Braz. j. . vol.83 número6

(1)

www.bjorl.org

Brazilian

Journal

of

OTORHINOLARYNGOLOGY

ORIGINAL

ARTICLE

Significant

association

between

osteoporosis

and

hearing

loss:

a

systematic

review

and

meta-analysis

夽

Sikarin

Upala

a,b

_,

_Pattara

_Rattanawong

c

_,

_Wasawat

_{Vutthikraivit}

c

_,

_Anawin

_Sanguankeo

a,b,∗

a_Bassett_Medical_Center_and_Columbia_University_College_of_Physicians_and_Surgeons,_Department_of_Internal_Medicine,

Cooperstown,UnitedStates

b_Mahidol_University,_Faculty_of_Medicine_Siriraj_Hospital,_Department_of_Preventive_and_Social_Medicine,_Bangkok,_Thailand c_University_of_Hawaii,_Department_of_Internal_Medicine,_Honolulu,_United_States

Received23May2016;accepted22August2016 Availableonline12September2016

KEYWORDS

Osteoporosis; Hearingloss; Meta-analysis

Abstract

Introduction:Thereisinconclusiveevidencewhetherosteoporosisincreasesriskofhearingloss incurrentliterature.

Objective:We conducted this meta-analysis to determine whether there is an association betweenhearinglossandosteoporosis.

Methods:Thissystematicreviewandmeta-analysiswasconductedfromstudiesofMEDLINE, EMBASE,andLILACS.OsteoporosiswasdefinedashavingabonemineraldensitywithaT-score oflessthan−2.5standarddeviation.Theoutcomewashearinglossasassessedbyaudiometry

orself-reportedassessment.Random-effectsmodelandpooledhazardratio,riskratio,orodds ratioofhearinglosswith95%confidenceintervalswerecomparedbetweennormalbonemineral densityandlowbonemineraldensityorosteoporosis.

Results:Atotalof16articlesunderwentfull-lengthreview.Overall,therewasastatistically sig-nificantincreasedoddsofhearinglossinthelowbonemineraldensityorosteoporosisgroupwith oddsratioof1.20(95%confidenceintervals1.01---1.42,p=0.04,I2₌_82%,_P

heterogeneity=0.01).

However,thestudyfromHelzneretal.reportedsignificantlyincreaseoddsofhearinglossin thelowbonemineraldensityinparticularareaandpopulationincludedfemoralneckofblack men1.37(95%confidenceintervals1.07---1.76,p=0.01)andtotalhipofblackmen1.36(95% confidenceintervals1.05---1.76,p=0.02).

Conclusion:Ourstudyproposedthefirst meta-analysisthatdemonstratedaprobable associ-ationbetween hearinglossandbonemineraldensity. Osteoporosiscouldbeariskfactorin hearinglossandmightplayanimportantroleinage-relatedhearingloss.

© 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

夽

Pleasecitethisarticleas:Upala S,RattanawongP,VutthikraivitW,SanguankeoA.Significantassociationbetweenosteoporosisand hearingloss:asystematicreviewandmeta-analysis.BrazJOtorhinolaryngol.2017;83:646---52.

∗_{Corresponding}_author.

E-mail:[email protected](A.Sanguankeo).

PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial.

http://dx.doi.org/10.1016/j.bjorl.2016.08.012

(2)

Osteoporosisandhearingloss 647

PALAVRAS-CHAVE

Osteoporose; Perdaauditiva; Metanálise

Associac¸ãosignificativaentreosteoporoseeperdaauditiva:umarevisãosistemática

emetanálise

Resumo

Introduc¸ão: Háevidênciasinconclusivassobreseaosteoporoseaumentaoriscodeperda audi-tivanaliteraturaatual.

Objetivo: Realizamosestametanáliseparadeterminarseexisteumaassociac¸ãoentreperda auditivaeosteoporose.

Método: Revisão sistemáticaemetanálise foramrealizadas apartirde estudosdoMedline,

Embase e Lilacs.A osteoporose foidefinida como tendouma densidade mineralóssea com

umescoreTdemenosque-2,5DP.Odesfechofoiaperdaauditiva,avaliadaporaudiometria ouavaliac¸ãoautorrelatada.Omodelodeefeitosaleatórioseriscocombinado,razãoderisco eoddsratiodeperdaauditivacomIntervalosdeConfianc¸ade95%foramcomparadosentre densidademineralósseanormaledensidademineralósseabaixaouosteoporose.

Resultados: Nototal,16artigosforamsubmetidosarevisãocompleta.Emgeral,houveaumento estatisticamentesignificativodaprobabilidadedeperdaauditivanogrupodebaixadensidade mineralósseaounogrupodeosteoporosecomoddsratiode1,20(intervalodeconfianc¸ade95% 1,01-1,42,p=0,04,p=82%,Pheterogeneidade=0,01).Noentanto,oestudodeHelzneretal.relatou

aumentosignificativodaprobabilidadedeperdaauditivanadensidademineral ósseabaixa, emdeterminadaáreaepopulaçãoqueincluiucolofemoraldehomensnegros1,37(intervalo deconfiançade95%1,07-1,76,p=0,01) equadriltotaldehomensnegros1,36(intervalode confiançade95%1,05-1,76,p=0,02).

Conclusão:Nossoestudopropôsaprimeirametanálisequedemonstrouumaprovávelassociac¸ão entreperdaauditivaedensidademineralóssea.Aosteoporosepodeserumfatorderiscopara perdaauditivaepodedesempenharumpapelimportantenaperdadeaudic¸ãorelacionadacom aidade.

© 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Publicado por Elsevier Editora Ltda. Este é um artigo Open Access sob uma licença CC BY (http:// creativecommons.org/licenses/by/4.0/).

Introduction

Hearing lossis acommonchronic condition ofa disability estimatedat24.9millionpeopleworldwide.Itwasreported by The World Health Organization as one of the leading causesofyearslivedwithdisability.1_The_estimated preva-lenceofhearinglosswas30%inthepopulationover65years oldand50%inthepopulationover75yearsold.2,3_Moreover, hearinglossisalsoassociatedwithdecreasingqualityoflife andfunctionaloutcomesincludingsocialisolation, depres-sion,safetyissues,mobilitylimitations,reducedincomeand employmentopportunities.4---7 _Risk_factors_influence_to_the degree and rate of deterioration of hearing loss include aging,geneticsusceptibility,ototoxicmedicationexposure, otologicaldisorders,smoking,andoccupationalandleisure noiseexposure.6,8---10

Osteoporosishasalsobeenidentifiedinsomestudiesas a risk factor of hearing loss. The underlying mechanism of hearing loss in osteoporosis is complex and undeter-mined. Some studies purposed that a possible underlying mechanism is systemic demineralization of the skeletal systeminosteoporosisincludestemporalbone,which con-tains thecochlea capsule andthe conductivesystem.11---13 However,therewerecontroversiesandinconsistentresults fromotherstudies thatshowednon-significantassociation betweenosteoporosisandhearingloss.Theaccuracyofthe results was limited due to the sample sizes of the study populations.2_Therefore,_we_conducted_this_{meta-analysis}_to determinewhetherthereisanassociationbetweenhearing lossandlowbonemassorosteoporosis.

Materials

and

methods

This systematic review and meta-analysis was conducted and reported according to the Meta-analysis Of Observa-tionalStudies in Epidemiologystatement14 _and_was regis-teredinPROSPERO(registrationnumber:CRD42015024987).

Searchstrategy

Two authors (AS, SU) independently searched published studies indexed in the MEDLINE, EMBASE, and LILACS (Literatura LatinoAmericanaem CiênciasdaSaúde) from theirdateofinceptiontoNovember2015.Referencesofall selectedstudies were also examined. The following main search terms were used: osteoporosis, osteopenia, bone density, bone mass, bone loss, hearing loss, audiometry, otoacoustic. The full search strategy was detailed in Appendix1.

Inclusionandexclusioncriteria

(3)

lowBMD or osteoporosis andhearingloss wasreportedas either adjusted or unadjusted hazard ratios (HRs), rela-tive risks (RRs), or odds ratios (ORs) with associated 95% confidenceintervals(CIs),orhearingsensitivityindecibels. Exclusioncriteriawere(1)reviews,casereports,abstracts, andunpublished studies,(2) studieswithout specific sam-pleorigins,(3)datainthestudywasnotpresentedclearly enough,and(4)participantswithknownotosclerosis.

Osteoporosiswasdefinedashavingabonemineral den-sity(BMD)withaT-scoreoflessthan−2.5SDasmeasured bydual-energyX-rayabsorptiometryorotherstandard tech-nique at anatomical bone sites including lumbar spine, femoralneck,andtotalhip.Themainoutcomeofthisstudy washearinglossasassessedbyaudiometryorself-reported assessment.Weusedthedefinitionofhearingloss (conduc-tive,sensorineural,ormixed)asdescribedbyeachstudy.

Dataextraction

Twoauthors(ASandSU)independentlyreviewedtitlesand abstracts of all citations that were identified. After all abstracts were reviewed, data comparisons between the twoinvestigators wereconductedtoensurecompleteness and reliability. The inclusion criteria were independently applied to all identified studies. Differingdecisions were resolvedbyconsensus.

Full-text versions of potentially relevant papers iden-tified in the initial screening were retrieved. If multiple articlesfromthesamestudy werefound, onlythe article with the most complete data was included. Data con-cerningstudydesign,participantcharacteristics,sourceof data,comorbidities,methodsofassessingBMDandhearing impairment,outcomeassessment, andfactorsadjusted in multivariableanalysiswereindependentlyextracted.

Assessmentofquality

Asubjectiveassessmentofmethodologicalqualityfor obser-vationalstudieswasevaluatedbytwoauthors(ASandSU) usingtheNewcastle---OttawaScale(NOS).TheNOSisa qual-ity assessment tool for non-randomized studies. The NOS includeseightitems,categorizedintothreedimensionsof selection,comparability,andoutcome.Foreachdimension, alistofresponseoptionsisprovided.Scoringisbasedona semi-quantitativeassessmentofstudy quality.The highest qualitystudiesarescoredamaximumofonepointforeach item.However,thereis an exception ofthe item related tocomparabilitythatallowstheassignmentoftwopoints. The range of NOS is between zero up to nine points.15 _A totalscoreof 3orlesswasconsideredpoor,4---6 was con-sidered moderate, and 7---9 was deemed high quality. We excluded studies fromour meta-analysisif theyhad poor quality.Discrepantopinionsbetweenauthorswereresolved byconsensus.

Statisticalanalysis

Weperformed meta-analysisof theincluded studies using Comprehensive Meta-Analysis 3.3 software from Biostat, Inc. We used a random-effects model if there was high

heterogeneity(I2_>_50%)_and_{fixed-effects}_model_if_there_was

lowheterogeneity(I2_<_50%)._We_calculated_pooled_HR,_RR,

orORofhearinglosswith95%confidenceintervals(CI) com-paringbetweenparticipantswithnormalBMDandwithlow BMD or osteoporosisat each anatomicalsiteandwithany anatomicalsites.Wealsocalculatedpooledmeandifference (MD) with95% CI of hearingsensitivity in each frequency comparing between the normal BMD group and the low BMD group. We excluded studies from meta-analysis and only presentedthe resultwithnarrativedescription when therewerenotsufficientcomparabledataavailablefor out-comeofinterest.Theheterogeneityofeffectsizeestimates acrossthesestudieswasquantifiedusingtheQstatistic,its p-value, and I2 ₍_p_<_0.10 _was _considered _{significant).}

Sub-group analysis by site of BMD was performed to find the sourceofheterogeneity.Publicationbiaswasassessedusing funnelplotandEgger’sregressiontest.

Results

Descriptionofincludedstudies

The initial search yielded 83 articles (Fig. 1); 67 articles wereexcludedbecausetheywerenotoriginalobservational studies (23articles), didnothave BMD data (12articles), didnothavehearinglossdata(6articles),ordidnot mea-sureassociationbetweenBMDandhearingloss(26articles).

Records identified through

database searching (n=127)

Medline=41

Embase=42

Lilacs=44

Records after duplicates removed

(n=83)

Records screened (n=83)

Full-text articles assessed for eligibility

Studies included in

qualitative synthesis

Records excluded

(n=67)

Full-text articles excluded,

with reasons

(n=9)

Data not available (n=2)

Non-observational study

(n=1)

No association assessment

(n=2)

No outcome (n=2)

Letter (n=2) Studies included in

quantitative synthesis (meta-analysis)

(4)

Osteoporosisandhearingloss 649 Study name Clark, 1995 Helzner, 2005 Helzner, 2005 Helzner, 2005 Helzner, 2005 Helzner, 2005 Helzner, 2005 Helzner, 2005 Helzner, 2005 Kahveci, 2014 Mendy, 2014 Yeh, 2015 Total

Femoral neck bone density Femoral neck-black men Femoral neck-black women Femoral neck-white men Femoral neck-white women Total hip-black men Total hip-black women Total hip-white men Total hip-white women Femur or spine Head

Spine, hip, or forearm

1.90 1.37 0.83 0.92 0.92 1.36 0.91 0.86 0.98 4.50 2.08 1.76 1.20 1.37 1.07 0.67 0.77 0.77 1.05 0.73 0.72 0.82 1.82 1.33 1.33 1.01 2.63 1.76 1.03 1.09 1.09 1.76 1.13 1.03 1.17 11.13 3.24 2.33 1.42 0.00 0.01 0.09 0.35 0.34 0.02 0.40 0.10 0.82 0.00 0.00 0.00 0.04 0.1 0.2

More hearing loss in normal BMD

More hearing loss in low BMD/osteoporosis

0.5 1 2 5 10

7.79 8.78 9.24 9.72 9.74 8.73 9.20 9.66 9.72 2.73 6.31 8.38

Subgroup Statistics for each study Odda ratio and 95% CI

Relative weight Odds ratio Lower limit Upper limit p-Value

Figure2 Forestplotofstudiescomparingoddsofhearinglossinpatientswhohadlowbonemineraldensityorosteoporosisand control.Adiamonddatamarkerrepresentstheoveralloddsratiosandits95%CI.

A total of 16 articles underwent full-length review. Data wereextractedfromeightstudies involving52,828 partic-ipants who had bone mineral density and hearing status assessed.2,12,13,16---20

Most of them had cross-sectional design; others were prospectivecohort,retrospectivecohort,andcase---control studies.IncludedstudieswerefromTurkey,USA,andKorea. Theseincludednationalpopulation-basedstudiesfromtwo nations. All participants were assessed by bone mineral densitybystandardizedmethods(dualenergyX-ray absorp-tiometryor DXA).Sites of BMD measurementwere femur, lumbar spine, head, and methods of assessing hearing status included audiometry, otoscopic examination, and self-reported. The characteristics of the eight extracted studiesincludedinthisreviewareoutlinedinTable1.

Qualityassessmentofincludedstudies

The qualityof ninecross-sectional,threecohortand,two case---controlstudieswereevaluatedbyNOS(Table1).Total scorerangedfrom3to8.Twostudieshadlowquality(total score=3)andwereexcludefromthemeta-analysis.

Meta-analysisresults

Fivestudies(2,12,13,16,20)wereincludedinthe meta-analysisofhearingloss.Therewasastatisticallysignificant increased odds of hearing loss in the low BMD or osteo-porosisgroupwithORof 1.20(95%CI1.01---1.42, p=0.04, I2₌_82%, _P

heterogeneity=0.01) (Fig. 2). The study from Clark

etal.,Kahvecietal.,Mendyetal.,andYehetal.allreported significantlyincreasedoddsofhearinglossinthelowBMD groupwithORof1.90(95%CI1.37---2.63,p<0.01),4.50(95% CI1.82---11.13,p<0.01),2.08(95%CI1.33---3.24,p<0.01), and 1.76 (95% CI 1.33---2.33, p<0.01), respectively. How-ever, the study from Helzner et al. reported significantly increasedoddsofhearinglossinthelowBMDgroup,in par-ticulartheareaandpopulationincluded thefemoralneck of black men 1.37 (95% CI 1.07---1.76, p=0.01) and total hipofblackmen1.36(95%CI1.05---1.76,p=0.02).

0.0 0.1 0.2 0.3 0.4 0.5

–2.0 –1.5 –1.0 –0.5 0.0

Log odds ratio

Funnel plot of standard error by log odds ratio

Standard error

0.5 1.0 1.5 2.0

Figure3 Funnelplotassessingpublicationbias.

Sensitivityanalysis

Toassessthestabilityoftheresultsofthemeta-analysis,we conductedasensitivityanalysisbyexcludingonestudyata time.Noneoftheresultswassignificantlyaltered,indicating thatourresultswererobust.

Publicationbias

Toinvestigatepotentialpublicationbias,weexaminedthe contour-enhanced funnel plot of the included studies in assessingchangeinlogORofhearingloss(Fig.3).The ver-ticalaxis representsstudy size(standard error) while the horizontalaxisrepresentseffectsize(logoddsratio).From thisplot,biasisnotpresent becausethereissymmetrical distributionofstudiesonbothsidesofthemean.TheEgger’s test was non-significant (p=0.36). Using the trimand fill methodsintherandom-effectsmodel,therewasno differ-enceoftheimputedOR(1.38)andits95%CI(1.08---1.7).

Discussion

(5)

Upala

S

et

al.

Table1 Characteristicsofincludedstudies.

Study,year, Country Design Characteristics Participants

(n)

Outcomedefinition Factorsadjustedinmultivariate

model

Age Female(%)

ClarkK.etal., 1995

USA Cross-sectional

descriptivestudy

Womenaged

60---85years

100 369 40dBHLat1000and2000Hzin

oneear.

40dBHLat1000or2000Hzin bothears.

Ageandcommunityofresidence

HelznerEL etal.,2004

USA Cross-sectional

study

Womenaged65

yearsorolder

100 6474 Mild=hearingatthemoreintense

level(40dBHL),butnottheless intenselevel(25dBHL).

Significant=failingtohearatboth intensitylevels.

Age,BMI,estrogenuse,sedative use,antidepressantuse

KimSHetal., 2002

SouthKorea Cross-sectional Womenaged50

yearsorolder

100 1830 40dBHLat1000and2000Hzin

oneear.

40dBHLat1000or2000Hzin bothears.

Age,bonemineraldensity,and serumconcentrationofestradiol

KahveciOK

etal.,2014

Turkey Case---controlstudy Osteoporosis,

osteopenia patientsand controlswas 26---85,22---83and 50---68years, respectively

100 125 Sensorineuralhearingloss=bone

conduction>25dBHLwithout air-bonegap.

Conductivehearingloss=normal

boneconductionthreshold

average,butanair-bone gap>10dBHL.

MendyA

etal.,2014

USA Cross-sectional

surveyofthe civilian,

noninstitutionalized U.S.population

Aged40yearsand older

Nohearingtrouble. Littlehearingtrouble. Significanthearingtrouble.

Age,gender,race/ethnicity, educationlevel,bodymassindex

HelznerEP etal.,2005

USA Prospectivecohort

study

Aged70---79 47.27 2052 Hearingloss=puretoneaverage

(PTA)>25dBHLintheworseear. Conductivehearingloss=15dBor greaterorgreaterair-bonegapat

anytwoconsecutivefrequency

tested(0.5,1,2and4kHz)inthe worseear.

Age,historyofearsurgery, alcoholuse,diabetes,smoking, cardiovasculardisease, cerebrovascular

disease,mini-mentalscore, hypertension,occupationalnoise exposure,useofsalicylates YehMCetal.,

2015

Taiwan Retrospective

cohortstudy

AllAge 89.79 42,640 SSNHL=failingtohearatleastone

frequencyatbothintensitylevels.

Agegroup,sex,diabetes,

hypertension,CAD,chronickidney disease,income,andarea. OzkirisM

etal.,2013

Turkey Cross-sectional Agerangefrom50

to55years

100 75 Meanvaluesofairandbone

conductionateachfrequency NodefinitionofSSNHL.

Noadjust

(6)

Osteoporosisandhearingloss 651

densityandhearingloss.Accordingtoourmeta-analysisof 5studiesfromdifferentcountries,agegroups,gendersand races,wefoundthatadecreaseinBMDorosteoporosiswas significantlyassociatedwithhearingloss.

Age related hearing loss or ‘‘presbycusis’’ is caused by multifactorialetiologies. Arecent study purposed that demineralized petrous temporal bone in addition to age-related bone mass loss could be the cause of developing presbycusis.11,21_{Interestingly,}_in_Paget_disease_of_the_bone, demineralization of the cochlear bone is associated with hearing loss. However, the etiology of the association is unclear.22_In_concordance_with_{demineralization}_in_Paget dis-easeofthebone,astudyconductedinotoslcerosispatients byhigh-resolutioncomputedtomographicevaluationofthe cochlear capsule showed decreased BMD at specific loca-tions onthecochlear capsule. Therefore,decreasing BMD physiologicallyassociateswithhearingloss.

The etiology ofPaget diseaseof thebone and otoscle-rosis share similar pathogenesisin the lateral wall of the cochlea,wheretheabnormalboneremodelingmanipulates thechangeinionandfluidhemostasisinperilymphaticspace ofthecochlea.23_However,_there_are_several_unique charac-teristicsofthepathologicchangeinotosclerosis,including fibrousthickeningandlossofcochlearbloodvessels,spiral ligamenthyalinizationandstriavascularisatrophy.24

Therefore,imbalanceinboneformationandbone resorp-tion from osteoporosis may play an important role in dysfunctional ionic metabolism leading to sensory neural hearingloss.

Normally,BMDsatperipheralsiteshasastrong correla-tionwithmeasurementsathipand spine.The correlation coefficients between peripheral sites and central sites is between 0.6 and 0.70 (25). However, some populations whose peripheral measurements are normal could have osteoporotichiporspine;forexample,thepostmenopausal womanwith significant osteoporoticrisk factors.25 There-fore,differentsitesofBMD measurementfromeachstudy may not accurately reflect total body BMD. With limited resultsfromprevious studies,ourstudy demonstratedthe firstmeta-analysisofcorrelationbetweenhearinglossand BMD.Everystudythatwasincludedinourmeta-analysisdid notreporttotalbodyBMD.Nevertheless,ourmeta-analysis has raised the concern of hearing loss in osteoporosis, sinceourresultisthestrongestevidenceoftheassociation betweenhearinglossandosteoporosiseverreported. There-fore,toevaluatemoreevidenceoftheassociation,further cohortstudies of theassociation between totalbodyBMD andhearinglossshouldbeevaluated.

Thelimitationsofourstudyincludedifferenthearingloss outcomesanddifferentsitesofBMDmeasurementfrom dif-ferentstudies.Hearing lossoutcomesweredeterminedin differentaspectsofmeasurementincludingaudiometryand patientself-evaluation.Variationintheoutcomeofhearing losscouldpotentiallyaltertheresultsandconclusion.Since differentsitesofBMDmeasurementmaynotbeaccurateas totalBMD,theinterpretationofourstudymaybelimited.

Conclusion

Inconclusion,ourstudyproposedthefirstmeta-analysisthat demonstratedaprobable associationbetweenhearingloss

andBMD.Osteoporosiscouldbeariskfactorinhearingloss andmightplayanimportantroleinage-relatedhearingloss.

Ethical

approval

Thisarticledoesnotcontainanystudieswithhuman partic-ipantsoranimalsperformedbyanyoftheauthors.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgment

WethankMatthewRoslundforvalidationofthesearch.

Appendix

1. Search

strategy

MEDLINE

1)Hearingloss.mp.orexpHearingLoss/ 2)Audiometry.mp.orexpAudiometry/

3)Otoacoustic.mp.[mp=title,abstract,originaltitle,nameof substanceword,subjectheadingword,keywordheading word,protocolsupplementaryconceptword,raredisease supplementaryconceptword,uniqueidentifier].

4)ExpOsteoporosis/orosteoporosis.mp. 5)Osteopenia.mp.

6)ExpBoneDensity/orbonedensity.mp. 7)Bonemass.mp.

8)Boneloss.mp. 9)BMD.mp.

10)Bonemineraldensity.mp. 11)1or2or3

12)4or5or6or7or8or9or10 13)11and12

14)limit13tohumans EMBASE

((’osteoporosis’/expor‘osteoporosis’and[embase]/lim)or (osteopeniaand[embase]/lim)or(’bonedensity’and [embase]/lim)or(’bonemass’and[embase]/lim)or(’bone loss’and[embase]/lim)or(bmdand[embase]/lim))and ((’hearingloss’/expor‘hearingloss’and[embase]/lim)or (’audiometry’/expor‘audiometry’and[embase]/lim))and [humans]/lim)and[embase]/limnot[medline]/lim.

References

1.FederK,MichaudD,Ramage-MorinP,McNameeJ,Beauregard Y.PrevalenceofhearinglossamongCanadiansaged20to79: audiometricresultsfromthe2012/2013CanadianHealth Meas-uresSurvey.HealthRep.2015;26:18---25.

2.Clark K, Sowers MR, Wallace RB, Jannausch ML, Lemke J, AndersonCV.Age-relatedhearinglossandbonemassina pop-ulation ofruralwomen aged60to 85years.Ann Epidemiol. 1995;5:8---14.

(7)

4.DaltonDS,CruickshanksKJ,KleinBE,KleinR,WileyTL,Nondahl DM.Theimpactofhearinglossonqualityoflifeinolderadults. Gerontologist.2003;43:661---8.

5.Kramer SE, Kapteyn TS, Kuik DJ, Deeg DJ. The association ofhearingimpairmentandchronicdiseaseswithpsychosocial healthstatusinolderage.JAgingHealth.2002;14:122---37.

6.WoodcockK,PoleJD.HealthprofileofdeafCanadians:analysis oftheCanadaCommunityHealth Survey.CanFamPhysician. 2007;53:2140---1.

7.WoodcockK,PoleJD.Educationalattainment,labourforce sta-tus and injury:a comparisonof Canadianswithand without deafnessandhearingloss.IntJRehabilRes.2008;31:297---304.

8.Hasson D, Theorell T, Westerlund H, Canlon B. Prevalence andcharacteristicsofhearingproblemsinaworkingand non-workingSwedishpopulation.JEpidemiol CommunityHealth. 2010;64:453---60.

9.FerriteS,SantanaV.Jointeffectsofsmoking,noiseexposure andageonhearingloss.OccupMed(Lond).2005;55:48---53.

10.HuangQ,TangJ.Age-relatedhearinglossorpresbycusis.Eur ArchOtorhinolaryngol.2010;267:1179---91.

11.KimJY,LeeSB,LeeCH,KimHM.Hearinglossinpostmenopausal women with low bone mineral density. Auris Nasus Larynx. 2016;43:155---60.

12.Yeh MC, Weng SF, Shen YC, Chou CW, Yang CY, Wang JJ, et al. Increased risk of sudden sensorineural hearing loss inpatientswithosteoporosis:apopulation-based,propensity score-matched,longitudinalfollow-upstudy.JClinEndocrinol Metab.2015;100:2413---9.

13.Kahveci OK, Demirdal US, YucedagF, CerciU. Patients with osteoporosis have higher incidence of sensorineural hearing loss.ClinOtolaryngol.2014;39:145---9.

14.StroupDF,BerlinJA,MortonSC,OlkinI,WilliamsonGD,Rennie D,etal.Meta-analysisofobservationalstudiesinepidemiology: aproposalforreporting.Meta-analysisOfObservationalStudies inEpidemiology(MOOSE)group.JAMA.2000;283:2008---12.

15.StangA.CriticalevaluationoftheNewcastle---Ottawascalefor theassessmentofthequalityofnonrandomizedstudiesin meta-analyses.EurJEpidemiol.2010;25:603---5.

16.Purchase-HelznerEL,CauleyJA,FaulknerKA,PrattS,Zmuda JM,TalbottEO,etal.Hearingsensitivityandtheriskofincident fallsand fractureinolderwomen:thestudyofosteoporotic fractures.AnnEpidemiol.2004;14:311---8.

17.KimSH,KangBM,ChaeHD,KimCH.Theassociationbetween serumestradiollevelandhearingsensitivityinpostmenopausal women.ObstetGynecol.2002;99:726---30.

18.Ozkiris M, Karacavus S, Kapusuz Z, Balbaloglu O, Saydam L. Does bone mineral density have an effect on hearing loss in postmenopausal patients. Ann Otol Rhinol Laryngol. 2013;122:648---52.

19.Helzner EP, CauleyJA, Pratt SR, WisniewskiSR, Talbott EO, ZmudaJM,etal.Hearingsensitivityandbonemineraldensity inolderadults:thehealth,agingandbodycompositionstudy. OsteoporosInt.2005;16:1675---82.

20.MendyA,VieiraER,AlbatinehAN,NnadiAK,LowryD,GasanaJ. Lowbonemineraldensityisassociatedwithbalanceandhearing impairments.AnnEpidemiol.2014;24:58---62.

21.ShinYJ,FraysseB,DeguineO,CognardC,CharletJP,SevelyA. Sensorineuralhearinglossandotosclerosis:aclinicaland radio-logicsurveyof437cases.ActaOtolaryngol.2001;121:200---4.

22.MonsellEM.ThemechanismofhearinglossinPaget’sdiseaseof bone.Laryngoscope.2004;114:598---606.

23.Wangemann P. Supporting sensory transduction: cochlear fluidhomeostasis and theendocochlear potential.J Physiol. 2006;576:11---21.

24.DohertyJK,LinthicumFHJr.Spiralligamentandstriavascularis changesincochlearotosclerosis:effectonhearinglevel.Otol Neurotol.2004;25:457---64.