JasonPark

TiffanyCraig
MicronutrientsDebate
Calciumsupplementationisnotasafeandefficaciousinterventionfortreating
osteoporosis.
Background:
Osteoporosisisachronic,progressivediseaseinwhichbonesbecomelessdense
(decreasedBMD),deteriorationofbonetissue(decreasedbonestrength)andchangesinthe
microarchitecture(structuraldeterioration),causinganincreaseinsusceptibilityofbone
fragilityfractures(5).Consequencesoffractureinthehip,vertebraeandfemurbones,arethe
mostcommon,andareassociatedwithanincreasedriskinmorbidityandmortality(1,2,4).The
mostcommonpopulationsatriskincludepostmenopausalwomen,menage50orolder,and
patientswithchronickidneydiseaseorrenalfailure(1).
Thesignificanceofosteoporosisinthesepatientpopulationsisevidencedby
osteoporosisbeingthemostcommonbonediseaseinhumans(1,5).Theprevalenceofthis
diseaseisseenin10millionAmericans50yearsoldorolder,andismostprevalentafterthe
ageof75(5)oneintwowomenandoneinfivemenover50yearsofagewillhavean
osteoporoticfractureintheirremaininglifetime(2).Theannualnumberofhipfracturesis
expectedtotripleby2050asthepopulationages(2).Theestimatedcostofosteoporotic
fracturesaloneintheUnitedStateswas$17.9intheUnitedStatesin2005,and3.5billion/year
intheUnitedKingdomin2000(2,5).
________________________________________________________________________
1.EscottStumpS.NutritionandDiagnosisRelatedCare.LippincottWilliams&Wilkins:
Baltimore(2012).
_______________________________________________________________________
GeneralInformation
1. Osteoporosisisthemostcommonbonediseaseinhumans,affectinganestimated10
millionAmericans(NOF,2009).
2. Diseaseischaracterizedbylowbonemass,structuraldeterioration,anddecreasedbone
strength.Sometimesasymptomaticuntilfracture,typicallyatthehiporproximal
humerus,occursresultinginsignificantphysicallimitationsandsometimesdeath.
3. Populationaffected:
a. Menage50orolder
b. Menwithrenalfailure,smokersandchronicuseofanticonvulsants,
corticosteroidsorbarbiturates.
c. Postmenopausalwomen(womencanloseupto20%ofbonemass57years
aftermenopause50%willexperienceanosteoporoticfracture).

Nutritiondiagnosisforosteoporosis:
1. Importantpreventionnutrients:calcium,magnesium,potassium,vitaminC,vitaminK,
Bvitamins,carotenoids
2. Allpatients:dietarycalciumgreaterthanorequalto1200mg/d
3. Postmenopausalwomenover65:1500mg/dcalcium
a. Equivalentof:1quartofmilkdailyoragedcheeses/yogurtaregoodsources.
d. Foodsourcesofcalcium:milk,cheese,yogurt,broccoli,kale,othergreens,
soybeans
e. Mineralwaters(goodbioavailabilityforcalcium)
f. AdequatesunexposurerelatedtoadequatevitaminD
g. Physicalactivity(walkingorrunning)
*Calciumsupplementsrecommendedonlywhendietaryproductsarenottolerated.Takeno
morethan500600mgtwoormoretimesdailyw/meals(absorptionapproxixmately3040%

JasonPark
TiffanyCraig
MicronutrientsDebate
frommostsources).UsewithvitaminDandmagnesium.

Conclusion
Osteoporosisismosteffectivelytreatedbypreventionpracticesofahealthydietwithadequate
calcium,vitaminD,magnesium,potassium,VitaminC/K/B,carotenoids.Inadditionregular
walkingorweightbearingactivitiesarerecommended.Theprimaryprotectivemeasureisto
achieveadequatecalciumintakeof12001500mg/dayofcalciumfromdietarysourcesfor
populationsatrisk.VitaminDintakeisrecommendedtonotexceed10,000IU/d.Ifdietary
intakeofcalciumandvitaminDisinadequatecosupplementationisrecommendedto
complementmedicaltreatmentforosteoporosis.Considerthedecreaseinabsorptionofcalcium
withageandabsorptionfromcalciumsupplementsisestimatedat3040%).Calcium,ironand
zinccompeteforabsorptionwhenpresentedtogetherinthegut.
_______________________________________________________________________
2.HolroydC,CooperC,DennisonE.Epidemiologyofosteoporosis.BestPractResClin
EndocrinolMetab.200822(5):67185.
_______________________________________________________________________
HistoryofOsteoporosis
TermcoinedinFrance/Germantodescribehumanbonehistologyinelderly
Priorworksuggestedagerelatedfractureswereduetoreducedbonemassorquality

SignificanceofOsteoporosisrelatedtomorbidityandmortality:
Allosteoporoticfracturesincreasepatientmorbidity
Mostcommonfragilityfracturesoccuratwrist,hiporspine
Fracturesofhipandvertebraelinkedtosignificantmortality
10millionAmericans>50yearsoldhaveosteoporosis
OsteoporoticfracturesalonecostUS$17.9billion/year
Increasedlifeexpectancyofpopulationsuggeststherewillbeanincreasein
epidemiologyofosteoporoticrelatedfractureasamajorpublichealthconcern

Risk
Oneintwowomenandoneinfivemenover50yearsofagewillhaveanosteoporotic
fractureintheirremaininglifetime
Upto5yearsfollowingfractureoffemur/hipassociatedwithincreasedmortality
Inwomen,increaseriskofdeathfromcardiovascularandpulmonarydiseasesrisewith
increasingnumberofvertebralfractures.
Hipfracturesrequirehospitalizationandsecondarycomplicationsarelikely(i.e.
infection).
Mortalityafterhipfracturedeclinesafter2yearswhereaspostvertebralfracturethe
riskprogressivelyincreases.
LowerfractureratesobservedinAfricanAmericanpopulationsthanCaucasianor
Asianpopulations.

Conclusion
Osteoporotic(fragility)fracturesareapublichealthconcernaffectingtheindividuals(elderly
men,postmenopausalwomen,Caucasian/Asian)aswellastheeconomy.Fracturesare
estimatedtoincreasebysixtimesfrom1990to2050duetoincreasedlifeexpectancyand
increaseinpopulation.Fracturesoccurringinthehip,vertebrae,femurandwristaremost
commontypicallyduetofalls.Increasedriskofmortalityandmorbidityassociatedwithhip

JasonPark
TiffanyCraig
MicronutrientsDebate
andvertebralfractures.
_______________________________________________________________________
3.NordinB.Calciumandosteoporosis.Nutrition.199713(78):664686.
_______________________________________________________________________
CalciumactivityandOsteoporosis
Calciumisthefifthmostabundantelementinthehumanbodyfoundprimarilyintheskeleton
(99%).Othertissuesthecontaincalciumincludeteeth,softtissue,plasmaandextracellular
fluid.Calciummetabolismisregulatedbytheparathyroid/vitaminDsystem.Sourcesof
calciuminthebodyaresuppliedbythegut(absorption)fromdietaryintakeandbybone
metabolism(resorption)andactivityofosteoblast/osteoclasts/osteocytes.Fractureriskis
inverselyrelatedtobonedensity(determinedbypeakbonemassandsubsequentrateofbone
loss)inosteoporoticpatients.

OsteoporosisEtiology

FunctionsofCalcium
Withintheskeletoncalciumisfoundinassociationwithphosphateascalciumphosphateor
hydroxyapatite,whicharecomponentsofcollagenfibrilsthatconstitutebonetissue.
Rigidityofbonesandteeth
Bonessupplycalciuminsettingofdeficiency

CalciumIntakeRequirementChangesasafunctionofMenopauseorviseversa
Atthetimeofmenopausethereareapparentchangesincalciummetabolismresultinginan
increasedrequirementforcalciumintaketopreventboneloss.Thelifestageofmenopauseis
significantduetodecreasedsynthesisofestrogen.Hormonalactivityofestrogenisrelatedto
calciummetabolismbypositiveaction
ofestrogenonGIabsorptionandrenal
tubularreabsorptionofcalciumand

JasonPark
TiffanyCraig
MicronutrientsDebate
inhibitoryeffectofestrogenonboneresorption.Calciumbalanceisequalcalciumintakeand
calciumabsorptionminusexcretion.Table1describesthevariabilityincalciumintake
requirementforwomenacrossdifferentlifecyclestages.

Experimentaltrialshavefavoredcalciumtherapytoreducebonelossinpostmenopausal
women.Datashow1%meanrateofbonelossperyearwithoutcalciumtherapyand0.014%
lossperyearwithcalciumtherapy(P<0.001).

Trialscomparingcalciumandestrogenhaveshownmorefavorableoutcomesforboneintegrity
andsomebonegaininestrogentreatment
groups.

VitaminDdeficiencyinelderlyiscommon
andmayeffectivelycreateasecondary
calciumdeficiencyduetoimpairedcalcium
absorptionthatisvitaminDdependent.

Conclusion
Calciumhomeostasisisaffectedby
calcium,estrogen,vitaminDandlifestage,
amongotherrequirements.Theetiologyof
osteoporosisideallywoulddictate
treatment,however,thecommonalityis
thatatsomepointnegativecalciumbalance
isalwaysafactor.

________________________________________________________________________
4.PooleKE,CompstonJE.Osteoporosisanditsmanagement.BMJ.2006333(7581):12516.
________________________________________________________________________
Osteoporosisisaconsequenceofdecreasedactivityof
osteoblastsandincreasedactivityofosteoclastsresulting
inreducedbonemassandrestructuringofthe
microarchitectureofbone.

Osteoporosisiscommoninmenandwomenovertheage
of50(1in2women,and1in5men).Theincidenceof
fractureispositivelycorrelatedwithagethemost
dramaticincreaseisobservedinpopulationsoverage75
(Fig2).Additionally,osteoporosisismorecommonin
postmenopausalwomenthanmenofthesameage,related
toachievementofalowerpeakbonemassin
developmentalyearsandincreasedbonelossatmenopause
(Fig5).

InvestigatorscollectedpublicationsfromPubmedfor
randomizedcontroltrials(124),systematicreviews(118),

JasonPark
TiffanyCraig
MicronutrientsDebate
metaanalyses(218),andCochranedatabases(15)withthecriteriaofosteoporosisplusrisk
factors.Otherrelevantspecializedjournalswerealsosearched.

Oftheevidencecollectedosteoporosishasbeenrelatedtothefollowingpathologiesinboth
menandwomen:
Agerelatedboneloss
Estrogendeficiency
VitaminDinsufficiency
Secondaryhyperparathyroidism
Reducedphysicalactivity
Decreasedproductionofinsulinlikegrowthfactor
Useoforalglucocorticoids
Investigatorsfoundnutrition(calciumandvitaminDintake),hormonestatus,andphysical
activitytobeinfluentialonreachingpeakbonemass,butwerenotcorrelatedwithlossofbone
masslaterinlife.

Othercommentaryonscreeningandtreatmentincludedthelimitationsofmeasuringbone
mineraldensityastheonlydiagnosticfactor.Authorsindicatethismeasurementistheprimary
basesfortheWHOdefinitionofosteoporosis,howeveritdoesnotaccountforotheraspectsof
bonecompositionsuchasbonesizeandgeometry,whichmayalsocontributetobonefragility
andfracture.Accordingtoresearchers,patientsshouldalsobeevaluatedwithconcerntoother
riskfactorssuchasage,previousfragilityfracture,maternalhistoryofhipfracture,oral
glucocorticoidtherapy,currentsmoking,alcoholintakegreaterthanorequalto3units/day,
Rheumatoidarthritis,BMIlessthanorequalto19,andhistoryoffalls.Authorsdefend
inclusionofthiscriteriabecauseosteoporosisdoesindicateahighlikelihoodoffracture,but
manyfracturesareobservedinpeoplewithbonedensityabovethedefinedlevel.

Managementofosteoporosisbypharmaceuticalswithcomplementarysupplementationof
calciumwithvitaminDsupplementswastheprimaryintervention.Evidenceofoutcomesfrom
supplementationofthesemicronutrientsalonehasnotbeenfoundtopreventosteoporotic
fractures,outsideinstitutionalizedelderlypeople.Additionalrecommendationsinclude
appropriatephysicalactivity,cessationoravoidanceofsmokingandalcoholintake.Lastly,the
estimatedannualexpensetotreatosteoporosisrelatedinjuries(i.e.fractures)is$3.5inthe
UnitedKingdom.
________________________________________________________________________
5.NationalOsteoporosisFoundation.Cliniciansguidetopreventionandtreatmentof
osteoporosis.BoneSource.20133:129.Availableat:http://nof.org/hcp/cliniciansguide.
AccessedMarch5,2014.
________________________________________________________________________
Primaryinclusionfromthisresourceisbasedontreatmentrecommendationsandefficacyof
thosetreatmentsforosteoporosismanagement.However,itisnoteworthytorelaythat
diagnosticcriteriaisprimarilybasedonbonemineraldensityaloneinatriskpatient
populations.Additionalinformationinthisdocumentcoversmoredetailforgeneral
informationonosteoporosis,pathophysiology,diagnosis,recommendationsandtherapy.

ThecurrentgeneralrecommendationsforosteoporosisbytheNationalOsteoporosis
Foundationforpostmenopausalwomenandmenovertheageof50yearold,includesthe
following:

JasonPark
TiffanyCraig
MicronutrientsDebate
Counselingforriskofosteoporosisandrelatedriskreductionoffractures
Adviceforconsumptionofabundantfruitsandvegetablestomeetadequatecalcium
recommendations(1,000mg/dmen50701,200mg/dwomen51orolder,andmen71
orolder).
CorrectvitaminDinsufficiencywithsupplementationifnecessaryforindividualsage
50andolder.
Assessriskfactorsforfallsandoffercomplementaryinterventions
Physicalactivitythatincludesweightbearingandmusclestrengtheningexercise(for
balanceandposturetoreduceriskoffalls)
Adviceforquittingsmokingandavoidingorlimitingalcoholintake
Trackheightannually
Prescriptionpharmaceuticalsifappropriate
Continuedmanagementandevaluation
Theprimaryrecommendationfortreatmentisinitiationofpharmaceuticalsforpatients
presentingwithfracturesinthehiporvertebra(osteoporosisiscommonlydiagnosedwhen
afterapatientsuffersafracture)orforpostmenopausalwomenandmenage50orolderwith
lowbonemineraldensitybelowthedefinedadequatelevel.Treatmentiscosteffective,
typicallywelltoleratedandmayreduceriskofrepeatfracturesby50%.However,only23%of
womenage67orolderthathadanosteoporosisrelatedfracturefollowedupwithmedicationor
abonemineraldensitytest.

JasonPark
TiffanyCraig
MicronutrientsDebate
OpposingWork(Con):

Whilecalciumsupplementationmayincreasebonemineraldensityinindividuals,itis
currentlyunclearhowthistranslatesintofractureprotection.Currentevidencefortheuseof
calciumsupplementationinreducingfracturesisconflicted.Studieshaveshownthatcalcium
supplementationwithvitaminDdoesnotcreateanysignificantreductionintheincidenceof
hip,vertebrae,lowerarmorwrist,andtotalfracture(7,9).Theefficacyofsupplementationof
calciumisquestionablebasedonthestudiesthathavenotshownprotectionagainstfractures.
Emergingevidencecurrentlyraisesquestionsaboutthesafetyofcalcium
supplementation.AccordingtoBollandet.alandLietal,evidenceshowsthatcalcium
supplementationhasbeenassociatedwithanincreasedriskformyocardialinfarctionevents
(6,8).AnotherstudybyRosset.al,showedthatcalciumsupplementsusedforprescriptionand
overthecounterbrandscontainedlead.OtherevidencedescribedbyJacksonet.alshoweda
nonsignificantreductioninhipandtotalfracturesinthesupplementalgroupreceivingcalcium
andvitaminDcomparedtoaplacebogroup,despitetheobservationthattheexperimental
groupshowedanincreaseinbonemineraldensityatthehip.Theexpectedprotectionof
supplementationagainstfracturewasnotobserved(7).AnotherinvestigationbyReidet.al,
performedametaanalysisofover5,500womenusingcalciumsupplementsaloneandfoundan
increasedrelativeriskofhipfracture.Takentogethertheresearchquestionsboththesafetyand
efficacyofcalciumsupplementationtomanageosteoporosis,thusadvisingforcautionaround
recommendationofthistreatment.
________________________________________________________________________
6.BollandMJ,AvenellA,BaronJA,etal.Effectofcalciumsupplementsonriskofmyocardial
infarctionandcardiovascularevents:metaanalysis.BMJ.2010341(jul291):c3691.
________________________________________________________________________
Bollandet.al.performedametaanalysistoassesscardiovascularoutcomesofsupplementation
ofcalciumforosteoporosistreatmentinatotalofabout12,000subjectsfrom1996to2010.
Calciumsupplementationforpreventionandtreatmentofosteoporosisiswidespread,
especiallyforpeopleovertheageof50.

Inclusioncriteriaforthestudies:
100ormoreparticipantsinstudy
Meanage40+yearsoldatbaseline
Durationofcalciumsupplementationatleast1year(studydurationmorethan1year)
ExcludedtrialscoadministeringcalciumwithvitaminD.

Theresearchincludedwasrelatedtocardiovasculareventsobservedinrandomizedplacebo
controlledtrialsofcalciumsupplementation(500mg/day).
5trialswithpatientleveldata
6trialswithtrialleveldata

Researchersfoundthatcalciumsupplements,withoutvitaminD,areassociatedwithan
increasedriskofMI.TheriskofMIassociatedwithcalciumsupplementationwasfoundtobe
abouta30%increase.However,notrialestablishedtheseresultswithstatisticalsignificance.
Medical/Nutritionalprescriptionofcalciumsupplementationtomanageosteoporosisshouldbe
recommendedwithcaution.Patientleveldata:RiskofMI,hazardratio1.31,95%CI1.021.67,
P=0.035.Trialleveldata:RiskofMI,pooledrelativerisk1.27,95%CI1.011.59,P=0.038.
Cardiovascularoutcomeswereselfreported,andsourcedfromhospitaladmissionsordeath

JasonPark
TiffanyCraig
MicronutrientsDebate
certificates.Cardiovasculareventincluded:MI,stroke,andsuddendeath.

Limitationsofthisstudyincludelackofstudieswithcoadministrationofcalciumwithvitamin
D,lackofstatisticalsignificance,andtrialleveldatawasincompletefor7trialsintheanalysis
(about15%ofparticipants).
_______________________________________________________________________
7.JacksonRD,LacroixAZ,GassM,etal.CalciumplusvitaminDsupplementationandthe
riskoffractures.NEnglJMed.2006354(7):66983.
_______________________________________________________________________
CalciumsupplementationwithvitaminDforthepreventionoffractureshasbeena
controversialissue.Thereisconflictingevidenceaboutthebenefitofcalciumsupplementation
toprovideprotectionagainstfracturesinhealthypostmenopausalwomen.Investigators
recruited36,282postmenopausalwomen,ages5079,fromtheWomensHealthInitiative
(WHI)clinicaltrial.Thewomeninthestudywererandomlyassignedtoreceive1,000mgof
calciumand400IUofvitaminD3dailyoraplacebo.Theincidencesoffractureswererecorded
fora7yearperiod.Bonemineraldensitywasassessedforeachsubgroupfromthesupplement
andplacebogroup.

TheauthorsfoundthatthewomenwithcalciumandvitaminDhadanonsignificant12%
reductioninhipfracturescomparedtotheplacebogroup.Therewasalsonosignificant
reductioninhip,vertebrae,lowerarmorwristandtotalfracturebetweenthesupplementand
placebogroup.Womeninthesupplementationgrouphadasignificantlyhigherhipbone
densitycomparedtotheplacebogroup.Anotherinterestingresultisthatthesupplementgroup
hadasignificantriskforrenalcalculi(kidneystones).

Basedontheseresults,isitevidentthatbonedensityisimprovedunderconditionsofcalcium
andvitaminDsupplementation.However,theresultsdidnotdemonstrateasignificant
reductioninhipfracturesinthecalciumandvitaminDsupplementgroup.Addingtothe
argumentagainstcalciumsupplementationisthefactthatthesupplementgrouphadan
increasedriskforrenalcalculi.
_______________________________________________________________________
8.LiK,KaaksR,LinseisenJ,RohrmannS.Associationsofdietarycalciumintakeandcalcium
supplementationwithmyocardialinfarctionandstrokeriskandoverallcardiovascularmortality
intheHeidelbergcohortoftheEuropeanProspectiveInvestigationintoCancerandNutrition
study(EPICHeidelberg).Heart.201298(12):9205.
_______________________________________________________________________
Investigatorsconductedaprospectivecohortstudyofover23kGermanparticipantsacrossand
averageof11yearstoevaluatetheeffectofcalciumintakefromthedietcomparedtointake
fromasupplement.Researchersexaminedassociationsofdietarycalcium(fromdairyand
nondairysources)andcalciumsupplementstoriskofMI,stroke,andCVDmortality.

DietaryintakeswerecollectedbyFFQ,24hourrecallsandinterviews.Intakeswereadjusted
fortotalenergyintakeof2200kcal/dayformenand1700kcal/dayforwomen.
DietarycalciumanddairycalciumintakesreducedtheriskofMIandthecohorttakingcalcium
supplementshadastatisticallysignificantincreaseMIrisk,especiallyifthesupplementwas
calciumalone.Themechanismoftheadverseeffectofcalciumsupplementsisattributedto
increasedserumcalciumlevelsgreaterthanwhatisobservedifthecalciumisconsumedin
foodsources.Serumcalciumlevelsmayincreaseriskofvascularcalcification.

JasonPark
TiffanyCraig
MicronutrientsDebate

Calciumsupplementationwasfoundtohavenoassociationwithincreasedriskofstrokeor
CVDmortality.Higherintakesofdietarycalciumwereassociatedwithotherfavorable
behaviors,whereasusersofcalciumsupplementswereassociatedwithmoreriskfactorsfor
morbidityandmortality.

Thelimitationsofthisstudyconcerndosageofcalciumsupplementation,whichwasnot
requestedinformationfromparticipants.Also,theincreasedriskofMIisbasedonalinear
modelovertimeofcalciumsupplementation.Thisriskthereforemaynotbeasapplicableto
elderlypeopletakingcalciumsupplements.
_______________________________________________________________________
9.ReidIR,BollandMJ,GreyA.Effectofcalciumsupplementationonhipfractures.
OsteoporosInt.200819(8):111923.
_______________________________________________________________________
Reid,Bolland,andGreyprovideametaanalysisontheeffectsofCalciumsupplementationon
hipfractures.Calciumsupplementationhasbeenacontroversialtreatmentforthepreventionof
fracturesassociatedwithosteoporosis.

Theauthorsmetaanalysisincluded9studies,whichhad52,000participants.Afternarrowing
downtheparticipantstoincludeonlythosewhodidcalciummonotherapy(5,5000),theresults
showthatcalciumwaseffectiveinincreasingbonemineraldensity,howeverthestudiesdidnot
showadecreaseinhipfracturerisk.Whiletherewasareductioninoverallfracturerisk,which
includednonhipfractures,therewasanincreasedriskforhipfracture.Riskratioforhip
fracturewas1.5(95%CI1.062.12)forthecalciumsupplementgroup.

Withtheevidencefromthestudiespointingtoanincreaseinriskforhipfractures,theefficacy
ofcalciumsupplementationinthepreventionofhipfracturehascomeintoquestion.The
authorsarguethathipfracturesshouldnotbecategorizedintoasinglefracturecategoryasitan
importanttypeoffracture.

Thisevidencehasdemonstratedthatcalciumsupplementationmaynotdecreaseriskforhip
fracturesinolderwomen.Furthermore,theauthorsstudyhasshownthatmoreevidenceis
neededtovouchfortheefficacyofcalciumsupplementationinthepreventionofhipfractures.
_______________________________________________________________________
10.RossEA,SzaboNJ,TebbettIR.Leadcontentofcalciumsupplements.JAMA.
2000284(11):14259.
_______________________________________________________________________
Calciumsupplementationhasgenerallybecometheacceptedmethodforthepreventionor
treatmentofosteoporosis.However,concernshavebeenraisedabouttheleadcontentwithin
calciumsupplementsandthehealthrisksassociatedwithexposure.Inordertoassesslead
contentincalciumsupplementsRossetal.analyzedavarietyofwidelyavailablecalcium
supplementproducts.

JasonPark
TiffanyCraig
MicronutrientsDebate

Theauthorsselectedcalciumsupplementproductsbasedonnationalmarketingandeasy
availabilitywithinthecommunity.Atotalof21calciumsupplementswereselected,each
containingcalciumcarbonate.Of21supplements,14werelabeledasrefinedand7were
labeledasnaturalsourceoroystershell.Twosupplements,1fromthenaturaland1fromthe
refined,werelabeledasleadfree.Inaddition,2prescriptioncalciumsupplementswere
included,onecontainingcalciumacetateandtheotherwithsevelamerhydrochloride.

Outofthe7naturalcalciumsupplements,4hadmeasurableamountsofleadcontentthat
constitutedtoabout1ug/dfora800mg/ddoseofcalcium,12ug/dfor1500mg/ddoseof
calcium,andupto10ug/dforcalciumdosegiventorenaldiseasepatients.Osteoporoticdoses
ofcalcium(1500mg/d)containedalmosthalfthetotaldailylimitoflead.

Withtheadventofcalciumsupplementationforosteoporosis,leadcontentpresentsanother
concernaboutthesafetyofsupplementation.Investigatorsconcludedthatcalcium
supplementationmayposeapublichealthriskduetotheleadcontent.

10

JasonPark
TiffanyCraig
MicronutrientsDebate
SupportiveWork:(Pro)

Calciumsupplementationforthepreventionandmanagementofosteoporosishasbeen
widelyacceptedinthemedicalcommunity.Basedonanunderstandingofmetabolismand
researchevidence,itisclearthatcalciumsupplementationprovidessomebenefitsindelaying
boneloss(12,13).Researchisstillconflictedonhowdelayedbonelosstranslatesintofracture
protection.However,thebenefitsofincreasedbonedensitycannotbeunderestimatedin
postmenopausalandelderlywomenwhomareatriskforcalciumandvitaminDdeficiency.
Studieshaveshownadecreasedriskinbonefractureinwomenwhosupplemented1,200mgof
calciumor1,200mgcalciumwith800IUvitaminDcomparedwithgroupswhoconsumeda
placebo(11,15).Onestudyshowedadecreasedriskinhipfracture,whichisasignificant
findingconsideringthefactofhighmortalityratesassociatedwithhipfracture(11).Basedon
thesefindings,supplementationofcalciumorcalciumwithvitaminDhasbeendemonstratedto
beefficaciousasapossiblepreventativeortreatmentmeasureforosteoporosis.
Thesafetyofcalciumsupplementationhasbeencalledintoquestionasevidencehas
surfacedofincreasedriskforcardiovascularevents.Tofurtherinvestigateclaimsofnegative
outcomesassociatedwithcalciumsupplementation,Prenticeetal.conductedadataanalysisof
theWomensHealthInitiativecohortstudy.Prenticeetal.concludedthatsupplementationof
1,000mgcalciumplus400IUvitaminD3isnotassociatedwithincreasedriskofMI,CHD,
totalheartdisease,stroke,oroverallcardiovasculardisease(14).Safetyofcalcium
supplementationremainsunclearwithevidencepointingtowardsbothdirections.
_______________________________________________________________________
11.ChapuyMC,ArlotME,DuboeufF,etal.VitaminD3andcalciumtopreventhipfractures
intheelderlywomen.NEnglJMed.1992327(23):163742.
_______________________________________________________________________

InordertoassesscalciumandvitaminD
supplementationefficacyonhipfracture,
Chapuyetal.studied3270elderlywomen
whowereambulatory,69106yearsofage,
livinginnursinghomesorassistedliving
facilities,foraperiodof18months.Women
whoweretakingmedicationsthataltered
bonedensitywereexcludedfromthestudy.

Womenwererandomlyassignedtotwo
groups.Thesupplementgroupreceived800
IUofvitaminD3and1.2gofcalciumdaily.
Theplacebogroupreceivedpillsoflactose,
kaolinandstarchdaily.Thewomenwere
assessedat6,12and18monthsfor
fractures,sideeffectsandclinicalstatus.

Womeninthesupplementgrouphad32%
fewernonvertebralfracturesand43%fewer
hipfracturescomparedtotheplacebogroup.
Fortywomeninthesupplementgroupand28intheplacebogroupreportedsideeffectssuchas
nausea,epigastricpain,anddiarrheathatledtodiscontinuationoftreatment.

11

JasonPark
TiffanyCraig
MicronutrientsDebate

Chapuyetal.,concludedthat18monthsupplementationofcalciumandvitaminD3issafeand
effectivelyreduceshipfracture.Themajorlimitationisthatthisstudydoesnotrepresentall
womenatrisk,especiallythoselivingindependently.
_______________________________________________________________________
12.DawsonHughesB,HarrisSS,KrallEA,DallalGE.EffectofcalciumandvitaminD
supplementationonbonedensityinmenandwomen65yearsofageorolder.NEnglJMed.
1997337(10):6706.
_______________________________________________________________________
InordertoassesscalciumandvitaminDsupplementationonbonedensity,DawsonHugheset
al.recruitedhealthy,ambulatorymenandwomenaged65yearsorolder.Atotalof445
participantswereenrolled(246womenand199men)inthisthreeyear,doubleblind,
placebocontrolledtrial.Among445participantstherewere430whites,11blacksand4asians.

ParticipantswererandomlyassignedtoeitherthecalciumandvitaminDsupplementgroupor
placebogroupwithstratificationaccordingtosex,raceanddecadeofage.Thesupplement
groupreceivedpillscontaining500mgofcalciumand700IUofvitaminDdaily.Theplacebo
groupreceivedpillscontainingcrocrystallinecellulose.

Womeninthesupplementgrouphadstatisticallysignificantreducedbonelosscomparedtothe
placebogroup.Menhadstatisticallysignificantreductioninbonelossinthefemoralneck,
spineandtotalbody.Allparticipantshadstatisticallysignificantreductioninbonelossintotal
body,femoralneckandspine.Overall,moderatebonelossreductionwasfoundinallthe
participantsthatsupplementedwithcalciumandvitaminD.

_______________________________________________________________________
13.DidanieleN,CarbonelliMG,CandeloroN,IacopinoL,DelorenzoA,AndreoliA.Effect
ofsupplementationofcalciumandvitaminDonbonemineraldensityandbonemineral
contentinperiandpostmenopausewomenadoubleblind,randomized,controlledtrial.
PharmacolRes.200450(6):63741.
_______________________________________________________________________
InordertoassesstheeffectsofcalciumandvitaminDsupplementationonboneloss,Di

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Danieleetal.recruited120Italianperiandpostmenopausalwomenaged4555inthis
randomizedplacebocontrolleddoubleblindtrial.Sixtywomenwereintheperimenopausal
phaseaged4550andtheother60womenwereinpostmenopausalphaseaged5055.
Exclusioncriteriaincluded:bonemineralmetabolismdisorders,decreasedspinebonemineral
density,historyofnontraumaticspineorhipfracture,majorgastrointestinaldisease,previous
treatmentwith
hormonetherapy,
bisphosphonateor
fluorideuse,smoking
morethan20packs
perday,anddrinking
alcoholmorethan3
timesperday.

Theparticipantswere
randomlyassigned
intoacalciumand
vitaminD
supplementationgroup
(oraltreatmentgroup)
oraplacebogroup
(oralplacebogroup)andstudiedovera30monthperiod.Thesupplementgroupreceived500
mgofcalciumand200IUofvitaminDinonetabletandtheplacebogroupreceivedsimilar
tabletswithoutcalciumandvitaminD.Baselinemeasurementsincludeddietaryintake,total
bonemineraldensity,andbonemineralcontent.Measurementsweretakenagainat15months
andthenat30months.

Womenintheoraltreatmentgrouphadastatisticallysignificantdifferenceinbonemineral
densityat15and30monthscomparedtotheplacebogroup.ThetreatmentgroupsBMDat
baselinewas1.101g/cm2,at15months1.111g/cm2,and30months1.111g/cm2.Comparedto
theplacebogroupwhichhadaBMDatbaselineof1.102,at15months1.098g/cm2andat30
months1.098g/cm2.Theplacebogrouphadareductioninbonemineraldensityat15and30
months,equatingtoabouta0.4%lossperyear.TheincreaseinBMDforthetreatmentgroup
equatestoabout1%differencecomparedtoplacebogroup.

AuthorsconcludedthatcalciumandvitaminDsupplementationisbeneficialforreducingbone
lossinhealthywomenwhoseintakeofthesemicronutrientsarelow.However,theauthorsdid
notspecificallymeasurebonedensityofthehip,whichisofmostconcernintermsofriskof
mortality.Totalbonedensitymayhaveimproved,butthelargerquestionishowthesefindings
maytranslateintoprotectionagainstfractures.
___________________________________________________________________
14.PrenticeRL,PettingerMB,JacksonRD,etal.Healthrisksandbenefitsfromcalciumand
vitaminDsupplementation:Women'sHealthInitiativeclinicaltrialandcohortstudy.
OsteoporosInt.201324(2):56780.
_______________________________________________________________________
Thisrandomizedcontroltrialinvestigatedtheeffectofsupplementationwithcalciumplus
vitaminDonincidenceofhipfracture,totalfractureandcolorectalcancerinapopulationof
over36kpostmenopausalwomen(ages5079)intheU.S.Theoccurrenceofcardiovascular

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disease,cancerandtotalmortalitywasalsoinvestigated.TheWomensHealthInitiative(WHI)
conductedthisstudy.

TheparticipantswererandomlyassignedtothecalciumandvitaminDsupplementgroupora
placebogroup.Supplementgroupreceived1,000mgcalciumplus400IUvitaminD3aday.

TheeffectsofsupplementationofcalciumplusvitaminDwerenotassociatedwithan
increasedriskofMI,CHD,totalheartdisease,stroke,overallcardiovasculardisease,colorectal
cancerortotalmortality.

TheonlydocumentedriskassociatedwithcalciumwithvitaminDsupplementationisan
elevatedriskofurinarytractstoneformation.
________________________________________________________________________
15.PrinceRL,DevineA,DhaliwalSS,DickIM.Effectsofcalciumsupplementationon
clinicalfractureandbonestructure:resultsofa5year,doubleblind,placebocontrolledtrialin
elderlywomen.ArchInternMed.2006166(8):86975.
________________________________________________________________________

Inordertoassesstheuseofcalciumsupplementationin
thepreventionofbonefractureandbonedensityloss,
Princeetal.recruited1460womenolderthan70years
ofagefromtheAustralianelectoralroll.The
participantswerefollowedforaperiodof5yearsinthis
doubleblindplacebocontrolledtrial.

Theparticipantswererandomlyassignedtothe
supplementgrouporplacebogroup.Participantswere
vitaminDsufficient.Thesupplementgroupreceived
600mgofcalciumcarbonatetabletstwiceperday,one
inthemorningandoneintheevening.Theplacebo
groupreceivedplacebotablets.Fractureincidence,
bonedensityandcomplianceweremeasuredovera60
monthperiod.Compliancewasmeasuredbycounting
returnedtabletsasapercentofoptimumintakeateach
12monthfollowup.Theparticipantswerefurther
categorizedintocompliantandnoncompliantgroups
andcompared.

Theincidenceoffractureingroupsgivensupplements
werecomparedtotheplacebogroup.Thecompliant
supplementgroup(consumed80%oftablets)hada
lowerincidenceofallsitefractures(HR0.6695%CI,
0.450.97)comparedtothenoncompliantgroupwho
hadahigherincidenceofallsitefractures(HR1.09
95%CI,0.771.54).Authorsconcludedthatbecauseofissueswithlongtermcompliance,
calciumsupplementationisnotrecommendedasapublichealthintervention.

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