteoporosisinclude
estrogenreceptormodulatorsinpostmenopausalwomenwithosteoporosis
raloxifene(Evista)60mgorallyoncedailymayreduceriskforvertebralfracturebutnot
nonvertebralfracture,andmayincreaseriskforvenousthromboembolism(level2[mid
level]evidence)
lasofoxifene(FablyninEurope)0.5mgorallyoncedailymayreduceriskoffracturesbut
increaseriskofvenousthromboembolism(level2[midlevel]evidence)
tibolone(LivialinEurope)1.25mgorallyoncedailyreducesriskoffracturesandsome
cancersbutincreasesriskofstroke(level1[likelyreliable]evidence)
denosumab(Prolia)60mgsubcutaneouslyevery6months(level2[midlevel]evidencefor
postmenopausalwomen,level3[lackingdirect]evidenceformen)
calcitoninbutlimitedevidenceforefficacy(level3[lackingdirect]evidence)andrisks(including
cancer)mayoutweighbenefits
reassessingmedicationuseafter35yearssuggesteddrugholidays(treatmentcessation)mightreduce
adverseeffectswithminimallossofefficacy
guidelinessuggestbonemineraldensitymonitoringevery12years,butmonitoringappearstohavelittle
effectonchangingtreatmentorpredictingclinicalresponsetotreatment
Diet:
balanceddietwithadequatenutrition,includingdairyproducts,importantinmanagementofosteoporosis
(ICSIStrongrecommendation,Lowqualityevidence)(2)
adequatecalciumandvitaminDintakerecommended(ICSIStrongrecommendation,Moderate
qualityevidence)
calcium
adequatecalciumintakeshouldbethroughdietalone,ifpossible,andshouldbemaintained
throughoutlifetime
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useavarietyofcalciumcontainingfoodbecausecalciumabsorptionfromfoodis
compromisedbyoxalicacid(foundindark,green,leafyvegetables)
2010DietaryReferenceIntakesforcalcium
adultsaged1950years,1,000mg/day
menaged5170,1,000mg/day
womenaged51years,1,200mg/day
menaged71years,1,200mg/day
pregnantorbreastfeedingwomenaged18years,1,300mg/day
ReferenceDietaryReferenceIntakesforCalciumandVitaminDPDF
seealsoCalciumandvitaminDfortreatmentandpreventionofosteoporosis
vitaminD
sunlightexposuremaynotproduceadequatevitaminD,sovitaminDintakeshouldbe
achievedthroughdiet,ifpossible,andsupplementation,ifnecessary
milkisonlydairysourceofvitaminD,butlevelsofvitaminDfortificationvarywidely
otherfoodsourcesofvitaminDvarybytimeofyearofharvesting
2010DietaryReferenceIntakesforvitaminD
adultsaged1870years,600units/day
adultsaged71years,800units/day
ReferenceDietaryReferenceIntakesforCalciumandVitaminDPDF
seeCalciumandvitaminDfortreatmentandpreventionofosteoporosisfor
additionalinformation
phosphorusintake700mg/day(UnitedStatesRecommendedDailyAllowances)recommendedto
preventhypophosphatemiainducedboneloss(MayoClinProc2004Jan79(1):91)
vitaminK2supplementsmaynotreduceincidenceoffractures(level2[midlevel]evidence)
butmayincreaselumbarbonemineraldensity(level3[lackingdirect]evidence)in
postmenopausalwomenwithosteoporosisinJapan
basedonsystematicreviewlimitedbystatisticalandclinicalheterogeneity
systematicreviewof19randomizedtrialsevaluatingoralvitaminK2supplementsfor
treatmentandpreventionofosteoporosisin6,759postmenopausalwomen
mosttrialsevaluatedmenatetrenone45mg/day
controlgroupwasplacebo,bisphosphonates,calcium,vitaminD3,orcalciumplus
vitaminD3
10trialsevaluatedvitaminK2fortreatmentofosteoporosis
heterogeneityininterventionregimens,controlgroup,anddurationoffollowuplimited
analyses
majorityoftrialswereconductedinJapan
nosignificantdifferencesbetweengroupsinfractureinanalysisof5trialswith3,672
women,resultslimitedbysignificantheterogeneity
vitaminK2supplementsassociatedwith
increasedlumbarbonemineraldensityat6monthsandat12monthsinanalysesof
4trialswith381women,resultslimitedbysignificantheterogeneity
increasedadverseeventsinanalysisof5trialswith4,363women
oddsratio1.27(95%CI1.011.59)
NNH271,537withadverseeventsin7%ofcontrolgroup
adverseeventsincludedmostlyminorgastrointestinalsymptomsanditching
ReferenceOsteoporosInt2015Mar26(3):1175
alcoholintake(2)
highalcoholintakeassociatedwithdecreasedbonemineraldensity(dataconflictingonmoderate
alcoholintake)
InstituteforClinicalSystemsImprovement(ICSI)recommendationsonmaximumalcoholintake
womenshouldhave1standarddrink/day(standarddrinkis12ouncesbeer,5ounces
wine,or1.5ounces80proofdistilledspirit)
menshouldhave2standarddrinks/day
seealsoAlcoholusedisorder
Activity:
recommendregularweightbearingandmusclestrengtheningexercisetoimproveagility,strength,
posture,andbalancetoincreasebonemineraldensity(BMD)andreduceriskoffallsandfractures(ICSI
Strongrecommendation,Lowqualityevidence)(1,2)
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highimpactexerciseandweighttrainingstimulateaccrualofbonemineralcontent(2)
comparedtoaerobicexercise,resistancetrainingmaybemaybemorebeneficialforsitespecific
accrualofbonemineralcontent
highintensityresistancetrainingimprovesstrengthandbalanceandincreasesmusclemass,
whichmayespeciallybenefitpatientswithosteoporosisbyincreasingbonemassanddecreasing
riskoffalls
threecomponentsofexerciseprogramnecessaryforstrongbonehealthincludeimpact,
strengthening,andbalancetraining
additionofexercisetoantiresorptivetherapymaybeassociatedwithincreasedlumbarspine
bonemineraldensityinadultswithosteoporosis(level3[lackingdirect]evidence)
basedonsystematicreviewwithoutclinicaloutcomes
systematicreviewof7randomizedtrialscomparingeffectsofexerciseplusantiresorptivetherapy
vs.antiresorptivetherapyaloneonbonemineraldensity(BMD)in420adultswithosteoporosis
typeofexercisevariedacrossstudies,butincludedstrengthorresistancetrainingatleast1time
perweekin6trialsandwholebodyvibrationin1trial
comparingexerciseplusantiresorptivetherapytoantiresorptivetherapyalone,exerciseplus
antiresorptivetherapyassociatedwithincreasedBMDatlumbarspineinanalysisof7trialswith
420adults(p<0.0001)
ReferenceOsteoporosInt2014May25(5):1585
exerciseforimprovedfunctionandqualityoflifeinpostmenopausalwomenwithosteoporosis
exerciseprogramsmayimprovequalityoflifeinpostmenopausalwomenwithosteoporosis
(level2[midlevel]evidence)
basedonsystematicreviewwithassessmentoftrialqualitynotreported
systematicreviewof4trialsevaluatingexerciseforimprovingqualityoflifein256
postmenopausalwomenwithosteoporosisorosteopenia
exerciseassociatedwithsignificantimprovementinphysicalfunction,pain,andvitality(p<
0.05)
ReferenceClinRehabil2009Oct23(10):888
progressivequadricepsstrengthandproprioceptiontrainingassociatedwithdecreasein
fallsinpostmenopausalwomenwithosteoporosis(level2[midlevel]evidence)
basedonrandomizedtrialwithallocationconcealmentnotstated
100sedentarypostmenopausalwomenaged5575yearswithosteoporosiswere
randomizedto18weekprogressivequadricepsstrengthandproprioceptiontrainingin
additiontoosteoporosisdrugtherapyvs.drugtherapyalone
85%completedstudy
strengthandproprioceptiontrainingassociatedwithdecreaseinnumberoffallsat24weeks
posttreatment(incidencerateratio0.263,95%CI0.10.68)
ReferenceOsteoporosInt2010Apr21(4):589
Pilatesassociatedwithgreaterimprovementinpain,functionalstatus,andqualityoflife
comparedwithhomebasedexerciseprograminwomenwithpostmenopausalosteoporosis
basedonrandomizedtrialwithmethodofrandomizationandallocationconcealmentnot
stated
70postmenopausalwomenaged4565yearswithosteoporosisrandomizedtoPilates
(supervisedPilatesexerciseprogramtwiceweeklyfor1year)vs.homebasedexercise
program(consistingofthoracicextensionexercises)
14%didnotcompletefollowupat1yearandwereexcludedfromanalyses
Pilatesassociatedwithgreaterimprovementinpain,functionalstatus,andqualityoflife(p
<0.05forall)
ReferenceJBodywMovTher2013Apr17(2):204
balancetrainingmayreducefallsandimprovequalityoflifeinolderwomenwith
osteoporosis(level2[midlevel]evidence)
basedonsmallrandomizedtrialwithoutattentioncontrol
60women65yearsoldwithsenileosteoporosisrandomizedtobalancetrainingvs.no
interventionfor12months
balancetrainingassociatedwith
improvedqualityoflife(p<0.001)
improvedfunctionalbalance(p<0.001)
reductioninfalls(50%vs.26.6%withcontrol)(p<0.025)
ReferenceMaturitas2010Jun66(2):206
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weightbearingexercisemayimprovewalkingendurance,legstrength,walkingspeed,and
bodyswayinolderwomenwithlowbonemineraldensity(level3[lackingdirect]evidence)
basedonrandomizedtrialwithoutclinicaloutcomes
160womenaged7073yearswithradialandhipBMD>2standarddeviationsbelow
referencevaluewererandomizedtoimpact,balancing,andstrengtheningexercisesvs.no
interventionfor30months
exerciseinterventionincluded
1hourtrainingsessionsonceweeklyfor6months(OctoberMarch)eachyear
advicetodo20minutes/dayathomeforother6monthseachyear
controlgroupreceivedgeneralhealthinformationatbaseline
comparingexercisevs.nointervention
meanchangeinendurance(distancewalkedin2minutes)was20.8metersvs.2
meters(p<0.001)
meanchangeinlegstrengthwas19.1kgvs.8kg(p<0.001)
meanchangeinwalkingspeedwas0.25meters/secondvs.0.07meters/second(p
<0.001)
bodyswayincreasedmoreincontrolgroupthaninexercisegroup(p<0.001)
ReferenceJBoneMinerRes2006May21(5):772
exercisetoimprovebalanceandstrengthmayimproveposturalcontrolandlowerlimb
strengthinolderwomenwithosteoporosis(level3[lackingdirect]evidence)
basedonsmallrandomizedtrialwithoutclinicaloutcomes
33womenaged65yearswithosteoporosisrandomizedtoexercisesforbalanceand
strengthvs.noexercisefor8weeks
82%adheredtoexerciseprogram
exerciseassociatedwithimprovedposturalcontrol(p0.02)andlowerlimbstrength(p
0.01)
ReferenceAmJPhysMedRehabil2010Jul89(7):549
exerciseforbalanceinmen
taichimayimprovebodybalanceinoldermenwithosteopeniaorosteoporosis(level3
[lackingdirect]evidence)
49menaged6082yearswithosteoporosisorosteopeniawererandomizedtotaichi
exerciseclassfor45minutestwiceweeklyvs.controlfor18weeks
bodybalanceassessedusingComputerPosturographicSystemPE90
bodybalanceimprovedfrom80.95%to84.45%(p0.01)intaichigroupvs.nosignificant
improvementincontrolgroup
ReferenceAmJChinMed200735(1):1
Counseling:
counselpatientswithtobaccousedisordertostopsmoking(ISCIStrongrecommendation,Moderate
qualityevidence)(2)
counselpatientstoachieveormaintainnormalbodymassindex(BMI)ofbetween20and25kg/m2(ICSI
Strongrecommendation,Lowqualityevidence)(2)
multifacetedosteoporosisgroupeducationmightimprovehealthrelatedqualityoflifeinadults
withosteoporosis(level2[midlevel]evidence)
systematicreviewof5randomizedtrialsand2observationalstudiescomparingmultifaceted
osteoporosisgroupeducationvs.controlin923adults45yearsoldwithosteoporosis
allinterventionsincludedinformationonosteoporosisandinterventionsformanagement
(medication,diet,exercise)
someinterventionsalsoaddressedactivitiesofdailyliving,pain,andfallsprevention
metaanalysisprecludedbyheterogeneityininterventionsandoutcomemeasures
multifacetedosteoporosisgroupeducationassociatedwithimproved
healthrelatedqualityoflifein2of3studies
painin2of3studies
Medications:
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Medicationslicensedforosteoporosistreatment:
FDAapprovedmedicationsformanagementofestablishedosteoporosisinclude(withlinkstodrugtopics)
bisphosphonatesalendronate,ibandronate,risedronate,zoledronicacid
parathyroidhormone(PTH)134(teriparatide)
raloxifene(anestrogenagonist/antagonist)
denosumab(areceptoractivatorofnuclearfactorkappaBligand[RANKL]inhibitor)
calcitonin
otherdrugsapprovedinsomecountriesinEuropeinclude(withlinkstoevidencesummaries)
recombinanthumanparathyroidhormone(rhPTH)(184)
lasofoxifene(anestrogenagonist/antagonist)
tibolone(aselectivetissueestrogenicactivityregulator)
strontiumranelate
osteoporosistreatmentsthatreducefracturesareassociatedwithreducedmortalityinelderly
persons(level2[midlevel]evidence)
basedonsystematicreviewwithoutassessmentoftrialquality
systematicreviewof8trialscomparingrisedronate,strontiumranelate,zoledronicacid,or
denosumabvs.placeboforosteoporosisin33,090elderlypatients
osteoporosistherapyassociatedwithreducedmortality(relativerisk0.89,95%CI0.80.99)
ReferenceJClinEndocrinolMetab2010Mar95(3):1174
Indicationsforpharmacologictherapy:
NationalOsteoporosisFoundationrecommendations (1)
medicationsrecommendedfortreatmentofosteoporosisif
hiporvertebralfracture(includingasymptomaticvertebralfracture)
Tscore2.5atfemoralneck,totalhip,orlumbarspinebydualenergyxray
absorptiometry(DEXA),afterappropriateevaluationtoexcludesecondarycauses
lowbonemass(Tscore1to2.5)atfemoralneck,totalhip,orlumbarspinebyDEXAand
10yearriskofhipfracture3%or10yearriskofmajorosteoporosisrelatedfracture
20%basedonUnitedStatesadaptedWorldHealthOrganization(WHO)absolute(Fracture
RiskAssessment[FRAX])
nopharmacotherapyshouldbeconsideredindefinite,repeatriskassessmentafter35years
InstituteforClinicalSystemsImprovement(ICSI)recommendations (2)
treatmentwithbisphosphonaterecommendedfor
postmenopausalwomenandmenwithosteoporosistoreducefracturerisk(bothvertebral
andnonvertebral)(ICSIStrongrecommendation,Moderatequalityevidence)
patientstakingglucocorticoids(ICSIStrongrecommendation,Moderatequalityevidence)
menwithosteoporosisundergoingandrogendeprivationtherapyforprostatecancer,
particularlyzoledronicacid5mgIVonceperyear(ICSIStrongrecommendation,High
qualityevidence)
followinghipfractureconsiderzoledronicacid5mgIVwithin90daysofhipfracturefor
bothmenandwomen(ICSIStrongrecommendation,Moderatequalityevidence)
anabolictherapywithparathyroidhormone134(teriparatide)indicatedforpatientsatparticularly
highriskoffuturefracture(ICSIStrongrecommendation,Highqualityevidence)
consider
selectiveestrogenreceptormodulator(SERM)treatmentwithraloxifeneinpostmenopausal
womentoreducevertebralfracturerisk
RANKLinhibitortreatmentwithdenosumabinpostmenopausalwomentoreducevertebral
andhipfractureincidence
nasalcalcitoninasthirdlinetreatment,particularlyforshorttermtherapyinwomen5
yearspostmenopausewithlowbonemass
similarrecommendationsfromAmericanCollegeofPhysicians(ACP)(AnnInternMed.2008Sep
16149(6):40415fulltext)andEndocrineSociety (4)
Bisphosphonates:
indicationsforbisphosphonates (1,2,4)
postmenopausalwomenandmen>50yearsoldtoreducefracturerisk(bothvertebraland
18/81
19/11/2015
nonvertebral)ifanyof(ICSIStrongrecommendation,Moderatequalityevidence)
hiporvertebralfracturewithoutmajortrauma(EndocrineSocietyStrongrecommendation,
Moderatequalityevidenceformen)
Tscore2.5atfemoralneck,totalhip,orlumbarspinebydualenergyxray
absorptiometry(DEXA),afterappropriateevaluationtoexcludesecondarycauses
(EndocrineSocietyStrongrecommendation,Lowqualityevidenceformen)
adultswithlowbonemass(Tscore1to2.5)atfemoralneck,totalhip,orlumbarspineby
DEXAand10yearriskofhipfracture3%or10yearriskofmajorosteoporosisrelated
fracture20%basedonUnitedStatesadaptedFRAX(EndocrineSocietyStrong
recommendation,Lowqualityevidenceformen)
patientstakinglongtermglucocorticoids,suchasindosesequivalenttoprednisone>7.5mg/day
(ICSIStrongrecommendation,Moderatequalityevidence,EndocrineSocietyStrong
recommendation,Lowqualityevidenceformen)
menwithosteoporosisundergoingandrogendeprivationtherapyforprostatecancer,particularly
zoledronicacid5mgIVonceyearly(ICSIStrongrecommendation,Highqualityevidence)
patientsfollowinghipfractureconsiderzoledronicacid5mgIVonceyearlywithin90daysofhip
fractureforbothmenandwomen(ICSIStrongrecommendation,Moderatequalityevidence)
fortreatmentofosteoporosis
bisphosphonatesFDAapprovedfortreatmentofosteoporosisinclude
alendronate(Fosamax,generic)10mgorallyoncedailyor70mgorallyonceweekly5mg
oncedailyislabeleddosefortreatmentofglucocorticoidinducedosteoporosis
ibandronate(Boniva,generic)150mgorallyoncemonthlyor3mgIVevery3months
risedronate(Actonel,Atelvia)5mgorallyoncedaily,35mgorallyonceweekly,75mgorally
on2consecutivedayseachmonth,or150mgorallyoncemonthly5mgoncedailyis
labeleddosefortreatmentofglucocorticoidinducedosteoporosis
zoledronicacid(Reclast)5mgIVoveratleast15minutesonceyearly(alsoapprovedfor
glucocorticoidinducedosteoporosis)
fortreatmentofpostmenopausalwomenwithosteoporosis
alendronate10mgorallyoncedailyreducesvertebral,hip,andwristfractures(level1[likely
reliable]evidence)
aftertakingalendronatefor35yearscontinuationofalendronatefor510yearsmight
decreaseriskforclinicalvertebralfracture(level2[midlevel]evidence)
ibandronate
oralibandronate(dailyorintermittentdosing)mayreduceincidenceofsymptomatic
andasymptomaticvertebralfracturesinpostmenopausalwomenwithosteoporotic
vertebralfractures(level2[midlevel]evidence)
ibandronatefor5yearsreportedtodecreaseclinicalfracturerateinpostmenopausal
womenwithosteoporosis(level3[lackingdirect]evidence)
forincreasingbonemineraldensity(BMD)inpostmenopausalwomenwith
osteoporosis,ibandronate150mgorallyoncemonthlyisatleastaseffectiveas
ibandronate2.5mgoncedaily(level3[lackingdirect]evidence),IVibandronateis
moreeffectivethanoralibandronate(level3[lackingdirect]evidence)
risedronate5mgoncedailymayreducevertebralandnonvertebralfracturesinwomenwith
osteoporosis(level2[midlevel]evidence)andmayreduceriskofnewvertebralfracturesin
osteoporoticwomen>80yearsold(level3[lackingdirect]evidence)
zoledronicacid5mgIVonceyearly
afterhipfracturereducesclinicalfracturerateandmortalityover23years(level1
[likelyreliable]evidence)
inpostmenopausalwomenmayreduceratesofhipfractureandvertebralfracture,
butassociatedwithflulikesymptomsandarrhythmias(level2[midlevel]evidence)
alendronatemayincreasebonedensitymorethanrisedronate(level3[lackingdirect]
evidence)
fortreatmentofmenwithosteoporosis
alendronate10mgorallyoncedailyiseffectiveforpreventionofvertebralfractures(level3
risedronate2.5mgorallyoncedailymayreduceriskforhipfractureinelderlymenwith
stroke(level2[midlevel]evidence)orParkinsondisease(level2[midlevel]evidence)
zoledronicacid5mgIVonceyearlyafterhipfracturemayreduceclinicalfracturerateand
mortalityover23years(level2[midlevel]evidence)(butdataformennotreported
separately)
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zoledronicacidandalendronatemayhavesimilarefficacyforincreasingbonedensity(level
3[lackingdirect]evidence)
forpatientswithcorticosteroidinducedosteoporosis
bisphosphonatesassociatedwithreductioninvertebralfractureinadultstreatedwith
glucocorticoidsforrheumatoiddisease(level3[lackingdirect]evidence)
IVibandronateassociatedwithlowerrateofnewvertebralfracturesandlessbackpainthan
oralalfacalcidol(level2[midlevel]evidence)
alendronateandrisedronateeachappeartoreduceincidenceofvertebralfracturesand
increaseBMDinpreventiontrialsinpatientstakingchroniccorticosteroids(level3[lacking
direct]evidence)
zoledronicacidmaybemoreeffectivethanrisedronateforincreasinglumbarspineBMD
(level3[lackingdirect]evidence)
forothercausesofsecondaryosteoporosis
fortransplantrecipients,efficacyofbisphosphonatesforreducingfractureincidencein
kidneytransplantrecipientsisuncertainbutvariousbisphosphonatesassociatedwith
improvedBMD(level3[lackingdirect]evidence)
inadultswithcysticfibrosis,bisphosphonatesmayincreaseBMD(level3[lackingdirect]
evidence)butmayincreasebonepainandmaynotreducefractures(level2[midlevel]
evidence)
limitedevidenceevaluatingbisphosphonatetherapyforchildrenwithsecondary
osteoporosis
estimatedmagnitudeofeffectforbisphosphonatesforpreventionofclinicalfractures
formenandwomenwithhipfractureNNT19forpreventionofanyclinicalfracture
forpostmenopausalwomenwithpriorvertebralfractureNNT2223forpreventionofanyclinical
fractureandNNT40forpreventionofclinicalvertebralfracture
forpostmenopausalwomenwithosteoporosisNNT4749forpreventionofnonvertebralfracture
forpostmenopausalwomenwithoutosteoporosisclinicalfracturereductionnotestablishedNNT
66forpreventionofvertebralfracture
forpatientstakingchroniccorticosteroidsclinicalfracturereductionnotestablishedNNT
estimatesforpreventionofvertebralfracturehighlyvariable(range972)acrossdifferent
populations
adverseeffects
oralbisphosphonatesmaybeassociatedwithadverseesophagealeffectssuchasdysphagia,
esophagitis,esophagealulcer
takewithfullglassofwater3060minutesbeforefirstoralintakewithinstructionstoremain
uprightfor3060minutes
discontinueifdysphagia,odynophagia,neworworseningheartburn,orretrosternalpain
bisphosphonatesassociatedwithincreasedriskofatrialfibrillationbutnotwithstrokeor
cardiovascularmortality(level2[midlevel]evidence)
severe,occasionallyincapacitating,bone,joint,and/ormusclepainreportedinfrequentlywith
bisphosphonatetherapy(level3[lackingdirect]evidence)
asepticosteonecrosisassociatedwiththeuseoforalbisphosphonates(level2[midlevel]
evidence)osteonecrosisofjawreported,mainlywithIVbisphosphonatesinpatientswithcancer
atypicalsubtrochantericandfemoralshaftfracturesrarebutmaybeassociatedwith
bisphosphonateuse(level2[midlevel]evidence)
evidenceregardingassociationofbisphosphonateuseandriskofesophagealcancerislimitedand
inconsistent
ocularadverseeffectshavebeenreportedwithbisphosphonates(level3[lackingdirect]evidence)
seeBisphosphonatesfortreatmentandpreventionofosteoporosisfordetails
unlessathighriskoffracture,assesspatientsfor35yearbisphosphonateholidayafter5years
continuoususe(1,2)
assessmentshouldincludeintervalclinicalhistory(especiallyintercurrentfracturehistoryandnew
chronicdiseasesormedications),heightmeasurement,vertebralimagingifheightlossoccurred,
andBMDtesting
fracturepreventioneffectspersistaftertreatmentstopped
decreasesincidenceofadverseevents(suchasatypicalfracturesoffemoralshaftand
osteonecrosisofjaw)whichbecomemorecommonafter5yearsofcontinuoususe
monitorbonedensityevery2yearsduringholiday,ifcanbedoneonsamemachinewithadequate
qualitycontrols
decreasedbonedensityorfractureduringholidaynecessitatesresumptionoftherapy,otherwise,
20/81
19/11/2015
FDArecommendsreassessmentforcontinuationoftherapyafter35years
Parathyroidhormone(PTH):
Teriparatide:
prescribinginformationandrecommendations
anabolictherapywithparathyroidhormone134(teriparatide)indicatedforpatientsatparticularly
highriskoffuturefracture(ICSIStrongrecommendation,Highqualityevidence),couldbefirstline
therapyinpatientsathighestriskforfracture(2)
teriparatide(brandnameForteo)isabiosyntheticfragmentofparathyroidhormone(134),
stimulatesboneformation
FDAapprovedfor3groupsofpatientswithhighriskforfracture
postmenopausalwomenwithosteoporosis
menwithprimaryorhypogonadalosteoporosis
menandwomenwithglucocorticoidinducedosteoporosis
recommendeddose20mcgsubcutaneouslyintothighorabdominalwalloncedaily
teriparatide(Forteo)suppliedasinjectorpenwith750mcg/3mL,discardpenafter28days
safetyandefficacyofteriparatidebeyond2yearsnotestablished
BLACKBOXWARNINGnotesosteosarcomainratsandstatesdonotuseifincreasedbaseline
riskforosteosarcomaduetoPagetdiseaseofbone,unexplainedalkalinephosphataseelevations,
openepiphyses,orpriorradiationtherapyofskeleton
othercontraindicationsaremetastases,historyofskeletalmalignancies,metabolicbonediseases
(otherthanosteoporosis),preexistinghypercalcemia
adverseeffectsincludehypercalcemia(maypredisposepatientstodigoxintoxicity),transient
orthostatichypotension,pain,arthralgia,asthenia,nausea,rhinitis,dizziness,headache,
hypertension,increasedcough,pharyngitis,constipation,diarrhea,dyspepsia
seealsoTeriparatide
efficacy
humanparathyroidhormone(134)oncedailymayreduceriskforvertebral(NNT11)and
nonvertebralfractures(NNT30)inpostmenopausalwomenwithpriorfractures(level2[mid
level]evidence)
systematicreviewfoundfracturedatamainlyfrom1trial
systematicreviewof12randomizedtrialsofhumanparathyroidhormoneforatleast
1year
9trialsinvolvedpostmenopausalwomen,3trialsinvolvedmen
10trialsevaluatedhumanparathyroidhormone(134),2trialsevaluated
humanparathyroidhormone(184)
humanparathyroidhormone(134)increasesbonemineraldensityatlumbarspine,
femoralneckandtotalhip
humanparathyroidhormone(134)reducesriskforvertebralandnonvertebral
fracturesinpostmenopausalwomenwithpriorfractures,basedon1trialdescribed
below
nocomparativeefficacydataforfractureriskwithhumanparathyroidhormone(134)
20mcgvs.otheractiveosteoporosisdrugs
humanparathyroidhormone(184)increaseslumbarspinebonemineraldensity
ReferenceCMAJ2006Jul4175(1):52fulltext,commentarycanbefoundinAm
FamPhysician2006Nov174(9):1595,ACPJClub2006NovDec145(3):71
accompanyingguidelinesfromOsteoporosisCanadacanbefoundinCMAJ2006Jul
4175(1):48fulltext
randomizedtrialwithallocationconcealmentnotstated
1,637ambulatorywomenwhowereatleast5yearspostmenopausalandhadatleast
2mildor1moderatevertebralfractureswererandomizedtorecombinanthuman
parathyroidhormone(134)20mcgvs.40mcgvs.placebosubcutaneouslyonce
daily
allpatientsgivencalcium1,000mgandvitaminD4001,200unitsdaily
mediandurationoffollowup21months
outcomeofnewvertebralfracturesassessedin1,326(81%)womenwithadequate
baselineandfollowupxrays
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19/11/2015
comparingparathyroidhormone(134)20mcgvs.40mcgvs.placebo
5%vs.4%vs.14%hadatleast1newvertebralfracture(p<0.001,NNT10
11)
ratesofnewnonvertebralfractureswere6.3%vs.5.8%vs.9.7%(p=0.04,p
=0.02,NNT30)
ratesofnewnonvertebralfragilityfractureswere2.6%vs.2.5%vs.5.5%(p=
0.02,p=0.01,NNT35)
parathyroidhormoneincreasedbonemineraldensity
adverseeffects
6%vs.11%vs.6%withdrawalduetoadverseevent(NNH20forparathyroid
hormone40mcg)
13%vs.18%vs.8%nausea
otheradverseeffectswereheadache,dizzinessandlegcramps
ReferenceNEnglJMed2001May10344(19):1434
reductioninnewvertebralfracturespersistedforatleast18monthsafter
discontinuationofteriparatideatendoftrial(NNT8)(ArchInternMed2004Oct
11164(18):2017)
teriparatidemaybemoreeffectivethanalendronateforreducingnonvertebralfractures(NNT
11)inpostmenopausalwomenwithosteoporosis(level2[midlevel]evidence)
basedonrandomizedtrialwithearlytrialtermination
146postmenopausalwomenwithosteoporosiswererandomizedtoteriparatide40mcg
subcutaneouslyoncedailyvs.alendronate10mgorallyoncedailyfor14monthsunder
doubleblindconditions
trialwasplannedfor2yearsbutterminatedearlyduetoincreaseinosteosarcomainrats
bonemineraldensitysignificantlyhigherwithteriparatideatlumbarspineandfemoralneck
butsignificantlyhigherwithalendronateatdistalradius
nonvertebralfractureincidence4.1%withteriparatidevs.13.7%withalendronate(p=
0.042,NNT11)
ReferenceJClinEndocrinolMetab2002Oct87(10):4528fulltext
teriparatidemaybemoreeffectivethanalendronateforreducingclinicalvertebralfracture
incidence(NNT42)andbonemineraldensity(BMD)lossduetocorticosteroids(level2[mid
level]evidence)
basedonrandomizedtrialwithhighdropoutrate
428patientsaged2289yearswithglucocorticoidinducedosteoporosiswererandomizedto
teriparatide20mcginjectedoncedaily(plusoralplacebo)vs.alendronate10mgorallyonce
daily(plusinjectableplacebo)for18months
294(69%)patientscompleted18monthtrial
comparingteriparatidevs.alendronateatlastmeasurement
meanincreaseinBMDoflumbarspine7.2%vs.3.4%(p<0.001)
meanincreaseinBMDofhip3.5%vs.2.1%(p<0.01)
11.7%interiparatidegroupvs.6.1%inalendronategroupdroppedoutduetoadverse
events(p=0.04,NNH17)
ReferenceNEnglJMed2007Nov15357(20):2028,editorialcanbefoundinNEnglJ
Med2007Nov15357(20):2084,commentarycanbefoundinNEnglJMed2008Mar
20358(12):1302
comparingteriparatidevs.alendronateat36months
1radiographicvertebralfracturein1.7%vs.7.7%(p=0.007,NNT17)inanalysis
of342patientswhohadspinalradiographsatbaseline
1clinicalvertebralfracturein0%vs.2.4%(p=0.037,NNT42)
nosignificantdifferenceincumulativenonvertebralfractures
comparingteriparatidevs.alendronateamong294patientswhoentered18month
continuationphase
meanincreaseinBMDoflumbarspine11%vs.5.3%(p<0.001)
ReferenceArthritisRheum2009Nov60(11):3346fulltext
rhPTH(184):
recombinanthumanparathyroidhormone(rhPTH)(184)notFDAapprovedforosteoporosis,butapproved
insomecountriesinEuropefortreatmentofosteoporosisinwomen(1)
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19/11/2015
rhPTH(184)mayreduceriskforneworworsenedradiographicvertebralfracturein
postmenopausalwomenwithosteoporosis(level3[lackingdirect]evidence)
2,679postmenopausalwomenwithosteoporosisrandomizedtorhPTH(184)100mcg/dayvs.
placebosubcutaneouslyfor18months
allwomengivencalcium700mg/dayandvitaminD3400units/day
2,532patients(95%)receivedassignedtreatmentandwereincludedinmodifiedintentiontotreat
analysis
1,701patients(63%)completedtrial
comparingrhPTH(184)vs.placebo
neworworsenedvertebralfracturein1.4%vs.3.4%(p=0.001,NNT50)
in2,061womenwithoutbaselinefracture,newvertebralfracturein0.7%vs.2.1%(p=
0.006,NNT72)
in471womenwithbaselinefracture,newvertebralfracturein4.2%vs.8.9%(p=0.04,
NNT22)
newnonvertebralfracturein5.6%vs.5.8%(notsignificant)
rateofsymptomaticvertebralfracturesnotreported
ReferenceAnnInternMed2007Mar6146(5):326,commentarycanbefoundinNatClinPract
EndocrinolMetab2007Nov3(11):746
parathyroidhormone(rhPTH,184)mayimprovepainandfunctionandacceleratehealingof
pelvicfractureinpostmenopausalwomenwithosteoporosisalsotakingvitaminDandcalcium
basedonsmallrandomizedtrial
65postmenopausalwomen(meanage83years)withosteoporosisandpelvicfracturewere
randomizedtoPTH(184)100mcgsubcutaneouslyoncedailyvs.placebountil24monthsafter
fracturehealing
allpatientsgivencalcium1,000mgandvitaminD3800unitsperday
PTHgroupincluded21women
comparingPTH(184)vs.placebo
meanreductioninpain(on010pointvisualanalogscale)4.4pointsvs.1.2points(p<
0.001)
meanTimed"UpandGo"testtimeat12weeks22.9secondsvs.54.3seconds(p<0.001)
meantimetofracturehealing7.8weeksvs.12.6weeks(p<0.001)
healingat8weeksin100%vs.9.1%(p<0.001,NNT2)
ReferenceJBoneJointSurgAm2011Sep793(17):1583
followuptreatmentwithalendronateaftercessationofrhPTH(184)therapymaybeneededto
maintainBMD(level3[lackingdirect]evidence)
238postmenopausalwomenaged5585yearswithosteoporosiswererandomizedto1of4groups
rhPTH(184)100mcg/dayfor1yearfollowedbyalendronate10mg/dayfor1year(PTH
thenalendronategroup)
rhPTHplusalendronatefor1yearthenalendronatefor1year(combinationgroup)
rhPTHfor1yearthenplacebo(PTHthenplacebogroup)
alendronatefor2years(alendronategroup)
forBMDintrabecularboneatspine,PTHthenalendronategrouphadmean31%increaseat2
yearswhichwassignificantlysuperiorto6%increasewithalendronate,11%increasewith
combination,and14%increasewithPTHthenplacebo
forBMDintrabecularboneathip,PTHthenalendronategrouphadmean13%increaseat2years
andcombinationgrouphadmeanincreaseof11%whichwassignificantlysuperiorto4%increase
withalendronateand4%increasewithPTHthenplacebo
PTHthenalendronategrouphadincreasesinBMDfromyear1toyear2,whilePTHthenplacebo
grouphaddecreasesfromyear1toyear2
ReferencePaTHtrial(NEnglJMed2005Aug11353(6):555fulltext),editorialcanbefoundinN
EnglJMed2005Aug11353(6):624,commentarycanbefoundinNEnglJMed2005Dec
15353(24):2616,ACPJClub2006JanFeb144(1):10
Denosumab:
denosumabisafullyhumanmonoclonalantibodywhichbindsreceptoractivatorofnuclearfactorkappaB
ligand(RANKL),rapideffectonboneturnoverisfullyreversibleondiscontinuation
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19/11/2015
denosumabinhibitsformation,function,andsurvivalofosteoclasts (2)
dosing60mgsubcutaneouslyevery6months,administeredbyhealthprofessional(1)
adverseeffectsincludehypocalcemia,seriousskininfections,osteonecrosisofjaw,andatypicalfemur
fractures (1)
ifdenosumabdiscontinuedbonelosscanberapidsoconsideralternativedrugstomaintainbonemineral
density (1)
denosumab60mg/mL(Prolia)FDAapprovedforincreasingbonemassin
menandpostmenopausalwomenwithosteoporosiswhoareathighriskoffracture(historyof
osteoporoticfractureormultipleriskfactorsforfracture)orhavefailedorareintolerantofother
availableosteoporosistherapies
menathighriskoffracturereceivingandrogendeprivationtherapyfornonmetastaticprostate
cancer
womenathighriskoffracturereceivingadjuvantaromataseinhibitortherapyforbreastcancer
denosumabassociatedwithreducedriskofvertebralfractures,nonvertebralfractures,andhip
fracturesinwomenwithosteoporosis(level2[midlevel]evidence)
7,868womenaged6090yearswithlumbar,spine,ortotalhipbonemineraldensity(BMD)Tscore
<2.5(but4)wererandomizedtodenosumab60mgvs.placebosubcutaneouslyevery6
monthsfor36months
allwomenreceivedcalcium1g/dayandvitaminD400units/dayorally
60womenfrom1centerexcludedduetounreliabilityofdata
76%receivedallinjections
cumulativeincidencecomparingdenosumabvs.placebo
vertebralfracturein2.3%vs.7.2%(p<0.001,NNT21)
clinicalvertebralfracturein0.8%vs.2.6%(p<0.001,NNT56)
nonvertebralfracturein6.5%vs.8%(p=0.01,NNT67)
hipfracturein0.7%vs.1.2%(p=0.04,NNT200)
nosignificantdifferencesinriskofcancer,infection,cardiovasculardisease,delayedfracture
healing,orhypocalcemia
denosumabassociatedwithmoreeczema,flatulence,andseriousadverseeventsofcellulitis
(thoughnosignificantdifferenceinoverallcellulitisincidence)
nocasesofosteonecrosisofjaw
ReferenceFREEDOMtrial(NEnglJMed2009Aug20361(8):756fulltext),correctioncanbe
foundinNEnglJMed2009Nov5361(19):1914
absolutereductioninfractureriskwithdenosumabappearsgreaterinwomenathigherrisk
fornewfractures(level2[midlevel]evidence)
basedonposthocsubgroupanalysesofFREEDOMtrial
subgroupanalysesforvarioushighriskgroups
highriskdefinedasanyofthefollowing
age75years(2,471women)
prevalentvertebralfractures(vertebralfracturesofanydegree,or1
vertebralfractureofmoderateorseveredeformityatbaseline)(759women)
femoralneckBMDTscore2.5(2,970women)
comparingdenosumabvs.placeboat3years
newvertebralfracturesinpatientswith
prevalentvertebralfractures7.5%vs.16.6%(p<0.001,NNT11)
BMDTscore2.5atfemoralneck3.1%vs.9.9%(p<0.001,NNT
15)
withbothriskfactors8.1%vs.20.1%(p=0.001,NNT9)
hipfracturesinpatients
>75yearsold0.9%vs.2.3%(p<0.01,NNT72)
BMDTscore2.5atfemoralneck1.4%vs.2.8%(p=0.02,NNT72)
withbothriskfactors1.7%vs.4.1%(p=0.02,NNT43)
ReferenceJClinEndocrinolMetab2011Jun96(6):1727
subgroupanalysisbyFractureRiskAssessment(FRAX)
womenfromFREEDOMtrialevaluatedonbaseline10yearfractureprobability
assessedbyFRAX
approximately15%probabilityformajorosteoporoticfracturewithBMD
approximately5%probabilityforhipfracture
denosumabfor3yearsassociatedwithoveralldecreasedriskof
24/81
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clinicalosteoporoticfractures(relativeriskreduction32%,95%CI20%42%)
hipfracture(relativeriskreduction36%,95%CI2%to60%)
greaterreductionsinfractureriskinwomenclassifiedasmoderatetohighriskby
FRAX
11%decreasedriskwith10%probabilitybyFRAX(notsignificant)
71%decreasedriskwith20%probabilitybyFRAX(p<0.001)
50%decreasedriskwith30%probabilitybyFRAX(p=0.001)
ReferenceJBoneMinerRes2012Jul27(7):1480
denosumabmayreducecomplicationratewithoutdelayinghealingofnonvertebral
fracturesinpostmenopausalwomenwithosteoporosis(level2[midlevel]evidence)
basedonsubgroupanalysisofFREEDOMtrial
667postmenopausalwomenwhohadnonvertebralfracturesduringfollowupwereanalyzed
comparingdenosumabvs.placebo
anycomplication(includinginfection)in2%vs.5%(p=0.009,NNT34)
lackofhealingby6monthsin0.7%vs.1.4%(nopvaluereported)
ReferenceJBoneJointSurgAm2012Dec594(23):2113,editorialcanbefoundinJBone
JointSurgAm2012Dec594(23):e1781
denosumabmaynotincreaseriskofcardiovascularadverseeventsat3yearsinhighrisk
basedonposthocsecondaryanalysisofFREEDOMtrial
2,363postmenopausalwomenathighriskofcardiovasculareventswereanalyzed
44%hadevaluablexraydataat3yearsandwereincludedinaorticcalcificationanalysis
comparingdenosumabvs.placeboat3years
cardiovascularadverseeventsin38%vs.40%(notsignificant)
aorticcalcificationprogressionin22%vs.22%(notsignificant)
ReferenceJBoneMinerRes2014Feb29(2):450
denosumabmayincreasebonemineraldensity(level3[lackingdirect]evidence)butmayincrease
riskofseriousadverseevents(includingseriousinfections)(level2[midlevel]evidence)
basedonsystematicreviewwithinadequateassessmentoftrialquality
systematicreviewof9trialsevaluatingdenosumabvs.placeboforlowbonemassin10,329
women
authorsdidnotassessallocationconcealment
denosumabassociatedwith
increasedlumbarspineandhipbonemineraldensitybutmetaanalysisnotpossibledueto
missingdata
nosignificantreductioninfractureriskinanalysisof3trialswith919patients
thisanalysisdidnotincludeFREEDOMtrial
earlyunpublishedresultsofFREEDOMtrial(withfeweroutcomesthanaspublished
above)werereportedintextanddidnotreachstatisticalsignificance
increasedriskofseriousadverseeventsinanalysisof3trialswith938patients
oddsratio(OR)1.83(95%CI1.13.04)
NNH20(95%CI9150)
increasedriskofseriousinfectionsinanalysisof3trialswith938patients
OR4.45(95%CI1.1517.14)
NNH50(95%CI121,119)
ReferenceHormMetabRes2009Oct41(10):721
denosumabmayincreasebonemineraldensityinmenwithosteoporosis(level3[lackingdirect]
evidence)
242men(meanage65years)withlowbonemineraldensity(BMD)randomizedtodenosumab60
mgsubcutaneouslyevery6monthsvs.placebofor1year
94.2%completedtrial
BMDincreaseatlumbarspinein5.7%withdenosumabvs.0.9%withplaceboat12months(p<
0.0001,NNT21)
denosumabalsoassociatedwithsignificantBMDincreaseattotalhip,femoralneck,and
trochanter(p<0.0001foreach)
ReferenceJClinEndocrinolMetab2012Sep97(9):3161
Estrogenreceptormodulators:
Raloxifene:
25/81
19/11/2015
prescribinginformation
raloxifene(Evista)isaselectiveestrogenreceptormodulator(SERM)withestrogenagonist
activityonboneandestrogenantagonistactivityonbreastanduterinetissue
dose60mgorallyoncedaily
raloxifeneusedforpreventionandtreatmentofosteoporosisinpostmenopausalwomen
contraindicatedifpregnancy(PregnancyCategoryX),potentialforpregnancy,breastfeeding,or
historyofvenousthromboembolism
raloxifenenotindicatedforandappearsineffectiveforprimaryandsecondarypreventionof
cardiovasculardisease
safetynotestablishedinpremenopausalwomenormen
commonadverseeffectsincludehotflushes,legcramps,peripheraledema,flulikesyndrome,
arthralgias,andsweating
seriousadverseeffectsincludeincreasedriskforvenousthromboembolismandstroke
mayinteractwithcholestyramine,diazepam,diazoxide,lidocaine,andwarfarin
seealsoRaloxifene
teriparatide,zoledronate,alendronate,andrisedronateeachreportedtobemoreeffectivethan
raloxifeneorcalciumplusvitaminDforpreventingnonvertebralfracturesinpatientswith
osteoporosis(level3[lackingdirect]evidence)
basedonsystematicreviewwithmostlyindirectcomparisons
systematicreviewof116randomizedtrialsevaluatingefficacyofpharmacologicalagentsfor
preventionofhip,vertebral,andnonvertebralfracturesin139,647patientswithoratriskfor
osteoporosis
mosttrialswereinpostmenopausalwomen
drugtherapyincludedteriparatide,denosumab,raloxifene,zoledronate,risedronate,ibandronate,
alendronate,vitaminD,calcium,andvitaminDpluscalcium
smallnumberofdirectcomparisontrialsreducesprecisionandconfidenceinresultsofnetwork
metaanalyses
innetworkmetaanalysesofplacebocontrolleddata(combiningdirectandindirectcomparisons),
significantreductionin
newhipfractureswithalendronate,risedronate,zoledronate,denosumab,andvitaminD
pluscalcium
newvertebralfractureswithteriparatide,denosumab,zoledronate,risedronate,alendronate,
raloxifene,andibandronate
newnonvertebralfractureswithteriparatide,risedronate,zoledronate,denosumab,and
alendronate
comparativeefficacyinnetworkmetaanalyses(combiningdirectandindirectcomparisons)
forpreventionofhipfractures
zoledronate,risedronate,andalendronateweremoreeffectivethanraloxifene
zoledronate,risedronate,andalendronateweremoreeffectivethancalciumand/or
vitaminD
denosumabwasmoreeffectivethancalciumaloneorvitaminDalone
forpreventionofnonvertebralfractures
teriparatide,zoledronate,andrisedronateweremoreeffectivethanraloxifeneand
calciumand/orvitaminD
teriparatidewasmoreeffectivethanalendronate
ibandronateandalendronateweremoreeffectivethancalciumplusvitaminD
ReferenceJClinEndocrinolMetab2012Jun97(6):1871fulltext
DynaMedcommentarystudyfundedinpartbyTheEndocrineSocietyinpreparationfor
evidencebasedguidelinedevelopment
efficacyofraloxifenefortreatmentofosteoporosisprimarilybasedonMOREandCOREtrial
raloxifenemayreduceriskofvertebralfracture(level3[lackingdirect]evidence)andclinical
vertebralfracture(level2[midlevel]evidence)butnotnonvertebralfractures(level2[mid
level]evidence)inpostmenopausalwomenwithosteoporosis
7,705womenaged3180yearsin25countrieswhohadbeenpostmenopausalfor2years
andmetWorldHealthOrganizationcriteriaforosteoporosiswererandomizedtoraloxifene
60mg/dayvs.120mg/dayvs.placeboandfollowedforupto3640months
allwomengivensupplementalcalcium500mg/dayandcholecalciferol400600units/day
6,828women(88.6%)hadevaluableradiographsat36months
RatesofNewVertebralFractureonXray:
26/81
19/11/2015
RatesofNewVertebralFractureonXray:
Raloxifene60
Raloxifene120
mg/day
mg/day
6.6%(NNT29)
5.4%(NNT21)
Placebo
Overallcohort
10.1%
Subgroupof2,304
womenwithprevious 14.7%(NNT15)
10.7%(NNT10)
21.2%
vertebralfractures
Subgroupof4,524
womenwith
2.3%(NNT45)
2.8%(NNT59)
4.5%
osteoporosisbutno
priorvertebralfracture
Abbreviation:NNT,numberneededtotreatfor3yearstoprevent1newvertebralfracture
comparedtousingplacebo.
nosignificantdifferencesinratesofnonvertebralfracturebyinterviews
comparedwithplacebo,raloxifeneincreasedbonemineraldensityinfemoralneckby
2.1%2.4%andinspineby2.6%2.7%(p<0.001)
womenreceivingraloxifenehad3.1timesincreasedriskofvenousthromboembolism(1%
withraloxifene60mgvs.1%withraloxifene120mgvs.0.3%withplacebo,NNH143)
adverseeventssignificantlymorecommonwithraloxifeneincludedinfluenzasyndrome,hot
flashes,legcramps,peripheraledema,andendometrialcavityfluidadverseevents
significantlymorecommonwithplaceboincludedhypertension,hypercholesterolemia,
hematuria
raloxifenedidnotcausevaginalbleedingorbreastpainandwasassociatedwithlower
incidenceofbreastcancer(statisticallysignificantbutabsolutenumbersnotgiven)
ReferenceMOREtrial(JAMA1999Aug18282(7):637fulltext),correctioncanbefoundin
JAMA1999Dec8282(22):2124,editorialcanbefoundinJAMA1999Aug18282(7):687,
commentarycanbefoundinJFamPract1999Nov48(11):911,JAMA2000May
3283(17):2236,ACPJClub2000MarApr132(2):58
raloxifenereducedincidenceofclinicalvertebralfractureinthistrial,withclinicalvertebral
fracturedefinedasnewvertebralfractureassociatedwithsignsandsymptomssuchas
backpain
among6,828women(88.6%)withbaselineandfollowupxraysover3years,new
clinicalvertebralfractureswerereportedin
3.5%placebogroup
2.1%withraloxifene60mg/day(NNT72)
1.7%withraloxifene120mg/day(NNT56)
ReferenceArchInternMed2002May27162(10):1140fulltext
reductioninnewvertebralfractureswithraloxifenestillsignificantat4years,nosignificant
differenceinnonvertebralfractures(JClinEndocrinolMetab2002Aug87(8):3609fulltext)
raloxifenereducedvertebralfracturesandbreastcancerinbothwomenwithandwithout
priorhormonetherapyinMOREtrial(JFamPract2004Oct53(10):789)
vitaminDdeficiencydidnotaffectresponsetoraloxifeneinthistrial(JClinEndocrinol
Metab2005Aug90(8):4566fulltext)
raloxifeneassociatedwithdecreasedriskofbreastcancerover8yearsinextensionof
MOREtrial(level2[midlevel]evidence)
basedonextensionofrandomizedtrialwithallocationconcealmentnotstated
5,213participantsofMOREtrialcontinuedraloxifene60mg/day(ifpreviouslyassigned60
mgor120mg)vs.placebo(ifpreviouslyassignedplacebo)foranother4years
comparingraloxifenevs.placebo
incidenceofinvasivebreastcancerduringtrialextensionwas2vs.5per1,000
womanyears(NNT334womanyears)
8yearriskofpulmonaryembolismwas0.62%vs.0.16%(NNH217)
nosignificantdifferenceinmortality
ReferenceCOREtrial(JNatlCancerInst2004Dec196(23):1751fulltext)
raloxifeneappearstoincreaseriskforvenousthromboembolicevents(level2[midlevel]
evidence)
basedonMOREtrialwithallocationconcealmentnotstated
anotherreportofMOREtrialincludesdifferentnumbersthan1999report,partiallyexplained
byaddingretinalveinthrombosistototalnumbers
27/81
19/11/2015
comparingcombinedraloxifenegroupsvs.placebogroup
deepveinthrombosisin0.84%vs.0.27%(p=0.01,NNH175)
pulmonaryembolismin0.35%vs.0.08%(notsignificant)
retinalveinthrombosisin0.08%vs.0.19%(notsignificant)
anyvenousthrombosisin1.15%vs.0.54%(p=0.01,NNH164)
ReferenceObstetGynecol2004Oct104(4):837
raloxifenenotassociatedwithreductionincardiovascularevents(level2[midlevel]
evidence)
basedonMOREtrial(withallocationconcealmentnotstated)andCOREtrial(extensionof
MOREtrial)
nooveralldifferencesincombinedoutcomeofcardiovascularevents(myocardialinfarction,
unstableangina,coronaryischemia,stroke,ortransientischemicattack)inMOREtrial
insubgroupof1,035womenwithincreasedcardiovascularriskatbaseline,
raloxifeneusewasassociatedwithsignificantlylowerriskofcardiovascularevents
ReferenceJAMA2002Feb20287(7):847,commentarycanbefoundinJFam
Pract2002May51(5):481,JAMA2002Jul3288(1):42
inCOREtrial(4yearfollowupofMOREtrial)
4,011postmenopausalwomenwithosteoporosisrandomizedtoraloxifene60mgvs.
placeboorallyoncedailyfor4yearsaspartofMOREtrial,then4moreyearsaspart
ofCOREtrial(range2.659.1monthsbetweenendofMOREtrialandbeginningof
COREtrial)
effectofraloxifeneonincidenceofcardiovasculareventsnotpredefinedobjectiveof
COREtrial,butadjudicationandanalysisforcardiovasculareventsspecifiedbefore
trialend
nosignificantdifferencescomparingraloxifenevs.placeboinincidenceof
cardiovascularevents(5.5%vs.4.7%)
cardiacevents(3.1%vs.2.6%)
cerebrovascularevents(2.7%vs.2.3%)
ReferenceAmJCardiol2006Feb1597(4):520fulltext
Lasofoxifene:
lasofoxifene(Fablyn)0.5mgapprovedinEuropefortreatmentofosteoporosisinpostmenopausalwomen
withincreasedriskoffracture(ClinIntervAging2010Feb25:19fulltext)
lasofoxifenenotFDAapprovedinUnitedStatesasofMay2014
lasofoxifene0.5mgassociatedwithreducedriskoffractures,estrogenreceptorpositivebreast
cancer,coronaryheartdisease,andstroke,butincreasedriskofvenousthromboembolicevents
inpostmenopausalwomenwithosteoporosis(level2[midlevel]evidence)
basedonrandomizedtrialwithallocationconcealmentandrandomizationmethodnotstated
8,556womenaged5980yearswithBMDTscore2.5atfemoralneckorspinewererandomized
tolasofoxifene(either0.25mgor0.5mg)oncedailyvs.placebofor5years
vertebralfracturesdefinedasmeeting2of3criteria1gradeincreaseon4pointratingofvertebral
deformity,decrease20%and4mminvertebralheight,orqualitativediagnosisofvertebral
fracture
Results:
Lasofoxifene
Lasofoxifene
Outcomes
Placebo
0.25mg
0.5mg
Vertebral
6.9%*(NNT37) 5.7%*(NNT26) 9.6%
fractures
ERpositive
0.4%
0.2%*(NNT167) 0.8%
breastcancer
Nonvertebral
9.4%
8%*(NNT42)
10.4%
fractures
Coronaryheart
2.6%
2.3%*(NNT100) 3.3%
diseaseevents
Stroke
1.1%*(NNT143) 1.1%*(NNT143) 1.8%
Venous
thromboembolic 1.7%*(NNH90) 1.3%*(NNH142) 0.6%
events
28/81
19/11/2015
3.2%**(NNH
2.6%
111)
Abbreviation:ER,estrogenreceptor.
Death
2.3%
*p<0.05vs.placebo.
**p=0.05vs.placebo.
ReferencePEARLtrial(NEnglJMed2010Feb25362(8):686fulltext),correctioncanbefound
inNEnglJMed2011Jan20364(3):290,editorialcanbefoundinNEnglJMed2010Feb
25362(8):752,commentarycanbefoundinNEnglJMed2010Jun10362(23):2227,ExpertOpin
Pharmacother2010Jul11(10):1773,AnnInternMed2010Jul20153(2):JC1
reductionincoronaryheartdiseasewithlasofoxifene0.5mgmainlyrelatedto"softer"outcomes
likerevascularizationandnotcoronarydeathormyocardialinfarction(level2[midlevel]evidence)
basedonsecondaryanalysisofPEARLtrial
lasofoxifene0.5mg/dayassociatedwithreducedriskof
majorcoronaryheartdiseaseevents(hazardratio[HR]0.68,95%CI0.50.93)definedas
coronarydeath,myocardialinfarction,documentednewischemicheartdisease,
hospitalizationforunstableangina,orcoronaryrevascularizationprocedure
coronaryrevascularization(HR0.56,95%CI0.320.98)
lasofoxifene0.5mg/dayassociatedwithnonsignificantlylowerratesof
hospitalizationforunstableangina(HR0.55,95%CI0.291.04)
newischemicheartdisease(HR0.75,95%CI0.261.04)
lasofoxifene0.5mg/daynotassociatedwithsignificantlylowerratesof
coronarydeath(HR0.85,95%CI0.461.6)
nonfatalmyocardialinfarction(HR0.82,95%CI0.471.42)
effectssimilaracrosspatientswithorwithoutcardiovascularriskfactors
lasofoxifene0.25mg/daynotassociatedwithsignificantdecreaseinmajorcoronaryheartdisease
events(HR0.76,95%CI0.561.03)
ReferenceCirculation2010Oct26122(17):1716fulltext
Arzoxifene:
arzoxifenenotFDAapprovedinUnitedStatesasofMay2014
arzoxifeneappearstoreduceriskofvertebralfractures(level3[lackingdirect]evidence)and
invasivebreastcancer(level2[midlevel]evidence)butnotclinicalfractures(level2[midlevel]
evidence)inpostmenopausalwomenwithosteoporosis,andmayincreaseriskofvenous
thromboembolism(level2[midlevel]evidence)
9,354womenaged6085yearswithosteoporosisorlowbonemassrandomizedtoarzoxifene20
mg/dayvs.placebo
osteoporosisdefinedasvertebralfractureorfemoralneckorlumbarspineBMDTscore
2.5
lowbonemassdefinedasBMDTscore1and>2.5
78%completed4yearfollowup
comparingarzoxifenevs.placebo
nonvertebralfracturesin7.1%vs.7.6%(notsignificant)
hipfracturein0.4%vs.0.6%(notsignificant)
clinicalvertebralfracturein1.1%vs.1%(notsignificant)
anyvertebralfracturein2.6%vs.4.3%(p<0.001,NNT59)
inpatientswithosteoporosis,anyvertebralfracturein3.4%vs.5.8%(p<0.001,
NNT42)
inpatientswithlowbonemass,anyvertebralfracturein1.6%vs.2.3%(not
significant)
invasivebreastcancerin1%vs.2.3%(p<0.001,NNT77)
VTEin1.3%vs.0.6%(p<0.001,NNH142)
chronicobstructivepulmonarydisease(COPD)in0.5%vs.0.2%(p=0.03,NNH333)
ReferenceJBoneMinerRes2011Feb26(2):397
Tibolone:
29/81
19/11/2015
tibolone(Livial)isasynthetic,tissuespecific,estrogenlikeagentthatmaypreventbonelossandreduce
menopausalsymptoms (1)
doesnotstimulatebreastoruterinetissue(1)
alsocalledselectivetissueestrogenicactivityregulator
notFDAapprovedforosteoporosisandnotavailableinUnitedStatesasofMay2014,butlicensedin
Europeforreductionoffractureriskinosteoporosisandtreatmentofvasomotorsymptomsof
menopause(1)
tiboloneassociatedwithreducedriskoffracturesandsomecancers,butmayincreaseriskof
strokeinpostmenopausalwomenwithosteoporosis(level2[midlevel]evidence)
basedonrandomizedtrialwithearlytermination
4,538postmenopausalwomenaged6085yearswithosteoporosisrandomizedtotibolone1.25mg
vs.placebooncedailyformedian34months
allwomenhadbonemineraldensityTscore2.5athiporspine,orTscore2and
radiologicevidenceofvertebralfracture
allwomenreceived24calcium/vitaminDtablets/day(calciumcitrate315mgplusvitamin
D3200unitspertablet)
studyterminatedearlyduetoincreasedriskofstrokewithtibolone
comparingtibolonevs.placebo
newvertebralfracturein3.1%vs.5.6%(p<0.001,NNT40)
nonvertebralfracturein5.9%vs.8%(p=0.01,NNT48)
strokein1.24%vs.0.58%(p=0.02,NNH151)
invasivebreastcancerin0.27%vs.0.84%(p=0.02,NNT176)
coloncancerin0.18%vs.0.58%(p=0.04,NNT250)
endometrialcancer(amongwomenwithuterus)in0.23%vs.0%(p=0.06,NNH434)
discontinuationduetoadverseeventin18.8%vs.13.1%(p<0.001,NNH17)
nosignificantdifferencesinnewonsetcoronaryheartdiseaseorvenousthromboembolism(VTE)
significantadverseeventsincludedvaginaldischarge,breastdiscomfort,vaginalbleeding,vaginal
infection,pelvicpain
ReferenceLIFTtrial(NEnglJMed2008Aug14359(7):697),editorialcanbefoundinNEnglJ
Med2008Aug14359(7):753,commentarycanbefoundinNEnglJMed2008Nov
13359(20):2172,ACPJClub2008Nov18149(5):8
tiboloneassociatedwithincreasedvaginalbleedingandendometrialcarcinoma
basedonsubgroupanalysisof3,519womenwithuterusinLIFTtrial
increaseingrade1endometrioidadenocarcinomaintibolonegroup(p=0.06)
prevalenceofvaginalbleeding10.8%intibolonegroupvs.2.8%inplacebogroup(p<
0.001,NNH12)
ReferenceObstetGynecol2008Sep112(3):653
Calcitonin:
calcitoninintranasally1nasalpuff(200units)oncedailyFDAapprovedfortreatmentofosteoporosisin
women5yearspostmenopause(1)
nasalcalcitoninconsideredathirdlinetreatmentforosteoporosisbutmaybeusefulinsomepopulations
forshorttermtherapy (2)
intranasalcalcitoninmayreduceriskforrecurrentvertebralfractures(level3[lackingdirect]
evidence)
basedonrandomizedtrialwithhighdropoutrateandwithoutclinicaloutcomes
1,255womenwithosteoporosis(817with15preexistingvertebralcompressionfractures)were
randomizedtocalcitoninnasalspray(100,200,or400units)vs.placebooncedailyfor5years
allwomentookcalciumandvitaminD
511women(41%)completed5years
newvertebralfracturesonperiodicxraysin17.8%withcalcitonin200unitsvs.25.9%with
placebo(p=0.03,NNT13),reductionwith100and400unitdoseswasnotstatisticallysignificant
noinformationavailableregardingsymptomaticfracturesorhipfractures
ReferenceAmJMed2000Sep109(4):267,editorialcanbefoundinAmJMed2000
Sep109(4):330
studyhasbeencriticizedbecauseinvestigatorswereawareofbonedensityresultsduringthe
studyand59%ofwomenwerelosttofollowup(TheMedicalLetter2000Oct1642(1090):97TOC)
calcitoninappearstopreservebonemassinsteroidinducedosteoporosis(level3[lackingdirect]
30/81
19/11/2015
evidence)
basedonCochranereviewoftrialswithmethodologiclimitationsandwithoutclinicalefficacy
outcomes
systematicreviewof9randomizedtrialsevaluatinguseofcalcitoninforpreventionortreatmentof
osteoporosisin441patientseitherinitiatingorcontinuingcorticosteroids,samplesizestoosmall
toadequatelyassessfractureprevention
alltrialshadatleast1oftheselimitations
unclearmethodsofrandomizationsequencegeneration
highdropoutrateorinadequateexplanationofdropoutrate
lackofblindingorinadequateexplanationofblinding
comparingcalcitonintoplacebo,calcitoninassociatedwith
increasedbonedensityatlumbarspineassessedat1yearinanalysisof6trialswith256
patients(meandifference[MD]2.83,95%CI1.374.29)
increasedbonedensityatdistalradiusassessedat6monthsinanalysisof3trialswith128
patients(MD2.92,95%CI1.414.42)
higherincidenceofadverseevents,suchas
nauseainanalysisof3trialswith122patients(riskratio[RR]8.65,95%CI1.61
46.54)
flushingorrashinanalysisof5trialswith126patients(RR5,95%CI1.3618.42)
protectiveeffectonbonemassmaybegreaterforpatientswhohavebeentakingcorticosteroids>
3months
comparingcalcitonin50100unitstocalcitonin200400units,calcitonin200400unitsassociated
withincreasedbonedensityatlumbarspineassessedat1yearinanalysisof3trialswith130
patients(MD2.44,95%CI0.294.59)
comparingintranasalroutetosubcutaneousroute,subcutaneousrouteassociatedwithincreased
bonedensityatlumbarspineassessedat1yearinanalysisof1trialwith40patients(MD6.5,
95%CI4.618.39)
ReferenceCochraneDatabaseSystRev2000(2):CD001983(reviewlastassesseduptodate
1999Oct26)
precautionswithcalcitonininclude
seriousallergictypereactionshavebeenreported,includingatleast1deathduetoanaphylaxis
possibilityofhypocalcemictetanyfollowingparenteralcalcitonin
tremoraddedasadversereactioninpackagelabelingApril2012(FDASafety2012May23)
FDApanelsuggestscalcitoninmayincreaseriskofcancerandrisksoutweighbenefits(National
OsteoporosisFoundation2013Mar13,FDA2013Mar5PDF)
Strontium:
strontiumranelatenotFDAapprovedforosteoporosisinUnitedStatesasofMay2014(1)
strontiumranelateapprovedfortreatmentofsevereosteoporosisinsomecountriesinEurope(1) ,but
EuropeanMedicinesAgency'sPharmacovigilanceRiskAssessmentCommittee(PRAC)has
recommendeditbewithdrawnfromuse(EuropeanMedicinesAgencypressrelease2014Jan10)
strontiummayreducevertebralandpossiblynonvertebralfractureratesinpostmenopausal
womenwithosteoporosis(level2[midlevel]evidence)
basedonCochranereviewoftrialswithmethodologiclimitations
systematicreviewof4randomizedplacebocontrolledtrialsofstrontiumranelatefor1yearin
postmenopausalwomen
trialsconsideredtreatmenttrialsifwomenhadprevalentvertebralfracturesand/orlumbarspine
BMDTscore<2.5standarddeviations
3treatmenttrialsevaluatedstrontiumdoses0.52g/day
3trialshadlossestofollowup>20%
only1trialreportedadequateallocationconcealment
strontium(2g/dayfor3years)associatedwith
reducedrateofvertebralfracturesinanalysisof2trialswith5,082patients
riskratio(RR)0.63(95%CI0.560.71)
NNT1117assuming21%outcomeincontrols
reducedrateofnonvertebralfracturesinanalysisof2trialswith6,572patients
RR0.86(95%CI0.750.98)
NNT33411assuming12%outcomeincontrols
strontiumincreasedBMDatlumbarspine,femoralneck,andtotalhip
31/81
19/11/2015
strontiumappearstohavedosedependenteffectonvertebralfracturesandBMD
someevidencethatstrontiumranelate2g/dayfor3yearsimproveshealthrelatedqualityoflife
strontium2g/daydidnotsignificantlyincreaseriskofwithdrawalsbutwasassociatedwithslightly
moreadverseevents,includingdiarrhea,VTE,pulmonaryembolism(PE),headaches,seizures,
memoryloss,andalteredconsciousness
ReferenceCochraneDatabaseSystRev2006Oct18(4):CD005326
strontiumranelatemayreduceriskofsymptomaticfractureandnewvertebralfracturein
postmenopausalwomenwithvertebralfracture(level2[midlevel]evidence)
1,649postmenopausalwomenwithvertebralfracturerandomizedtostrontiumranelate2gvs.
placeboorallyoncedailyortwicedailyfor3years
allpatientsgivencalciumandvitaminD
vertebralxraysrepeatedannually
9patientsexcludedsincenotreatmentreceived,198patientsexcludedsincenofollowupxrays
1,442patients(87%)inintentiontotreatanalysis
1,260(76%)completed3yearsoffollowup
comparingstrontiumranelatevs.placebo
newvertebralfractureat1yearin6.4%vs.12.2%(p<0.001,NNT18)
symptomaticfractureat1yearin3.1%vs.6.4%(p=0.003,NNT31)
newvertebralfractureat3yearsin20.9%vs.32.8%(p<0.001,NNT89)
strontiumranelateimprovedBMD
diarrheain6.1%vs.3.6%(p=0.02,NNH40)
ReferenceNEnglJMed2004Jan29350(5):459fulltext,editorialcanbefoundinNEnglJMed
2004Jan29350(5):504,commentarycanbefoundinNEnglJMed2004May6350(19):2001,
EvidenceBasedMedicine2004SepOct9(5):149
strontiumranelatemayreducevertebralfracturesinpostmenopausalwomen,butappearsless
costeffectivethanalendronate
basedonsystematicreviewof3randomizedtrials
ReferenceHealthTechnolAssess2007Feb11(4):1fulltext
Combinationtherapy:
Bisphosphonateplusteriparatide:
combinationofteriparatideandantiresorptivetherapynotrecommendedinEndocrineSociety
recommendationsformenwithosteoporosis(EndocrineSocietyStrongrecommendation,Lowquality
evidence)(4)
combinationofzoledronicacidandteriparatidemayincreasebonemineraldensity(BMD)more
thaneitheronealoneinpostmenopausalwomenwithosteoporosis(level3[lackingdirect]
evidence)
basedonrandomizedtrialwithoutplacebocontrolandclinicaloutcomes
412postmenopausalwomenwithosteoporosis(meanage65years)wererandomizedtozoledronic
acid5mginfusiononceplusteriparatide20mcg/daysubcutaneouslyvs.zoledronicacidalonevs.
teriparatidealonefor1year
comparingcombinationtherapyvs.teriparatidealonevs.zoledronicacidalone
increaseinlumbarspineBMDat52weeks7.5%vs.7%vs.4.4%(p<0.001for
combinationandteriparatidealonegroupsvs.zoledronicacidalonegroup)
increaseintotalhipBMDat52weeks2.3%vs.1.1%vs.2.2%(p<0.01forcombination
groupvs.teriparatidealonegroup)
ReferenceJBoneMinerRes2011Mar26(3):503
additionofparathyroidhormonetoalendronatemayincreasespinalbonemineraldensity(BMD)
inwomenwithosteoporosis(level3[lackingdirect]evidence)
basedonnonclinicaloutcomesfromrandomizedtrial
126womenwithosteoporosistakingalendronateforatleast1yearcontinuedalendronateand
wererandomizedto1of3groupsfor15months
parathyroidhormone(PTH)(134)25mcg/daysubcutaneously
PTH(134)25mcg/dayfor3monthperiodsalternatingwithnoPTHfor3monthperiods
noPTH
comparingdailyPTHvs.cyclicPTHvs.noPTH
spinalBMDincreased6.1%vs.5.4%vs.nosignificantimprovement(p<0.001forboth
32/81
19/11/2015
parathyroidgroupsvs.alendronategroupdifferencebetweenparathyroidgroupsnot
statisticallysignificant)
nosignificantdifferencesbetweengroupsinhiportotalBMD
neworworseningvertebraldeformitiesoccurredin3%vs.6%vs.11%(notsignificant)
clinicalnonspinalfracturesoccurredin10.5%vs.6%vs.5.5%(notsignificant)
ReferenceNEnglJMed2005Aug11353(6):566fulltext,editorialcanbefoundinNEnglJMed
2005Aug11353(6):624,commentarycanbefoundinNEnglJMed2005Dec15353(24):2616
additionofteriparatidetoalendronatemayincreasebonemineraldensity(BMD)in
postmenopausalwomenwithosteoporosiscomparedtoswitchingfromalendronatetoteriparatide
basedonrandomizedtrialwithoutblindingandwithoutclinicaloutcomes
198postmenopausalwomenwithosteoporosisonalendronateorraloxifene>18monthswere
randomizedtoadditionofteriparatidetoalendronateorraloxifenevs.switchingtoteriparatidealone
for18months
combinationofteriparatideplusalendronateassociatedwithsignificantincreaseinBMDinlumbar
spine,totalhip,andfemoralneckcomparedtoteriparatidealoneat18months
nosignificantdifferencesinBMDat18monthscomparingteriparatideplusraloxifenevs.
teriparatidealone
teriparatidealoneassociatedwithgreaterboneturnover
ReferenceJClinEndocrinolMetab2009Oct94(10):3772
combinationofalendronateandteriparatidemaynotimprovebonemineraldensity(BMD)at
femoralneck,hip,andspinecomparedtomonotherapywithalendronateinmenandwomenwith
lowBMD(level3[lackingdirect]evidence)
basedon2randomizedtrialswithoutclinicaloutcomes
83menaged4685yearswithlowBMD(atleast2standarddeviationsbelowmeanforyoung
normalmen)wererandomizedtoalendronate10mgoncedailyvs.teriparatide40mcg
subcutaneouslyoncedailyvs.bothfor30months(teriparatidenotgivenduringfirst6months)
BMDathipandspineincreasedinallgroups,butincreaseswithPTHweregreaterthan
increaseswithcombinationtherapywhichweregreaterthanincreaseswithalendronate
teriparatidealonereducedBMDatradialshaft,whichincreasedwithalendronateor
combinationtherapy
ReferenceNEnglJMed2003Sep25349(13):1216fulltext,editorialcanbefoundinN
EnglJMed2003Sep25349(13):1277,commentarycanbefoundinACPJClub2004May
Jun140(3):63
93postmenopausalwomenwithlowBMD(atleast2standarddeviationsbelowmeanforyoung
normalwomen)wererandomizedtoalendronate10mg/dayalonevs.teriparatide40mcg/day
subcutaneouslyalonevs.alendronateplusteriparatidefor30months
BMDoflumbarspine,proximalfemur,proximalradius,andtotalbodymeasuredbydual
energyxrayabsorptiometry(DEXA)every6months
womenwith1repeatDEXAscanontherapyincludedinanalysis(74%patients)
teriparatidealoneassociatedwithsignificantlygreaterincreaseinspineandfemoralneck
BMDcomparedwith
alendronatealone
alendronateplusteriparatide
ReferenceJClinEndocrinolMetab2010Apr95(4):1838fulltext
BisphosphonateplusrhPTH(184):
combinationofalendronateandrhPTH(184)maynotincreaseBMDcomparedtomonotherapy
238postmenopausalwomenwithlowBMD(Tscore<2.5or<2withotherosteoporosisrisk
factor)whowerenotusingbisphosphonateswererandomizedtofulllengthPTH(184)
subcutaneouslyoncedailyvs.alendronate10mgorallyoncedailyvs.bothfor12monthsunder
doubleplacebocontrolledconditions
allpatientsgivencalciumcarbonate(elementalcalcium500mg)andmultivitamincontaining
vitaminD400units
effectsoftreatmentgrouponBMDvariedwithsite,typeofbone,andtypeofmeasure
neitherPTHnoralendronatealonehadmostfavorableresultsconsistentlyforalloutcomes
combinationtherapytypicallyperformedinbetweeneithermonotherapy
33/81
19/11/2015
ReferenceNEnglJMed2003Sep25349(13):1207fulltext,editorialcanbefoundinNEnglJ
Med2003Sep25349(13):1277,commentarycanbefoundinNEnglJMed2004Jan
8350(2):189,ACPJClub2004MayJun140(3):62
concurrentrhPTH(184)andibandronatemayhavesimilareffectonbonemineraldensity
comparedtosequentialtherapyinpostmenopausalwomenwithlowbonemass(level3[lacking
direct]evidence)
44postmenopausalwomen(meanage62years)withlowbonemassrandomizedto1of2
treatmentsfor2years
rhPTH(184)100mcg/daysubcutaneouslyplusibandronate150mgoncemonthlyorallyfor
6monthsfollowedbyibandronatealonefor18months(concurrent)
rhPTH(184)for3monthsfollowedbyibandronatefor9monthsfor2cycles(sequential)
atbaseline,allwomenhadBMDTscore1.5atfemoralneck,totalhip,orlumbarspine,orBMD
Tscore1plusatleast1riskfactorincludingage65years,priorpostmenopausalfracture,and
maternalhistoryofhipfracture
allwomenreceivedsupplementationwithcalcium600625mgplusvitaminD500900unitsper
day
nosignificantdifferencebetweengroupsinBMDatfemoralneck,totalhip,orlumbarspine
adverseeventratesweresimilarandmostcommonwerenauseaandinjectionsitebruisingor
soreness
ReferencePICStrial(JClinEndocrinolMetab2012Oct97(10):3522fulltext)
Teriparatideplusdenosumab:
teriparatideplusdenosumabassociatedwithincreasedbonemineraldensitycomparedtoeither
therapyaloneinpostmenopausalwomenwithosteoporosisathighriskoffracture(level3[lacking
direct]evidence)
basedonrandomizedtrialwithoutclinicaloutcomesandwithoutblinding
100postmenopausalwomen(meanage66years)withosteoporosiswererandomizedto1of3
treatmentsfor1year
teriparatide20mcgsubcutaneouslyoncedaily
denosumab60mgsubcutaneouslyonceevery6months
teriparatideplusdenosumab
allwomenhadhighfractureriskdefinedasanyof
Tscore2.5atspine,hip,orfemoralneck
Tscore2with1riskfactor
Tscore1withhistoryoffragilityfracture
94%wereincludedinanalysis
comparingteriparatideplusdenosumab(combinationtreatment)vs.teriparatidealonevs.
denosumabalone
increaseinposterioranteriorlumbarspineBMD9.1%vs.6.2%vs.5.5%
p=0.014forcombinationtreatmentvs.teriparatidealone
p=0.0005forcombinationtreatmentvs.denosumabalone
increaseinfemoralneckBMD4.2%vs.0.8%vs.2.1%
p=0.0007forcombinationtreatmentvs.teriparatidealone
increaseintotalhipBMD4.9%vs.0.7%vs.2.5%
p<0.0001forcombinationtreatmentvs.teriparatidealone
nosignificantdifferenceinposterioranteriorlumbarspineorfemoralneckBMDcomparing
teriparatidealonevs.denosumabalone
ReferenceDATAtrial(Lancet2013Jul6382(9886):50),editorialcanbefoundinLancet2013
May14Jul6382(9886):5
consistentfindingsat2years
basedon12monthextensionofaboveDATArandomizedtrial
womencontinuedassignedtreatmentforadditional12monthsandhadbloodsamplingand
dualenergyxrayabsorptiometry(DXA)scansat0,3,6,12,18,and24months
94womencompleted1postbaselinevisitand83womencompletedallvisitsover2years
combinationtreatmentassociatedwithincreasedlumbarspine,femoralneck,andtotalhip
BMDcomparedtoteriparatideordenosumabalone(p0.01foreach)
34/81
19/11/2015
ReferenceJClinEndocrinolMetab2014May99(5):1694
Comparativeefficacy:
teriparatide,zoledronate,alendronate,andrisedronateeachreportedtobemoreeffectivethan
raloxifeneorcalciumplusvitaminDforpreventingnonvertebralfracturesinpatientswith
basedonsystematicreviewwithmostlyindirectcomparisons
systematicreviewof116randomizedtrialsevaluatingefficacyofpharmacologicalagentsfor
preventionofhip,vertebral,andnonvertebralfracturesin139,647patientswithoratriskfor
osteoporosis
mosttrialswereinpostmenopausalwomen
drugtherapyincludedteriparatide,denosumab,raloxifene,zoledronate,risedronate,ibandronate,
alendronate,vitaminD,calcium,andvitaminDpluscalcium
smallnumberofdirectcomparisontrialsreducesprecisionandconfidenceinresultsofnetwork
metaanalyses
innetworkmetaanalysesofplacebocontrolleddata(combiningdirectandindirectcomparisons),
significantreductionin
newhipfractureswithalendronate,risedronate,zoledronate,denosumab,andvitaminD
pluscalcium
newvertebralfractureswithteriparatide,denosumab,zoledronate,risedronate,alendronate,
raloxifene,andibandronate
newnonvertebralfractureswithteriparatide,risedronate,zoledronate,denosumab,and
alendronate
comparativeefficacyinnetworkmetaanalyses(combiningdirectandindirectcomparisons)
forpreventionofhipfractures
zoledronate,risedronate,andalendronateweremoreeffectivethanraloxifene
zoledronate,risedronate,andalendronateweremoreeffectivethancalciumand/or
vitaminD
denosumabwasmoreeffectivethancalciumaloneorvitaminDalone
forpreventionofnonvertebralfractures
teriparatide,zoledronate,andrisedronateweremoreeffectivethanraloxifeneand
calciumand/orvitaminD
teriparatidewasmoreeffectivethanalendronate
ibandronateandalendronateweremoreeffectivethancalciumplusvitaminD
ReferenceJClinEndocrinolMetab2012Jun97(6):1871fulltext
DynaMedcommentarystudyfundedinpartbyTheEndocrineSocietyinpreparationfor
evidencebasedguidelinedevelopment
denosumabmayincreasebonemineraldensity(BMD)morethanbisphosphonates(level3
[lackingdirect]evidence)butisnotclearlymoreeffectiveforreducingfracturerisk
basedonsystematicreviewswithlargemetaanalysesofindirectcomparisonsandsmallmeta
analysesofdirectcomparisons
inlargestnetworkmetaanalysis(summarizedabove),denosumabwasnotstatisticallysuperiorto
othertreatmentsforfractureprevention
denosumabreportedtoreduceriskofnewvertebralfracturescomparedtostrontium
ranelate,raloxifene,alendronate,andrisedronateinpostmenopausalwomenwith
basedonsystematicreviewwithindirectcomparisonsandsignificantdifferencesmostly
limitedtononclinicaloutcomes
systematicreviewof34randomizedtrialsevaluatingdrugtherapyforreductionoffractures
in73,464postmenopausalwomenwithosteoporosis
drugtherapyincludeddenosumab,strontiumranelate,raloxifene,teriparatide,zoledronic
acid,alendronate,etidronate,ibandronate,andrisedronate
indirectplacebocontrolledanalyses
significantlyreducedriskof
newvertebralfractureswithallagentsexceptetidronate
nonvertebralfractureswithdenosumab,strontiumranelate,teriparatide,
zoledronicacid,alendronate,andrisedronate
hipfractureswithdenosumab,zoledronicacid,andrisedronate
nosignificantdifferencesinwristfracturesforanyagent
35/81
19/11/2015
inindirectactivetreatmentcontrolledanalyses
reducedriskofnewvertebralfractureswithdenosumabcomparedto
strontiumranelate
raloxifene
risedronate
alendronate
denosumabvs.strontiumranelatewasonlyindirectcomparisonofactivetreatments
withsignificantdifferencesforclinicalvertebralfractures
nosignificantdifferencesbetweendenosumabandanyotheragentforreducingrisk
ofnonvertebral,hip,orwristfractures
ReferenceOsteoporosInt2013Jan24(1):209fulltext
DynaMedcommentarymultipleauthorsareemployeesofandhavestockownershipin
Amgen,Inc.whichmanufacturesdenosumab
denosumabmaynotreducefractureriskcomparedtoalendronateinpostmenopausal
womenwithosteoporosis(level2[midlevel]evidence)
basedonsystematicreviewoftrialswithunclearallocationconcealment
systematicreviewof4randomizedtrialscomparingdenosumab60mgsubcutaneously
every6monthsvs.alendronate70mg/weekfor12monthsin1,942postmenopausal
womenwithosteoporosis
nosignificantdifferencesinriskof
fractureinanalysisof3trials
infectioninanalysisof4trials
neoplasminanalysisof3trials
denosumabassociatedwithimprovedBMDat
distalradius(meandifference0.53%,95%CI0.18%0.89%)inanalysisof2trials
totalhip(meandifference1.14%,95%CI0.93%1.36%)inanalysisof3trials
lumbarspine(meandifference0.77%,95%CI0.43%1.1%)inanalysisof3trials
femoralneck(meandifference0.79%,95%CI0.42%1.15%)inanalysisof2trials
ReferenceIntJClinPract2012Apr66(4):399
denosumabmayincreasebonemineraldensity(BMD)morethanalendronatein
postmenopausalwomen(level3[lackingdirect]evidence)
504postmenopausalwomenwithosteoporosisonalendronate70mgonceweeklyfor1
monthwerethenrandomizedtocontinueweeklyalendronatevs.denosumab60mg
subcutaneouslyevery6monthsfor12months
denosumabassociatedwithgreaterincreasesinBMDthanalendronateat12months
attotalhip,lumbarspine,femoralneck,andradius
ReferenceJBoneMinerRes2010Jan25(1):72
247postmenopausalwomenrandomizedtodenosumab60mgsubcutaneouslyevery6
monthsvs.alendronate70mgorallyonceweeklyvs.placebofor12months
denosumabassociatedwithimprovementinBMD(p<0.001vs.placebo,p0.024
vs.alendronate)
ReferenceJBoneMinerRes2010Aug25(8):1886
412postmenopausalwomenwithlowBMDrandomizedtodenosumab(7differentregimens
rangingfrom6mgevery3monthsto210mgevery6months)vs.alendronate70mgonce
weeklyvs.placebofor12months
alendronategroupwasnotblinded
denosumabassociatedwithincreaseinBMDof3%6.7%atlumbarspineand
0.4%1.3%atdistalthirdofradius
alendronateassociatedwithincreaseinBMDof4.6%atlumbarspineanddecrease
of0.5%atdistalthirdofradius
ReferenceNEnglJMed2006Feb23354(8):821fulltext,correctioncanbefound
inNEnglJMed2006Aug10355(6):638,editorialcanbefoundinNEnglJMed
2006Feb23354(8):860,commentarycanbefoundinNEnglJMed2006Jun
1354(22):2390,CurrOncolRep2006Jul8(4):267,NephrolDialTransplant2006
Aug21(8):2075fulltext,NatClinPractEndocrinolMetab2006Nov2(11):600,Curr
RheumatolRep2007Apr9(1):48
denosumabassociatedwithincreasedbonemineraldensity(BMD)comparedwith
ibandronateinpostmenopausalwomenwithlowbonemineraldensitypreviouslytreated
withabisphosphonate(level3[lackingdirect]evidence)
basedonopenlabelrandomizedtrialwithoutclinicaloutcomes
36/81
19/11/2015
833postmenopausalwomenwithlowBMDpreviouslytreatedwithabisphosphonate
randomizedtodenosumab60mgsubcutaneouslyevery6monthsvs.ibandronate150mg
orallyeverymonthfor12months
allwomenreceivedcalcium500mgandvitaminD800units/day
treatmentdiscontinuedin6%withdenosumabvs.14%withibandronate(p<0.05)
comparingdenosumabvs.ibandronate,increasedBMDfor
totalhipby2.3%vs.1.1%(p<0.001,NNT84)
femoralneckby1.7%vs.0.7%(p<0.001,NNT100)
lumbarspineby4.1%vs.2%(p<0.001,NNT48)
ReferenceObstetGynecol2013Jun121(6):1291
calcitoninlesseffectivethanalendronateforbonemineraldensity(BMD)effect(level3[lacking
direct]evidence)
calcitoninmaintainsbonemineraldensity(BMD)lesseffectivelythanalendronate(level3
299womenwithosteoporosisrandomizedto1of3groupsfor12months
alendronate10mgorallyoncedaily
calcitonin200unitsintranasallyoncedaily
placeboorallyoncedaily
comparingalendronatevs.calcitonin
increaseinBMDatlumbarspine5.16%vs.1.18%(p<0.001)
increaseinBMDattrochanter4.73%vs.0.47%(p<0.001)
increaseinBMDatfemoralneck2.78%vs.0.58%(p<0.001)
ReferenceJClinEndocrinolMetab2000May85(5):1783
calcitoninmayproducesignificantlysmallerincreasesinfemoralneckandtrochanteric
bonemineraldensity(BMD)thanalendronateinpostmenopausalwomenwithosteoporosis
andrheumatoidarthritis(level3[lackingdirect]evidence)
50postmenopausalwomenwithosteoporosisandrheumatoidarthritistreatedwithlowdose
corticosteroidswererandomizedtoalendronate10mg/dayvs.salmoncalcitonin200
units/dayfor24months
allwomenreceivedcalciumsupplementation1,000mgandvitaminD400units/day
comparingcalcitoninvs.alendronate
meanchangeinfemoralneckBMD2.52%vs.3.76%(p<0.001)
meanchangeintrochantericBMD1.29%vs.0.81%(p<0.05)
ReferenceRheumatolInt2005Nov26(1):21
teriparatidemaybemoreeffectivethanalendronateforreducingclinicalvertebralfracture
incidenceandbonemineraldensity(BMD)lossduetocorticosteroids(level2[midlevel]evidence)
428patientsaged2289yearswithglucocorticoidinducedosteoporosiswererandomizedto
teriparatide20mcginjectedoncedaily(plusoralplacebo)vs.alendronate10mgorallyoncedaily
(plusinjectableplacebo)for18months
294(69%)patientscompleted18monthtrial
comparingteriparatidevs.alendronateatlastmeasurement
meanincreaseinBMDoflumbarspine7.2%vs.3.4%(p<0.001)
11.7%interiparatidegroupvs.6.1%inalendronategroupdroppedoutduetoadverseevents(p=
0.04,NNH17)
ReferenceNEnglJMed2007Nov15357(20):2028,editorialcanbefoundinNEnglJMed2007
Nov15357(20):2084,commentarycanbefoundinNEnglJMed2008Mar20358(12):1302
comparingteriparatidevs.alendronateat36months
1radiographicvertebralfracturein1.7%vs.7.7%(p=0.007,NNT17)inanalysisof342
patientswhohadspinalradiographsatbaseline
1clinicalvertebralfracturein0%vs.2.4%(p=0.037,NNT42)
nosignificantdifferenceincumulativenonvertebralfractures
comparingteriparatidevs.alendronateamong294patientswhoentered18month
continuationphase
meanincreaseinBMDoflumbarspine11%vs.5.3%(p<0.001)
ReferenceArthritisRheum2009Nov60(11):3346fulltext
37/81
19/11/2015
Othermedications:
Fluoride:
notFDAapprovedforosteoporosisasofMay2014(1)
fluoridetherapyiscontroversialandhasconflictingevidence(1)
fluoridemayincreasebonemineraldensity(BMD)atspineandhip(level3[lackingdirect]
evidence)butonlylowdoses(20mg/day)associatedwithreducedvertebralandnonvertebral
fracturerisk(level2[midlevel]evidence)
basedonsystematicreviewlimitedbyheterogeneity
systematicreviewof25trialsevaluatinganyformulationoffluorideforosteoporosis(including
secondaryorglucocorticoidinducedosteoporosis)in2,348patients
spineandhipBMDincreasedwithfluoridetreatmentbutnosignificanteffectonvertebraland
nonvertebralfracturerisk
lowdosefluoride(20mg/day)reducedvertebralfracturerisk(oddsratio[OR]0.3,95%CI0.1
0.9)andnonvertebralfracturerisk(OR0.5,95%CI0.30.8)insubgroupanalysis
fluoridecanincreasebonemineraldensityatlumbarspine,butmaynotpreventvertebral
fractures(level3[lackingdirect]evidence)andhighdosesmayincreaseriskfornonvertebral
fracture(level2[midlevel]evidence)
basedonCochranereviewwithoutsignificantdifferencesinclinicaloutcomesinoverallanalyses
systematicreviewof11trialswith1,429patients
increasingdosesoffluorideassociatedwithincreasedriskofnonvertebralfracturesand
gastrointestinalsideeffectswithoutanyeffectonvertebralfracturerate
ReferenceCochraneDatabaseSystRev2000(4):CD002825(reviewupdated2008Sep17),
commentarycanbefoundinJAmGeriatrSoc2001Oct49(10):1387
sustainedreleasesodiumfluorideassociatedwithreducedvertebralfracturerateinwomen65
yearsoldwithosteoporosis(level3[lackingdirect]evidence)
85ambulatorywomen65yearsoldwith1nontraumaticvertebralcompressionfracturewere
randomizedtosustainedreleasesodiumfluoride25mgvs.placebotwicedailyfor42months
treatmentassociatedwithstatisticallysignificantreductioninvertebralfracturerate
ReferenceArchInternMed2001Oct22161(19):2325fulltext
lowdosefluoridetabletsmaynotimprovebonemineraldensityinpostmenopausalwomenwith
osteopenia(level3[lackingdirect]evidence)
180postmenopausalwomenwithosteopeniarandomizedtovariouslowdosesfluoride(2.5mgvs.
5mgvs.10mg)perdayorallyvs.placebofor1year
nosignificantdifferencescomparinganyfluoridedosevs.placeboinbonemineraldensityat
lumbarspine,hip,orforearm
ReferenceJClinEndocrinolMetab2013Jun98(6):2301
waterfluoridationdoesnotappeartoincreasefractureriskforolderwomen(level2[midlevel]
evidence)
basedoncohortstudy
9,704whiteambulatorywomen>65yearsoldinUnitedStatesfollowedformean7years
interviewsclassifiedwomenaccordingtolevelsoffluorideexposurebasedontheircommunity
eachyearfor44years
increasedfluorideexposureassociatedwithincreasedBMDandslightlydecreasedriskfor
fractures
ReferenceBMJ2000Oct7321(7265):860fulltext,editorialcanbefoundinBMJ2000Oct
7321(7265):844fulltext
Nitroglycerin:
nitroglycerinointmentreportedtoincreasebonedensity(BMD)inpostmenopausalwomen(level
3[lackingdirect]evidence)
243postmenopausalwomenwithlowBMDwererandomizedtonitroglycerinointment15mg/day
38/81
19/11/2015
vs.placeboatbedtimefor2years
nitroglycerinassociatedwithincreasedBMDat2years(allp<0.001)
6.7%forlumbarspine
6.2%fortotalhip
7%forfemoralneck
discontinuationduetoheadachein5.6%withnitroglycerinvs.1.7%withplacebo(nopvalue
reported)
nosignificantdifferencesinseriousadverseevents
ReferenceJAMA2011Feb23305(8):800,editorialcanbefoundinJAMA2011Feb
23305(8):826
DynaMedcommentarynotFDAapprovedforosteoporosisasofMay2014
Odanacatib:
odanacatib(cathepsinKinhibitor)mayincreasebonedensityinpostmenopausalwomen(level3
399postmenopausalwomenwithlowBMDrandomizedtoodanacatib350mg/weekvs.placebo
for24months
allwomenreceivedvitaminDwithcalciumsupplementationasneeded
comparingodanacatibvs.placeboat24months
changeinlumbarspineBMD5.5%vs.0.2%
changeintotalhipBMD3.2%vs.0.9%
ReferenceJBoneMinerRes2010May25(5):937,editorialcanbefoundinJBoneMiner
Res2010May25(5):934
odanacatibfor3yearsassociatedwithprogressiveincreaseinbonemineraldensity
(BMD)(level3[lackingdirect]evidence)
basedon1yearextensionofrandomizedtrialabove
189womencompleting2years'treatmentinbasestudyagainrandomizedto
odanacatib50mg/weekvs.placebofor12months
odanacatibfor3yearsassociatedwithsignificantlyimprovedBMD
+7.9%atspineand+5.8%athipvs.baseline
+2.3%atspineand+2.4%athipvs.odanacatibat2years
discontinuationofodanacatibat2yearsassociatedwithbonelossatallsites(but
BMDmaintainedatorabovebaseline)atendofyear3
nosignificantdifferenceinoveralladverseeventrates
ReferenceJBoneMinerRes2011Feb26(2):242,editorialcanbefoundinJBone
MinerRes2011Feb26(2):239
214postmenopausalwomenwithlowarealBMD(gramsofmineralpersquarecmscannedbone)
randomizedtoodanacatib50mg/weekvs.placebofor2years
odanacatibassociatedwith
increasedarealBMDatlumbarspine(differenceof3.5%,p<0.001)
decreasedCtelopeptideoftype1collagenlevelsat6monthsand2years(p<0.001
foreach)
nosignificantdifferenceinprocollagenINterminalpeptidelevelsat2years
ReferenceJClinEndocrinolMetab2013Feb98(2):571
DynaMedcommentaryodanacatibnotFDAapprovedasofMay2014
Chineseherbalmedicines:
someChineseherbalmedicinesmayincreasebonemineraldensityinpatientswithosteoporosis
basedonnonclinicaloutcomeinCochranereview
systematicreviewof108randomizedtrialsevaluatingChineseherbalmedicinesin10,655patients
withosteoporosis
alltrialsconductedinpatientsofChineseethnicity
99differentChineseherbalmedicineswereevaluated,notrialscomparedsameChineseherbal
medicinevs.samecontrol
ReferenceCochraneDatabaseSystRev2014Mar6(3):CD005467
39/81
19/11/2015
Followup:
Treatmentmonitoring:
Bonemineraldensity(BMD)monitoring:
dualenergyxrayabsorptiometry(DEXA)recommendedasbesttestformonitoringresponseto
treatments(ICSIStrongrecommendation,Moderatequalityevidence)(2)
noconsensusonhowoftenpatientsshouldbemonitoredduringosteoporosistherapy
NationalOsteoporosisFoundationrecommendedmonitoring12yearsafterinitiatingtreatment,
thenevery2years (1)
noevidencetobenefitfrommorefrequentrepeatBMDtesting,buttestingevery612monthsmay
bewarrantedinpatientstakingglucocorticoidsorsuppressivedosesofthyroidhormone(2)
formenwithosteoporosisEndocrineSocietysuggestsmonitoringBMDwithDEXAatspineand
hipevery12years,butfrequencyofmonitoringmaybereducedifBMDplateaus(Endocrine
SocietyWeakrecommendation,Moderatequalityevidence)(4)
BMDmonitoringalsorecommendedevery2yearsduring"drugholiday"ifstopping
bisphosphonatesafter5yearsofuse(2)
CanadianAssociationofNuclearMedicinerecommendsagainstrepeatingDEXAscansmoreoften
thanevery2yearsinabsenceofhighriskornewriskfactors(ChoosingWiselyCanada2015Jun
2)
routinebonedensitymonitoringmaynotbenecessarywithinfirst3yearsof
bisphosphonatetherapy
basedonsecondaryanalysisofFITtrial(randomizedtrialofalendronatevs.placeboin
postmenopausalwomen)
meanhipbonemineraldensityincreasedby0.03g/cm2afteralendronatetreatmentfor3
years
alendronatetreatmentestimatedtoincreasehipbonedensity0.019g/cm2in97.5%
patients
variationinbonemineraldensitybetweenpatientsdidnotappeartobeclinicallyrelevant
ReferenceBMJ2009Jun23338:b2266fulltext,editorialcanbefoundinBMJ2009Jun
23338:b1276
changesinBMDduringtherapymaynotbedirectlyassociatedwithfracturerisk
antiresorptivetherapymayreduceriskoffracturemorethanexpectedfromimprovedspine
bonemineraldensityinpostmenopausalwomen(level2[midlevel]evidence)
systematicreviewof12randomizedtrialsevaluatinganyantiresorptivedrugvs.placeboon
bonemineraldensity(BMD)andriskofvertebralfracturein21,404postmenopausalwomen
modelestablishedforobservedvs.expectedrelativeriskofvertebralfracturesuggests
antiresorptivetherapyreducesriskoffracturemorethanexpectedfromimprovedspine
BMD(relativerisk0.55vs.0.80)inanalysisof12trials
ReferenceAmJMed2002Mar112(4):281
improvedbonemineraldensitymaynotbeassociatedwithreducedfractureriskinpatients
aged>50yearsoldsupplementingwithcalciumeitherwithorwithoutvitaminD(level2
[midlevel]evidence)
systematicreviewof15randomizedtrialsevaluatingcalciumsupplementationwithor
withoutvitaminDsupplementationvs.placeboornotreatmentin47,365patientsaged>50
yearsold
nosignificantreductioninfractureriskwithimprovedbonemineraldensity(BMD)atlumbar
spinefrombaselinetostudyendpointinanalysisof12trials
monitoringdualenergyxrayabsorptiometryscansreportedtoinfrequentlyresultintreatment
changesinwomenwithlowbonemineraldensitytakingbisphosphonates(level3[lackingdirect]
evidence)
basedoncaseseries
549womenreceivingtreatmentforlowbonemineraldensity(meanage68years,78%white,99%
treatedwithbisphosphonates)had1,647dualenergyxrayabsorptiometry(DXA)scans(mean3
scansperpatients,meanintervalbetweenscans2.4years)
40/81
19/11/2015
amongrandomsampleof92women(196scans)fromabove
primaryphysicianrationalefororderingDXAscansbecausetheywere"due"for90%of
scans
165scans(84%)resultedinnotreatmentchanges
26of36scans(72%)showingsignificantdecreaseinbonemineraldensityresultedinno
treatmentchanges
ReferenceJAMAInternMed2013Nov25173(21):2007
Boneturnovermarkers(BTMs)intreatmentmonitoring:
EndocrineSocietysuggestsconsiderationofBTMmonitoring36monthsafterstartingosteoporosis
treatmentinmen,withtypeofBTMdependingontypeoftherapy(EndocrineSocietyWeak
recommendation,Moderatequalityevidence)(4)
forantiresorptivetherapyboneresorptionmarkersuchasserumCtelopeptideoftypeIcollagen
(CTX)orserumorurineNtelopeptideoftypeIcollagen(NTX)
foranabolictherapyboneformationmarkersuchasserumprocollagenINpropeptide(PINP)
evidencethatchangeinBTMcorrelateswithfractureriskreductionisderivedfromwomen(no
suchstudiesinmen),andoptimalBTMresponsetotreatmentnotestablished
serumBTMsforbonemetabolism(1,3)
serumBTMsmayhelpshowresponsetotherapy(usually36monthsafterinitiationoftreatment)
orassessriskoffracture
serumformationmarkers(osteoblastactivity)include
osteocalcin(sOC)
totalalkalinephosphatase(ALP)
bonespecificalkalinephosphatase(boneALP)
procollagentypeICterminalpropeptide(P1CP)
procollagentypeINterminalpropeptide(P1NP)
serumresorptionmarkers(osteoclastactivity)include
collagentypeIcrosslinkedCtelopeptide(sCTX)
carboxyterminaltelopeptideoftypeIcollagen(ICTP)
tartrateresistantacidphosphatase(TRACP)
tartrateresistantacidphosphatase5b(sTRACP5b)
considerations
BTMsareaffectedbymanyfactors,suchasage,sex,timeofday,physicalactivity
overpast24hours,fracturesoverpastmonths,etc.,sogreatcaremustbetakenin
samplecollection
sampleinmorningfromfastedpatientswhohaveabstainedfromphysicalexercise
for24hours
donotsamplepatientswithinseveralmonthsafterfracture
use1tubeforallBTMstested
carefullycontroltemperatureduringallsampleprocess,storage,andtransport(short
termstorageat4degreesC[39.2degreesF]orlongtermstorageat70degreesC
[94degreesF],andavoidrepeatedfreezethawcycles)
monitoringosteoporosistreatment
treatmentmechanismofaction,dose,androuteofadministrationallaffectdirection,
magnitude,andtimecourseofBTMs
considerexpectedlevelsandtimecourseforchangeforindividualtreatmentsin
individualpatientswheninterpretingBTMdatausedtomonitortreatment
reportedpatterns
antiresorptivetreatments(bisphosphonates,raloxifene,denosumab)
associatedwithdecreasedboneresorptionmarkerswithindaysorweeksof
beginningtreatmentfollowedbydecreasedboneformationmarkersafter
about1month
anabolictreatments(teriparatide)associatedwithincreasedboneformation
markersandbiphasicresponseofboneresorptionmarkers(initialdecrease
5%15%within1monthfollowedbysignificantincrease)
ReferenceCurrOpinEndocrinolDiabetesObes2012Dec19(6):468
urineBTMsforbonemetabolism(2)
urineBTMsvs.serumBTMs(especiallycollagentypeIcrosslinkedCtelopeptide)
intraindividualvariabilityaround10%15%forserummarkersvs.20%30%forurine
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markers
serummarkersdonotneedcorrectionforglomerularfiltrationrate
automatedtechnologyiscurrentlyavailableforserumtelopeptideoftypeIcollagen
andprocollagenIextensionpeptides
serumreferencerangesarebetterestablished,especiallyforwomen
ReferenceCurrOpinEndocrinolDiabetesObes2012Dec19(6):468
urinaryresorptionmarkers(osteoclastactivity)include
collagentypeIcrosslinkedNtelopeptide(uNTX)
collagentypeIcrosslinkedCtelopeptide(uCTX)
totalpyridinoline(uPYD)
totaldeoxypyridinoline(uDPD)
Treatmentadherence:
lowadherenceratesreportedforosteoporosisdrugtherapy
basedonsystematicreviewandmetaanalysisof24studiesofdrugtherapyforosteoporosis
pooledmedicationpersistence(lengthoftherapycontinuation)rates
52%fortreatmentlasting16months
52%fortreatmentlasting>24months
pooledmedicationadherence(correctdoseandfrequency)rates
pooledrefillcompliancerate
pooledselfreportedcompliancerate
ReferenceMayoClinProc2007Dec82(12):1493
simplificationofdosingregimensmayimprovemedicationadherenceandpersistenceinpatients
withosteoporosis(level2[midlevel]evidence)
basedonsystematicreviewwithtrialspecificqualitymeasuresnotreported
systematicreviewof16randomizedornonrandomizedtrialsand4caseseriesevaluating
interventionstoimprovemedicationadherenceandpersistencein14,662adultswithosteoporosis
followuprangedfrom4to48months
improvedmedicationadherencewith
simplificationofdosingregimen,specifically
ibandronateoncemonthlypluspatientsupportprogramvs.alendronateonceweekly
in1trialwith1,076adults
denosumabsubcutaneouslyonceevery6monthscomparedtoalendronateorally
onceweeklyin2trialswith471adults
decisionaidin1trialwith100adults
monitoringin1trialwith73adults
resultsforpatientandphysicianeducationinterventions
groupbasededucationsignificantlyincreasedadherencein1trialwith450adults
nosignificantdifferenceinadherencewith
patientandphysicianeducationin1trialwith2,742patientsand436general
practitioners
telephonebasedcounselingin1trialwith2,087adults(below)
inconsistentresultsforpharmaceuticalcare
decentralizedclinicalpharmacybasedosteoporosismanagementservicesignificantly
improvedadherence(basedonmedicationpossessionratio)vs.centralizednursebased
servicein1studywith362adults
pharmacistdirectededucationandcounselingsignificantlyincreasedadherencebasedon
patientquestionnaire,butnosignificantdifferencebasedonpillcountin1trialwith198
adults
improvedpersistencewith
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simplificationofdosingregimensin3trialswith1,547adults
electronicprescriptionin1trialwith245adults
nosignificantdifferenceinpersistencewithmonitoring/supervision(4trials),educationprograms(3
trials),andpatientsupportprogram(1trial)
ReferenceOsteoporosInt2013Dec24(12):2907
telephonecounselingnotassociatedwithsignificantimprovementinmedicationadherence(level
2[midlevel]evidence)
basedonrandomizedtrialwithoutattentioncontrol
2,087patients(meanage78years)newlyprescribedmedicationforosteoporosisrandomizedto
telephonebasedmotivationalcounselingvs.mailededucationalmaterial(control)
adherenceat1year49%withtelephonecounselingvs.41%withcontrol(p=0.07)
ReferenceArchInternMed2012Mar26172(6):477,editorialcanbefoundinArchInternMed
2012Mar26172(6):463
ComplicationsandPrognosis
Complications:
vertebralfracture
hipfracture
Colles(distalradius)fracture
riskfactorsforfallswhichmayleadtofractureinclude(2)
impairedeyesight
medicationsthataffectbalance
poorhealth
frailty
lowphysicalfunction(forinstance,slowgaitanddecreasedquadricepsstrength)
dementia
historyofpastfalls
agerelatedmuscleloss
seealsoFallsintheelderly
osteoporosisassociatedwithsignificantlyincreasedriskforclinicalfracturesat1year
NationalOsteoporosisRiskAssessmentenrolled200,160ambulatorypostmenopausalwomen>
50yearsoldwithnopreviousosteoporosisdiagnosisfromprimarycarepracticesin34United
States
peripheralbonedensitometrymeasuredatheel,finger,orforearm
basedonWorldHealthOrganizationcriteria,39.6%hadosteopenia(Tscore1to2.49)and7.2%
hadosteoporosis(Tscore2.5orless)
163,979womenreturnedquestionnairesat1yearwhichincludedinformationonclinicalfractures
fractureratesper100personyears(foranyosteoporoticfracture)were0.86forwomenwithnormal
Tscores,1.55forosteopenicwomen,and3.47forosteoporoticwomen
increasedincidenceofanyfractureat1year(per100personyears)for
womenwithosteoporosisvs.womenwithnormalTscores(rateratio[RR]4.03,95%CI
3.594.53)
womenwithosteoporosisvs.womenwithlowbonemass(RR2.24,95%CI2.012.50)
womenwithlowbonemass(osteopenia)vs.womenwithnormalTscores(RR1.8,95%CI
1.492.18)
ReferenceJAMA2001Dec12286(22):2815fulltext,editorialcanbefoundinJAMA2001Dec
12286(22):2865,commentarycanbefoundinJAMA2002Mar6287(9):1109
lowtotalhipbonemineraldensityassociatedwithincreasedriskofbothhighandlowtrauma
fracturesinwomenandmen65yearsold
basedon2prospectivecohortstudiesofcommunitylivingwomenandmenassessedforbone
mineraldensityatbaselineandhighorlowtraumafractureduringfollowup
8,022womenwerefollowedformean9.1years,264(3.29%)hadhightraumafracture,3211
(40%)hadlowtraumafracture
5,995menwerefollowedformean5.1years,94(1.57%)hadhightraumafracture,346
(5.77%)hadlowtraumafracture
relativehazardoffractureforeachstandarddeviationreductionintotalhipbonemineraldensity
(multivariateanalysis)
1.45(95%CI1.231.72)forhightraumafractureand1.49(95%CI1.421.57)forlowtrauma
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fractureinwomen
1.54(95%CI,1.21.96)forhightraumafractureand1.69(95%CI1.491.91)forlowtrauma
fractureinmen
ReferenceJAMA2007Nov28298(20):2381fulltext,editorialcanbefoundinJAMA2007Nov
28298(20):2418,commentarycanbefoundinJAMA2008Apr2299(13):1542
Prognosis:
Bonedensitytestingforpredictingfracturerisk:
dualenergyxrayabsorptiometry(DEXA)preferredmethodtopredictfractureriskinosteoporosisorlow
bonemineraldensity(BMD)(ICSIStrongrecommendation,Moderatequalityevidence)(2)
DEXAconsideredbesttestforpredictingfractureriskinpostmenopausalwomen
basedonreviewof2systematicreviewsand6observationalstudies
quantitativeultrasound(QUS)maybecomparabletoDEXAformeasurementofBMD,maybe
usefulwhereDEXAnotavailable
quantitativecomputedtomography(QCT)maybeaseffectiveasDEXAbutusesmoreradiation
ReferenceCanadianAgencyforDrugsandTechnologiesinHealth(CADTH)HealthTechnology
Assessment2007DecPDF
fracturepredictionmodelcombininghipandlumbarspinebonemineraldensitymeasurements
predictsfractureriskbetterthanmodelwithsinglesitemeasurements
recordsfrom16,505women>50yearsoldattimeofbaselineDEXAofspineandhipwere
assessedforDEXABMDmeasurementsandfractureoutcomes
osteoporoticfracturedefinedaship,spine,forearm,orproximalhumerusfracturewithsitespecific
fracturereduction,fixation,orcastingcodeinrecords
BMDassociatedwithosteoporoticfractureat
totalhip(adjustedhazardratio[HR]1.85,95%CI1.72.01)
trochanter(HR1.77,95%CI1.631.92)
femurneck(HR1.76,95%CI1.621.92)
lumbarspine(HR1.61,95%CI1.391.87)
additionofanyindividualhipmeasurementtomodeloffracturepredictioninoverallpopulation
containinglumbarspinemeasurementsignificantlyimprovedmodelprediction(p<0.001)
additionoflumbarspinemeasurementtomodeloffracturepredictioncontainingfemurneck
measurementsignificantlyimprovedmodelprediction(p=0.02)
nosignificantimprovementwithadditionoflumbarspinemeasurementtomodeloffracture
predictioncontainingtotalhiportrochantermeasurement
ReferenceArchInternMed2007Aug1327167(15):1641fulltext,JClinEndocrinolMetab2007
Jan92(1):77
measurementofbonemineraldensityisneithersensitivenorspecificenoughtopredictfracture
riskinindividualsbutmaybeusefulforestimatingriskinpopulations
basedonmetaanalysisof11prospectivestudieswith>90,000personyearsoffollowupand>
2,000fractures
allmeasuringsites(exceptspineforpredictingvertebralfractureandhipforpredictinghipfracture)
usedtodetectdecreasedBMDhadsimilarpredictiveabilities,relativerisk(RR)1.5(95%CI1.4
1.6)
spineBMDandhipBMDhadbetterpredictiveabilitythanothersites
spineRR2.3(95%CI1.92.8)
hipRR2.6(95%CI2.03.5)
predictiveperformanceofBMD1standarddeviation(2.6forhip)belowageadjustedmeanwith
lifetimeincidenceofhipfractureof3%(lowrisk)
sensitivity47%
specificity83%
predictiveperformanceofBMD1standarddeviation(2.6forhip)belowageadjustedmeanwith
lifetimeincidenceofhipfractureof30%(highrisk)
sensitivity34%
specificity89%
ReferenceBMJ1996May18312(7041):1254fulltext
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repeatBMDtestingdoesnotappeartoimprovefractureriskpredictioninelderlypatients,event48
yearsafterinitialBMDtesting
bonemineraldensitymeasurements8yearsafterinitialbonedensitymeasurementappear
equivalentatpredictingfractureriskinwomen
basedonprospectivecohortstudy
4,124womenaged65years(meanage72years)hadtotalhipBMDtestingbyDEXAat
baselineandthenagainatmean8years(range6.39.8years)
atmean5yearsafterrepeatassessment,incidentnontraumatic,nonspinefracturein877
women(including275hipfractures)
afteradjustmentforageandweight,nosignificantdifferencesinfracturerisks(per1
standarddeviationreductioninBMD)predictedusingmodelsbasedonbaselineBMD,
repeatBMD,changeinBMDover8years,orinitialBMDpluschangeinBMDover8years
fornonspine,spine,orhipfractures
ReferenceArchInternMed2007Jan22167(2):155fulltext
BMDonquantitativeultrasound(QUS)forpredictionoffracturerisk
reductionsofbonemineraldensityoncalcanealquantitativeultrasoundassociatedwith
increasedriskofhipandnonspinefracturesinmen65yearsold
basedoncohortstudy
5,607men65yearsoldhadcalcanealQUSandxrayforBMDofhipandwerefollowed
formean4.2years
239nonspinefractures,including49hipfractures
eachstandarddeviationreductiononcalcanealQUSandBMDassociatedwithincreased
riskoffracture
calcanealQUS
hipfracture(adjustedrelativehazard2,95%CI1.52.8)
nonspinefracture(adjustedrelativehazard1.6,95%CI1.41.8)
BMDtotalhip
hipfracture(adjustedrelativehazard2.9,95%CI2.24)
nonspinefracture(adjustedrelativehazard1.6,95%CI1.41.9)(not
significantcomparedtobroadbandultrasonicattenuation[BUA])
BMDfemoralneck
hipfracture(adjustedrelativehazard3.5,95%CI2.54.9)
nonspinefracture(adjustedrelativehazard1.6,95%CI1.41.9)(notsignificant
comparedtoBUA)
findingsusingBMDassociatedwithsignificantlyhigherriskoftotalhipfracture
ReferenceMrOSstudy(OsteoporosInt2007Jun18(6):771)
increasedriskofhipfracturesinwomen>65yearsold
basedoncohortstudy
6,189women>65yearsoldhadcalcanealquantitativeBUAandBMDofcalcaneusand
hip,thenwerefollowedforhipandothernonspinalfracturesfor2years
eachstandarddeviationreductioninBUAandBMDsimilarlypredictedriskforhipfractures
BUA(relativerisk[RR]2,95%CI1.52.7)
BUA(adjustedforBMDRR1.5,95%CI12.1)
BMD(RR2.2,95%CI1.93)andfemoralneck(RR2.6,95%CI1.93.8)
ReferenceArchInternMed1997Mar24157(6):629
increasedriskoffracturesinmenandwomenaged4282years
basedoncohortstudy
14,824menandwomenaged4282yearshadquantitativeultrasoundofcalcaneumand
werefollowedformean1.9years
121incidentfracturesrequiringhospitaladmission,including31hipfractures
comparedtoupper30%ofcalcaneumBUAdistribution,lower10%hadincreasedriskof
fracture(relativerisk[RR]4.44,95%CI2.248.89,p<0.0001)
reductionof1standarddeviation(20decibels[dB]/megahertz[MHz])inBUAindependently
associatedwithincreasedrisk(adjustedRR1.95,95%CI1.52.52,p<0.0001)
ReferenceEPICNorfolkperspectivepopulationstudy(Lancet2004Jan17363(9404):197),
commentarycanbefoundinLancet2004Mar27363(9414):1076
Calculatorsforpredictingfracturerisk:
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WorldHealthOrganization(WHO)FractureRiskAssessmentTool(FRAX)predicts10yearriskofhip
fractureandmajorosteoporoticfracture(clinicalvertebral,forearm,hip,orshoulderfractureavailablein
multiplelanguages)
QFracture2013RiskCalculatorpredicts10yearriskofosteoporoticfractures(level1[likely
reliable]evidence)
basedonderivationandvalidationcohortstudy
derivationcohortincluded1,598,294womenand1,544,379menaged30100yearsfollowedfor10
years
newosteoporoticfractures(vertebral,distalradius,proximalhumerus,orhip)in45,476
womenand14,296men
newhipfracturesin14,864womenand5,164men
validationcohortincluded804,563womenand778,810menaged30100yearsfollowedfor10
years
newosteoporoticfracturesin21,677womenand7,008men
newhipfracturesin7,089womenand2,521men
goodoverallcorrelationbetweenpredictedandobservedfractureratesover10yearsinvalidation
cohort
QFracture2013RiskCalculatorwasmoreaccurateforpredictingfractureriskcomparedtooriginal
QFractureScoreinareaunderreceiveroperatorcurveanalysis
onlinecalculatorcanbefoundatQFracture2013RiskCalculator
ReferenceBMJ2012May22344:e3427fulltext
derivationandvalidationoforiginalQFractureScorecanbefoundinBMJ2009Nov
19339:b4229fulltext,BMJ2011Jun22342:d3651fulltext
GarvanInstituteFractureRiskCalculatorpredicts10yearriskoflowtraumafracture(level1[likely
reliable]evidence)
basedonindependentderivationandvalidationcohortstudies
derivationcohortincluded1,358women(meanage71years)followedformedian13yearsand858
men(meanage70years)followedformedian12years,fromAustraliancohortoftheDubbo
OsteoporosisEpidemiologyStudy
426(31.4%)womenand149(17.4%)meninderivationcohorthadlowtraumafractures(excluding
morphometricvertebralfractures)
factorssignificantlyassociatedwithfractureriskinderivationcohortandusedtodevelop
nomogramsforriskprediction
gender
age
numberoffracturessinceage50years
numberoffallsduringprior12months
bonemineraldensity(BMD)
validationcohortincluded4,152women(meanage67years)followedformean8.6yearsand
1,606men(meanage67years)followedformean8.3yearsfromCanadianMulticentre
OsteoporosisStudy
583(14%)womenand116(7.2%)meninvalidationcohorthadlowtraumafractures(excluding
thoseofskull,face,hands,ankles,andfeet)
invalidationcohortFractureRiskCalculatorhad
goodcorrelationbetweenpredictedandobserved10yearrisksforlowtraumafractureby
quintilesrisksslightlyoverestimatedinhighestriskquintile(10yearrisk25%)
goodcorrelationbetweenpredictedandobserved10yearrisksforhipfracturebyquintiles
risksoverestimatedinhighestriskquintileforwomen(10yearrisk10%)
onlinecalculatorcanbefoundatGarvanInstituteFractureRiskCalculator
References
derivationstudy(OsteoporosInt2008Oct19(10):1431)
validationstudy(CMAJ2011Feb8183(2):E107fulltext),editorialcanbefoundinCMAJ
2011Feb8183(2):171fulltext
FRAXwithoutbonemineraldensityandOsteoporosisSelfAssessmentScreeningToolmayeach
helpidentifyelderlypersonsatlowriskwhomaynotrequirebonemineraldensitytestingduring
osteoporosisscreening(level2[midlevel]evidence)
basedonretrospectivecohortstudywithoutindependentvalidation
626personsaged70years(meanage78years,55%male)whohaddualenergyxray
absorptiometryscreeningwereassessedforriskofmajorosteoporoticfractureby2prediction
tools
FRAXwithoutbonemineraldensity(BMD)
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OsteoporosisSelfAssessmentScreeningTool(OST)
osteoporosisdefinedasTscore<2.5
referencestandardwasosteoporosisdefinedbybonemineraldensitytestingoflumbarspine,
femoralneck,totalhip,worsthip(femoralneckortotalhip),andworstoverallsite
thresholdscoresforeachpredictiontoolwerederivedtoidentifypersonsatlowriskof
osteoporosis
3%onFRAXwithoutBMD10yearhipfractureriskscore
6%onFRAXwithoutBMD10yearmajorosteoporoticfractureriskscore
0onOSTscore
usingthesethresholds,BMDtestingrateswouldbereducedby33%36%inpersonsbeing
screenedforosteoporosis,with7.8%10.4%ofosteoporosiscasesbeingmissed
forpredictionofosteoporosis(rangesindicateperformancebasedonBMDmeasurementsat
differentsites)
FRAX10yearriskofhipfracturescorewithcutoff3%hadsensitivity81.3%92.2%and
specificity34.3%37.1%
FRAX10yearriskofmajorosteoporoticfracturescorewithcutoff6%hadsensitivity
87.5%94.1%andspecificity35%37.1%
OSTwithcutoff0hadsensitivity90.6%94.1%andspecificity37.5%39.9%
ReferenceJAmGeriatrSoc2014Mar62(3):442
DynaMedcommentarycommonlyusedversionofFRAXincludesbonemineraldensity
assessment
Otherfactorsforpredictingfracturerisk:
historyoffractureassociatedwithincreasedriskforfuturefractures
previousclinicalfractureandlowBMDassociatedwithnewclinicalfracturesin
postmenopausalwomen
basedonprospectivestudyof759postmenopausalwomenaged5080years
12.5%hadnewclinicalfracture,with5yearabsoluterisk
50.1%ifpreviousfracturewithin5years
21.2%ifpreviousfracture>5yearsprior
13.8%ifnopreviousfracturebutTscore<1
7%ifnopreviousfractureandTscore1
ReferenceBMCMed2006Oct94:24fulltext
historyoflowtraumafractureassociatedwithincreasedriskofsubsequentfracture
basedonprospectivecohortof2,245communitydwellingwomenand1,760men>60
yearsoldinAustraliafollowedforupto16years
905womenand337menhadinitialfracture
253womenand71menhadsubsequentfracture
increasedriskoccurredforvirtuallyallclinicalfracturesandpersistedforupto10years
ReferenceJAMA2007Jan24297(4):387fulltext,commentarycanbefoundinACPJ
Club2007JulAug147(1):22
ratesofmajoreventsinpostmenopausalwomenwithosteoporosis
basedonprospectivecohortstudyofplacebogroupfromMOREtrial
2,565postmenopausalwomen(meanage61years)withosteoporosistreatedwithcalcium
andvitaminDwhowerefollowedfor3years
eventratesper100patientyearsin1,627womenwithoutvertebralfracturesatbaseline
4.54foranyfracture
1.52forvertebralfracture
0.47forclinicalvertebralfracture
0.09forhipfracture
0.83foranycardiovascularevent
0.52forbreastcancer
eventratesper100patientyearsin938womenwithvertebralfracturesatbaseline
11.74foranyfracture
7.71forvertebralfracture
2.57forclinicalvertebralfracture
0.58forhipfracture
1.51foranycardiovascularevent
0.26forbreastcancer
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ReferenceJAmGeriatrSoc2004Sep52(9):1543
boneturnovermarkers(BTMs)infractureprediction
InternationalOsteoporosisFoundation(IOF)andInternationalFederationofClinicalChemistryand
LaboratoryMedicine(IFCC)bonemarkerstandardsworkinggrouprecommendationsonuseof
boneturnovermarkersinclinicalpractice
boneturnovermarkers,especiallyboneresorptionmarkers,mayhavesomeutilityfor
predictingfractureoutcomes
highlevelsofBTMsmaypredictfractureriskindependentlyfromBMDinpostmenopausal
women
referencestandardsrecommendedforresearchonuseofboneturnovermarkers
useserumcollagentypeIcrosslinkedCtelopeptide(sCTX)asreferencestandard
forboneresorption
useserumprocollagentypeINterminalpropeptide(P1NP)asreferencestandardfor
boneformation
collectsampleinethylenediaminetetraaceticacid(EDTA)tube,ifpossible
useautomatedanalyzers,ifavailable,butifnot,useenzymelinkedimmunosorbent
assay(ELISA)kit
Fracturesassociatedwithincreasedmortality:
osteoporoticfracturesassociatedwithincreasedmortality
basedonprospectivecohortstudyinAustralia
614communitydwellingpersons60yearsoldwhosustainedlowtraumafractureprovideddata
within5yearspriortofractureandwithin1yearafterfracture
medianfollowupafterfracture13.1yearsforwomenand9.5yearsformen
deathin48.4%womenand57.4%men
ageadjustedstandardizedmortalityratio(MR)for5yearspostfracturesignificantlyincreased
forwomenofallagesafter
hipfractures(standardizedMR2.53,95%CI2.043.13)
vertebralfractures(standardizedMR1.76,95%CI1.432.17)
majorfractures(standardizedMR1.6,95%CI1.22.13)
minorfractures(standardizedMR1.38,95%CI1.11.74)
formenofallagesafter
hipfractures(standardizedMR3.52,95%CI2.584.8)
vertebralfractures(standardizedMR2.26,95%CI1.722.98)
majorfractures(standardizedMR2.01,95%CI1.382.92)
minorfractures(standardizedMR1.64,95%CI1.162.31)
predictorsofmortalityafteranyfragilityfracture
olderageforbothwomen(hazardratio[HR]1.36,95%CI1.221.51)andmen(HR1.42,
95%CI1.21.68)
subsequentfractureforbothwomen(HR1.53,95%CI1.152.04)andmen(HR1.8,95%CI
1.122.89)
lowBMDatfemoralneckforwomen(HR1.46,95%CI1.241.72)
ReferenceJAMA2009Feb4301(5):513fulltext
PreventionandScreening
Prevention:
Preventionoverview:
riskpredictionforosteoporoticfracture
WorldHealthOrganization(WHO)FractureRiskAssessmentTool(FRAX)predicts10yearriskof
hipfractureandmajorosteoporoticfracture
QFracture2013RiskCalculatorpredicts10yearriskofosteoporoticfracture(level1[likely
reliable]evidence)
reliable]evidence)
universalpreventivemeasurestoreducefractureriskinpostmenopausalwomenandmen>50yearsold
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calciumandvitaminDintakeadequatecalciumintake(atleast1,0001,200mg/day)andvitamin
Dintake(8001,000units/day)mayreduceriskforfracture(level2[midlevel]evidence)
exerciseaerobic,weightbearing,andresistanceexercisesmayincreasebonemineraldensity
(BMD)inpremenopausalwomen,postmenopausalwomen,andmenwithoutosteoporosis(level3
smokingcessationseeTobaccousedisorder
avoidexcessalcoholintakeseeAlcoholusedisorder
additionaloptionsforpreventionofosteoporosisinpostmenopausalwomen
bisphosphonates
alendronatemayreducevertebralfracturesandincreasebonedensity(level3[lacking
direct]evidence)
hipfracturereductiondemonstratedwithalendronateinwomenwithParkinsondisease
(level1[likelyreliable]evidence)andrisedronateinwomenwithAlzheimerdisease(level1
[likelyreliable]evidence)andParkinsondisease(level2[midlevel]evidence)
zoledronicacidinfusionmayincreaseBMD(level3[lackingdirect]evidence)
vitaminK(menaquinone4orally45mg/day)associatedwithreducedrateoffracturesinJapanese
estrogen(withprogestin)reducesratesofhip,vertebral,andanyosteoporoticfractures,but
increasesrisksformyocardialinfarction,stroke,breastcancer,andvenousthromboembolism
(VTE)(level1[likelyreliable]evidence)
raloxifene(Evista)reducesriskofbreastcancerandclinicalvertebralfracture,butincreasesrisk
offatalstrokeandvenousthromboembolism(level1[likelyreliable]evidence)
lessestablishedpreventivestrategies(withinsufficientevidencetosupportclinicaluse)include
isoflavones,testosterone,dehydroepiandrosterone(DHEA),andthiazidediuretics
nointerventionestablishedtopreventclinicalfracturesinpatientstakingchroniccorticosteroidsbut
calciumplusvitaminDcandecreaseboneloss(level3[lackingdirect]evidence)
bisphosphonatesmayreduceincidenceofvertebralfracture(level3[lackingdirect]evidence)
othermedicationswhichmaypreservebonemassincludecalcitonin,hormonereplacement
therapy(HRT)inhypogonadalwomen,andtestosteroneinmen(level3[lackingdirect]evidence)
Recommendations:
NationalOsteoporosisFoundation(NOF)guidelines(1)
universalrecommendationsforpostmenopausalwomenandmen>50yearsold
counselonriskofosteoporosisandrelatedfractures
checkforsecondarycauses
adviseondietaryintakeincluding
balanceddietrichinlowfatdairyproducts,fruits,andvegetables
adequatecalciumintakeatleast1,000mg/dayformenaged5070yearsand1,200
mg/dayforwomen51yearsoldandmen71yearsold
vitaminDintake8001,000units/day,includingsupplementsifnecessary
recommendregularweightbearingandmusclestrengtheningexercise
assessneedforspecificriskfactorreduction
fallpreventionhomesafetyassessment,balancetrainingexercises,correctionof
vitaminDdeficiency,useofbifocals,avoidingcertainmedications
tobaccousecessation
avoidanceofexcessivealcoholintake
pharmacologictreatmentrecommendedifosteoporosis,butalsorecommendedifosteopenia(BMD
Tscore1to2.5)atfemoralneck,totalhip,orlumbarspineondualenergyxrayabsorptiometry
(DEXA)and10yearhipfractureprobability3%or10yearmajorosteoporosisrelatedfracture
probability20%basedonFRAX
3%cutofffor10yearprobabilityofhipfracturebasedoncosteffectivenessanalysis
(OsteoporosInt2008Apr19(4):437fulltext)
similarrecommendationsonpreventioninwomenandmenfromInstituteforClinicalSystems
Improvement(ICSI)andinmenatriskofosteoporosisfromEndocrineSociety (2,4)
AmericanCollegeofRheumatology(ACR)recommendationsforpreventionofglucocorticoidinduced
osteoporosis
usesmallestdoseofglucocorticoidforshortestdurationpossible
seebisphosphonatesforpharmacologicrecommendationsforpostmenopausalwomenandmen
50yearsoldstartingglucocorticoidswithanticipatedduration3monthsorthosealreadytaking
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glucocorticoidsfor3months
ensureadequateintakeof
calcium1,2001,500mg/daywithdietandsupplements(ACRLevelA)
vitaminDthroughsupplementation,suchas8001,000units/dayorenoughtoreach
therapeuticlevel(ACRLevelA)
forpatientsstartingglucocorticoids(anydose)withanticipatedduration3months
recommendedcounselingforlifestylechanges(ACRLevelC)
weightbearingactivities
smokingcessation
avoidanceofexcessivealcoholintake(>2drinks/day)
nutritionalcounselingoncalciumandvitaminDintake
baselineassessments(ACRLevelC)
fallriskassessment
dualxrayabsorptiometry
serum25hydroxyvitaminDlevel
height
evaluationforprevalentfragilityfractures
considerradiographicimagingofspineorvertebralfractureifreceivingprednisone
5mg/dayoritsequivalent
recommendedmonitoringforpatientsalreadytakingglucocorticoidsfor3months(ACRLevelC)
considerserialbonemineraldensitytesting
considerannualserum25hydroxyvitaminDmeasurement
annualheightmeasurement
evaluationforincidentfragilityfracture
evaluateforcompliancewithosteoporosismedication
ReferenceArthritisCareRes(Hoboken)2010Nov62(11):1515fulltext
Diet:
discussimportanceofabalanceddietwithadequatenutrition,includinginformationonimportanceof
alcoholrestriction,calciumintake,andvitaminDintake(ICSIStrongrecommendation,Lowquality
evidence)(2)
lowfatdietdoesnotappeartoreduceriskofosteoporotichipfractures(level2[midlevel]
evidence)
basedonrandomizedtrialwithoutattentioncontrol
48,835postmenopausalwomenaged5070yearsrandomizedtolowfatdietvs.nodietarychange
andfollowedformean8.1years
dailygoaloflowfatdietwas20%ofenergyasfat,5servingsofvegetablesandfruit,and6
servingsofgrains
lowfatdietgroupreceivedintensivebehavioralmodificationprogramof18groupsessionsduring
year1followedbyquarterlymaintenancesessions
hipfracturesin0.14%inlowfatgroupvs.0.12%incontrolgroup(notsignificant)
insubgroupanalysisof3,951women,hipBMDatyears3,6,and9was0.4%0.5%lowerinlow
fatgroupvs.control(p=0.003)
ReferenceAmJClinNutr2009Jun89(6):1864fulltext
highermagnesiumintakeassociatedwithhigherBMDinmenandwomenofwhiterace(butnot
blackrace)(level3[lackingdirect]evidence)
basedoncrosssectionalstudyof2,038personsaged7079years
ReferenceJAmGeriatrSoc2005Nov53(11):1875
verylittleevidencetosupportrecommendationsformilkorotherdairyproductsinchildrenforbonehealth
scantevidencefoundtosupportnutritionguidelinesfocusedonincreasingmilkorother
dairyproductsforpromotingchildandadolescentbonemineralization
basedonsystematicreview
58studiesfoundbut11excludedduetonotcontrollingforweight,pubertalstatus,and
exercise
9of10randomizedtrialsofsupplementalcalciumshowedmodestpositivebenefitsonbone
mineralizationinchildrenandadolescents
27studiesofdairyorunsupplementeddietarycalciumintakefoundnorelationshipbetween
dairyordietarycalciumintakeandmeasuresofbonehealth
9studiessuggestedsmalleffectsonbonehealthbut3ofthesestudieswereconfounded
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byvitaminDfortifiedmilk
ReferencePediatrics2005Mar115(3):736fulltext,editorialcanbefoundinPediatrics
2005Mar115(3):792,commentarycanbefoundinPediatrics2006Jan117(1):259fulltext,
BMJ2005Jul16351(7509):119,AmFamPhysician2005Nov172(9):1894,Pediatrics
2006Jan117(1):259fulltext
milkmayhelpincreasebonedensityinadolescentgirls(level3[lackingdirect]evidence)
82healthywhiteadolescentgirls(meanage12years)randomizedtonormaldietvs.diet
plus1pint/dayofwholeorreducedfatmilkfor18months
comparingadditionofmilktodietvs.normaldiet
increaseinbonedensityin9.6%vs.8.5%(p=0.017)
increaseinbonemineralcontentin27%vs.24.1%(p=0.009)
ReferenceBMJ1997Nov15315(7118):1255fulltext,commentarycanbefoundinBMJ
1998Jun6316(7146):1747
dietaryphytoestrogenintake
soyfoodconsumptionmightbeassociatedwithlowerriskoffracture(level2[midlevel]
evidence)
basedoncohortstudy
24,403postmenopausalwomenwithmeanfollowup4.5years,1,770incidentfractures
lowestquintileofsoyfoodconsumptionassociatedwithhigherriskoffracturecomparedto
otherquintiles
ReferenceArchInternMed2005Sep12165(16):1870fulltext
highdietaryphytoestrogenintake(isoflavones)associatedwithhigherlumbarbonemineral
densityamongpostmenopausalbutnotpremenopausalwomen(level3[lackingdirect]
evidence)
basedoncohortstudy
650Chinesewomenaged1986yearshaddietaryphytoestrogenintakeestimatedbyfood
frequencyquestionnaireandhadDEXAscantodetermineBMDatlumbarspineandhip
inpostmenopausalwomen,thosewithhighestadjustedintakeofisoflavonehadhigher
BMDthanthosewithlowestadjustedintake
atlumbarspine,0.820vs.0.771(p<0.05)
athip,0.450vs.0.415(p<0.05)
nosignificantdifferencesinBMDinpremenopausalwomen
ReferenceJClinEndocrinolMetab2001Nov86(11):5217
Exercise:
discussimportanceofregularexercisetopreventosteoporosis(ICSIStrongrecommendation,Moderate
qualityevidence)(2)
exercisemaybeassociatedwithincreasedbonemineraldensityinhealthypremenopausalwomen
basedonsystematicreviewoftrialswithoutclinicaloutcomes
systematicreviewof7randomizedtrialsevaluatingeffectofexerciseonfemoralneckandlumbar
spinebonemineraldensityin521healthypremenopausalwomen
typeofexercisevariedacrossstudies,butincludedstrengthtrainingand/oraerobicexercisefrom
27daysperweekfor24104weeks
comparedtonoexercise,exerciseassociatedwithincreasedbonedensityat
femoralneckinanalysisof7trialswith521women(p0.001)
lumbarspineinanalysisof7trialswith521women(p=0.04)
ReferenceIntJEndocrinol20132013:741639fulltext
highimpactexercisesessionsof<30minutesmaybeassociatedwithincreasedbonemineral
densityatfemoralneckandhipinhealthypremenopausalwomen(level3[lackingdirect]
evidence)
basedonsystematicreviewwithoutclinicaloutcomes
systematicreviewof6randomizedtrialsevaluatingeffectofbrief(duration<30minutes)high
impactexercisesessionsonbonemineraldensity(BMD)atlumbarspine,femoralneck,ortotal
hipin255healthypremenopausalwomen
exercisesessionswereunguidedandcompletedathomeinmosttrials
highimpactexerciseconsistedofhoppingorjumpingexercisesinterspersedwithrestperiodsand
rangedfrom26sessionsperweek
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comparingbriefhighimpactexercisesessionstonoexerciseorstretchingexercise,highimpact
exerciseassociatedwithincreasedBMDat
femoralneckinanalysisof6trialswith255women(p<0.0001)
hipinanalysisof6trialswith255women(p=0.006)
nosignificantdifferenceinBMDatlumbarspineinanalysisof6trialswith255women
ReferenceOsteoporosInt2012Jan23(1):109
exerciseincreasesbonemineraldensityinpostmenopausalwomenbuteffectonfractures
uncertain(level3[lackingdirect]evidence)
basedonCochranereviewwithinsufficientdatatoassessclinicaloutcomes
systematicreviewof43randomizedtrialsevaluatingexerciseforpreventionofbonelossand
fracturesin4,320postmenopausalwomen
only4trialsreportedontotalnumberoffractures
nosignificantdifferenceintotalnumberoffracturesinmetaanalysisof4trialswith539
patients
1highqualitytrialfoundsignificantreductionintotalnumberoffractures
160patientsfollowedformean7.1years
exerciseinterventionincludedjumpingandbalanceexercises,includingwalking,
kneebends,leglifts,heelrisesanddrops,dancing,stamping,stairclimbing,and
steppingupanddownfrombenches
fracturesoccurredin7%ofcombinationexercisegroupvs.21%ofusualactivity
group(p0.05,NNT8)
exerciseassociatedwithincreasedBMDat
spine,basedonanalysisof24trialswith1,441patients
totalhip,basedonanalysisof13trialswith863patients
trochanter,basedonanalysisof10trialswith815patients
mosteffectivetypeofexerciseforincreaseinBMDatfemoralneckappearstobenonweight
bearinghighforceexercisesuchasprogressiveresistancestrengthtrainingforlowerlimbs
mosteffectivetypeofexerciseforincreaseinBMDatspineappearstobecombinationexercise
programs
ReferenceCochraneDatabaseSystRev2011Jul6(7):CD000333
exercisenotassociatedwithlongtermreductioninfracturerate(level2[midlevel]evidence)
basedonfollowupoftrialwithoutintentiontotreatanalysis
aftercompletionof30monthtrial,womenfollowedupyearlyformean7.1years(exercisegroup)
vs.6.9years(controlgroup)
100womenhad6yearfollowupvisit
comparingexercisevs.control
fractureincidenceratesper1,000personyearswere0.05forexercisegroupvs.0.08for
controlgroup(notsignificant)
nowomenintheexercisegrouphadhipfracture,5hipfracturesincontrolgroup
exerciseassociatedwithsignificantimprovementsinposturalsway,legstrength,walking
speed,anddepressionscores
ReferenceArchInternMed2010Sep27170(17):1548
exercisemayincreasebonestrengthinprepubertalboysbutnotingirlsorwomenoradolescent
boys(level3[lackingdirect]evidence)
basedonsystematicreviewwithmethodologiclimitations
systematicreviewof5randomizedtrialsofchildrenand5randomizedtrialsofpreand
postmenopausalwomenassessingimpactofexerciseonbonestrengthin1,769patients
methodologiclimitationsinclude
blindingproblemsin5trials
incompletedatain2trials(imbalancebetweenwithdrawalsincontrolsandtrainees,no
intentiontotreatresults)
potentialbiasin7trials(inadequateexercisedose,smallsamplesize,shortfollowuptime)
variedintensityanddurationofexerciseprograms
exerciseassociatedwith
nosignificantdifferenceinbonestrengthin
lowerlimbsofyounggirlsinanalysisof3trialswith599adolescentgirls
adolescentboysandgirlsatfemoralneckinanalysisof2trialswith51adolescents
premenopausalwomeninanalysisof2trialswith160premenopausalwomen
postmenopausalwomeninanalysisof5trialswith837postmenopausalwomen
significantincreaseinbonestrengthinlowerlimbsofyoungboysinanalysisof4trialswith
759earlypubertalboys(p=0.03)
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ReferenceBMCMed2010Jul218:47fulltext
prolongedlowtomoderatephysicalactivitymaybeassociatedwithhigherbonemineraldensity
thansedentarylifestyleorendurancetrainedathleticactivity(level3[lackingdirect]evidence)
basedoncrosssectionalstudyof63postmenopausalwomen
physicalactivitycategorizedas
sedentary(20women)
activenonathletic(20women)
endurancetrainedathlete(23women)
halfofeachgrouponhormonereplacementtherapy
ReferenceJAmGeriatrSoc2001Nov49(11):1411,editorialcanbefoundinJAmGeriatrSoc
2001Nov49(11):1565
strengthtrainingimprovesbonedensityinfemoraltrochanterin1yearrandomizedtrialof140women
aged4466years,nosignificantdifferencesatfemoralneckorlumbarspine(MedSciSportsExerc2003
Jan35(1):10)
backexercisesassociatedwithsmallerreductioninbackextensorstrengthinpostmenopausal
women(level3[lackingdirect]evidence)
basedonfollowupofrandomizedtrialwithoutclinicaloutcomes
50postmenopausalwomenaged4865yearsrandomizedtoprogressive,resistiveback
strengtheningexercisesvs.controlfor2years
comparingbackstrengtheningexercisevs.control
backextensorstrengthat10yearswas32.9kg(72.5lbs)vs.26.9kg(59.3lbs)(p=0.001)
followupat10yearsin79%vs.74%
1compressionvertebralfracturein3%vs.7%(p=0.085)
ReferenceBone2002Jun30(6):836inAnnInternMed2003Dec16139(12):1003
resistancetrainingmightbeassociatedwithincreasedbonemineraldensityinmen(level3
basedonnonclinicaloutcomefromsystematicreviewofmostlymoderatequalitytrials
systematicreviewof8randomizedtrialsevaluatingexerciseinmiddleagedandoldermen
heterogeneityinexerciseprotocolsandbonemineraldensitymeasurementsitesprecludedmeta
analysis
exerciseinterventionsassociatedwithsignificantimprovement
resistancetrainingassociatedwithincreasedbonemineraldensityatlumbarspineand
femoralneckcomparedtowalkingprogramin1trial
highvelocitypowerresistancetrainingassociatedwithincreasedbonemineraldensityat
femoralneckcomparedtocontrolin1trial
nosignificantdifferencesinbonemineraldensitycomparingexercisetocontrolgroupsinother
trials
ReferenceOsteoporosInt2013Nov24(11):2749
weightbearingactivitymaybeasbeneficialasresistancetrainingonbonemineraldensity(BMD)
inmen(level3[lackingdirect]evidence)
143menaged5580yearsrandomizedtoresistancetraining(1hoursessions3timesweekly)vs.
activecontrol(recommendedwalking30minutes3timesweekly)andfollowedfor12months
bothgroupshadsignificantincreaseinhipBMDoverbaseline(butnotsignificantlydifferent
betweengroups)
resistancetrainingassociatedwithgreaterincreaseinleanbodymass,fitnesslevel,andlower
limbmusclestrengthvs.activecontrol(allp<0.05)
ReferenceOsteoporosInt2010Sep21(9):1529
taichihasinsufficientevidenceforpreventionortreatmentofosteoporosis
basedonsystematicreviewof5randomizedtrialsand2controlledtrials
inconsistentresultsforBMD
taichimaynotimprovebonemineraldensityinpostmenopausalwomenwithosteopenia(level3
86postmenopausalwomenaged4570yearswithosteopeniarandomizedtotaichiplususualcare
vs.usualcarealonefor9months
nosignificantdifferenceinBMDofproximalfemurorlumbarspinebyintentiontotreatanalysis
taichiassociatedwithincreasedfemoralneckBMD(p=0.05)byperprotocolanalysis(including
taichiparticipantswhocompleted75%trainingrequirements)
ReferenceBMCComplementAlternMed2012Jan3012:7fulltext
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taichiassociatedwithimprovedqualityoflifeinwomenwithosteopenia(level2[midlevel]
evidence)
basedonsmallrandomizedtrialwithoutintentiontotreatanalysis
61communitydwellingwomen65yearsoldwithlowbonemassrandomizedtotaichi(60minute
sessions3timesweeklyfor24weeks)vs.controlgroup
13%ofpatientslosttofollowupandnotincludedinanalysisat24weeks
taichiassociatedwithimprovementsingeneralhealth,vitality,andbodilypain
nosignificantdifferenceinbalanceparameters
ReferenceClinRehabil2010Dec24(12):1080
wholebodyvibrationtherapydoesnotappeartoaffectbonedensityandstructurein
postmenopausalwomenwithosteopenia(level3[lackingdirect]evidence)
202healthypostmenopausalwomenwithBMDTscores1to2.5whowerenotreceiving
prescriptionbonemedicationswererandomizedtowholebodywavevibrationtherapy20
minutes/dayvs.nowholebodywavevibrationtherapyfor12months
wholebodywavevibrationtherapyconsistedofstandingonplatformvibratingat90hertz
(Hz)or30Hz
allwomenreceivedcalciumandvitaminD
adherencetowholebodyvibrationtherapy65%79%
nosignificantdifferencesin
trabecularvolumetricBMDatdistaltibia(primaryoutcome)
changesinBMDatthefemoralneck,totalhip,andlumbarspine
ReferenceAnnInternMed2011Nov15155(10):668,commentarycanfoundinAnnInternMed
2011Nov15155(10):680
wholebodyvibrationmayincreasebonemineraldensitycomparedtowalking(level3[lacking
direct]evidence)
28physicallyuntrainedpostmenopausalwomenrandomizedtowholebodyvibrationvs.walkingfor
8months
ReferenceBMCMusculoskeletDisord2006Nov307:92fulltext
aerobicexercisemayhelpmaintainlumbarspineBMDinpostmenopausalwomen(level3[lacking
direct]evidence)
basedonmetaanalysisof10trialswithoutclinicaloutcomesin330postmenopausalwomen
ReferenceJAmGeriatrSoc1998Feb46(2):143
additionofibuprofen400mgafterweightbearingexercisemayincreasebonemineraldensity
(BMD)inpremenopausalwomen(level3[lackingdirect]evidence)
73healthypremenopausalwomenaged2140yearsinsupervisedweightbearingexercisetraining
programwererandomizedto1of3treatmentsandfollowedfor9months
ibuprofen400mgbeforeexerciseplusplaceboafterexercise
placebobeforeexerciseplusibuprofen400mgafterexercise
placebobeforeexerciseplusplaceboafterexercise
74%compliantwithexerciseandincludedinanalysis
meanchangeintotalhipBMD(p<0.05)
0.2%foribuprofenbeforeexercise
+2.1%foribuprofenafterexercise
+0.4%forcontrol
ReferenceJBoneMinerRes2010Jun25(6):1415fulltext
Behavioralinterventionsandcounseling:
smallgroupeducationforhealthywomenaged2544yearsassociatedwithincreasedbone
mineraldensity(BMD)athipbutnotlumbarspine(level3[lackingdirect]evidence)
470womenwhoreceivedindividualizedBMDfeedbackwererandomizedtoosteoporosis
informationleafletvs.smallgroupeducationfor2years
differencesattributedtostartingcalciumsupplementsandincreasingphysicalactivitylevels
ReferenceBMCPublicHealth2006Jan236:12fulltext
behavioralinterventionmayincreaseBMDinadolescentgirls(level3[lackingdirect]evidence)
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228healthyadolescentgirlsaged1416yearswithbodymassindex(BMI)belownationalmedian
wererandomizedtobehavioralinterventionvs.usualcarefor2years
interventionincludedbimonthlygroupmeetings,quarterlycoachingtelephonecalls,andweekly
selfmonitoringdesignedtoimprovedietandincreasephysicalactivity
interventionassociated
significantlyhigherBMDinspineandtrochanterregions
significantlygreaterrelativedecreaseinNterminaltelopeptidebiomarkerofboneresorption
significantlygreaterconsumptionofcalcium,fruits,andvegetablesduringbothyears
significantlygreaterconsumptionofvitaminDduringfirstyear
nonsignificantchangesinosteocalcinconsistentwithmorebonebuildingwithintervention
nosignificantdifferencesinsodaconsumptionortargetexerciserates
ReferenceArchPediatrAdolescMed2006Dec160(12):1269fulltext,commentarycanbefound
inAmFamPhysician2007Aug1576(4):583
Vitaminsandsupplements:
CalciumandvitaminD:
tomeetdailyintakegoalsofcalciumandvitaminD(2)
achievingadequatecalciumintakebydietaloneisideal,butsupplementscanbeusedifneeded
supplementsoftenneededtomeetdailyintakegoalsforvitaminD
calciumandvitaminDforpreventionofosteoporosis
NationalOsteoporosisFoundationrecommendspostmenopausalwomenandmen>50yearsold
maintainadequatecalciumintake(atleast1,0001,200mg/day)andvitaminDintake(8001,000
units/day)
UnitedStatesPreventiveServicesTaskForce(USPSTF)findsinsufficientevidencetoassess
balanceandharmsofcombinedvitaminDandcalciumsupplementationforprimarypreventionof
fracturesinmen,premenopausalwomen,andpostmenopausalwomen(USPSTFGradeI)and
recommendsagainstdailysupplementationwithlowerdosesofvitaminD3(400units/day)and
calcium(1,000mg/day)inpostmenopausalwomen(USPSTFGradeD)
considerationsforcalciumsupplementation
calciumcarbonateischeapestmaximumabsorptionoccurswith500mgdoses
calciumcitratehasbestabsorptionpreferredifachlorhydria,constipation,orgaswith
calciumcarbonate,orhistoryofrenalstones
calciumcontentofsomefoods
calciumfortifiedorangejuice330350mg
calciumfortifiedbreakfastcereals(1serving)200400mg
cheese(1ounce)156314mg,dependingonvariety
cottagecheese,1%milkfat(1cup)138mg
milk(1cup)nonfat306mg,lowfat290mg,whole276mg,soymilk93mg(368mg
ifcalciumfortified)
vitaminDnecessaryforcalciumabsorption
calciumsupplementationmayincreaseriskofmyocardialinfarction(level2[midlevel]
evidence)
inolderadults(menandwomencombined),fractureriskappearsreducedwith
calciumsupplementation(level2[midlevel]evidence)
calciumplusvitaminD(level2[midlevel]evidence)
vitaminDalonedoesnotreducefractureriskinolderadults(level1[likelyreliable]
evidence)
inpostmenopausalwomen
calciumsupplementationinpostmenopausalwomenappearstoimprovebonedensitybut
effectsonfractureuncertain(level3[lackingdirect]evidence),fracturereductionmaybe
limitedtohighlycompliantwomen(level2[midlevel]evidence)
vitaminDsupplementationdoesnotappeartoincreasebonemineraldensityin
postmenopausalwomen,exceptpossiblyinfemoralneck(level3[lackingdirect]evidence)
combinedcalciumplusvitaminDhasconflictingevidenceforefficacyforreductionin
clinicalfracturerate
calcium1,200mg/dayandvitaminD3800units/daymayreducehipfractureratesinfemale
ambulatorynursinghomeandassistedlivingresidents(level2[midlevel]evidence)
inmen
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calciumsupplementation,orcalciumplusvitaminD3,mayincreasebonemineraldensity
vitaminDsupplementationnotclearlyshowntoreducefractureratesinoldermen(level2
[midlevel]evidence)
inhealthychildrencalciumsupplementationhaslittleeffectonbonemineralcontentorbone
mineraldensity(level3[lackingdirect]evidence)
inspecificpopulations
forpreventingrecurrentfracturesinpatients>70yearsold,vitaminD3aloneisineffective
(level1[likelyreliable]evidence)andcalciumaloneorwithvitaminD3appearsineffective
AmericanCollegeofRheumatologyrecommendsglucocorticoidtreatedpatientsconsume
elementalcalcium1,2001,500mg/dayandvitaminD8001,000units/daycalciumand
vitaminDsupplementationdecreasesbonelossinpatientstakinglongtermcorticosteroids
highdosevitaminDmayincreasebonemineraldensityinadultswithlowbonemineral
densitytakinganticonvulsants(level3[lackingdirect]evidence)
1alphahydroxyvitaminD3supplementationassociatedwithreducedincidenceoffractures
inolderpatientswithParkinsondisease(level2[midlevel]evidence)
seeCalciumandvitaminDfortreatmentandpreventionofosteoporosisfordetails
sunlightexposuremaydecreasefractureratesinchronicallyhospitalizedpatientswithvitaminD
deficiency(level2[midlevel]evidence)
basedon2randomizedtrialswithoutintentiontotreatanalyses
264hospitalizedpatientswithAlzheimerdiseaseandvitaminDdeficiencywererandomizedto
regularsunlightexposure15minutes/dayvs.sunlightdeprivationandfollowedfor1year
allpatientsgivencalcium1,200mg/day
meanhospitalizationperiod1.7yearsinbothgroupsandbothgroupshaddecreased
activitiesofdailyliving
sunlightexposuregrouphad3,616minutessunlight/year
17patientswhodiedand4patientswhowithdrewnotincludedinanalysis
comparingsunlightexposurevs.deprivation
fracturesin3(2.5%)vs.11(9.1%)(p=0.0362,NNT15)
mean+2.7%vs.5.6%changeinBMD,measuredinsecondmetacarpalbone(p<
0.0001)
mean+28.2nmvs.13.3nmchangein25hydroxyvitaminDlevels
ReferenceJBoneMinerRes2005Aug20(8):1327,commentarycanbefoundinJBone
MinerRes2006Mar21(3):491
258chronicallyhospitalized,disabledstrokepatientswererandomizedtoregularsunlightexposure
15minutes/dayvs.sunlightdeprivationfor12months
bothgroupswerevitaminDdeficientatbaseline(mean25hydroxyvitaminD1718nmol/L)
21patientswhodiedand20patientswhowithdrewnotincludedinanalysis
comparingsunlightexposurevs.deprivation
hipfractureonhemiplegicsidein1(0.9%)vs.6(5.6%)(p=0.0421,NNT22)
meanchangein25hydroxyvitaminDlevels+34nmol/Lvs.4nmol/L
changeinBMD+3.1%vs.3.3%(p=0.0001)
meanfallsperpersonwas1.3vs.1.4(notsignificant)
ReferenceNeurology2003Aug1261(3):338
additionofcholinestabilizedorthosilicicacidtocalciumandvitaminDreportedtoimprovebone
formationmarkers(level3[lackingdirect]evidence)
ReferenceBMCMusculoskeletDisord2008Jun119:85fulltext
VitaminK:
vitaminK(menaquinone4orally45mg/day)associatedwithreducedrateoffracturesinJapanese
basedonsystematicreviewoftrialswithunclearallocationconcealment
systematicreviewof13randomizedtrialsoforalphytonadioneormenaquinone4inadults
13trialshadoutcomedataonboneloss,7trialshadoutcomedataonfractures
mosttrialsconductedinpostmenopausalwomeninJapan
11trialsusedmenaquinone4(includingall7trialswithfracturedata),2trialsused
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phytonadione
mostcommondosestudiedwasmenaquinone4orally45mg/day
only2trialshaddropoutrates>20%
only2trialsreportedallocationconcealment,neitherofthesetrialsreportedfracturedata
vitaminKassociatedwithreducedbonelossin12of13trials
onlytrialwithnegativeresultswasGermanstudyofphytonadioneinpremenopausalathletic
women
vitaminKassociatedwithreducedfractureratein7of7trials
absoluteriskreductioninhipfractures6%(NNT17,95%CI1134)inmetaanalysisof5
trials
absoluteriskreductioninvertebralfractures13%(NNT8,95%CI517)inmetaanalysisof
4trials
absoluteriskreductioninallnonvertebralfractures9%(NNT11,95%CI817)inmeta
analysisof5trials
reviewauthorsrecommenddietrichinvitaminK(greenleafyvegetablesandsomevegetableoils)
insteadofsupplementsuntilresultsconfirmedinlargerandomizedtrial
ReferenceArchInternMed2006Jun26166(12):1256fulltext,commentarycanbefoundinArch
InternMed2007Jan8167(1):93,ArchInternMed2007Jan8167(1):94
DynaMedcommentarythisdoseofvitaminKwouldnegatetheanticoagulanteffectsofwarfarin
orothervitaminKantagonists
vitaminK2supplementsmaynotreduceincidenceoffracturesorimprovevertebralbonemineral
densityinpostmenopausalwomenwithoutosteoporosis(level2[midlevel]evidence)
systematicreviewof19randomizedtrialsevaluatingoralvitaminK2supplementsfortreatment
andpreventionofosteoporosisin6,759postmenopausalwomen
mosttrialsevaluatedoralmenatetrenone45mg/day
controlgroupwasplacebo,bisphosphonates,calcium,vitaminD3,andcalciumplusvitamin
D3
9trialsevaluatedvitaminK2forpreventionofosteoporosis
heterogeneityinK2dosageandfollowupdurationlimitedanalyses
nosignificantdifferencesbetweengroupsin
incidenceoffracturesinanalysisof2trialswith487women
adverseeventsinanalysisof5trialswith866women
lumbarbonemineraldensityat6months(2trialswith300women)or12months(6trials
with1,093women)
additionofvitaminKtocalciumandvitaminDsupplementationinelderlypatientsnotassociated
withimprovementsinBMD(level3[lackingdirect]evidence)
452menandwomenaged6080yearsrandomizedtorecommendeddosesofcalciumandvitamin
Dvs.recommendeddosesofcalciumandvitaminDplusvitaminK(phylloquinone500mcg/day)
401(89%)includedinanalysis
groupreceivingvitaminKreceivednoadditionalbenefitforbonedensitymeasuredatspineorhip
ReferenceJClinEndocrinolMetab2008Apr93(4):1217fulltext
vitaminKmayimprovebonestrengthbutnotBMD(level3[lackingdirect]evidence)
325postmenopausalwomenrandomizedtovitaminK2(menatetrenone45mg/day)vs.placebofor
3years
nosignificantdifferencesbetweengroupsinBMDonDEXA
hipbonestrengthmaintainedinvitaminK2groupanddecreasedinplacebogroup
vitaminK2grouphadincreasedbonemineralcontentandfemoralneckwidthcomparedtoplacebo
ReferenceOsteoporosInt2007Jul18(7):963fulltext
insufficientevidenceregardingcosteffectivenessofvitaminK1vs.alendronateforpreventionof
fracturesinolderwomen
basedonsystematicreviewfindingnopublishedeconomicevaluationofvitaminK
ReferenceHealthTechnolAssess2009Sep13(45):iiifulltext
Isoflavones:
soyisoflavone
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soyisoflavonesmaynotpreventbonelossorimprovebonemineraldensityin
postmenopausalwomen(level3[lackingdirect]evidence)butmayincreasehotflashes
basedon4randomizedtrials(3withoutclinicaloutcomesand1withhighdropoutrate)
403postmenopausalwomenrandomizedtosoyhypocotylaglyconeisoflavones80mg/day
vs.120mg/dayvs.placebofor2years
allwomenalsogivencalciumandvitaminD
changesinwholebodyandregionalBMD,bonemineralcontent,Tscores,and
serumbiochemicalmarkersofbonemetabolismmeasuredannuallyover2years
soyisoflavone120mgassociatedwithsmallerreductioninwholebodyBMDvs.
placeboat1yearand2yearsinadjustedanalyses(p<0.05)
nosignificantdifferencesinregionalBMD,bonemineralcontent,Tscores,orserum
biochemicalmarkersofbonemetabolism
ReferenceAmJClinNutr2009Nov90(5):1433fulltext
248womenaged4560yearswithmenopausewithin5yearsandwithTscore2in
lumbarspineortotalhiprandomizedtosoyisoflavone200mg/dayvs.placeboandfollowed
for2years
dropoutrate27%
nosignificantdifferenceinbonemineraldensityinspine,totalhip,orfemoralneck
hotflashesin48.4%withsoyisoflavonesvs.31.7%withplacebo(p=0.02,NNT6)
nosignificantdifferencesinotheradverseevents
ReferenceArchInternMed2011Aug8171(15):1363,commentarycanbefoundin
ArchInternMed2011Aug8171(15):1369,ArchInternMed2011Dec
12171(22):2067,Climacteric2011Dec14(6):694
224healthypostmenopausalwomenaged4565yearswithoutosteoporosiswere
randomizedtosoyproteinisoflavones(80mg/dayvs.120mg/day)vs.placebofor36
months
allwomenalsoreceivedcalcium500mgandvitaminD3600units
nosignificantdifferencesinBMDatspine,femur,neck,orwholebody(BMD
decreasedinallgroups)
isoflavones120mgappearedprotectiveforBMDatneck(vs.placebo)after
adjustments(p=0.03)
ReferenceAmJClinNutr2010Jan91(1):218fulltext
237healthypostmenopausal(meantime33monthssincelastmenses)women(meanage
53years)randomizedtodailyintakeoffoodscontaining110mgisoflavoneaglyconesvs.
controlproductsfor1yearwhilecontinuingusualdietandlifestyle
nosignificantdifferencesinBMDfortotalbodyorlumbarspine(BMDdecreasedin
bothgroups)
ReferenceAmJClinNutr2008Mar87(3):761fulltext
ipriflavone
nodemonstratedpositiveeffectonbonedensity,boneturnovermarkers,orfractureriskinwomen
withosteoporosis (3)
availablewithoutprescriptioninUnitedStatesandCanada(3)
inconsistentevidenceonefficacyforpreventingpostmenopausalboneloss
ipriflavonemaynotpreventbonelossoraffectmarkersofbonemetabolism(level3
basedon3yearrandomizedtrialof474postmenopausalwomenaged4575years
withhighdropoutrateandwithoutclinicaloutcomes
only292of492individualscompletedthestudy,severalwomendeveloped
lymphocytopenia(NNH8)(AlternativeMedicineAlert2001Jul4(7):84)
ReferenceJAMA2001Mar21285(11):1482fulltext,commentarycanbefoundin
JAMA2001Oct17286(15):1836
ipriflavonemayslowbonelossandreduceboneturnoverratefollowingmenopause
453postmenopausalwomen(agerange5065years)withvertebralorradialBMD<1
standarddeviationthanagematchedcontrolsrandomizedtocalcium1gorallyper
dayplusipriflavone200mgorally3timesperdaywithmealsvs.placeboandwere
followedfor2years
boneturnovermeasuredwithserumboneGlaproteinandurinary
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hydroxyproline/creatinineevery6months
BMDincreasedwithipriflavonetreatmentby(bothp<0.05)
1.6%atvertebrae
3.5%atradius
serumboneGlaproteinandurinaryhydroxyproline/creatininedecreasedwith
ipriflavonetreatment(nopvaluereported)
ReferenceCalcifTissueInt199761(Suppl1):S19
56postmenopausalwomen(postmenopausalage<5years)withlowvertebralbone
densityrandomizedtocalcium1gorallyperdayplusipriflavone200mgorally3
timesperdayvs.placeboandwerefollowedfor2years
vertebralbonedensitydecreasedfrombaselineat2yearswithplacebobut
notipriflavone,(4.9,p=0.001)vs.(0.4,nopvaluereported)
ReferenceMenopause1998Spring5(1):9
78womentreatedwithgonadotropinhormonereleasinghormoneagonistleuprorelin
acetate3.75mg/monthfor6monthsrandomizedtoipriflavone200mgorally3times
perdayvs.placebo
bonedensitydecreasedwithplacebobutnotipriflavoneatspine(p<0.001)
andtotalbody(p<0.05)
concentrationofbiochemicalboneturnovermarkersincreasedwithplacebo
butnotipriflavone,forurinaryhydroxyproline(p<0.01)andplasma
osteocalcin(p<0.05)
ReferenceCalcifTissueInt199761(Suppl1):S15
32womenthathadbilateraloophorectomyrandomizedtocalcium500mgorallyper
dayplusipriflavone600mgorallyperdayvs.placebofor12months
radialbonedensitydecreasedwithplacebobutnotipriflavone(p<0.01)
urinaryhydroxyproline,serumalkalinephosphatase,andplasmaboneGla
proteinconcentrationincreasedwithplacebobutnotipriflavone(p<0.01)
ReferenceJEndocrinolInvest1993May16(5):333
otherisoflavones
FosteumFDAapprovedfordietarymanagementofmetabolicprocessesofosteopeniaand
osteoporosis
capsulecontainsgenistein27mg,zincchelazome20mg,andcholecalciferol200units
ReferenceMonthlyPrescribingPreference2007Aug:A12
genistein(anisoflavonephytoestrogen)maybeassociatedwithincreasedBMD(level3
389postmenopausalwomenwithBMD<0.795g/cm2atfemoralneckwererandomizedto
genistein54mg/dayvs.placebofor24months
bothgenisteinandplacebotabletscontainedcalciumandvitaminD
BMDincreasedwithgenisteinanddecreasedwithplaceboatanteroposteriorlumbarspine
andfemoralneck
gastrointestinalsideeffectsin19%womentakinggenisteinand8%womentakingplacebo
(p=0.002,NNH9)
ReferenceAnnInternMed2007Jun19146(12):839
redcloverderivedisoflavonesupplementmayreducelumbarbonelossbutnotaffecthip
boneloss(level3[lackingdirect]evidence)
basedon12monthrandomizedplacebocontrolledtrialwith205womenaged4965years
ReferenceAmJClinNutr2004Feb79(2):326fulltext
Medicationsforpreventionofosteoporosis:
Bisphosphonates:
forpreventionofosteoporosis
bisphosphonatesFDAapprovedforpreventionofosteoporosisinclude
alendronate(Fosamax,generic)5mgorallyoncedailyor35mgorallyonceweekly
ibandronate(Boniva,generic)150mgorallyoncemonthly
risedronate(Actonel)5mgorallyoncedaily,35mgorallyonceweekly,75mgorallyon2
consecutivedayseachmonth,or150mgorallyoncemonthly
zoledronicacid(Reclast)5mgIVoveratleast15minutesonceevery2years
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forpostmenopausalwomenwithoutosteoporosis
alendronate10mgorallyoncedailymayreducevertebralfractures(level3[lackingdirect]
evidence)aftertakingalendronatefor35yearscontinuationofalendronatefor510years
mightdecreaseriskforclinicalvertebralfracture(level2[midlevel]evidence)
alendronate5mgorallyoncedailymayofferbestbenefit/riskbalanceforpreventing
postmenopausalboneloss(level3[lackingdirect]evidence)
alendronate35mgonceweeklynearlyaseffectiveas5mgoncedailyforincreasingbone
density(level3[lackingdirect]evidence)
risedronate2.5mgorallyoncedailyreducesriskofhipfractureinelderlywomenwith
Alzheimerdisease(level1[likelyreliable]evidence)
zoledronicacidinfusion(variousdosesandfrequencies)mayincreasebonemineraldensity
(BMD)(level3[lackingdirect]evidence)
forelderlywomenwithParkinsondisease
alendronate5mgorallyoncedailyreducesincidenceofhipfractureinelderlywomen
withParkinsondisease(level1[likelyreliable]evidence)
risedronate17.5mgorallyonceweeklymayreduceriskofhipfractureinelderly
womenwithParkinsondisease(level2[midlevel]evidence)
forpreventionofcorticosteroidinducedosteoporosis
AmericanCollegeofRheumatology(ACR)recommendationsforpreventionandtreatmentof
glucocorticoidinducedosteoporosis
forpostmenopausalwomenandmen50yearsold
assessriskusingFractureRiskAssessmentTool(FRAX)
bisphosphonates(usuallyalendronate,risedronate,orzoledronicacid)
recommendedif
lowrisk,anticipateddurationofglucocorticoids3months,anddose
equivalenttoprednisone7.5mg/day
mediumriskandanticipateddurationofglucocorticoids3months
highrisk,withanydoseordurationofglucocorticoidtreatment
forpremenopausalwomenandmen<50yearsoldwithhistoryoffragilityfracture
ifanticipateddurationofglucocorticoids13months,startalendronate,
risedronate,orzoledronicacid,exceptinwomenwithchildbearingpotential
ifanticipateddurationofglucocorticoids3months
inwomanwithchildbearingpotentialanddoseequivalenttoprednisone
7.5mg/day,startalendronate,risedronate,orteriparatide
inman<50yearsoldorwomanwithnochildbearingpotentialtaking
anydoseofglucocorticoids,startalendronate,risedronate,zoledronic
acid,orteriparatide
monitorpatientsonprevalentglucocorticoidtherapy(bonemineraldensity,serum25
hydroxyvitaminD,height,incidentfragilityfracture,andcompliancewith
osteoporosismedication)
bisphosphonatesassociatedwithreductioninvertebralfractureandbonelossinadults
takingchroniccorticosteroids(level3[lackingdirect]evidence)
alendronate5or10mgoncedailyincreasesbonedensityandmayreduceincidenceofnew
vertebralfractureinpatientsoncorticosteroids(level3[lackingdirect]evidence)andmay
bemoreeffectivethanalfacalcidolforpreventionsteroidinducedboneloss(level3[lacking
direct]evidence)
alendronate70mgonceweeklyincreasesbonedensityinpatientstakingcorticosteroids
risedronate2.55mgorallyoncedailymayreduceincidenceofvertebralfracturesand
increaseBMDinpatientstakingchroniccorticosteroids(level3[lackingdirect]evidence)
zoledronicacidmaypreventsteroidinducedbonelossinpatientswithCrohn'sdisease
zoledronicacidmaybemoreeffectivethanrisedronateforpreventionandtreatmentofbone
lossassociatedwithglucocorticoidinducedosteoporosis(level3[lackingdirect]evidence)
forotherpatients
risedronate2.5mgorallyoncedailymayreduceriskofhipfractureinelderlymenwith
stroke(level2[midlevel]evidence)orwithParkinsondisease(level2[midlevel]evidence)
efficacyofbisphosphonatesforreducingfractureincidenceinkidneytransplantrecipientsis
uncertain,butweeklyoralrisedronateassociatedwithimprovedBMDfollowingrenal
transplantation(level3[lackingdirect]evidence)
inadultswithcysticfibrosis,bisphosphonatesappeartoincreaseBMD(level3[lacking
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direct]evidence)butmayincreasebonepainandmaynotreducefractures(level2[mid
level]evidence)
zoledronicacidmaypreventbonelossinbreastcancerpatientshavingadjuvant
chemotherapy(level3[lackingdirect]evidence),andafterlivertransplant(level3[lacking
direct]evidence)
adverseeffects
oralbisphosphonatesmaybeassociatedwithadverseesophagealeffectssuchasdysphagia,
esophagitis,esophagealulcer
takewithfullglassofwater3060minutesbeforefirstoralintakewithinstructionstoremain
uprightfor3060minutes
discontinueifdysphagia,odynophagia,neworworseningheartburn,orretrosternalpain
bisphosphonatesassociatedwithincreasedriskofatrialfibrillationbutnotwithstrokeor
cardiovascularmortality(level2[midlevel]evidence)
severe,occasionallyincapacitating,bone,joint,and/ormusclepainreportedinfrequentlywith
bisphosphonatetherapy(level3[lackingdirect]evidence)
asepticosteonecrosisassociatedwiththeuseoforalbisphosphonates(level2[midlevel]
evidence)osteonecrosisofjawreported,mainlywithIVbisphosphonatesinpatientswithcancer
atypicalsubtrochantericandfemoralshaftfracturesrarebutmaybeassociatedwith
bisphosphonateuse(level2[midlevel]evidence)
evidenceregardingassociationofbisphosphonateuseandriskofesophagealcancerislimitedand
inconsistent
ocularadverseeffectshavebeenreportedwithbisphosphonates(level3[lackingdirect]evidence)
seeBisphosphonatesfortreatmentandpreventionofosteoporosisfordetails
Thiazidediuretics:
hydrochlorothiazidemightbeassociatedwithimprovementofbonemineraldensity(BMD)(level3
hydrochlorothiazidemightbeassociatedwithpreservationofBMD(level3[lackingdirect]
evidence)
320healthynormotensivepersonsaged6079yearsrandomizedtohydrochlorothiazide
12.5mgvs.hydrochlorothiazide25mgvs.placeboorallyoncedailyfor3years
97%followupat3years
differenceswerenotstatisticallysignificantbutstrongtrendsfavoringhydrochlorothiazide
ReferenceAnnInternMed2000Oct3133(7):516PDF
hydrochlorothiazidemightbeassociatedwithsustainedimprovementinbonemineral
density(level3[lackingdirect]evidence)
basedon2yearextensionofrandomizedtrialwithoutclinicaloutcomes
122healthypostmenopausalwomenwhowererandomizedtohydrochlorothiazide50mgvs.
placebocontinuedrandomizedtrialfor2yearextension
BMDimprovementsobservedinfirst2yearsoftrialmaintainedduring2yearextension
significantbetweengroupdifferencesat4yearsforchangeinbonedensityattotalbody,
legs,midforearm,ultradistalforearm
nosignificantdifferencesatlumbarspineorfemoralneck
Selectiveestrogenreceptormodulators(SERMs):
Raloxifene:
raloxifene(Evista)60mgorallyoncedailyFDAapprovedforpreventionortreatmentofosteoporosisin
postmenopausalwomen
firstofclassofdrugscalledselectiveestrogenreceptormodulators
mayantagonizewarfarin
maycausehotflashes,legcramps,andoccasionallyvenousthromboembolicevents
seeRaloxifeneforprescribinginformation
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raloxifenereducesriskofbreastcancerandclinicalvertebralfracture,butincreasesriskoffatal
strokeandvenousthromboembolism(level1[likelyreliable]evidence)
basedonrandomizedtrial
10,101postmenopausalwomen>55yearsoldwithcoronaryheartdiseaseormultipleriskfactors
forcoronaryheartdiseasewererandomizedtoraloxifene(Evista)60mgvs.placebooncedailyfor
median5.6years
913(9%)discontinuedthestudyand1,149(11%)diedduringthestudy
nosignificantdifferencescomparingraloxifenevs.placeboformanyoutcomes
primarycoronaryevents(533vs.553,or2.06%vs.2.16%peryear)
totalstroke(249eventsvs.224events,or0.95%vs.0.86%peryear)
totaldeath(554deathsvs.595deaths,or2.07%vs.2.25%peryear)
cardiovasculardeath(362deathsvs.355deaths,or1.35%vs.1.34%peryear)
clinicalnonvertebralfractures(428vs.438,or1.67%vs.1.73%peryear)
raloxifenereducedriskforsomeoutcomes
invasivebreastcancerin40casesvs.70cases,or0.15%vs.0.27%peryear(NNT833
peryear)
clinicalvertebralfracturesin64vs.97,or0.24%vs.0.37%peryear(NNT769peryear)
raloxifeneincreasedriskforsomeoutcomes
fatalstrokesin59vs.39(NNH1,428peryear)
venousthromboembolismeventsin103vs.71(NNH833peryear)
hotflashesin8%vs.4.8%(NNH31)
legcrampsin9.7%vs.6.7%(NNH33)
peripheraledemain14.4%vs.12.1%(NNH43)
gallbladderdiseasein5.6%vs.4.5%(NNH91)
ReferenceRUTHtrial(NEnglJMed2006Jul13355(2):125fulltext),editorialcanbefoundinN
EnglJMed2006Jul13355(2):190fulltext,commentarycanbefoundinCMAJ2006Jul
18175(2):147fulltext,AmFamPhysician2006Nov174(9):1598,ACPJClub2006Nov
Dec145(3):73
resultsofRUTHtrialdidnotdifferacrosssubgroups,exceptriskofstrokedifferedbysmoking
status(Stroke2009Jan40(1):147fulltext)
raloxifenemayincreasebonemineraldensityinpostmenopausalwomen(level3[lackingdirect]
evidence)
raloxifenemayincreasebonemineraldensityandlowertotalandLDLcholesterollevels
withoutstimulatingendometrium(level3[lackingdirect]evidence),butmaynotimprove
hotflashesorvaginalbleeding(level2[midlevel]evidence)
601mostlywhitewomen28yearspostmenopausalwithnormalbonemineraldensitywere
randomizedtoraloxifene30,60,or150mgorallyoncedailyvs.placebofor24months
25%dropoutrate
nosignificantdifferencesinadverseevents
studyfundedbydrugmanufacturer,otherclinicaloutcomes(mortality,fractures,myocardial
infarction)notassessed
ReferenceNEnglJMed1997Dec4337(23):1641fulltext,editorialcanbefoundinN
EnglJMed1997Dec4337(23):1686,commentarycanbefoundinNEnglJMed1998Apr
30338(18):1313
raloxifenemaintainsbonemineraldensityat3years(level3[lackingdirect]evidence)
basedon2randomizedtrialsofidenticaldesignwithoutclinicaloutcomes
1,145healthypostmenopausalwomenaged4560yearswererandomizedtoraloxifene30
mg/dayvs.60mg/dayvs.150mg/dayvs.placebofor3years
allwomengivenelementalcalcium400600mg
lumbarspineBMDchangedfrombaselineto36monthsby0.71%inraloxifene30mggroup
vs.1.28%inraloxifene60mggroupvs.1.2%inraloxifene150mggroupvs.1.32%in
placebogroup
comparableBMDchangesinhip
changeinserumlowdensitylipoproteincholesterolat36months
12.1%withraloxifene150mg(p<0.001vs.placebo)
2%withplacebo
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nosignificantdifferencesinstudywithdrawalsduetoanyreason(37%)orwithdrawalsdue
toadverseevents(14%),onlysignificantadverseeffectwashotflashes(25%in60mg
groupvs.18%inplacebogroup,NNH14)
ReferenceArchInternMed2000Dec1125160(22):3444fulltext
raloxifeneimprovesbonedensitycomparedtoplacebobutlessthanconjugatedequine
estrogen,andmayreduceLDLcholesterollevels(level3[lackingdirect]evidence)
619postmenopausalwomen(meanage53years)withpriorhysterectomywererandomized
toraloxifene(60mg/dayor150mg/day)vs.conjugatedequineestrogen0.625mg/dayvs.
placebofor3years
bonedensityinlumbarspinedeclinedby2%intheplacebogroup,wasstableinboth
raloxifenegroups,andincreasedby4.6%inestrogengroupconsistentresultsinbone
densityintotalhip
raloxifeneandestrogeneachreducedlowdensitylipoprotein(LDL)cholesterollevels,but
onlyestrogenincreasedhighdensitylipoprotein(HDL)cholesterollevels
estrogenbutnotraloxifenewasassociatedwithurinaryincontinence
ReferenceArchInternMed2004Apr26164(8):871fulltext
Bazedoxifene:
bazedoxifenecombinedwithconjugatedestrogens(Duavee)FDAapprovedtopreventpostmenopausal
osteoporosisandreducehotflashesinpostmenopausalwomenwithauterus(FDAapproval2013Oct3)
bazedoxifeneassociatedwithimprovedlumbarspine,hip,femoralneck,andgreatertrochanter
bonemineraldensity(level3[lackingdirect]evidence)butnotdecreasedfracturerate(level2
[midlevel]evidence)inpostmenopausalwomenwithosteoporosis
basedonrandomizedtrialwithmethodofrandomizationandallocationconcealmentnotstated
429Japanesepostmenopausalwomen85yearsoldwithosteoporosisandanintactuterus
randomizedtobazedoxifene20mgvs.bazedoxifene40mgvs.placebooncedailyfor2years
meanchangeinlumbarspineBMD(primaryoutcome)
2.43%forbazedoxifene20mg
2.74%forbazedoxifene40mg(notsignificantvs.bazedoxifene20mg)
0.65%forplacebo(p<0.001vs.bazedoxifene20mgand40mg)
bazedoxifene20mgand40mgassociatedwithimprovedBMDoftotalhip,femoralneck,and
greatertrochantervs.placebo(p<0.001forall)
rateofnewvertebralfractures
4.7%forplacebo(notsignificantvs.bazedoxifene20mgor40mg)
rateofnewnonvertebralfractures
3.1%forplacebo(notsignificantvs.bazedoxifene20mgor40mg)
ReferenceJBoneMinerRes2011Mar26(3):519
Tamoxifen:
tamoxifenmaypreventbonelossinwomenwithbreastcancer(JClinOncol1996Jan14(1):78,Arch
InternMed1994Nov28154(22):2585)
tamoxifen10mgorallyoncedailybutnot20mg/dayassociatedwithreducedriskoffractures(from7.6%
to3.2%)incrosssectionalstudyofoldernursinghomeresidents
multiplevalidityproblemsinstudydesignprecludefirmconclusionsforclinicaldecisionsbut
suggestneedforrandomizedtrial
ReferenceJAmGeriatrSoc1998Aug46(8):968
Estrogen:
estrogenisFDAapprovedforpreventionofosteoporosis (1)
estrogendoesnotcorrectosteoporosisinanorexia,becausethepathogenesisofosteoporosisinanorexia
nervosaismoreassociatedwithhypercortisolismthanwithsexhormonedeficiency(Medicine(Baltimore)
1995Sep74(5):254)
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estrogensupplementation(postmenopausalHRT)
hormonereplacementtherapy(HRT)preventsboneloss(increasesbonemineraldensity)(level3
[lackingdirect]evidence)andfracturesinrandomizedtrials,butrisksoflongtermusemay
outweighbenefits
largestrandomizedtrialofestrogen/progestincombinationtherapy(Women'sHealthInitiative
[WHI]with16,608patients)showedreductioninhipfractures(NNT2,000peryear),vertebral
fractures(NNT1,429peryear)andosteoporoticfractures(NNT228peryear)
estrogenalonemayreducefractureratesbutincreasesriskforstrokeandpossiblyvenous
thromboembolism(level2[midlevel]evidence)
systematicreviewsofrandomizedtrialsbeforeWHItrialfoundHRTassociatedwithreducedrisk
for
nonvertebralfractures,butonlysignificantforwomen<60yearsold
vertebralfractures
observationalstudiesfindassociationbetweenlongtermHRTuseandreducedfractures
fractureriskreductionmayrequireuseofHRTforatleast5years
fractureriskreductionappearstodiminishrapidlyaftercessationofHRT
alendronate(Fosamax)10mgorallyoncedailypreventsbonedensitylossafterdiscontinuationof
HRT
seeHormonalreplacementtherapy(HRT)andosteoporosisfordetails
seealsoHormonalreplacementtherapy(HRT)
hormonereplacementtherapyassociatedwithhigherbonemineraldensityinyounghypogonadal
womenonchronicsteroids(level3[lackingdirect]evidence)
28women(meanage37years)withsystemiclupuserythematosusonchronicsteroidtherapy,
withprovenovarianfailureandosteopenia,wererandomizedtoHRT(conjugatedestrogens0.625
mgplusmedroxyprogesteroneacetate5mgoncedailyfor21days/cycle)vs.calcitriol0.5
mcg/day
allwomengivencalciumcarbonate1g/day
HRTassociatedwithhigherBMDat2yearsinlumbarspineandradiuscomparedtocalcitriol
ReferenceRheumatology(Oxford)1999Dec38(12):1239fulltext
Testosteroneanddehydroepiandrosterone(DHEA):
formanagementofmenwithhypogonadismathighriskoffracture(4)
formenreceivingtestosteronetherapywhoareathighriskforfracture,addingmedicationwith
antifractureefficacy(suchasbisphosphonateorteriparatide)suggested(EndocrineSocietyWeak
recommendation,Verylowqualityevidence)
testosteronetherapysuggestedformenwith
highriskforfracturewithtestosteronelevels<200ng/dL(6.9nmol/L)whodonothave
standardindicationsfortestosteronetherapybutwhohavecontraindicationstoapproved
pharmacologicalagentsforosteoporosis(EndocrineSocietyWeakrecommendation,Low
qualityevidence)
borderlinehighriskforfracturewhohaveserumtestosteronelevels<200ng/dL(6.9
nmol/L)on>1assessment,plussomeevidenceofhypogonadism(EndocrineSociety
Weakrecommendation,Lowqualityevidence)
evidenceofhypogonadismmaybe
signsorsymptomsofandrogendeficiency(suchaslowlibido,unexplained
chronicfatigue,lossofbodyhair,hotflashes)
"organic"hypogonadism(suchasduetohypothalamic,pituitary,orspecific
testiculardisorder)
ifsymptomsofandrogendeficiencynotalleviatedafter36months,discontinueand
considerothertherapy
testosteronemaybeassociatedwithincreasedbonedensityinoldermenwithlowtestosterone
levels(level3[lackingdirect]evidence)
70men>65yearsoldwithlowserumtestosterone(<350mg/dL)wererandomizedto1of3
groupsfor36months
testosteroneenanthate200mgintramuscularlyevery2weeks
testosteroneintramuscularlyevery2weeksplusfinasteride5mg/dayorally
placebo
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bonedensityincreasedsignificantly(about10%atlumbarspine,about2.5%athip)inbothactive
treatmentgroups
prostatespecificantigenlevelsincreasedsignificantlyonlyintestosteronealonegroup
prostatesizeincreasedinallgroupsbutlesssowithfinasteride
onethirdoftestosteronepatientsrequireddosereductionsforhematocrit>52%
ReferenceJClinEndocrinolMetab2004Feb89(2):503
neithertransdermaltestosterone(inelderlymen)norDHEA(inelderlymenorwomen)appearto
havephysiologicallyrelevanteffects(level2[midlevel]evidence)
basedon2smallrandomizedtrials
87men>60yearsoldwithsulfatedDHEA<1.57mcg/mL(4.3mcmol/L)andbioavailable
testosterone<103ng/dL(3.6nmol/L)wererandomizedtotransdermaltestosterone5mg/dayvs.
oralDHEA50mg/dayvs.placebofor2years
onlystatisticallysignificantdifferenceinbodycompositionwas1.39kgincreaseinfatfree
masswithtestosterone,nosignificantdifferencesinweightorBMI
onlystatisticallysignificantdifferenceinBMDwasincreaseatfemoralneck(0.02g/cmwith
DHEA,0.03g/cmwithtestosterone)
nosignificantdifferencesinphysicalperformanceorqualityoflife
57women<60yearsoldwithsulfatedDHEA<0.95mcg/mL(2.6mcmol/L)wererandomizedto
oralDHEA50mg/dayvs.placebofor2years
nosignificantdifferencesinbodycomposition
onlystatisticallysignificantdifferenceinBMDwasincreaseatultradistalradius(0.02g/cm)
nosignificantdifferencesinphysicalperformanceorqualityoflife
ReferenceNEnglJMed2006Oct19355(16):1647fulltext,editorialcanbefoundinNEnglJ
Med2006Oct19355(16):1724,commentarycanbefoundinNEnglJMed2007Feb8356(6):635
testosteronereplacementmighthelppreventsteroidinducedosteoporosisinmen(level3[lacking
direct]evidence)
basedonsmallrandomizedcrossovertrialwithoutclinicaloutcomes
15menwithasthmarequiringlongtermglucocorticoidswererandomizedtotestosterone(250
mg/monthtestosteroneesters)intramuscularlyvs.notherapyfor12monthsbeforecrossover
afterwashoutperiodfortestosteronegroup,groupscrossedoverfornext12months
allgotcalcium1,000mg/day,averagedoseofprednisone10mg/day
testosteroneincreasedspinalBMDbyabout5%,decreasedfatmass,increasedleanbodymass,
anddecreasedboneresorption
ReferenceArchInternMed1996Jun10156(11):1173
DHEA50mg/daymayincreasebonemineraldensity(level3[lackingdirect]evidence)
basedonsubgroupanalysesof2randomizedtrialswithborderlinestatisticalsignificanceand
withoutclinicaloutcomes
DHEAsupplement50mg/daymayincreaseBMDandreduceboneresorptioninwomenbutnotin
men
basedon1yearrandomizedtrialin225healthyadultsaged5585years
statisticallysignificanteffectreportedonlumbarspineBMDinwomen,butnotinhip,
femoralneck,ortotalbodyBMD,orinmen
ReferenceOsteoporosInt2008May19(5):699fulltext
DHEA50mg/dayorallyassociatedwithnonsignificantincreaseinBMD
basedon12monthrandomizedplacebocontrolledtrialin70menand70womenaged6088
yearswithlowserumDHEAlevels
ReferenceJClinEndocrinolMetab2006Aug91(8):2986
Strontiumranelate:
strontiumranelateassociatedwithincreaseinBMDbutlimiteddataonfracturerateswhenused
forpreventionofosteoporosis(level3[lackingdirect]evidence)
basedonCochranereviewwithoutclinicaloutcomes
systematicreviewofrandomizedtrialsofstrontiumranelatefor1yearinpostmenopausal
women
1trialfoundevaluatingpreventionpopulation(womenwithoutosteoporosis),evaluatingstrontium
doses0.125g/day,0.5g/day,and1g/day
strontium1g/dayfor2yearsassociatedwithincreaseinBMDatlumbarspine,femoralneck,and
totalhip,basedon60women
strontiumappearstohavedosedependenteffectonBMD
65/81
19/11/2015
ReferenceCochraneDatabaseSystRev2006Oct18(4):CD005326
Romosozumab:
romosozumabisamonoclonalantibodythatbindstosclerostin
notFDAapprovedasofMay2014
romosozumabmayincreasebonemineraldensityinpostmenopausalwomenwithlowbone
mass(level3[lackingdirect]evidence)
basedonnonclinicaloutcomefromrandomizedtrial
419postmenopausalwomenaged5585yearswithlowbonemassrandomizedto1of8
interventions
romosozumab(70mgvs.140mgvs.210mg)subcutaneouslyoncemonthly
romosozumab(140mgvs.210mg)subcutaneouslyonceevery3months
placebosubcutaneously
alendronate70mgorallyonceweeklyunblinded
teriparatide20mcgsubcutaneouslyoncedailyunblinded
baselinecharacteristics
allwomenhadlowbonemineraldensity(definedasTscore2atlumbarspine,totalhip,
orfemoralneckand3.5atall3sites)
nowomenhadhistoryofvertebralfractureorfragilityfractureatwrist,humerus,hip,or
pelvis
romosozumab(alldoses)associatedwithsignificantincreasesinbonemineraldensitycompared
toplacebo
5.4%11.3%increaseatlumbarspine
1.3%4.1%increaseintotalhip
0.6%4.2%increaseatfemoralneck
mildinjectionsitereactionsmorecommonwithromosozumab(nopvaluesreported)
ReferenceNEnglJMed2014Jan30370(5):412,editorialcanbefoundinNEnglJMed2014
Jan30370(5):476
Screening:
Recommendations:
NationalOsteoporosisFoundation(NOF)recommendsbonemineraldensity(BMD)testingfor(1)
allwomen65yearsold
allmen70yearsold
perimenopausalwomen,postmenopausalwomen<65yearsold,andmenaged5069yearswith
clinicalriskfactorsforfracture
anyadultwithfractureafterage50years
anyadultwithcondition(suchasrheumatoidarthritis)oruseofmedication(suchas
glucocorticoidsfor3months)associatedwithlowbonemassorboneloss
UnitedStatesPreventiveServicesTaskForce(USPSTF)recommendationsforroutinescreening
USPSTFrecommendsroutineosteoporosisscreeningforwomen65yearsoldwithoutprevious
knownfracturesorsecondarycausesofosteoporosis(USPSTFGradeB)
USPSTFrecommendsroutinescreeningforwomen<65yearsoldwhose10yearfractureriskis
greaterthanorequaltothatofa65yearoldwhitewomanwithnoadditionalriskfactors(USPSTF
GradeB)
65yearoldwhitewomanwithoutadditionalriskfactorshad9.3%10yearfracturerisk
accordingtoFractureAssessmentTool(FRAX)
USPSTFdeterminesinsufficientevidencetomakerecommendationsregardingoptimalintervals
forrepeatscreeninginwomen
2yearintervalmaybeneededtomeasurechangeinbonemineraldensity(BMD)dueto
limitationsinprecisionoftesting
repeatBMDmeasurementsmaynothaveadditionalpredictivevalueforupto8yearsafter
initialBMDmeasurement
USPSTFmakesnorecommendationforroutinescreeninginmenwithoutpreviousknownfractures
orsecondarycausesofosteoporosis(USPSTFGradeI)
currentcriteriareliesondualenergyxrayabsorptiometry(DEXA)ofhipandlumbarspinefor
screeningtest
66/81
19/11/2015
ReferenceUSPSTF2011Jan,AnnInternMed2011Mar1154(5):356fulltextoratNational
GuidelineClearinghouse2011May9:25316
supportingsystematicreviewcanbefoundinAnnInternMed2010Jul20153(2):99
EndocrineSocietyindicationsforscreeningforosteoporosisinmen(4)
measureBMDinmenatincreasedriskofosteoporosis,suchas(EndocrineSocietyWeak
recommendation,Lowqualityevidence)
age70years
age5069yearsifadditionalriskfactors,includinganyof
historyoffractureafterage50years
delayedpuberty
hypogonadism
hyperparathyroidism
hyperthyroidism
chronicobstructivepulmonarydisease(COPD)
treatmentwithglucocorticoidsorgonadotropinreleasinghormoneagonists
alcoholabuse
smoking
obtainDEXAofspineandhipinmenatriskofosteoporosis(EndocrineSocietyStrong
measureforearmDEXA(onethirdor33%radius)ifanyof(EndocrineSocietyWeak
spineorhipBMDcannotbeinterpreted
hyperparathyroidism
manreceivingandrogendeprivationtherapyforprostatecancer
similarrecommendationsonscreeninginOsteoporosisCanada2010clinicalpracticeguidelineon
diagnosisandmanagementofosteoporosis(CMAJ2010Nov23182(17):1864PDF),editorialcanbe
foundinCMAJ2010Nov23182(17):1829fulltext
Riskassessment:
forriskprediction
WorldHealthOrganization(WHO)FractureRiskAssessmentTool(FRAX)predicts10yearriskof
hipfractureandmajorosteoporoticfracture
QFracture2013RiskCalculatorpredicts10yearriskofosteoporoticfracture(level1[likely
reliable]evidence)
reliable]evidence)
seeOsteoporosiscausesandriskfactorsforadditionalinformation
historicalheightloss>6cmmayidentifyprevalentvertebralfracture
studyof323postmenopausalwomen>50yearsoldreferredforspecialistassessmentof
osteoporosisrisk
historicalheightlosscalculatedasdifferencebetweenpatient'stallestrecalledheightandcurrent
measuredheight
vertebralfracturesdefinedasvertebralheightratio<0.8measuredbyradiographicmorphometry
historicalheightloss>6cmassociatedwith30%sensitivityand94%specificityforvertebral
fractures
positivelikelihoodratioforfracture2.8withhistoricalheightloss6.18cmand9.8withhistorical
heightloss>8cm
Screeningevidence:
bonedensitytesting(DEXAathip)associatedwithlowerincidenceofhipfracture(level2[mid
level]evidence)
basedoncohortstudy
1,422adults>65yearsoldinCaliforniaandPennsylvaniawhohadDEXAathipcomparedwith
1,685adults>65yearsoldinMarylandandNorthCarolinawhodidnothaveDEXAathip
followup6years
incidenceofhipfracturesper1,000personyearswas4.8inscreenedgroupvs.8.2inusualcare
group(33[2.3%]vs.69[4.1%]patientshadhipfracture,NNT56)
67/81
19/11/2015
ReferenceAnnInternMed2005Feb1142(3):173,editorialcanbefoundinAnnInternMed2005
Feb1142(3):217
universalbonedensitometryforwomen>65yearsoldfollowedbyalendronateforwomenwith
osteoporosisreportedtobecosteffectiveindecisionanalysis(JAmGeriatrSoc2005Oct53(10):1697)
bonedensitometry(andtreatmentforosteoporosis)inmenreportedtobecosteffectiveformen>65
yearsoldwithpriorclinicalfractureandmenaged8085yearswithnopriorfracture(JAMA2007Aug
8298(6):629fulltext),commentarycanbefoundinJAMA2007Nov14298(18):2136
BMDincombinationwithagepredictsfractureriskinpostmenopausalwomen,basedonsystematic
review(JAMA2002Oct16288(15):1889fulltext),correctioncanbefoundinJAMA2002Dec
11288(22):2825,discussionofclinicalapplicationscanbefoundinJAMA2002Oct16288(15):1898full
text,commentarycanbefoundinJAMA2003Feb26289(8):982
Screeningintervals:
elderlywomenwithnormalbonemineraldensity(BMD)ormildosteopeniaatfirstscreening
appeartohavelowriskofprogressiontoosteoporosisordevelopmentofhipfractureorclinical
vertebralfractureover15years
4,957women67yearsoldwithnormalBMDorosteopeniabyDEXAwerefollowedforupto15
years
exclusioncriteriaincludedhistoryofhiporclinicalvertebralfractureandosteoporosisatbaseline
womenwerestratifiedbyTscoreatbaseline(lowerofTscoresatfemoralneckandtotalhip)
normalBMD(Tscore1)
mildosteopenia(Tscore1.01to1.49)
moderateosteopenia(Tscore1.5to1.99)
advancedosteopenia(Tscore2to2.49)
osteoporosis(Tscore2.5)developedin
0.8%fornormalBMD
4.6%formildosteopenia
20.9%formoderateosteopenia
62.3%withadvancedosteopenia
BMDtestingintervaldefinedastimefor10%ofwomentomaketransitiontoosteoporosisbefore
havinghiporclinicalvertebralfracturepriortoinitiationofosteoporosistreatment
estimatedBMDtestinginterval
17.4years(95%CI11.526.3years)fornormalBMD
16.5years(95%CI13.620.2years)formildosteopenia
4.6years(95%CI4.15.1years)formoderateosteopenia
1year(95%CI0.81.1years)foradvancedosteopenia
2.4%hadhiporclinicalvertebralfracturebeforetransitiontoosteoporosis
estimatedtimetohiporclinicalvertebralfracturein2%ofwomen
>15yearsfornormalBMDormildosteopenia
5yearsformoderateoradvancedosteopenia
ReferenceNEnglJMed2012Jan19366(3):225fulltext
repeattestingofBMDtodiagnoseosteoporosismaybedelayedtoevery5yearsinabsenceof
additionalriskfactorsortherapy
basedoncohortstudy
9,423personsaged2585yearshadmeasurementofBMDinlumbarspine,totalhip,andfemoral
neckatbaseline,3years(thoseaged4060yearsonly),and5years
ReferenceCMAJ2008Jun17178(13):1660fulltext,editorialcanbefoundinCMAJ2008Jun
17178(13):1683fulltext
Screeningtests:
dualenergyxrayabsorptiometry(DEXA)isrecommendedtestforosteoporosisscreening
quantitativeultrasound(QUS)ofheelplusclinicalriskfactorsmaybealternativewhenDEXAnot
available,butlimitedsensitivityandspecificityforosteoporosisonDEXA(level2[midlevel]evidence)
otherimagingmodalities
abdominalcomputedtomographyscansobtainedforotherindicationsmighthelpidentify
patientswithosteoporosis(level2[midlevel]evidence)
basedonretrospectivecohortstudywithoutvalidation
68/81
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1,867patients(meanage59years)whohadabdominalcomputedtomography(CT)scanfor
indicationotherthanosteoporosisandDEXAoflumbarspineandproximalfemorawithin6
monthswereassessed
vertebralBMDwasestimatedfromCTscanbymeasuringCTattenuationatL1vertebra
BMDmeasuredbyDEXAwasreferencestandard
22.9%hadosteoporosis(Tscore2.5orpresenceofmoderatetoseverevertebral
compressionfracture)
44.8%hadosteopenia(Tscore1to2.5)
32.3%hadnormalBMD(Tscore1)
fordetectionofosteoporosisL1CTattenuation160Hounsfieldunitshad
sensitivity75.5%
specificity75.4%
positivepredictivevalue47.2%(positivelikelihoodratio1.89)
negativepredictivevalue91.3%(negativelikelihoodratio0.19)
ReferenceAnnInternMed2013Apr16158(8):588fulltext,editorialcanbefoundatAnn
InternMed2013Apr16158(8):630
metacarpaldigitalxrayradiogrammetry(DXR)andphalangealradiographicabsorptiometry
(RA)maybeusefulforidentifyingpostmenopausalwomenwhowillhaveosteoporosison
DEXAscreening
221postmenopausalCaucasianwomenaged5075yearshadBMDmeasuredbyDEXAat
lumbarspineandtotalhipandthenhadcalcanealquantitativeultrasound(QUS),
metacarpalDXR,andphalangealRA
osteoporosisdefinedasTscore2.5atspineorhiponDEXA
41(18.5%)womenhadosteoporosis
sensitivityforidentifyingwomenwithosteoporosiswas67.6%withQUSvs.76.9%with
DXRvs.82.9%withRA
negativepredictivevaluewas94%forDXRandRAand90%forQUS
ReferenceOsteoporosInt2005Jan16(1):93
phalangealbonedensityfromstandardhandxrayfilmsmaybesignificantpredictorof
futurehipfracturerisk
basedoncohortstudy
3,481noninstitutionalizedpersonsaged4574yearsfollowed1216years,98%completed
study
hospitalrecordsanddeathcertificatesidentified72hipfracturecases
phalangealbonedensityatbaselinemeasuredusingphotodensitometryandlater
reanalyzedbyradiographicabsorptiometry
bothmeasurementsshowedsignificantinverserelationshiptohipfracturerisk
ReferenceArchInternMed1997Feb24157:433
Increasingscreeninguptake:
specialistosteoporosisandfractureliaisonnursepresentinclinictoreviewnotesmayimprove
catchmentrateofpatientsneedingosteoporosisassessment
154adults>50yearsoldwithfracturepresentingtoorthopedicclinicevaluatedandnumberof
referralstoosteoporosisassessmentcalculatedafter1weekof
physicianreferralonly
selfreferralafterreadingleafletonosteoporosisplusphysicianreferral
osteoporosisandfractureliaisonnursereferral
referralstoosteoporosisassessment
1.6%physicianonly
63%selfreferralplusphysician(p<0.0001vs.physicianonly)
77%osteoporosisandfractureliaisonnurse(p=0.036vs.selfreferralplusphysician)
ReferenceAnnRCollSurgEngl2009Oct91(7):596fulltext
specificchartremindersplusmailedpatienteducationmayincreaselevelsofbonedensitytesting
inprimarycare
basedonclusterrandomizedtrial
5primarycarepracticesrandomizedto1of3groups
2practicestochartreminderalone
69/81
19/11/2015
2practicestochartreminderplusmailedpatienteducation
1practicetousualcare
204women65yearsoldrecruitedthroughpractices
BMDtestingcompleted
withchartreminderalonein31.4%
withchartreminderplusmailedpatienteducationin45.2%(p=0.029vs.usualcare)
withusualcarein9.7%
ReferenceJAmBoardFamMed2009JulAug22(4):360fulltext
screeningandeducationbycommunitypharmacistmayincreasepatientcomplianceinbone
mineraldensitytesting(level3[lackingdirect]evidence)
262patientseligibleforbonedensityscreeningrandomizedtoeducationandscreeningultrasound
fromcommunitypharmacistvs.nointervention
bonemineraldensitytestingcompletedwithin4monthsin22%withinterventionvs.10%without
intervention(p<0.05)
notificationsaboutfracturessenttophysiciansmayincreaseuptakeofbonemineraldensity
testing(level3[lackingdirect]evidence)
4,264patients50yearsoldreportingmajorfracturesrandomizedto1of3groups
mailednotificationoffracturesenttoprimarycarephysician
mailednotificationoffracturesenttobothphysicianandpatient
usualcare
notificationtopatientnotassociatedwithbenefitcomparedtonotificationtophysicianonly
notificationassociatedwithincreaseduptakeofbonemineraldensitytesting
oddsratio4.73(95%CI3.496.4)forphysiciannotification
oddsratio5.5(95%CI4.087.42)forpatientandphysiciannotification
notificationassociatedwithsignificantincreaseinstartingofpharmacologictreatment
ReferenceCMAJ2012Feb21184(3):290fulltext
QualityImprovement
PhysicianQualityReportingSystemQualityMeasures:
24.Osteoporosis:CommunicationwiththePhysicianManagingOngoingCarePostFractureofHip,
Spine,orDistalRadiusforMenandWomen50yearsold
Percentageofpatients50yearsoldtreatedforahip,spine,ordistalradialfracturewith
documentationofcommunicationwiththephysicianmanagingthepatient'songoingcarethata
fractureoccurredandthatthepatientwas,orshouldbe,testedortreatedforosteoporosis
39.ScreeningorTherapyforOsteoporosisforWomenAged65YearsandOlder
Percentageoffemalepatients65yearsoldwhohaveacentraldualenergyXrayabsorptiometry
(DXA)measurementorderedorperformedatleastoncesinceage60orpharmacologictherapy
prescribedwithin12months
40.Osteoporosis:ManagementFollowingFractureofHip,Spine,orDistalRadiusforMenandWomen
50yearsold
Percentageofpatients50yearsoldwithfractureofthehip,spine,ordistalradiuswhohada
centraldualenergyXrayabsorptiometry(DXA)measurementorderedorperformedor
pharmacologictherapyprescribed
41.Osteoporosis:PharmacologicTherapyforMenandWomen50yearsold
Percentageofpatients50yearsoldwithadiagnosisofosteoporosiswhowereprescribed
pharmacologictherapywithin12months
seePhysicianQualityReportingSystemQualityMeasuresforadditionalinformation
QualityandOutcomesFrameworkIndicators:
OST4(NM29).Contractorestablishesandmaintainsthefollowingregistersofpatients
patientsaged5074yearswithrecordoffragilityfractureonorafter1April2012anddiagnosisof
70/81
19/11/2015
osteoporosisconfirmedondualenergyxrayabsorptiometry(DXA)scan
patientsaged75yearsoldwithrecordofafragilityfractureonorafter1April2014anddiagnosis
ofosteoporosis
OST2(NM30).Percentageofpatientsaged5074yearswithfragilityfractureonorafter1April2012in
whomosteoporosisisconfirmedondualenergyxrayabsorptiometry(DXA)scanwhoarecurrently
treatedwithappropriatebonesparingagent
OST5(NM31).Percentageofpatients75yearsoldwithfragilityfractureonorafter1April2014anda
diagnosisofosteoporosiswhoarecurrentlytreatedwithappropriatebonesparingagent
seeQualityandOutcomesFrameworkIndicatorsforadditionalinformation
ChoosingWiselyCanada:
CanadianAssociationofNuclearMedicinerecommendsagainstrepeatingDEXAscansmoreoftenthan
every2yearsinabsenceofhighriskornewriskfactors(ChoosingWiselyCanada2015Jun2)
Qualityindicators:
13qualityindicatorsforthecareofosteoporosisinvulnerableelderscanbefoundinJAmGeriatrSoc
2007Oct55Suppl2:S392
GuidelinesandResources
Guidelines:
Guidelinecomparison:
comparisonof4guidelines(AmericanCollegeofPreventiveMedicine/TheNorthAmericanMenopause
Society/UniversityofMichiganHealthSystem/U.S.PreventiveServicesTaskForce[ACPM2009/NAMS
2010/UMHS2011/USPSTF2011])onscreeningandriskassessmentforosteoporosiscanbefoundat
NationalGuidelineClearinghouse2012Nov26:38658
Internationalguidelines:
InternationalSocietyforClinicalDensitometry(ISCD)guidelineson
bonedensitometryinchildrenandadolescentscanbefoundinPediatrics2011
Jan127(1):189fulltext
diagnosisofosteoporosisinmen,premenopausalwomenandchildrencanbefoundinJClin
Densitom2004Spring7(1):17
clinicaluseofquantitativecomputedtomography(QCT)andperipheralQCTinmanagementof
osteoporosisinadultscanbefoundinJClinDensitom2008JanMar11(1):123
dualenergyxrayabsorptiometry(DEXA)assessmentinchildrenandadolescentswithdiseases
thatmayaffectskeletoncanbefoundinJClinDensitom2008JanMar11(1):29
DEXAinterpretationandreportinginchildrenandadolescentscanbefoundinJClinDensitom
2008JanMar11(1):43
DEXAtechnicalissuescanbefoundinJClinDensitom2008JanMar11(1):109
fracturepredictionanddefinitionofosteoporosisinchildrenandadolescentscanbefoundinJClin
Densitom2008JanMar11(1):22
indicationsofDXAinwomenyoungerthan65yrandmenyoungerthan70yrcanbefoundinJ
ClinDensitom2013OctDec16(4):467oratNationalGuidelineClearinghouse2014Nov3:48211
normativedatabasescanbefoundinJClinDensitom2013OctDec16(4):472oratNational
GuidelineClearinghouse2014Nov3:48213
peripheralDEXAinmanagementofosteoporosiscanbefoundinJClinDensitom2008Jan
Mar11(1):188
peripheralQCTinchildrenandadolescentscanbefoundinJClinDensitom2008JanMar11(1):59
quantitativeultrasoundinmanagementofosteoporosiscanbefoundinJClinDensitom2008Jan
Mar11(1):163
vertebralfractureassessmentcanbefoundinJClinDensitom2013OctDec16(4):482orat
71/81
19/11/2015
NationalGuidelineClearinghouse2014Nov3:48212
expertguidelineondiagnosticandtherapeuticconsensusinmaleosteoporosiscanbefoundin
OsteoporosInt2011Nov22(11):2789fulltext
UnitedStatesguidelines:
comprehensiveguidelinesondiagnosis/prevention/treatment
NationalOsteoporosisFoundation(NOF)clinician'sguideonhealthybonesforlifecanbefoundat
NOF2014PDF
NationalOsteoporosisFoundation(NOF)clinician'sguideonpreventionandtreatmentof
osteoporosiscanbefoundatNOF2013PDF,previousversioncanbefoundatNOF2010PDF
AmericanCollegeofPhysicians(ACP)clinicalpracticeguidelineonpharmacologictreatmentof
lowbonedensityorosteoporosistopreventfracturescanbefoundinAnnInternMed2008Sep
16149(6):404,commentarycanbefoundinAnnInternMed2009Feb17150(4):285
MichiganQualityImprovementConsortium(MQIC)guidelineonmanagementandpreventionof
osteoporosiscanbefoundatMQIC2014JanPDForatNationalGuidelineClearinghouse2014
Jun9:47804
InstituteforClinicalSystemsImprovement(ICSI)guidelineondiagnosisandtreatmentof
osteoporosiscanbefoundatICSI2013JulPDF
AmericanAssociationofClinicalEndocrinologists(AACE)medicalguidelineondiagnosisand
treatmentofpostmenopausalosteoporosiscanbefoundinEndocrPract2010NovDec16Suppl
3:1oratNationalGuidelineClearinghouse2012Mar26:34968
AmericanMedicalDirectorsAssociation(AMDA)guidelineonosteoporosisandfracture
preventioninlongtermcaresettingcanbefoundatAMDA(loginrequired)oratNationalGuideline
Clearinghouse2011Jan31:15592
UniversityofMichiganHealthSystem(UMHS)guidelineonosteoporosispreventionandtreatment
canbefoundatUMHS2011DecPDForatNationalGuidelineClearinghouse2012Jun11:35236
AmericanCollegeofObstetriciansandGynecologists(ACOG)
ACOGCommitteeOpinion534onwellwomanvisitcanbefoundinObstetGynecol2012
Aug120(2Pt1):421,reaffirmed2014Jul,commentarycanbefoundinACOGNews
Release2012Jul23
ACOGPracticeBulletin129onosteoporosiscanbefoundinObstetGynecol2012
Sep120(3):718,reaffirmed2014Dec,oratNationalGuidelineClearinghouse2012Nov
5:38413,commentarycanbefoundinACOGNewsRelease2012Aug21
ACOGCommitteeOpinion534onwellwomanvisitcanbefoundatObstetGynecol2012
Aug120(2Pt1):421
ACOGguidelineonassessmentsandrecommendationsforwellwomancarecanbefound
atACOG2012
screeningguidelines
AmericanCouncilofPreventiveMedicine(ACPM)positionstatementonscreeningfor
osteoporosisinadultsinUnitedStatescanbefoundinAmJPrevMed2009Apr36(4):366
AmericanCollegeofRadiology(ACR)AppropriatenessCriteriaonosteoporosisandbonemineral
densitycanbefoundatACR2010PDFandatNationalGuidelineClearinghouse2011Feb
14:23824
UnitedStatesPreventiveServicesTaskForce(USPSTF)recommendationstatementon
screeningforosteoporosiscanbefoundinAnnInternMed2011Mar1154(5):356,commentary
canbefoundinAmFamPhysician2011May1583(10):1197fulltext
specificinterventionguidelines
UnitedStatesPreventiveServicesTaskForce(USPSTF)recommendationstatementonvitamin
DandcalciumsupplementationtopreventfracturesinadultscanbefoundinAnnInternMed2013
May7158(9):691fulltextoratNationalGuidelineClearinghouse2013Jun24:43793,editorialcan
befoundinAnnInternMed2013May7158(9):I,commentarycanbefoundinAnnInternMed
2013Dec17159(12):856
AmericanCollegeofSportsMedicine(ACSM)statementonphysicalactivityandbonehealthcan
befoundinMedSciSportsExerc2004Nov36(11):1985
specialpopulations
EndocrineSocietyclinicalpracticeguidelineonosteoporosisinmencanbefoundinJClin
EndocrinolMetab2012Jun97(6):1802oratNationalGuidelineClearinghouse2012Oct1:37827
NorthAmericanMenopauseSociety(NAMS)2010positionstatementonmanagementof
osteoporosisinpostmenopausalwomencanbefoundinMenopause2010JanFeb17(1):25PDF
72/81
19/11/2015
AmericanCollegeofPhysicians(ACP)clinicalpracticeguidelineonscreeningforosteoporosisin
mencanbefoundinAnnInternMed2008May6148(9):680fulltext,correctioncanbefoundin
AnnInternMed2008Jun3148(11):888,commentarycanbefoundinAnnInternMed2008Oct
7149(7):514
AmericanCollegeofRheumatology(ACR)2010recommendationsonpreventionandtreatmentof
glucocorticoidinducedosteoporosiscanbefoundinArthritisCareRes(Hoboken)2010
Nov62(11):1515fulltext
DepartmentofVeteransAffairs(VA)suggestedguidelineoncorticosteroidinducedosteoporosis
canbefoundinArchInternMed2003Nov24163(21):2619
AmericanGastroenterologicalAssociation(AGA)medicalpositionstatementson
osteoporosisingastrointestinaldiseasescanbefoundinGastroenterology2003
Mar124(3):791
osteoporosisinhepaticdisorderscanbefoundinGastroenterology2003Sep125(3):937
UnitedKingdomguidelines:
NationalInstituteforHealthandClinicalExcellence(NICE)guidelineson
percutaneousvertebroplastyandpercutaneousballoonkyphoplastyfortreatmentofosteoporotic
vertebralfracturescanbefoundatNICE2013Apr:TA279PDForatNationalGuideline
Clearinghouse2013Oct21:45130
assessingriskoffragilityfracturecanbefoundatNICE2012Aug:CG146PDForatNational
GuidelineClearinghouse2013Feb4:38410,summarycanbefoundinBMJ2012Aug
8345(7869):e3698
alendronate,etidronate,risedronate,raloxifene,andstrontiumranelateforprimarypreventionof
osteoporoticfragilityfracturesinpostmenopausalwomencanbefoundatNICE2010
Jan:TA160PDF
alendronate,etidronate,risedronate,raloxifene,strontiumranelate,andteriparatideforthe
secondarypreventionofosteoporoticfragilityfracturesinpostmenopausalwomencanbefoundat
NICE2010Jan:TA161PDF
denosumabforpreventionofosteoporoticfracturescanbefoundatNICE2010Oct:TA204PDFor
atNationalGuidelineClearinghouse2011Jun20:25677
BritishNationalOsteoporosisGuidelineGroup(NOGG)guidelineondiagnosisandmanagementof
osteoporosisinpostmenopausalwomenandmenfromageof50yearscanbefoundinMaturitas2009
Feb2062(2):105
ScottishIntercollegiateGuidelinesNetwork(SIGN)nationalclinicalguidelineonmanagementof
osteoporosiscanbefoundatSIGN2003JunPDF
Canadianguidelines:
SocietyofObstetriciansandGynaecologistsofCanada(SOGC)guidelineonosteoporosisinmenopause
canbefoundinJObstetGynaecolCan2014Sep36(9):839
CanadianAssociationofGastroenterology(CAG)positionstatementonhipfractureandprotonpump
inhibitortherapycanbefoundatCAG2013AugPDF
BritishColumbiaMedicalServicesCommissionguidelineonosteoporosisdiagnosis,treatment,and
fracturepreventioncanbefoundat2011May1PDForatNationalGuidelineClearinghouse2012Feb
27:34286
OsteoporosisCanadaguidelineson
diagnosisandmanagementofosteoporosisinCanadacanbefoundinCMAJ2010Nov
23182(17):1864PDF,editorialcanbefoundinCMAJ2010Nov23182(17):1829fulltext,
summarycanbefoundinCanAssocRadiolJ2011Nov62(4):243
useofparathyroidhormoneintreatmentofosteoporosiscanbefoundinCMAJ2006Jul
4175(1):48fulltext,supportingsystematicreviewcanbefoundinCMAJ2006Jul4175(1):52full
text
CanadianTaskForceonPreventiveHealthCarerecommendationsonpreventionofosteoporosisand
osteoporoticfracturesinpostmenopausalwomencanbefoundinCMAJ2004May25170(11):1665,
commentarycanbefoundinCMAJ2004Oct26171(9):1022
l'UniversitduQubecTroisRiviresDiagnosticguidelineonimagingformusculoskeletalcomplaintsin
adults(lowerextremitydisorders)canbefoundinJManipulativePhysiolTher2007NovDec30(9):684
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Europeanguidelines:
NationalAuthorityforHealth(HauteAutoritdeSant[HAS])2012updateofFrenchguidelineon
pharmacologicaltreatmentofpostmenopausalosteoporosiscanbefoundinJointBoneSpine2012
May79(3):304[French]
SpanishSocietyofRheumatologyconsensusstatementonosteoporosiscanbefoundinReumatolClin
2011NovDec7(6):357fulltext
BoneMetabolismWorkingGroupofSpanishSocietyofEndocrinologyclinicalpracticeguidelineon
evaluationandtreatmentofosteoporosisassociatedtoendocrineandnutritionalconditionscanbefound
inEndocrinolNutr2012Mar59(3):174[Spanish]
EuropeanSocietyforClinicalandEconomicAspectsofOsteoporosisandOsteoarthritis(ESCEO)
guidelinesondiagnosisandmanagementofpostmenopausalosteoporosiscanbefoundinDtschMed
Wochenschr2009Jan134(3):92[German]
EuropeanMenopauseandAndropauseSociety(EMAS)positionstatementonbonedensitometry
screeningforosteoporosiscanbefoundinMaturitas2011Jan68(1):98,correctioncanbefoundin
Maturitas2011Jun69(2):e5
BelgianBoneClubevidencebasedguidelineonpharmacologictreatmentofpostmenopausal
osteoporosiscanbefoundinOsteoporosInt2010Oct21(10):1657fulltext
BelgianBoneClubevidencebasedguidelineonuseofbiochemicalmarkersofboneturnoverduring
bisphosphonatetreatmentinosteoporosiscanbefoundinIntJClinPract2009Jan63(1):19fulltext
AustrianSocietyforBoneandMineralResearch(OsterreichischeGesellschaftfurKnochenundMineral
Forschung)guidelineupdateonpharmacologicaltreatmentofosteoporosisinpostmenopausalwomen
canbefoundinWienMedWochenschrSuppl2009(122):1[German]
ItalianOsteoporosisSociety(SocietItalianadell'Osteoporosi)guidelineondiagnosis,preventionand
treatmentofosteoporosiscanbefoundinReumatismo2009OctDec61(4):260[Italian]
ItalianexpertconsensusondefinitionandmanagementofsevereosteoporosiscanbefoundinJ
EndocrinolInvest2009Oct32(9):783
2011expertguidelineondiagnosisandtreatmentofosteoporosisinGreececanbefoundinJ
MusculoskeletNeuronalInteract2012Mar12(1):38PDF
Asianguidelines:
BureauofHealthPromotion/DepartmentofHealthTaiwanpracticeguidelinesonosteoporosiscanbe
foundatNationalGuidelineClearinghouse2013Jul15:39382
SingaporeMinistryofHealth(SMOH)clinicalpracticeguidelineonosteoporosiscanbefoundatSMOH
2009JanPDForatNationalGuidelineClearinghouse2013Jun10:39349
OsteoporosisSocietyofthePhilippinesFoundationInc./PhilippineOrthopedicAssociation(OSPFI/POA)
consensusstatementsonosteoporosisdiagnosis,prevention,andmanagementcanbefoundinIntJ
RheumDis2011Aug14(3):223
AsiaPacificTiboloneConsensusGroupupdatedclinicalrecommendationsonuseoftiboloneinAsian
womencanbefoundinClimacteric2010Aug13(4):317fulltext
AsianMetaforumconsensusstatementonVitaminDandmanagementofosteoporosiscanbefoundin
PublicHealthNutr2009Apr12(4):578
Chineseexpertclinicalpracticeguidelineontraditionalmedicineforprimaryosteoporosiscanbefoundin
ChinJIntegrMed2011Jan17(1):52
JapanOsteoporosisSociety,JapaneseSocietyforBoneandMineralResearch,JapanOsteoporosis
Foundationandresearchgrouponosteoporosis(fundedbyMinistryofHealth,LabourandWelfare)2006
guidelineonpreventionandtreatmentofosteoporosiscanbefoundatMindsguidelinelisting(
)[Japanese]
Mexicanguidelines:
GruposdeDesarrollodelasInstitucionesPblicasdelSistemaNacionaldeSaluddeMxico(Secretara
deSalud,IMSS,ISSSTE,SEDENA,SEMAR,DIF,PEMEX)guasdeprcticaclnicaenDiagnsticoy
tratamientodeosteoporosiseneladultosepuedenencontrarenSecretaradeSaludMxico2009PDF
[Spanish]
MexicanCollegeofOrthopedicsandTraumatology(ColegioMexicanodeOrtopediayTraumatologia
[CMOT])positionstatementondiagnosisandtreatmentofosteoporosiscanbefoundinActaOrtopMex
2011SepOct25(5):303[Spanish]
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CentralandSouthAmericanguidelines:
CommitteeforOsteoporosisandBoneMetabolicDisordersoftheBrazilianSocietyof
Rheumatology/BrazilianMedicalAssociation/BrazilianAssociationofPhysicalMedicineand
Rehabilitation(BSR/BMA/BAPMR)guidelineonpreventionandtreatmentofglucocorticoidinduced
osteoporosiscanbefoundinRevBrasReumatol2012Aug52(4):580fulltext[English,Portuguese]
BrazilianSocietyforClinicalDensitometrypositionpaperonclinicaldensitometrycanbefoundinArq
BrasEndocrinolMetabol2009Feb53(1):107fulltext[Portuguese]
AustralianandNewZealandguidelines:
RoyalAustralianCollegeofGeneralPractitioners(RACGP)clinicalguidelineson
osteoporosiscanbefoundatRACGP2013JunPDForatNationalGuidelineClearinghouse2013
Sep9:43860
preventionandtreatmentofosteoporosisinpostmenopausalwomenandoldermencanbefound
atRACGP2010FebPDF
AustralianandNewZealandBoneandMineralSociety/OsteoporosisAustralia/EndocrineSocietyof
AustraliapositionstatementoncalciumandbonehealthcanbefoundinMedJAust2009Mar
16190(6):316
AustralianandNewZealandBoneandMineralSociety/EndocrineSocietyofAustralia/Osteoporosis
Australia(ANZBMS/ESA/OA)positionstatementonvitaminDandhealthinadultsinAustraliaandNew
ZealandcanbefoundinMedJAust2012Jun18196(11):686,summarycanbefoundatOsteoporosis
Australia2013OctPDF
expertguidelineonbazedoxifeneuseinpostmenopausalosteoporosiscanbefoundinDrugsAging2012
Apr129(4):329
MiddleEasternguidelines:
SaudiArabianexpertrecommendationsondiagnosisandmanagementofosteoporosis:localperspective
canbefoundinAnnSaudiMed2011MarApr31(2):111fulltext
Reviewarticles:
generalreviews
reviewcanbefoundinAnnInternMed2011Jul5155(1):ITC11
reviewcanbefoundinAmFamPhysician2009Feb179(3):193fulltext,editorialcanbefoundin
AmFamPhysician2009Feb179(3):189fulltext
reviewcanbefoundinNEnglJMed2007May31356(22):2293
reviewcanbefoundinBMJ2006Dec16333(7581):1251fulltext,commentarycanbefoundin
BMJ2007Jan6334(7583):8fulltext
reviewofscreeningforosteoporosiscanbefoundinJAMA2015Apr14313(14):1467
reviewofsevereosteoporosisanditsidentificationcanbefoundinAgingClinExpRes2011Apr23(2
Suppl):6
reviewoftestingforsecondarycausesofosteoporosiscanbefoundinBMJ2010Dec16341:c6959
reviewofboneturnovermarkerstomonitortreatmentofpatientswithosteoporosiscanbefoundinCurr
OsteoporosRep2010Mar8(1):15
reviewofpremenopausalosteoporosiscanbefoundinArchInternMed2004Mar22164(6):603
reviewsofpostmenopausalosteoporosis
reviewcanbefoundinNEnglJMed2005Aug11353(6):595,commentarycanbefoundinNEngl
JMed2005Nov3353(18):1974
reviewcanbefoundinAHRQEvidenceReport2001Feb:28
editorialreviewcanbefoundinBMJ2003Aug16327(7411):355fulltext,commentarycanbe
foundinBMJ2003Nov1327(7422):1051fulltext
reviewofimplicationsforfracturehealingofcurrentandnewosteoporosistreatmentscanbefoundin
CalcifTissueInt2012May90(5):343
reviewofdrugtherapyforosteoporosiscanbefoundinLancet2011Apr9377(9773):1276fulltext
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reviewofdualenergyxrayabsorptiometry(DEXA)scanninginclinicalpracticecanbefoundinQJM
2008Aug101(8):605fulltext
reviewofmanagementofosteoporosisinelderlywomencanbefoundinAnnalsofLongTermCare2009
Oct17(10):35
reviewsoffractureprevention
AHRQcomparativeeffectivenessreviewontreatmenttopreventfracturesinmenandwomenwith
lowbonedensityorosteoporosiscanbefoundatAHRQComparativeEffectivenessReview2012
Mar:53PDF
reviewoffracturepreventioninpostmenopausalwomencanbefoundinAmFamPhysician2008
May1577(10):1447fulltext
reviewofraloxifeneforpreventionofosteoporoticfracturescanbefoundinAmFamPhysician
2005Jul172(1):132fulltext
reviewsinmen
reviewofosteoporosisinmencanbefoundinAmFamPhysician2010Sep182(5):503fulltext
reviewofosteoporosisinmencanbefoundinNEnglJMed2008Apr3358(14):1474,
commentarycanbefoundinNEnglJMed2008Aug21359(8):868
reviewofosteoporosisinmencanbefoundinCMAJ2007Jan30176(3):345fulltext,commentary
canbefoundinCMAJ2007Oct23177(9):1069fulltext
reviewsinspecialpopulations
reviewoffemaleathletetriadanditscomponents:towardimprovedscreeningandmanagement
canbefoundinMayoClinProc2013Sep88(9):996
reviewoffemaleathletetriad(osteoporosis,disorderedeating,menstrualdisorders)canbefound
inBMJ2005Jan29330(7485):244fulltext
reviewofhealthrelatedconcernsoffemaleathletecanbefoundinAmFamPhysician2009Mar
1579(6):489fulltext
reviewoffemaleathletetriadcanbefoundinAmFamPhysician2000Jun161(11):3357fulltext
casepresentationonunderstandingspectrumoffemaleathletetriadcanbefoundinObstet
Gynecol2010Dec116(6):1444
reviewofmanagementofbonelossinpoststrokepatientscanbefoundinAgeAgeing2008
Mar37(2):142fulltext
reviewofsoycanbefoundinAmFamPhysician2009Jan179(1):43fulltext
reviewofeffectsofisoflavonesonbonehealthcanbefoundinClimacteric2011Apr14(2):204
MEDLINEsearch:
tosearchMEDLINEfor(Osteoporosis)withtargetedsearch(ClinicalQueries),clicktherapy,diagnosis,or
prognosis
PatientInformation
comprehensiveinformation
handoutfromNationalInstitutesofHealth
handoutfromPatientUKPDF
handoutfromAmericanAcademyofFamilyPhysiciansorinSpanish
handoutfromAmericanCollegeofRheumatology
bonemineraldensityinformation
handoutonbonemassmeasurementfromNationalInstitutesofHealth
handoutondualenergyxrayabsorptiometry(DEXA)scanfromPatientUKPDF
handoutonbonedensitytestingfromNationalOsteoporosisFoundation
medicationandsupplementinformation
handoutontypesofosteoporosismedicationsfromNationalOsteoporosisFoundation
handoutonmedicationsforosteoporosisfromMayoClinic
handoutonHowtotakecalciumfromKimA.Carmichael,MD
handoutonfemaleathletetriadfromAmericanAcademyofFamilyPhysiciansorinSpanish
ICD9/ICD10Codes
ICD9codes:
733.0osteoporosis
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733.00osteoporosis,unspecified
733.01senileosteoporosis
733.02idiopathicosteoporosis
733.03disuseosteoporosis
733.09otherosteoporosis
781.91lossofheight
V13.51personalhistoryofpathologicfracture
V58.68longterm(current)useofbisphosphonates
V82.81specialscreeningforotherspecifiedconditions,osteoporosis
ICD10codes:
optionalsubclassificationcodestoindicatesiteofinvolvementforM80,M81,M82
0multiplesites
1shoulderregion
2upperarm
3forearm
4hand
5pelvicregionandthigh
6lowerleg
7ankleandfoot
8other
9siteunspecified
M80osteoporosiswithpathologicalfracture
M80.0postmenopausalosteoporosiswithpathologicalfracture
M80.1postoophorectomyosteoporosiswithpathologicalfracture
M80.2osteoporosisofdisusewithpathologicalfracture
M80.3postsurgicalmalabsorptionosteoporosiswithpathologicalfracture
M80.4druginducedosteoporosiswithpathologicalfracture
mayuseadditionalexternalcausecode(ChapterXX)toidentifydrug
M80.5idiopathicosteoporosiswithpathologicalfracture
M80.8otherosteoporosiswithpathologicalfracture
M80.9unspecifiedosteoporosiswithpathologicalfracture
M81osteoporosiswithoutpathologicalfracture
M81.0postmenopausalosteoporosis
M81.1postoophorectomyosteoporosis
M81.2osteoporosisofdisuse
M81.3postsurgicalmalabsorptionosteoporosis
M81.4druginducedosteoporosis
mayuseadditionalexternalcausecode(ChapterXX)toidentifydrug
M81.5idiopathicosteoporosis
M81.6localizedosteoporosis[Lequesne]
M81.8otherosteoporosis
M81.9osteoporosis,unspecified
M82osteoporosisindiseasesclassifiedelsewhere
M82.0osteoporosisinmultiplemyelomatosis
M82.1osteoporosisinendocrinedisorders
M82.8osteoporosisinotherdiseasesclassifiedelsewhere
References
Generalreferencesused:
1.NationalOsteoporosisFoundation(NOF).Clinician'sguidetopreventionandtreatmentof
osteoporosis.NOF2013PDF
2.InstituteforClinicalSystemsImprovement(ICSI).Diagnosisandtreatmentofosteoporosis.ICSI2013
JulPDF
3.NorthAmericanMenopauseSociety.Managementofosteoporosisinpostmenopausalwomen:2010
positionstatementofTheNorthAmericanMenopauseSociety.Menopause.2010JanFeb17(1):2554
4.WattsNB,AdlerRA,BilezikianJP,etalEndocrineSociety.Osteoporosisinmen:anEndocrine
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Societyclinicalpracticeguideline.JClinEndocrinolMetab.2012Jun97(6):180222
5.InternationalSocietyforClinicalDensitometry(ISCD).Skeletalhealthassessmentinchildrenfrom
infancytoadolescence.ISCD2013
6.InternationalSocietyforClinicalDensitometry(ISCD).Indicationsforbonemineraldensity(BMD)
testing.ISCD2013
Recommendationgradingsystemsused:
AmericanCollegeofRheumatologylevelsofevidence
LevelAdataderivedfrommultiplerandomizedclinicaltrialsormetaanalyses
LevelBdataderivedfromsinglerandomizedtrialornonrandomizedstudies
LevelConlyconsensusopinionsofexperts,casestudies,orstandardofcare
ReferenceACR2010recommendationsonpreventionandtreatmentofglucocorticoidinduced
osteoporosis(ArthritisCareRes(Hoboken)2010Nov62(11):1515fulltext)
InstituteforClinicalSystemsImprovement(ICSI)gradingsystem
strengthofrecommendation
Strongrecommendationbenefitsoutweighrisksorharms,recommendationappliesto
mostpatients
Weakrecommendationbenefitsandharmsarebalancedoruncertaintyexistsaboutbest
estimatesofbenefitsandharmsrecommendationmaydependonlocalcircumstances,
patientvalues,orpreferences
qualityofevidence
Highqualityevidencefurtherresearchunlikelytochangeconfidenceinestimateofeffect
Moderatequalityevidencefurtherresearchmayimpactrecommendationandconfidencein
estimateofeffect
Lowqualityevidencefurtherresearchverylikelytohaveimportantimpactonconfidence
inestimateofeffectandlikelytochange,soanyestimateofeffectisveryuncertain
ReferenceICSIguidelineondiagnosisandtreatmentofosteoporosis(ICSI2013JulPDF)
EndocrineSocietyusesGradingofRecommendations,Assessment,Development,andEvaluation
(GRADE)system
strengthofrecommendation
Strongrecommendationguidelinepanelmembershavehighconfidencethatdesirable
effectsofrecommendationoutweighundesirableeffects(orviceversa)
Weakrecommendationguidelinepanelmembersconcludewithlessconfidencethat
desirableeffectsofrecommendationprobablyoutweighundesirableeffects,orbenefitsand
harmsarefinelybalanced,orappreciableuncertainty
qualityofevidence
Highqualityevidenceconsistentevidencefromwellperformedrandomizedcontrolled
trials,orexceptionallystrongevidencefromunbiasedobservationalstudies
Moderatequalityevidencerandomizedcontrolledtrialswithimportantlimitations
(inconsistentresults,methodologicalflaws,indirectorimpreciseevidence),orunusually
strongevidencefromunbiasedobservationalstudies
Lowqualityevidence1criticaloutcomefromobservationalstudies,randomized
controlledtrialswithseriousflaws,orindirectevidence
Verylowqualityevidence1ofthecriticaloutcomesfromunsystematicclinical
observationsorveryindirectevidence
ReferenceEndocrineSocietyclinicalpracticeguidelineonosteoporosisinmen(JClinEndocrinol
Metab2012Jun97(6):1802fulltext)
UnitedStatesPreventiveServicesTaskForce(USPSTF)gradesofrecommendation(June2007June
2012)
GradeAUSPSTFrecommendstheservicewithhighcertaintyofsubstantialnetbenefit
GradeBUSPSTFrecommendstheservicewithhighcertaintyofmoderatenetbenefitor
moderatecertaintyofmoderatetosubstantialnetbenefit
GradeCcliniciansmayprovidetheservicetoselectpatientsdependingonindividual
circumstances,however,onlysmallbenefitislikelyformostindividualswithoutsignsor
symptoms
GradeDUSPSTFrecommendsagainstprovidingtheservicewithmoderatetohighcertaintyof
nonetbenefitorharmsoutweighingbenefits
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GradeIinsufficientevidencetoassessbalanceofbenefitsandharms
ReferenceUSPSTFGradeDefinitions
UnitedStatesPreventiveServicesTaskForce(USPSTF)gradesofrecommendation(afterJuly2012)
GradeAUSPSTFrecommendstheservicewithhighcertaintyofsubstantialnetbenefit
GradeBUSPSTFrecommendstheservicewithhighcertaintyofmoderatenetbenefitor
moderatecertaintyofmoderatetosubstantialnetbenefit
GradeCUSPSTFrecommendsselectivelyofferingorprovidingtheservice(basedon
professionaljudgmentandpatientpreference)withatleastmoderatecertaintyofsmallnetbenefit
GradeDUSPSTFrecommendsagainstprovidingtheservicewithmoderatetohighcertaintyof
nonetbenefitorharmsoutweighingbenefits
GradeIinsufficientevidencetoassessbalanceofbenefitsandharms
ReferenceUSPSTFGradeDefinitions
SynthesizedRecommendationGradingSystemforDynaMedPlus:
DynaMedsystematicallymonitorsclinicalevidencetocontinuouslyprovideasynthesisofthemostvalid
relevantevidencetosupportclinicaldecisionmaking(See7StepEvidenceBasedMethodology).
GuidelinerecommendationssummarizedinthebodyofaDynaMedtopicareprovidedwiththe
recommendationgradingsystemusedintheoriginalguideline(s),andallowDynaMeduserstoquickly
seewhereguidelinesagreeandwhereguidelinesdifferfromeachotherandfromthecurrentevidence.
InDynaMedPlus,wesynthesizethecurrentevidence,currentguidelinesfromleadingauthorities,and
clinicalexpertisetoproviderecommendationstosupportclinicaldecisionmakingintheOverview&
Recommendationssection.
WeusetheGradingofRecommendationsAssessment,DevelopmentandEvaluation(GRADE)to
classifysynthesizedrecommendationsasStrongorWeak.
Strongrecommendationsareusedwhen,basedontheavailableevidence,clinicians(without
conflictsofinterest)consistentlyhaveahighdegreeofconfidencethatthedesirable
consequences(healthbenefits,decreasedcostsandburdens)outweightheundesirable
consequences(harms,costs,burdens).
Weakrecommendationsareusedwhen,basedontheavailableevidence,cliniciansbelievethat
desirableandundesirableconsequencesarefinelybalanced,orappreciableuncertaintyexists
aboutthemagnitudeofexpectedconsequences(benefitsandharms).Weakrecommendationsare
usedwhencliniciansdisagreeinjudgmentsofrelativebenefitandharm,orhavelimitedconfidence
intheirjudgments.Weakrecommendationsarealsousedwhentherangeofpatientvaluesand
preferencessuggeststhatinformedpatientsarelikelytomakedifferentchoices.
DynaMedPlussynthesizedrecommendations(intheOverview&Recommendationssection)are
determinedwithasystematicmethodology:
Recommendationsareinitiallydraftedbyclinicaleditors(including1withmethodological
expertiseand1withcontentdomainexpertise)awareofthebestcurrentevidenceforbenefits
andharms,andtherecommendationsfromguidelines.
Recommendationsarephrasedtomatchthestrengthofrecommendation.Strong
recommendationsuse"shoulddo"phrasing,orphrasingimplyinganexpectationtoperformthe
recommendedactionformostpatients.Weakrecommendationsuse"consider"or"suggested"
phrasing.
RecommendationsareexplicitlylabeledasStrongrecommendationsorWeak
recommendationswhenaqualifiedgrouphasexplicitlydeliberatedonmakingsucha
recommendation.Groupdeliberationmayoccurduringguidelinedevelopment.Whengroup
deliberationoccursthroughDynaMedinitiatedgroups:
ClinicalquestionswillbeformulatedusingthePICO(Population,Intervention,Comparison,
Outcome)frameworkforalloutcomesofinterestspecifictotherecommendationtobe
developed.
Systematicsearcheswillbeconductedforanyclinicalquestionswheresystematic
searcheswerenotalreadycompletedthroughDynaMedcontentdevelopment.
Evidencewillbesummarizedforrecommendationpanelreviewincludingforeachoutcome
therelativeimportanceoftheoutcome,theestimatedeffectscomparinginterventionand
comparison,thesamplesize,andoverallqualityratingforthebodyofevidence.
Recommendationpanelmemberswillbeselectedtoincludeatleastthreemembersthat
togetherhavesufficientclinicalexpertiseforthesubject(s)pertinenttothe
recommendation,methodologicalexpertisefortheevidencebeingconsidered,and
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experiencewithguidelinedevelopment.
Allrecommendationpanelmembersmustdiscloseanypotentialconflictsofinterest
(professional,intellectual,andfinancial),andwillnotbeincludedforthespecificpanelifa
significantconflictexistsfortherecommendationinquestion.
PanelmemberswillmakeStrongrecommendationsifandonlyifthereisconsistent
agreementinahighconfidenceinthelikelihoodthatdesirableconsequencesoutweigh
undesirableconsequencesacrossthemajorityofexpectedpatientvaluesandpreferences.
PanelmemberswithmakeWeakrecommendationsifthereislimitedconfidence(or
inconsistentassessmentordissentingopinions)thatdesirableconsequencesoutweigh
undesirableconsequencesacrossthemajorityofexpectedpatientvaluesandpreferences.
Norecommendationwillbemadeifthereisinsufficientconfidencetomakea
recommendation.
Allstepsinthisprocess(includingevidencesummarieswhichweresharedwiththepanel,
andidentificationofpanelmembers)willbetransparentandaccessibleinsupportofthe
recommendation.
Recommendationsareverifiedby1editorwithmethodologicalexpertise,notinvolvedin
recommendationdraftingordevelopment,withexplicitconfirmationthatStrongrecommendations
areadequatelysupported.
Recommendationsarepublishedonlyafterconsensusisestablishedwithagreementinphrasing
andstrengthofrecommendationbyalleditors.
Ifconsensuscannotbereachedthentherecommendationcanbepublishedwithanotationof
"dissentingcommentary"andthedissentingcommentaryisincludedinthetopicdetails.
Ifrecommendationsarequestionedduringpeerrevieworpostpublicationbyaqualifiedindividual,
orreevaluationiswarrantedbasedonnewinformationdetectedthroughsystematicliterature
surveillance,therecommendationissubjecttoadditionalinternalreview.
DynaMededitorialprocess:
DynaMedtopicsarecreatedandmaintainedbytheDynaMedEditorialTeam.
Over500journalsandevidencebasedsources(DynaMedContentSources)aremonitoreddirectlyor
indirectlyusinga7Stepevidencebasedmethodforsystematicliteraturesurveillance.DynaMedtopics
areupdateddailyasnewlydiscoveredbestavailableevidenceisidentified.
TheparticipatingmembersoftheDynaMedEditorialTeamhavedeclaredthattheyhavenofinancialor
othercompetinginterestsrelatedtothistopic.
Theparticipatingreviewershavedeclaredthattheyhavenofinancialorothercompetinginterestsrelated
tothistopic,unlessotherwiseindicated.
McMasterUniversityisapartnerthatprovidessupportinidentifyingPracticeChangingDynaMed
Updates.Over1,000practicingphysiciansfrom61disciplinesin77countriesratethesearticlestohelp
youfindthemostusefulnewevidenceaffectingyourpractice.
F1000isapartnerthatprovidessupportinidentifyingPracticeChangingDynaMedUpdates.Over2,000
practicingcliniciansfrom20disciplinesin60countriesratethesearticlestohelpyoufindthemostuseful
newevidenceaffectingyourpractice.
Specialacknowledgements:
WilliamAhrens,MD(CoreFaculty,GrandRapidsMedicalEducationPartners,MichiganStateUniversity
CollegeofHumanMedicineMichigan,UnitedStates)providespeerreview.
KimA.Carmichael,MD,FACP(AssociateProfessorofMedicine,DivisionofEndocrinology,Metabolism
andLipidResearch,WashingtonUniversityMissouri,UnitedStates)providespeerreview.
Dr.CarmichaeldeclaresreceivingspeakingfeesfromMerckandJanssen.
Howtocite:
ForattributioninotherpublicationsseeHowtoCiteInformationfromDynaMed.
YouareviewingaDynaMedsummary.UseofDynaMedindicatesacceptanceofDynaMedTermsofUse.
LimitationsofDynaMedarecontainedintheDynaMedTermsofUse.
PleasegiveusyourfeedbackbyemailingDynaMedat:DynaMedEditor@ebscohost.com
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