BONEFRACTURE

MinakoWakasugi,MD,MPH,PhD.DivisionofComprehensiveGeriatricsinCommunity,

NiigataUniversityGraduateSchoolofMedicalandDentalSciences

KDIGO

OUTLINE

Hipfracture•  Poorsurvival•  GPandDialysispts•  RegionalvariaKon•  Dialysismodality•  TrendVertebralfracture

KDIGO

5cmsubtrochantericfx

Hipfracture

KDIGO

HIPFRACTUREISASSOCIATEDWITHPOOROUTCOMEINTHEGENERALPOPULATION KohGC,etal.OsteoporosInt.2013;24:1981-9.

TheSingaporeChineseHealthStudy,apopulaKon-basedcohortof63,257middle-agedandelderlyChinesemenandwomeninSingaporerecruitedbetween1993and1998.

Hipfracture

Hipfracture

NohipfractureNohipfracture

Male Female

KDIGO

HIPFRACTUREISASSOCIATEDWITHPOOROUTCOMEAMONGDIALYSISPATIENTS Mi_alhenkleA,etal.AmJKidneyDis.2004;44:672-9.

Hipfracture

Nohipfracture

Survival

AmatchedcohortstudyofdialysispaKentsusingdatafromtheUSRDS

KDIGO

HIPFRACTUREISASSOCIATEDWITHPOOROUTCOME

Nofracture/NoCVD

Survival

Nofracture/CVDFracture/NoCVDFracture/CVD

AmatchedcohortstudyofdialysispaKentsusingdatafromtheUSRDS

Mi_alhenkleA,etal.AmJKidneyDis.2004;44:672-9.

KDIGO

DIALYSISPATIENTSHAVEMORERISKSOFHIPFRACTURECOMPAREDWITHTHEGENERALPOPULATION

DialysispaKent-specificfactorsAbeta-2M-amyloidosisandrelatedosteopathy,CKD-MBD,dialysismodality,etc.

Dialysispa)entsGeneralpopula)on

?

CommonriskfactorsOlderage,femalegender,lowBMI,lowBMD,earlymenopause,smoking,physicalacKvitylevels,etc.

KDIGO

HIPFRACTUREINCIDENCEAMONGDIALYSISPATIENTSWAS4TIMESHIGHERTHANTHATOFTHEGENERALPOPULATION.

Dialysispa)entsGeneralpopula)on

Rochester,Minesota

HipfractureincidenceamongAmericanCaucasianpopulaKonsfrom1983to1992.

HipfractureincidenceamongallCaucasianpaKentswhobegandialysisbetween1989and1996

4Kmes

ThisstudyincludedonlyCaucasians.

HowaboutAsians?AlemAM,etal.KidneyInt2000;58:396-9.

KDIGO

DIALYSISPATIENTSHAVEDEFINITELYHIGHERRISKOFHIPFRACTURECOMPAREDWITHTHEGENERALPOPULATION

HipfractureincidenceamongJapanesegeneralpopulaKon

HipfractureincidenceamongJapaneseHDpaKents

HDpa)entsGeneralpopula)on

5-6Kmes

WakasugiM,etal.JBoneMinerMetab.2013;31:315-21. INCIDENCE:11.3/1,000PATIENT-YEARS(95%CI,10.7TO11.9)

JRDR:theJapaneseSocietyforDialysisTherapyRegistry

KDIGO

0

10

20

30

40

50

60

70

0

10

20

30

40

50

60

70

THEOVERALLINCIDENCEOFHIPFRACTUREAMONGJAPANESEHDPTSWAS5-TO6-FOLDGREATERTHANINTHEGENERALPOPULATION.

Incide

nce,per1,000

person-years

Age,years

Men Women

StandardizedIncidenceRa)o6.2(95%CI5.7-6.8)4.9(95%CI4.6-5.3)

HDpaKentsGeneralpopulaKon

WakasugiM,etal.JBoneMinerMetab.2013;31:315-21.

KDIGO

SIRSAREALREADYHIGHINPTSW/SHORTDIALYSISVINTAGE

WakasugiM,etal.JBoneMinerMetab.2013;31:315-21.

1

2

4

8

16

1

2

4

8

16 Standardize

dincide

nceraKo

Vintage,years

Men Women

Meanage64.864.964.864.362.159.5　　　 67.667.267.466.063.561.5　　(SD)　　 　(12.7)　 (12.6)(12.5)(12.3)(12.1)(10.1)　　 　　　 　(12.7)(13.2)(12.8)(12.7)(12.1)(10.1)

Errorbarsindicate95%confidenceintervals.

5.5 3.8KDIGO

THECOUNTRY-SPECIFICRATEFORHIPFRACTUREINTHEDIALYSISPOPULATIONISHIGHERTHANREPORTEDRATESFORHIPFRACTUREINTHEGENERALPOPULATION.

TentoriFetal.KidneyInt2014

DialysispaKentsfacehigherrisksforhipfracturecomparedtothegeneralpopulaKon.KDIGO

LinZZ,etal.Bone2014;64:235–239

TAIWANNATIONALCOHORTSTUDY1903PATIENTSHADAHIPFRACTURE(INCIDENCE:89.21/10,000)

1903/𝑃𝑎𝑡𝑖𝑒𝑛𝑡 𝑡𝑖𝑚𝑒 𝑎𝑡 𝑟𝑖𝑠𝑘 = 89.21/10,000 

Patient time at risk = 213316.9

95% CI = 85.2 to 93.3/10,000

KDIGO

THEQUESTIONARISESWHYHIPFRACTUREINCIDENCEVARIESSOMUCH

TentoriFetal.KidneyInt2014

8.9

8.5

9.3

LinZZetal.Bone2014

WakasugiMetal.JBMM2013

11.310.7

11.9

TaiwanNaKonalCohortStudy

JapaneseSocietyforDialysisTherapyRegistry(JRDR)

KDIGO

THEQUESTIONARISESWHYHIPFRACTUREINCIDENCEVARIESSOMUCH

CommonriskfactorsOlderage,femalegender,lowBMI,lowBMD,earlymenopause,smoking,physicalacKvitylevels,etc.

DialysispaKent-specificfactorsAbeta-2M-amyloidosisandrelatedosteopathy,CKD-MBD,dialysismodality,etc.

Dialysispa)entsGeneralpopula)on

THEREASONSARENOTKNOWN

KDIGO

LARGEVARIATIONSINFRACTUREINCIDENCEEXISTINTHEGENERALPOPULATION

CommonriskfactorsOlderage,femalegender,lowBMI,lowBMD,earlymenopause,smoking,physicalacKvitylevels,etc.

Generalpopula)on

KDIGO

AGE-STANDARDIZEDINCIDENCERATESOFHIPFRACTUREVARIESABOUT10-FOLDINTHEGENERALPOPULATION

KanisJA,etal.OsteoporosInt2012;23(9):2239–56.

Hipfractureratesformenandwomencombinedindifferentcountriesoftheworldcategorisedbyrisk.

WhereesKmatesareavailable,countriesarecolourcodedred(annualincidence>250/100,000),orange(150-250/100,000)orgreen(<150/100,000)

KDIGO

HIPFRACTUREINCIDENCEAMONGASIANSAREAPPROXIMATELYHALFTHATOFCAUCASIANSFORBOTHSEXES

YamamotoKetal.OsteoporosisInt(1993)Suppl.1:S48-50

Niigata(1985)To_ori(1986-88)Okinawa(1987)

Rochester(1965-74)

Oslo(1978-79)Stockholm(1972-81)

Singapore(1962-63)

Japan

Asia

WhyAsianshavelowerincidenceofhipfracturecomparedtoCaucasians?AsianshaveabonedensitysimilartoorlowerthanthatofCaucasians.

KDIGO

THEREASONSWHYASIANSHAVELOWERINCIDENCEOFHIPFRACTURECOMPAREDTOCAUCASIANSARENOTWELLUNDERSTOOD

Japanese-styletoilets(squapngpantoilet)

Shortlegs

Sometradi)onallifestylecharacteris)csmaypreventhipfracture.

Tatami(tradiKonalJapanesemat)

Futonbedding

SuzukiTetal.Bone1997;21:461-7.YaegashiYetal.EurJEpidemiol2008;23:219-25.YamamotoKetal.OsteoporosisInt1993;Suppl.1:S48-50.CummingsSRetal.OsteoporosisInt1994;4:226-9.

Thecustomoflivingandsleepingontheflooronatatami,andusingfutonbedding.

Japanesegreentea

tofusoyproductscontainingahighamountofisoflavones

na@ofermentedsoybeansrichinvitaminK2(menaquinone-7)

KDIGO

INADDITIONTOLARGEVARIATIONSINFRACTURERATESAROUNDTHEWORLD,

KanisJA,etal.OsteoporosInt2012;23(9):2239–56.

Hipfractureratesformenandwomencombinedindifferentcountriesoftheworldcategorisedbyrisk.

WhereesKmatesareavailable,countriesarecolourcodedred(annualincidence>250/100,000),orange(150-250/100,000)orgreen(<150/100,000)

KDIGO

HIPFRACTURERATESVARYWITHINCOUNTRIESJAPANESEGENERALPOPULATION

1.20~

1.10~1.19

1.00~1.09

0.90~0.99

~0.89

Standardized incidence ratio (SIR)

Men Women

HipfractureincidenceishigherinwesternJapanthanineasternJapan.

CreatedbasedupondatafromYaegashiYetal.EurJEpidemiol2008;23:219-25

easternJapan

westernJapan

easternJapan

westernJapan

KDIGO

HIPFRACTURERATESVARYWITHINCOUNTRIESJAPANESEHDPATIENTS WakasugiM,etal.TherApherDial2014;18:162-6.

1.4≤1.20-1.391.00-1.19

0.70-0.89

≤0.49

0.90-1.09

0.50-0.69

StandardizedincidenceraKo(SIR)

HipfractureincidenceishigherinwesternJapanthanineasternJapan.

Men Women

easternJapan

westernJapan

easternJapan

westernJapan

KDIGO

THEQUESTIONARISESWHYHIPFRACTUREINCIDENCEVARIESSOMUCH

CommonriskfactorsOlderage,femalegender,lowBMI,lowBMD,earlymenopause,smoking,physicalacKvitylevels,etc.

DialysispaKent-specificfactorsAbeta-2M-amyloidosisandrelatedosteopathy,CKD-MBD,dialysismodality,etc.

Dialysispa)entsGeneralpopula)on

THEREASONSARENOTKNOWN

KDIGO

UNADJUSTEDTEMPORALTRENDININCIDENCEOFHIPFRACTURESOVERTIME:HDCOMPAREDTOPD

MathewAT,etal.AmJNephrol2014;40:451–457

PD

HD

KDIGO

CUMULATIVEINCIDENCEOFHIPFRACTUREAFTERBEGINNINGDIALYSISSTRATIFIEDBYDIALYSISMODALITY LinZZ,etal.Bone2014;64:235–239

KDIGO

0

500

1000

1500

2000

2500

PATIENTSONPDHADABOUT30%LOWERRISKOFHIPFRACTURETHANDIDTHOSEONHD

Incide

nce,per10,00

0pe

rson

-years

Age,years

Men Women

SIR0.64(95%CI0.49–0.81)0.69(95%CI0.55–0.85)

0

500

1000

1500

2000

2500

PaKentsonHD

PaKentsonPD

Errorbarsindicate95%confidenceintervals.

Calculated using data from Tables S3-S5 in Wakasugi M, et al. Am J Kidney Dis. 2018;71:173-181.

KDIGO

FIGURE11.12PERCENTAGEDISTRIBUTIONOFTYPEOFRENALREPLACEMENTTHERAPYMODALITYUSEDBYESRDPATIENTS,BYCOUNTRY,IN2015

JapanTaiwan

Philippines

MalaysiaThailand

SingaporeRep.ofKorea

HongKong

TheUSRDS2017AnnualDataReporth_ps://www.usrds.org/2017/view/Default.aspx

KDIGO

INCIDENCERATESFORHIPFRACTUREHAVEDECLINEDSINCE2005AMONGINCIDENTDIALYSISPATIENTSINTHEUS

NairSS,etal.ClinJAmSocNephrol2013;8:1336–42.

2005KDIGO

TRENDSAREDIFFERENTBETWEENTHEGENERALNON-ESRDPOPULATIONANDHDPATIENTS

Theimprovedtrendinthehemodialysisptsissuggestedtobedueto

factorsspecifictohemodialysispts.

ArnesonTJ,etal.AmJKidneyDis.2013;62:747-754.

Medicarenon-ESRD

Hemodlialysisaged ≥ 66years2005KDIGO

AGE-STANDARDIZEDHIPFRACTUREINCIDENCEINJAPANHAVEDECLINEDINFEMALEANDSHOWEDNOCHANGEINMALEDIALYSISPATIENTS

Openandfilledcirclesrepresentthecrudeandage-standardizedrates,respecKvely.ThereferencepopulaKonwasthe2013populaKonofJapanesedialysispaKents.Linesarefi_edratesbasedonjoinpointanalysis.

APC-3.6%(95%CI;-6.9to-0.2)

APC-1.4%(95%CI;-5.7to3.0)

WakasugiM,etal.AmJKidneyDis.2018;71:173-181.

KDIGO

JAPANESEGENERALPOPULATIONHASACONTINUINGINCREASEINAGE-ADJUSTEDRATESOFHIPFRACTURE

CooperC,etal.OsteoporosInt2011;22:1277–88

KDIGO

EVIDENCE-BASEDGUIDELINESANDTHECONCEPTOFCKD-MBDMAYCONTRIBUTETOTHEIMPROVEMENTS

WakasugiM,etal.AmJKidneyDis.2018;71:173-181.

2008

ThisisthefirstclinicalguidelinestobepublishedatertheclinicalconceptofCKD-MBDwasintroducedbyKDIGO.

TheJSDTclinicalpracKceguidelinesformanagementofsecondary

hyperparathyroidisminmaintenancedialysispaKents

waspublishedin2006KDIGO

THETARGETRANGEFORINTACTPTHISMUCHLOWERTHANTHOSEFROMOTHERCOUNTRIES

WakasugiM,etal.AmJKidneyDis.2018;71:173-181.

2008

TheJSDTclinicalpracKceguidelinesformanagementofsecondary

hyperparathyroidisminmaintenancedialysispaKents

waspublishedin2006

TargetrangefordialysispaKents

theJSDTclinicalpracKceguideline

in2006

theJSDTclinicalpracKceguideline

in2012IntactPTH 60-180pg/mL 60-240pg/mL

KDIGO

POSTMENOPAUSALFEMALEDIALYSISPATIENTSHAVEMOREBONELOSSTHANMALEDIALYSISPATIENTSWITHCOMPARABLEPTHCONCENTRATIONS

HamanoT,etal.Bone.2009;45:S19-S25.

ConcentraKonsofserumboneresorpKonmarkersaresignificantlyhigherinpostmenopausalfemalehemodialysispaKentscomparedwithmaleswithsimilarserumPTHconcentraKons.

KDIGO

WakasugiM,etal.AmJKidneyDis.2018;71:173-181.

THETARGETRANGEINJAPANMAYBEFAVORABLEFORFEMALEBONES

TargetrangefordialysispaKents

theJSDTclinicalpracKceguideline

in2006

theJSDTclinicalpracKceguideline

in2012IntactPTH 60-180pg/mL 60-240pg/mL

HamanoT,etal.Bone.2009;45:S19-S25.

KDIGO

NairSS,etal.ClinJAmSocNephrol2013;8:1336–42.

THEIMPROVEDTRENDINTHEDIALYSISPATIENTISLIKELYDUETOFACTORSSPECIFICTODIALYSISPATIENTS.

20052005

ArnesonTJ,etal.AmJKidneyDis.2013;62:747-754.

WakasugiM,etal.AmJKidneyDis.2018;71:173-181.

2008

TheapprovalofcinacalcetinMarch2004

Theapprovalofcinacalcetin2008

TheapprovalofcinacalcetinMarch2004

KDIGO

<<SUMMARY

DialysispaKent-specificfactorsAbeta-2M-amyloidosisandrelatedosteopathy,CKD-MBD,dialysismodality,etc.

Dialysispa)entsGeneralpopula)on

CommonriskfactorsOlderage,femalegender,lowBMI,lowBMD,earlymenopause,smoking,physicalacKvitylevels,etc.

Pooroutcome

HipfractureKanisJA,etal.OsteoporosInt2012;23(9):2239–56.

KDIGO

AGE-SPECIFICINCIDENCERATESINHONGKONGCOMPAREDTOJAPANESEANDSWEDISHCAUCASIANSFORHIPFRACTURE

BowCH,etal.OsteoporosInt23:879–885,2012

Japan

HongKong

Sweden Japan

HongKong

Sweden

Men Women

KDIGO

AGE-SPECIFICINCIDENCERATESINHONGKONGCOMPAREDTOJAPANESEANDSWEDISHCAUCASIANSFORCLINICALVERTEBRALFRACTURE

BowCH,etal.OsteoporosInt23:879–885,2012

Japan

HongKongSweden

Japan

HongKong

Sweden

Men Women

KDIGO

OUTLINE

Hipfracture•  Poorsurvival•  GPandDialysispts•  RegionalvariaKon•  Dialysismodality•  TrendVertebralfracture

KDIGO