Vitamin D and Calcium Supplementation to Prevent Fractures in Adults U - PDF document

VitaminDandCalciumSupplementationtoPreventFracturesinAdults:U.S.PreventiveServicesTaskForceRecommendationVirginiaA.Moyer,MD,MPH,onbehalfoftheU.S.PreventiveServicesTaskForce*NewU.S.PreventiveServicesTaskForce(USPSTF)recommendationstatementonvitaminDandcalciumsupplemen-tationtopreventfracturesinadults.TheUSPSTFcommissioned2systematicevidencere-viewsandameta-analysisonvitaminDsupplementationwithorwithoutcalciumtoassesstheeffectsofsupplementationonbonehealthoutcomesincommunity-dwellingadults,theassociationofvitaminDandcalciumlevelswithbonehealthoutcomes,andtheadverseeffectsofsupplementation.Theserecommendationsapplytononinstitutionalizedorcommunity-dwellingasymptomaticadultswithoutahistoryoffractures.ThisrecommendationdoesnotapplytothetreatmentofpersonswithosteoporosisorvitaminDdeficiency.TheUSPSTFconcludesthatthecurrentevi-denceisinsufficienttoassessthebalanceofthebenefitsandharmsofcombinedvitaminDandcalciumsupplementationforthepri-marypreventionoffracturesinpremenopausalwomenorinmen.(Istatement)TheUSPSTFconcludesthatthecurrentevidenceisinsufficienttoassessthebalanceofthebenefitsandharmsofdailysupplemen-tationwithgreaterthan400IUofvitaminDandgreaterthan1000mgofcalciumfortheprimarypreventionoffracturesinnoninstitutionalizedpostmenopausalwomen.(Istatement)TheUSPSTFrecommendsagainstdailysupplementationwith400IUorlessofvitaminDand1000mgorlessofcalciumfortheprimarypreventionoffracturesinnoninstitutionalizedpostmeno-pausalwomen.(Drecommendation) heU.S.PreventiveServicesTaskForce(USPSTF)makesrecommendationsabouttheeffectivenessofspeciÞcclinicalpreventiveservicesforpatientswithoutrelatedsignsorItbasesitsrecommendationsontheevidenceofboththebeneÞtsandharmsoftheserviceandanassessmentofthebalance.TheUSPSTFdoesnotconsiderthecostsofprovidingaserviceinthisassessment.TheUSPSTFrecognizesthatclinicaldecisionsinvolvemoreconsiderationsthanevidencealone.CliniciansshouldunderstandtheevidencebutindividualizedecisionmakingtothespeciÞcpatientorsituation.Similarly,theUSPSTFnotesthatpolicyandcoveragedecisionsinvolveconsiderationsinadditiontotheevidenceofclinicalbeneÞtsandharms.UMMARYOFECOMMENDATIONSANDTheUSPSTFconcludesthatthecurrentevidenceisinsufÞcienttoassessthebalanceofthebeneÞtsandharmsofcombinedvitaminDandcalciumsupplementationfortheprimarypreventionoffracturesinpremenopausalwomenorinmen.(Istatement)TheUSPSTFconcludesthatthecurrentevidenceisinsufÞcienttoassessthebalanceofthebeneÞtsandharmsofdailysupplementationwithgreaterthan400IUofvi-taminDandgreaterthan1000mgofcalciumfortheprimarypreventionoffracturesinnoninstitutionalizedpostmenopausalwomen.(Istatement)TheUSPSTFrecommendsagainstdailysupplementa-tionwith400IUorlessofvitaminDand1000mgor ClinicalGuideline7May2013 AnnalsofInternalMedicine Volume158¥Number9 691 AnnalsofInternalMedicine Seetheforasummaryoftherecommendationandsuggestionsforclinicalpractice.AppendixTable1describestheUSPSTFgrades,andAppendixTable2describestheUSPSTFclassiÞcationoflevelsofcertaintyaboutnetbeneÞt(bothtablesareavail-ableatwww.annals.org).Fractures,particularlyhipfractures,areassociatedwithchronicpainanddisability,lossofindependence,de-creasedqualityoflife,andincreasedmortality(1).Onehalfofallpostmenopausalwomenwillhaveanosteoporosis-relatedfractureduringtheirlifetime.AppropriateintakeofvitaminDandcalciumarees-sentialtooverallhealth.TheInstituteofMedicinehaspublishedrecommendeddietaryallowances().How-ever,thebeneÞtsandharmsofdailysupplementationwithgreaterthan400IUofvitaminDandgreaterthan1000mgofcalciumtopreventfracturesarenotclearlyBenefitsofPreventiveMedicationInpremenopausalwomenandinmen,thereisinade-quateevidencetodeterminetheeffectofcombinedvita-minDandcalciumsupplementationontheincidenceoffractures.Inpostmenopausalwomen,thereisadequateev-idencethatdailysupplementationwith400IUofvitamincombinedwith1000mgofcalciumhasnoeffectontheincidenceoffractures.However,thereisinadequateevidenceabouttheeffectofhigherdosesofcombinedvi-taminDandcalciumsupplementationonfractureinci-denceinnoninstitutionalizedpostmenopausalwomen.HarmsofPreventiveMedicationAdequateevidenceindicatesthatsupplementationwith400IUorlessofvitaminDand1000mgorlessof VitaminDandcalciumsupplementationtopreventfracturesinadults:clinicalsummaryofU.S.PreventiveServicesTaskForcerecommendation. VITAMIN D AND CALCIUM SUPPLEMENTATION TO PREVENT FRACTURES IN ADULTSCLINICAL SUMMARY OF U.S. PREVENTIVE SERVICES TASK FORCE RECOMMENDATIONPreventive Medications RecommendationsBalance of Benefits and Harms Appropriate intake of vitamin D and calcium are essential to overall health. However, there is inadequate evidence to determine the effect of combined vitamin D and calcium supplementation on the incidence of fractures in men or premenopausal women.There is adequate evidence that daily supplementation with 400 IU of vitamin D and 1000 mg of calcium has no effect on the incidence of fractures in postmenopausal women. There is inadequate evidence regarding the effect of higher doses of combined vitamin D and calcium supplementation on fracture incidence in community-dwelling postmenopausal women.The USPSTF has made recommendations on screening for osteoporosis and vitamin D supplementation to prevent falls in community-dwelling older adults. These recommendations are available at www.uspreventiveservicestaskforce.org.Men or premenopausalNo recommendation.No recommendation. regarding the benefit of for the primary prevention of fractures, and the for the primary prevention of fractures.Evidence is lacking regarding the benefit of prevention of fractures in postmenopausal For a summary of the evidence systematically reviewed in making this recommendation, the full recommendation statement, and supgo to www.uspreventiveservicestaskforce.org. ClinicalGuideline VitaminDandCalciumSupplementationtoPreventFracturesinAdults 7May2013 AnnalsofInternalMedicine Volume158¥Number9 calciumincreasestheincidenceofrenalstones.TheUSPSTFassessedthemagnitudeofthisharmassmall.USPSTFAssessmentNoninstitutionalized,Community-DwellingPostmenopausalTheUSPSTFconcludesthatevidenceislackingaboutthebeneÞtofdailysupplementationwithgreaterthan400IUofvitaminDandgreaterthan1000mgofcalciumfortheprimarypreventionoffractures,andthebalanceofbeneÞtsandharmscannotbedetermined.TheUSPSTFconcludeswithmoderatecertaintythatdailysupplementationwith400IUorlessofvitaminDand1000mgorlessofcalciumhasnonetbeneÞtfortheprimarypreventionoffractures.MenandPremenopausalWomenTheUSPSTFconcludesthatevidenceislackingaboutthebeneÞtofvitaminDsupplementationwithorwithoutcalciumfortheprimarypreventionoffractures,andthebalanceofbeneÞtsandharmscannotbedetermined.PatientPopulationUnderConsiderationThisrecommendationappliestononinstitutionalizedorcommunity-dwellingasymptomaticadultswithoutahistoryoffractures.ÒCommunity-dwellingÓisdeÞnedasnotlivinginanassistedlivingfacility,nursinghome,orotherinstitutionalcaresetting.ThisrecommendationdoesnotapplytopersonswithosteoporosisorvitaminDConsiderationsforPracticeRegardingtheIStatementsPotentialPreventableBurdenThehealthburdenoffracturesissubstantialintheolderadultpopulation.PotentialHarmsIntheWomenÕsHealthInitiative(WHI),astatisti-callyincreasedincidenceofrenalstonesoccurredinwomentakingsupplementalvitaminDandcalcium.Onewomanwasdiagnosedwithaurinarytractstoneforevery273womenwhoreceivedsupplementationovera7-yearVitaminDandcalciumsupplementsareinexpensiveandreadilyavailablewithoutaprescription.CurrentPracticeVitaminDandcalciumsupplementationareoftenrecommendedforwomen,especiallypostmenopausalwomen,topreventfractures.Surveysestimatethat56%ofwomenaged60yearsoroldertakesupplementalvitaminDand60%takeasupplementcontainingcalcium.Theexactdosageisnotwell-known(2).OtherApproachestoPreventionTheUSPSTFrecommendsscreeningforosteoporosisinwomenaged65yearsorolderandinyoungerwomenwhosefractureriskisequaltoorgreaterthanthatofa65-year-oldwhitewomanwhohasnoadditionalriskfac-tors.ThisrecommendationstatementisavailableontheUSPSTFWebsite(www.uspreventiveservicestaskforceTheUSPSTFrecommendsvitaminDsupplementa-tion(themediandoseofvitaminDinavailablestudieswas800IU)topreventfallsincommunity-dwellingadultsaged65yearsorolderwhoareatincreasedriskforfallsbecauseofahistoryofrecentfallsorvitaminDdeÞciency(Brecommendation).ThisrecommendationstatementisavailableontheUSPSTFWebsite(wwwResearchNeedsandGapsResearchisneededtodeterminewhetherdailysupple-mentationwithgreaterthan400IUofvitaminDgreaterthan1000mgofcalciumreducesfractureincidenceinpostmenopausalwomenoroldermen.ThecomparativeeffectivenessofdifferentpreparationsofvitaminD(forexample,Dvs.D)ordifferentcalciumformulationsshouldbeevaluated.ProspectivestudiesshouldassessthepotentialbeneÞtsofvitaminDandcalciumsupplementa-tioninearlyadulthoodonfractureincidencelaterinlife.StudiesareneededtoevaluatetheeffectsofvitaminDsupplementationondiversepopulations.Becausewhite InstituteofMedicine2011RecommendedDietaryAllowancesforVitaminDandCalcium* PopulationRecommendedDailyDoseVitaminD,Aged19–50y6001000Aged51–70y600120070y8001200Pregnantwomen18y600130018y6001000Breastfeedingwomen18y600130018y6001000Aged19–50y6001000Aged51–70y600100070y8001200Datafromreferences11and12. ClinicalGuidelineVitaminDandCalciumSupplementationtoPreventFracturesinAdults 7May2013 AnnalsofInternalMedicine Volume158¥Number9 693 womenhavethehighestriskforosteoporoticfractures,mostfracturepreventionstudiesaredoneinthispopula-tionanditisdifÞculttoextrapolateresultstononwhiteBurdenofDiseaseEachyear,approximately1.5millionosteoporoticfracturesoccurintheUnitedStates.Nearlyhalfofallwomenolderthan50yearswillhaveanosteoporosis-relatedfractureduringtheirlifetime.Fracturesareassoci-atedwithchronicpain,disability,anddecreasedqualityoflife.HipfracturessigniÞcantlyincreaseillnessanddeath.DuringtheÞrst3monthsafterahipfracture,apersonÕsmortalityriskis2.8to4timesthatofapersonofsimilaragelivinginthecommunitywithoutafracture.Nearly20%ofpatientswithhipfracturearesubsequentlyinstitu-tionalizedinlong-termcarefacilities(3).ScopeofReviewTheUSPSTFused2systematicevidencereviewsandanupdatedmeta-analysisonvitaminDsupplementationwithorwithoutcalcium(4Ð6)toassesstheeffectsofsup-plementationonbonehealthoutcomesincommunity-dwellingadults,theassociationofvitaminDandcalciumlevelswithbonehealthoutcomes,andtheadverseeffectsofsupplementation.TheUSPSTFdidnotconsiderquestionsrelatingtoadequatedailyintakeofcalciumandvitaminD,nordiditexaminetheeffectofcalciumsupplementationalone.Thesystematicreviewsdidnotexamineotherhealthoutcomes,suchaspregnancycomplications,preventionoffalls,cardiovasculardisease,oroverallmortality.TheassessmentofvitaminDsupplementationwithorwithoutcalciumtopreventcancerwasremovedfromthisrecommendationstatementandwillbeincorporatedintoaseparate,upcomingrecommendationstatement.EffectivenessofPreventiveMedicationSixteenrandomized,controlledtrialswithconsider-ableheterogeneityinpopulations,settings,andinterven-tionsexaminedtheeffectofvitaminDsupplementationwithorwithoutcalciumonfractureincidenceinadults(6).Postmenopausalwomenrepresentedthelargestgroupofparticipantsinthetrials;notrialsincludedwomenofchildbearingageormenyoungerthan50years.Almostalltrialparticipantswerewhite.Sixtrialsreportedahistoryoffracturesin10.6%to26%ofparticipants.Twotrialsin-cludedonlyadultswithahistoryoffractures,and5trialsincludedonlyelderlyinstitutionalizedadults.VitaminDdosesrangedfrom300to1370IUdaily,althoughmosttrialsusedatleast800IUdaily.FivetrialscomparedvitaminDwithplaceboornotreatment,8trialscomparedvitaminDandcalciumwithplaceboornotreat-ment,4trialscomparedvitaminDandcalciumwithcal-ciumalone,and1trialcomparedvitaminDandcalciumwithvitaminDalone;1trialhadseveralcomparisons.MostofthetrialsusedvitaminDastheintervention,but3usedvitaminD.Calciumsupplementationalsovaried.Mosttrialsusedcalciumcarbonate,whereasothersusedcitrate-,lactate-,orphosphate-basedpreparations.Meth-odsforfractureascertainmentincludedself-report,radio-graphconÞrmation,administrativedata,physicianveriÞca-tion,orsomecombination.TheUSPSTFconsidered6randomizedtrialsevaluat-ingtheuseofvitaminDandcalciumsupplementationwithinthescopeofthisrecommendation.Thesetrialswereconductedincommunity-dwellingadults,andfewerthan26%hadahistoryoffractures.NostatisticallysigniÞcantreductioninfractureswasobservedinthesestudies(pooledrelativerisk,0.89[95%CI,0.76to1.04]).Thelargesttrialoffractureoutcomesincludedinthemeta-analysiswastheWHItrial(7),whichenrolled36282healthypostmeno-pausalwomenaged50to79years.Approximately83%ofenrolledwomenwerewhite,9%wereblack,4%wereHis-panic,and4%wereofotherraces.Theinterventiongroupreceived400IUofvitaminDand1000mgofcalciumdaily;thecontrolgroupreceivedplacebo.Thisstudyre-portednostatisticallysigniÞcantreductioninhipfracture(hazardratio,0.88[CI,0.72to1.08])ortotalfractures(hazardratio,0.96[CI,0.91to1.02]).However,theUSPSTFcouldnotgeneralizetheresultsoftheWHItrialbeyondthespeciÞcdose,preparation,andpopulationstudied.Nearly30%ofstudyparticipantswerealreadytaking500mgormoreofcalciumdailybeforethestartofthetrial.TrialsofvitaminDsupplementationaloneshowednostatisticaldifference(pooledrelativerisk,1.03[CI,0.84to1.26]).Ofthe12trialsreportingbaselinelevelsofvitaminD,5reportedmeanvitaminDlevelslessthan30nmol/L,alevelconsideredtobevitaminDÐdeÞcient.However,neitherbaselinevitaminDstatusnorsupplementdosecor-relatedwithsupplementefÞcacy.Anindividualpatientdatameta-analysis(8)publishedaftertheUSPSTFÕsreviewincluded31022personsaged65yearsorolderfrom11trials,manyofwhichwerein-cludedintheUSPSTFreview.Themeta-analysiscon-cludedthatfracturesmaybereducedforpersonstakinghigherdosesofvitaminD(800IUdaily).Theeffectwasseeninbothinstitutionalizedandcommunity-dwellingadults.ThesubgroupthresholdswerenotpredeÞnedbytheoriginaltrialauthors,andthereductionwasnotcon-sideredstatisticallysigniÞcantwhenadjustedforseveralsubgroupanalyses.Therefore,anypositiveÞndingsshouldbeviewedwithcaution.PotentialHarmsofPreventiveMedicationReportingofadverseoutcomesinclinicaltrialsandobservationalstudiesofvitaminDandcalciumsupple-mentationislimited.TheWHItrial(9)reportedanin-creasedriskfornephrolithiasis(hazardratio,1.17[CI,1.02to1.34]).Theabsoluteriskwas2.5%intheinterventiongroupand2.1%intheplacebogroup,withanumber ClinicalGuideline VitaminDandCalciumSupplementationtoPreventFracturesinAdults 7May2013 AnnalsofInternalMedicine Volume158¥Number9 neededtoharmof273.ItisuncertainifthisadverseeffectoccursinvitaminDÐdeÞcientpopulations.Ameta-analysisofcalciumsupplementation(10)suggestsanasso-ciationbetweencalciumuseandincreasedriskforcardio-vasculardisease,butthelinkhasnotbeenconsistentlydemonstrated.TheeffectwasprimarilyseeninpersonstakingcalciumaloneandnotincombinationwithvitaminD.NoneofthestudiesreviewedbytheUSPSTFreportedthisadverseeffect.EstimateofMagnitudeofNetBenefitExceptforpostmenopausalwomen,thereisinade-quateevidencetoestimatethebeneÞtsofvitaminDorcalciumsupplementationtopreventfracturesinnoninsti-tutionalizedadults.DuetothelackofeffectonfractureincidenceandtheincreasedincidenceofnephrolithiasisintheinterventiongroupoftheWHItrial,theUSPSTFcon-cludeswithmoderatecertaintythatdailysupplementationwith400IUofvitaminDand1000mgofcalciumhasnonetbeneÞtfortheprimarypreventionoffracturesinnoninstitutionalized,postmenopausalwomen.AlthoughwomenenrolledinWHIwerepredominatelywhite,thelowerriskforfracturesinnonwhitewomenmakesitveryunlikelythatabeneÞtwouldexistinthispopulation.ResponsetoPublicCommentsAdraftversionofthisrecommendationstatementwaspostedforpubliccommentontheUSPSTFWebsitefrom12Juneto10July2012.TheUSPSTFreceivedmorethan40comments.Inresponse,informationwasaddedtotheRationalesectiontoreinforcethebasicdietaryrequire-mentsforvitaminDandcalcium.Severalrecentlypub-lishedstudiesonthebeneÞtsandharmsofvitaminDandcalciumsupplementationwerereviewed,andtheirresultswerehighlightedintheDiscussionsection.ThedoseofcalciumusedintheWHItrialwasclariÞedthroughouttheHowDoesEvidenceFitWithBiologicalUnderstanding?Calciumisoneofthemainbuildingblocksofbonegrowth.VitaminDhelpsbonesabsorbcalcium.Normalhealthybonesturnovercalciumconstantly,replacingcal-ciumlosswithnewcalciumreceivedfromdietaryintake.Thereare2mainsourcesofvitaminDinthehumanbody.Ergocalciferol,orvitaminD,isconsumedinthediet,mainlyintheformoffattyÞsh.FortiÞedfoods,suchasmilk,yogurt,andorangejuice,provideotherdietarysourcesofvitaminD.Cholecalciferol,orvitaminD,issynthesizedintheskinbyultravioletBraysfromthesun.VitaminDisconvertedtoitsactiveformbymeansofenzymaticprocessesintheliverandkidney.MostcellscontainspeciÞcreceptorsfortheactiveformofvitaminD.Stimulationofskeletalmusclereceptorspromotesproteinsynthesis,andvitaminDhasabeneÞcialeffectonmusclestrengthandbalance.VitaminDcontrolscalciumabsorp-tioninthesmallintestines,interactswithparathyroidhor-monetohelpmaintaincalciumhomeostasisbetweenthebloodandbones,andisessentialforbonegrowthandmaintainingbonedensity.InsufÞcientamountsofvitaminDobtainedthroughthedietorsunexposurecanleadtoinadequatelevelsofthehormonecalcitriol(theactiveformofvitaminD),whichinturncanleadtoimpaireddietarycalciumabsorption.Subsequently,thebodyusescalciumfromskeletalstores,whichcanweakenexistingbones.ECOMMENDATIONSOFTheInstituteofMedicine()(11)andtheWorldHealthOrganization(12)haverecommendedstandardsforadequatedailyintakeofcalciumandvitaminDasapartofoverallhealth.Neitherorganizationhasmaderec-ommendationsspeciÞctofractureprevention.TheInsti-tuteofMedicinenotesthechallengeofdeterminingdietaryreferenceintakesgiventhecomplexinterrelationshipbe-tweencalciumandvitaminD,theinconsistencyofstudiesexaminingbonehealthoutcomes,andtheneedtolimitsunexposuretominimizeskincancerrisk.FromtheU.S.PreventiveServicesTaskForce,Rockville,Maryland.RecommendationsmadebytheUSPSTFareindependentoftheU.S.government.TheyshouldnotbeconstruedasanofÞcialposi-tionoftheAgencyforHealthcareResearchandQualityortheU.S.DepartmentofHealthandHumanServices.FinancialSupport:TheUSPSTFisanindependent,voluntarybody.TheU.S.CongressmandatesthattheAgencyforHealthcareResearchandQualitysupporttheoperationsoftheUSPSTF.PotentialConflictsofInterest:Nonedisclosed.DisclosureformsfromUSPSTFmemberscanbeviewedatwww.acponline.org/authors/icmjeRequestsforSingleReprints:ReprintsareavailablefromtheUSPSTFWebsite(www.uspreventiveservicestaskforce.org).NelsonHD,HaneyEM,DanaT,BougatsosC,ChouR.Screeningforosteoporosis:anupdatefortheU.S.PreventiveServicesTaskForce.AnnInternMed.2010;153:99-111.[PMID:20621892]GahcheJ,BaileyR,BurtV,HughesJ,YetleyE,DwyerJ,etal.supplementuseamongU.S.adultshasincreasedsinceNHANESIII(1988-1994).NCHSDataBrief.2011:1-8.[PMID:21592424]OfÞceoftheSurgeonGeneral.BoneHealthandOsteoporosis:AReportoftheSurgeonGeneral.Rockville,MD:U.S.DepartmentofHealthandHumanServices,OfÞceoftheSurgeonGeneral;2004.Accessedatwww.ncbi.nlm.nih.gov/books/NBK45513/on31May2012.CranneyA,HorsleyT,OÕDonnellS,WeilerH,PuilL,OoiD,etal.EffectivenessandSafetyofVitaminDinRelationtoBoneHealth.EvidenceReport/TechnologyAssessmentNo.158.Rockville,MD:AgencyforHealthcareResearchandQuality;2007.Accessedatwww.ncbi.nlm.nih.gov/books/NBK38410/on31May2012.ChungM,BalkEM,BrendelM,IpS,LauJ,LeeJ,etal.VitaminDandCalcium:ASystematicReviewofHealthOutcomes.EvidenceReport/Technol-ogyAssessmentNo.183.Rockville,MD:AgencyforHealthcareResearchandQuality;2009.Accessedatwww.ncbi.nlm.nih.gov/books/NBK32603/on31May2012.ChungM,LeeJ,TerasawaT,LauJ,TrikalinosTA.VitaminDwithorwithoutcalciumsupplementationforpreventionofcancerandfractures:anup- ClinicalGuidelineVitaminDandCalciumSupplementationtoPreventFracturesinAdults 7May2013 AnnalsofInternalMedicine Volume158¥Number9 695 datedmeta-analysisfortheU.S.PreventiveServicesTaskForce.AnnInternMed.2011;155:827-38.[PMID:22184690]JacksonRD,LaCroixAZ,GassM,WallaceRB,RobbinsJ,LewisCE,etal;WomenÕsHealthInitiativeInvestigators.CalciumplusvitaminDsupplemen-tationandtheriskoffractures.NEnglJMed.2006;354:669-83.[PMID:Bischoff-FerrariHA,WillettWC,OravEJ,OrayEJ,LipsP,MeunierPJ,etal.ApooledanalysisofvitaminDdoserequirementsforfractureprevention.NEnglJMed.2012;367:40-9.[PMID:22762317]WallaceRB,Wactawski-WendeJ,OÕSullivanMJ,LarsonJC,CochraneB,GassM,etal.UrinarytractstoneoccurrenceintheWomenÕsHealthInitiative(WHI)randomizedclinicaltrialofcalciumandvitaminDsupplements.AmJClinNutr.2011;94:270-7.[PMID:21525191]BollandMJ,AvenellA,BaronJA,GreyA,MacLennanGS,GambleGD,etal.Effectofcalciumsupplementsonriskofmyocardialinfarctionandcardio-vascularevents:meta-analysis.BMJ.2010;341:c3691.[PMID:20671013]RossCA,TaylorCL,YaktineAL,DelValleHB,eds;CommitteetoReviewDietaryReferenceIntakesforVitaminDandCalcium;InstituteofMedicine.DietaryReferenceIntakesforCalciumandVitaminD.Washington,DC:Na-tionalAcademyPress;2011.Accessedatwww.nap.edu/catalog.php?record13050on31May2012.WorldHealthOrganizationandFoodandAgricultureOrganizationoftheUnitedNations.VitaminandMineralRequirementsinHumanNutrition.2nded.Geneva,Switzerland:WorldHealthOrganization;2004.Accessedatwww.who.int/nutrition/publications/micronutrients/9241546123/en/index.htmlon31May2012. o f Annals — articles since1 9 2 7 for printing or o Where is that article I read in Interested? Go to www.annals.org availableonline reading ClinicalGuideline VitaminDandCalciumSupplementationtoPreventFracturesinAdults 7May2013 AnnalsofInternalMedicine Volume158¥Number9 :U.S.PMembersoftheU.S.PreventiveServicesTaskForceatthetimethisrecommendationwasÞnalizedareVirginiaA.Moyer,MD,MPH,(BaylorCollegeofMedicine,Houston,Tex-as);MichaelL.LeFevre,MD,MSPH,Co-ViceChairofMissouriSchoolofMedicine,Columbia,Missouri);AlbertL.Siu,MD,MSPH,Co-ViceChair(MountSinaiSchoolofMedi-cine,NewYork,andJamesJ.PetersVeteransAffairsMedicalCenter,Bronx,NewYork);LindaCiofuBaumann,PhD,RN(UniversityofWisconsin,Madison,Wisconsin);KirstenBibbins-Domingo,PhD,MD(UniversityofCalifornia,SanFrancisco,SanFrancisco,California);SusanJ.Curry,PhD(UniversityofIowaCollegeofPublicHealth,IowaCity,Iowa);MarkEbell,MD,MS(UniversityofGeorgia,Athens,Georgia);GlennFlores,MD(UniversityofTexasSouthwestern,Dallas,Texas);AdelitaGonzalesCantu,RN,PhD(UniversityofTexasHealthScienceCenter,SanAntonio,Texas);DavidC.Grossman,MD,MPH(GroupHealthCooperative,Seattle,Washington);JessicaHerzstein,MD,MPH(AirProducts,Allentown,Pennsylvania);WandaK.Nicholson,MD,MPH,MBA(UniversityofNorthCarolinaSchoolofMedicine,ChapelHill,NorthCarolina);andDouglasK.Owens,MD,MS(VeteranAffairsPaloAltoHealthCareSystem,PaloAlto,California,andStanfordUniversity,Stanford,California).FormerUSPSTFmemberswhocontrib-utedtothedevelopmentofthisrecommendationareDianaPe-titti,MD,MPH;TimothyJ.Wilt,MD,MPH;andBernadetteMelnyk,PhD,RN.ForalistofcurrentTaskForcemembers,gotowwwAnnalsofInternalMedicine 7May2013 AnnalsofInternalMedicine Volume158¥Number9 W-293 AppendixTable1.WhattheUSPSTFGradesMeanandSuggestionsforPractice GradeDefinitionSuggestionsforPracticeATheUSPSTFrecommendstheservice.ThereishighcertaintythatthenetbenefitisOffer/providethisservice.BTheUSPSTFrecommendstheservice.ThereishighcertaintythatthenetbenefitismoderateorthereismoderatecertaintythatthenetbenefitismoderatetoOffer/providethisservice.Note:Thefollowingstatementisundergoingrevision.Cliniciansmayprovidethisservicetoselectedpatientsdependingonindividualcircumstances.However,formostindividualswithoutsignsorsymptoms,thereislikelytobeonlyasmallbenefitfromthisservice.Offer/providethisserviceonlyifotherconsiderationssupportofferingorprovidingtheserviceinanindividualpatient.DTheUSPSTFrecommendsagainsttheservice.Thereismoderateorhighcertaintythattheservicehasnonetbenefitorthattheharmsoutweighthebenefits.Discouragetheuseofthisservice.IstatementTheUSPSTFconcludesthatthecurrentevidenceisinsufficienttoassessthebalanceofbenefitsandharmsoftheservice.Evidenceislacking,ofpoorquality,orconflicting,andthebalanceofbenefitsandharmscannotbemeasured.ReadtheClinicalConsiderationssectionoftheUSPSTFRecommendationStatement.Iftheserviceisoffered,patientsshouldunderstandtheuncertaintyaboutthebalanceofbenefitsandharms. AppendixTable2.USPSTFLevelsofCertaintyRegardingNetBenefit LevelofHighTheavailableevidenceusuallyincludesconsistentresultsfromwell-designed,well-conductedstudiesinrepresentativeprimarycarepopulThesestudiesassesstheeffectsofthepreventiveserviceonhealthoutcomes.Thisconclusionisthereforeunlikelytobestronglyaffectedbytheresultsoffuturestudies.ModerateTheavailableevidenceissufficienttodeterminetheeffectsofthepreventiveserviceonhealthoutcomes,butconfidenceintheestimateiconstrainedbysuchfactorsas:thenumber,size,orqualityofindividualstudies;inconsistencyoffindingsacrossindividualstudies;limitedgeneralizabilityoffindingstoroutineprimarycarepractice;andlackofcoherenceinthechainofevidence.Asmoreinformationbecomesavailable,themagnitudeordirectionoftheobservedeffectcouldchange,andthischangemaybelargeenoughtoaltertheconclusion.LowTheavailableevidenceisinsufficienttoassesseffectsonhealthoutcomes.Evidenceisinsufficientbecauseof:thelimitednumberorsizeofstudies;importantflawsinstudydesignormethods;inconsistencyoffindingsacrossindividualstudies;gapsinthechainofevidence;findingsthatarenotgeneralizabletoroutineprimarycarepractice;andalackofinformationonimportanthealthoutcomes.Moreinformationmayallowanestimationofeffectsonhealthoutcomes.TheUSPSTFdeÞnesasÒlikelihoodthattheUSPSTFassessmentofthenetbeneÞtofapreventiveserviceiscorrect.ÓThenetbeneÞtisdeÞnedasbeneÞtminusharmofthepreventiveserviceasimplementedinageneralprimarycarepopulation.TheUSPSTFassignsacertaintylevelonthebasisofthenatureoftheoverallevidenceavailabletoassessthenetbeneÞtofapreventiveservice. W-294 7May2013 AnnalsofInternalMedicine Volume158¥Number9