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3GD DLP NE SGHR SGDRHR HR SN HCDMSHEX FDMDSHB @MC DMUH NMLDMS@K HRJ E@BSN R NE NRSDNON NRHR R@ BNODMH@ @MC SGDH RDPTDKR H D E@KKR @MC E @BST DR 3GD DOHCDLHNKNFHB@K RSTC HDR VD D DLADCCDC VHSGHM SGD 5RWWHuGDP 6WxG 56 @ O NRODBSHUD ONOTK@SHNM A@RDC RSTCX HMBKTCHMF HMG@AHS@MSR NE SGD .LLNN C CHRS HBS HM SGD BHSX NE 1NSSD C@L SGD -DSGD K@MCR @MC CHUHCDC HMSN SG DD BNGN SR /@ SHBHO@MSR TMCD VDMS @ VHCD @MFD NE OD HNCHB DW@LHM@SHNMR HM @ DRD@ BG E@BHKHSX HM SGD BDMS D NE SGDH CHRS HBS DOD@SDC DUD X XD@ R TRHMF @MC BNLOKDLDMSDC VHSG GNLD HMSD UHDVR 3GD &DMDSHB +@AN @ SN X NE SGD @RLTR , O DEN LDC SGD FDMNSXOHMF NE @KK SG DD 12 BNGN SR 3GD RSTCX HR @OO NUDC AX SGD LDCHB@K DSGHBR BNLLHSSDD @MC @KK O@ SHBHO@MSR G@UD O NUHCDC V HSSDM HMEN LDC BNMRDMS SN O@ SHBHO@SD HM SGD DRD@ BG &DMDSHB RSTCHDR NE SGD 12 @ D B@ ried out within the setting of large collaborative e orts, namely the *(qHWLf )DfWRuV IRu 26WHRSRuRVLV *()26 @MC RKRuWV IRu HDuW DqG HDOWK 5HVHDufK Lq *HqRPLf (SLGHPLRORj 5*( BNMRN SH@ 3GDRD @ D HMSD M@SHNM@K MDSVN JR HMUNKUHMF U@ HNTR O NLHMDMS DRD@ BG F NTOR @ NTMC SGD VN KC VHSG @ FDMD @K NAIDBSHUD SN HCDMSHEX SGD FDMDSHB CDSD LHM@MSR NE LTRBTKNRJDKDS@K @MC @FHMF DK@SDC S @HSR (M @CCHSHNM VD L@CD TRD NE SGD 8. %LREDqN 6WxG NMD NE SGD K@ FDRS FDMDSHB AHNA@MJR HM SGD VN KC
KDSWHu @CC DRRDR SGD CDSD LHM@MSR NE NRSDNON NRHR @MC E @BST D HRJ (M KDS WHu we estimated the incident rates and trends of site-speci c non-vertebral E @BST DR HM SGD 1NSSD C@L 2STCX NUD XD@ R NE ENKKNV TO @MC CDSD LHMD SGD O DCHB SHUD U@KTD NE NMD RHMFKD !,# LD@RT DLDMS KDSWHu HR @M NARD U@SHNM@K RSTCX which explores the e ects of metabolic syndrome and its components on di erent @RODBSR NE ANMD GD@KSG KDSWHu DW@LHMDR SGD @RRNBH@SHNM ADSVDDM NRSDNB@KBHM @CHONRHSX @MC ANMD GD@KSG HM DKCD KX ODNOKD TRHMF @ B NRR RDBSHNM@K RSTCX CDRHFM KDSWHu HR @ DUHDV O@OD RTLL@ HYHMF SGD BT DMS RS@SD @MC DUNKTSHNM NE SGD RSTCHDR NM SGD FDMDSHBR NE NRSDNON NRHR @MC E @BST D HRJ KDSWHu HR @ &6 2 RSTCX VGHBG @HLDC SN CHRDMS@MFKD SGD FDMDSHB A@BJF NTMC NE BH BTK@SHMF NRSDNB@KBHM
KDSWHu O NUHCDR HMRHFGSR HMSN SGD FDMDSHBR NE SNS@K ANCX !,# @MC DW@LHMDR possible age-speci c e ects using GWAS approach while KDSWHu DWOKN DR SGD FDMDSHB @MC BKHMHB@K CDSD LHM@MSR NE HRJ NE E @BST D VHSGHM @ &6 2 @MC ,1 RSTCX CDRHFM %R[ KDSWHu HR @ DUHDV O@OD NE SGD B@TR@K HMED DMBD ,DMCDKH@M @MCNLHY@SHNM @M@KXRDR SG@S G@UD ADDM OD EN LDC HM DK@SHNMRGHO VHSG ANMD -DWS
KDSWHu ENBTRDR NM R@ BNODMH@ BNMRHCD DC @ MNUDK FD H@S HB RXMC NLD @MC HSR HRJ E@BSN R @MC BNMRDPTDMBDR (M KDSWHu VD DRSHL@SDC SGD OGDMNSXOHB BN DK@SHNMR between a variety of bone and muscle parameters derived from DXA and pQCT. In KDSWHu VD DRSHL@SDC SGD NUD @KK O DU@KDMBD NE R@ BNODMH@ HM NKCD @CTKSR @MC DWOKN DC SGD LNRS BNLLNM BKHMHB@K BN DK@SDR NE SGHR O@SGNKNFX (M KDSWHu VD BNMCTBSDC @ RXRSDL@SHB DUHDV @MC LDS@ @M@KXRHR SN DRSHL@SD SGD NUD @KK O DU@KDMBD
37 5
NE R@ BNODMH@ HM O@SHDMSR VHSG BG NMHB NARS TBSHUD OTKLNM@ X CHRD@RD VGD D@R HM KDSWHu VD DU@KT@SDC SGD DK@SHNMRGHO ADSVDDM ANCX BNLONRHSHNM @MC R@ BNODMH@ VHSG MNM @KBNGNKHB E@SSX KHUD CHRD@RD HM @M NARD U@SHNM@K RSTCX NE DKCD KX ODNOKD
KDSWHu examines the pleiotropic e ects in the musculoskeletal system KDSWHu HR @ DUHDV O@OD NM SGD BT DMS JMNVKDCFD NE SGD ANMD @MC LTRBKD HMSD @BSHNMR HM GTL@MR (M KDSWHu VD TRDC @ AHU@ H@SD FDMNLD VHCD @OO N@BG SN RD@ BG EN ONR sible pleotropic genes a ecting bone and muscle whereas in KDSWHu VD DWOKN DC SGD FDMDSHB K@MCRB@OD NE E@KKHMF HRJ AX O DEN LHMF &6 2 @M@KXRHR @MC DRSHL@SDC SGD RG@ DC GD HS@AHKHSX NE E@KKR VHSG ANMD @MC LTRBKD OGDMNSXODR (M KDSWHu VD DW@LHMDC SGD RG@ DC FDMDSHBR ADSVDDM NRSDN@ SG HSHR @MC !,# TRHMF @ RXRSDL@SHB NUD K@O @M@KXRHR NM @ FDMNLD VHCD RB@KD %HM@KKX KDSWHu discusses the ndings @MC O NUHCDR RTFFDRSHNMR EN ETST D DRD@ BG
%R[ [ &KNRR@ X NE ,DMCDKH@M @MCNLHR@SHNM
,DMCDKH@M @MCNLHY@SHNM ,1 HR @ RS@SHRSHB@K SDBGMHPTD SG@S KDUD @FDR FDMDSHB HMEN L@SHNM HM N CD SN O NUHCD DUHCDMBD EN @ B@TR@K DK@SHNMRGHO ADSVDDM LNCH
able risk factors and diseases. 1DWxuDO H[SHuLPHqW
3GD ,1 @OO N@BG TRDR FDMDSHB U@ H@MSR @R HMRS TLDMS@K U@ H@AKDR EN SGD HRJ E@BSN NE HMSD DRS #TD SN SGD @MCNL @KKNB@SHNM NE @KKDKDR CT HMF F@LDSD EN L@ SHNM SGD FDMDSHB U@ H@MSR @ D KDRR KHJDKX SN AD @RRNBH@SDC VHSG @MX BNMENTMCD R Importantly, they cannot be a ected by reverse causation. Therefore, the MR @OO N@BG B@M O NUHCD LN D NATRS DUHCDMBD NE B@TR@K @RRNBH@SHNMR BNLO@ DC SN SGD S @CHSHNM@K NARD U@SHNM@K RSTCHDR .H DVVxPSWLRqV 3GD FDMDSHB U@ H@MSR LTRS AD @RRNBH@SDC VHSG SGD HRJ E@BSN TMCD HMUDRSHF@ SHNM 3GD FDMDSHB U@ H@MSR @ D MNS @RRNBH@SDC VHSG @MX BNMENTMCD SG@S B@M AH@R SGD @RRNBH@SHNM ADSVDDM SGD HRJ E@BSN @MC SGD NTSBNLD
The genetic variants a ect the disease under investigation only through the HRJ E@BSN NE HMSD DRS
6WxG GHVLjq
2QH VDPSOH 05 VGDM ANSG SGD HRJ E@BSN @MC NTSBNLD @ D LD@RT DC HM SGD RSTCX ONOTK@SHNM
,1752 8 7,21
7ZR VDPSOH 05 – when the risk factor and outcome are measured in two di erent RSTCX ONOTK@SHNMR 3GHR LDSGNCNKNFX G@R ADDM E@BHKHS@SDC AX SGD @CUDMS NE K@ FD RB@KD &6 2 SG@S G@UD KDC SN RTARS@MSH@K HMB D@RDR HM SGD RS@SHRSHB@K ONVD NE SGD ,1 @OO N@BG
/LPLWDWLRqV
• Heterogeneity – Presence of di erences in e ects estimates between the ge MDSHB U@ H@MSR TRDC @R HMRS TLDMS@K U@ H@AKDR EN SGD HRJ E@BSN TMCD HMUDRSHF@ SHNM SG@S B@MMNS AD DWOK@HMDC AX R@LOKHMF U@ H@SHNM @KNMD
• Population strati cation – Presence of di erences in allele frequencies and/ N CHRD@RD O DU@KDMBD @SDR ADSVDDM RTAF NTOR HM SGD SNS@K RSTCX ONOTK@SHNM VGHBG B@M BNMENTMC SGD @RRNBH@SHNM ADSVDDM SGD HRJ E@BSN @MC SGD CHRD@RD NE HMSD DRS
• Pleiotropy – When one genetic variant is associated with more than one trait VGHBG HR @ RD HNTR UHNK@SHNM NE SGD SGH C ,1 @RRTLOSHNM
• Canalization – When the individuals’ response to genetic and environmental in uences is attenuated or absent as a result of the presence of so-called “bu D HMF LDBG@MHRLR SG@S @BS @F@HMRS SGD DWODBSDC FDMDSHB @MC DMUH NMLDMS@K e ects.
• Weak instruments – When the genetic variants explain a small proportion of the U@ H@SHNM NE SGD HRJ E@BSN R ,1 B@M O NUHCD AH@RDC B@TR@K DRSHL@SDR CTD SN UD X KNV RS@SHRSHB@K ONVD
37 5
5()(5(1 (6
G HRSDMRDM * #NAKG@LLD & 1@T 1 5@TODK ) 6 FDHMF ONOTK@SHNMR SGD BG@K
KDMFDR @GD@C +@MBDS +NMCNM MFK@MC
%NMS@M@ + ,NCTK@SHMF GTL@M @FHMF @MC @FD @RRNBH@SDC CHRD@RDR !HNBGHL !HNOGXR BS@
%DID 1 1TGD 6G@S HR SGD O DU@KDMBD NE LTRBTKNRJDKDS@K O NAKDLR HM SGD DKCD KX
ONOTK@SHNM HM CDUDKNODC BNTMS HDR RXRSDL@SHB B HSHB@K KHSD @ST D DUHDV GH NO ,@M 3GD @O
% DDLNMS 'NXK@MC ) ,N OGNKNFX LDBG@MHRLR @MC O@SGNKNFX NE LTRBTKNRJDKDS@K
@FDHMF ) /@SGNK
&!# #HRD@RD @MC (MIT X (MBHCDMBD @MC / DU@KDMBD NKK@AN @SN R 2 + DS @K &KNA@K
DFHNM@K @MC M@SHNM@K HMBHCDMBD O DU@KDMBD @MC XD@ R KHUDC VHSG CHR@AHKHSX EN
CHRD@RDR @MC HMIT HDR EN BNTMS HDR @MC SD HSN HDR @ RXRSDL@SHB @M@KXRHR
EN SGD &KNA@K !T CDM NE #HRD@RD 2STCX +@MBDS +NMCNM MFK@MC
! NVM & +HUHMF SNN KNMF SGD BT DMS ENBTR NE LDCHB@K DRD@ BG NM HMB D@RHMF SGD
PT@MSHSX @SGD SG@M SGD PT@KHSX NE KHED HR C@L@FHMF NT GD@KSG @MC G@ LHMF SGD DBNMNLX ,!. 1DO
*@MHR ) RRDRRLDMS NE E @BST D HRJ @MC HSR @OOKHB@SHNM SN RB DDMHMF EN ONRSLDMN O@TR@K NRSDNON NRHR RXMNORHR NE @ 6'. DON S 6'. 2STCX & NTO .RSDNON NR (MS
'@ UDX - DS @K 3 @ADBTK@ ANMD RBN D 3!2 @R @ MDV BNLOKDLDMS@ X @OO N@BG EN
NRSDNON NRHR DU@KT@SHNM HM BKHMHB@K O @BSHBD !NMD
1NRDMAD F ( ' 2@ BNODMH@ . HFHMR @MC KHMHB@K 1DKDU@MBD ) -TS 2 2
Cruz-Jentoft, A. J. et al. Sarcopenia: European consensus on de nition and diagnosis: 1DON S NE SGD T NOD@M 6N JHMF & NTO NM 2@ BNODMH@ HM .KCD /DNOKD FD FDHMF %HDKCHMF 1 DS @K 2@ BNODMH@ M 4MCH@FMNRDC NMCHSHNM HM .KCD CTKSR T DMS NM sensus De nition: Prevalence, Etiology, and Consequences. International Working Group NM 2@ BNODMH@ ) L ,DC #H RRNB
GDM + * DS @K 2@ BNODMH@ HM RH@ NMRDMRTR 1DON S NE SGD RH@M 6N JHMF & NTO EN
2@ BNODMH@ ) L ,DC #H RRNB
2STCDMRJH 2 DS @K 3GD %-(' 2@ BNODMH@ / NIDBS 1@SHNM@KD 2STCX #DRB HOSHNM NMED DMBD 1DBNLLDMC@SHNMR @MC %HM@K RSHL@SDR )NT M@KR &D NMSNK 2D
Cruz-Jentoft, A. J. et al. Sarcopenia: revised European consensus on de nition and diagno RHR FD FDHMF MJD 2 # ,N KDX ) UNM '@DGKHMF 2 6DKBNLD SN SGD ( # BNCD EN R@ BNODMH@ ) @BGDWH@ 2@ BNODMH@ ,TRBKD )NGMDKK . *@MHR ) M DRSHL@SD NE SGD VN KCVHCD O DU@KDMBD @MC CHR@AHKHSX @RRNBH @SDC VHSG NRSDNON NSHB E @BST DR .RSDNON NR (MS *@MHR ) DS @K 3GD !T CDM NE .RSDNON NSHB % @BST DR ,DSGNC EN 2DSSHMF (MSD UDMSHNM 3G DRGNKCR .RSDNON NRHR (MSD M@SHNM@K 2O HMFD 5D K@F +NMCNM +HLHSDC
,1752 8 7,21
& DDMD # -@TFGSNM & C@OSHUD 2JDKDS@K 1DRONMRDR SN ,DBG@MHB@K +N@CHMF CT
HMF CNKDRBDMBD 2ON S ,DC
5D RBGTD DM 2 DS @K 2@ BNODMH@ @MC HSR DK@SHNMRGHO VHSG ANMD LHMD @K CDMRHSX HM LHCCKD @FDC @MC DKCD KX T NOD@M LDM .RSDNON NR (MS '@ UDX - DS @K ,D@RT DR NE /GXRHB@K /D EN L@MBD @MC ,TRBKD 2S DMFSG @R / DCHBSN R NE % @BST D 1HRJ (MCDODMCDMS NE %1 7 %@KKR @MC @!,# ,DS@ M@KXRHR NE SGD .RSDNON NSHB % @BST DR HM ,DM , .2 2STCX ) !NMD ,HMD 1DR !TBJHMW % DS @K /HSE@KKR HM SGD LD@RT DLDMS NE LTRBKD L@RR @ MDDC EN @ DED DMBD RS@M C@ C ) @BGDWH@ 2@ BNODMH@ ,TRBKD
+@MCH % DS @K 2@ BNODMH@ @R @ HRJ E@BSN EN E@KKR HM DKCD KX HMCHUHCT@KR 1DRTKSR E NL SGD HK2(1 -3 RSTCX KHM -TS
Quality statement 2: Multifactorial risk assessment for older people at risk of falling | Falls in older people | Quality standards | NICE.
'@XDR 6 DS @K SHNKNFX @MC O DUDMSHNM NE @FD DK@SDC GHO E @BST DR !NMD 2 2
2GTLV@X NNJ HNK , & TAD 6 1NAHMRNM (MBHCDMBD NE @MC HRJ E@BSN R EN
E@KKR ENKKNVHMF GHO E @BST D HM BNLLTMHSX CVDKKHMF NKCD @CTKSR /GXR 3GD
T SHR +HSVHB NNOD #DMMHRNM #DSD LHM@MSR NE ,TRBKD @MC !NMD FHMF ) DKK /GXRHNK '@RR@M ! #TPTD & .RSDNR@ BNODMH@ MDV FD H@S HB RXMC NLD TRS %@L /GXRHBH@M 1DFHMRSD ) 8 !D@TC@ S !TBJHMW % ! TX D . .RSDNON NRHR @MC R@ BNODMH@ T .OHM KHM -TS ,DS@A @ D %DKRDMSG@K - 9DKYD ,DBG@MHB@K DFTK@SHNM NE LTRBTKNRJDKDS@K RXRSDL CDUDKNOLDMS #DUDKNOLDMS
'@L HBJ , 6 NKD EN LXNJHMDR HM LTRBKD ANMD HMSD @BSHNMR WD B 2ON S 2BH 1DU 4MCD B@ ANWXK@SDC NRSDNB@KBHM LTRBKD RS DMFSG @MC HMCHBDR NE ANMD GD@KSG HM NKCD VNLDM !NMD
*HL ) DS @K RRNBH@SHNM NE RD TL RBKD NRSHM KDUDKR VHSG KNV RJDKDS@K LTRBKD L@RR 3GD *N D@M 2@ BNODMHB .ADRHSX 2STCX *2.2 !NMD
3 @I@MNRJ@ * 1HU@CDMDH @ % 3GD FDMDSHB @ BGHSDBST D NE NRSDNON NRHR @MC E @BST D HRJ
!NMD
3 @I@MNRJ@ * 1HU@CDMDH @ % *HDK # / *@ @RHJ # &DMDSHBR NE !NMD @MC ,TRBKD (MSD @B
SHNMR HM 'TL@MR T .RSDNON NR 1DO
,HBGNT + OHFDMDSHBR NE ANMD CHRD@RDR )S !NMD 2OHMD
,N DRH 5 ,@ NMBDKKH - /HFM@ C@LN 2 OHFDMDSHBR NE ,TRBKD #HRN CD R ,DC
OHFDMDSHBR CNH !
,DCHM@ &NLDY DS @K !HU@ H@SD FDMNLD VHCD @RRNBH@SHNM LDS@ @M@KXRHR NE ODCH@S HB
musculoskeletal traits reveals pleiotropic e ects at the SREBF1/TOM1L2 locus. Nat. Com LTM
&TN 8 % DS @K 2TFFDRSHNM NE &+8 3 FDMD TMCD KXHMF U@ H@SHNM NE ANMD RHYD @MC ANCX KD@M L@RR @R DUD@KDC AX @ AHU@ H@SD FDMNLD VHCD @RRNBH@SHNM RSTCX 'TL &DMDS
37 5
'T@MF ) DS @K , 33+ (R @ /NSDMSH@K /KDHNS NOHB &DMD EN .RSDNON NRHR @MC 2@ BNODMH@
BSHMF 3G NTFG SGD ,NCTK@SHNM NE SGD -% κ! 2HFM@KHMF /@SGV@X ) !NMD ,HMD 1DR
(J @L , DS @K 3GD 1NSSD C@L 2STCX TOC@SD NM NAIDBSHUDR CDRHFM @MC L@HM
DRTKSR T ) OHCDLHNK
Rivadeneira, F. et al. Twenty bone-mineral-density loci identi ed by large-scale meta-@M@KXRHR NE FDMNLD VHCD @RRNBH@SHNM RSTCHDR -@S &DMDS
2TCKNV DS @K 4* !HNA@MJ M .ODM BBDRR 1DRNT BD EN (CDMSHEXHMF SGD @TRDR NE @
Determinants of
Osteoporosis and
Fracture risk
Fracture incidence and
secular trends between 1989
and 2013 in a
population-based cohort: The Rotterdam
Study
Katerina Trajanoska, Josje D Schoufour, Ester A L de Jonge, Brenda C T
Kieboom, Marlies Mulder, Bruno H Stricker, Trudy Voortman, Andre G
Uitterlinden, Edwin H G Oei, M Arfan Ikram, M Carola Zillikens, Fernando
Rivadeneira, Ling Oei
37 5
%675 7
% @BST D HMBHCDMBD MDDCR SN AD DU@KT@SDC NUD SHLD SN @RRDRR SGD HLO@BS NE SGD DM larging population burden of fractures (due to increase in lifespan) and the efficacy NE E @BST D O DUDMSHNM RS @SDFHDR 3GD DEN D VD @HLDC SN DU@KT@SD SGD @RRNBH@SHNM NE EDLN @K MDBJ ANMD LHMD @K CDMRHSX %- !,# LD@RT DC TRHMF CT@K DMD FX 7 @X @ARN OSHNLDS X #7 @S A@RDKHMD VHSG E @BST D HRJ NUD @ KNMF ENKKNV TO SHLD OD HNC (MBHCDMS MNM UD SDA @K E @BST DR VD D @RRDRRDC HM HMCHUHCT@KR O@ SHBHO@SHMF HM SGD 1NSSD C@L 2STCX VHSG TO SN XD@ R NE ENKKNV TO #T HMF @ LD@M ENKKNV TO NE o XD@ R O@ SHBHO@MSR G@C @S KD@RS NMD HMBHCDMS MNM UD SDA @K fracture. The risk for any non-vertebral fracture was 1.37 (95% Con dence Interval
( @MC ( EN LDM @MC VNLDM DRODBSHUDKX 3GD L@IN HSX HM LDM @MC HM VNLDM NE @KK E @BST DR NBBT DC @LNMF O@ SHBH O@MSR VHSG @ MN L@K N NRSDNODMHB 3 RBN D 3GD HMBHCDMBD @SDR OD OD RNM XD@ R EN SGD LNRS BNLLNM E @BST DR VD D ( EN GHO ( EN V HRS @MC ( EN GTLD TR 3N DW@LHMD SGD O DCHBSHUD @AHKHSX NE !,# SG NTFG ENKKNV TO SHLD VD CDSD LHMDC E @BST D G@Y@ C @SHNR '1 OD RS@MC@ C deviation decrease in femoral neck BMD across ve-year bins. No di erences were observed, with a HR of 2.5 (95%CI: 2.0-3.1) after the rst 5 years, and of 1.9 (95%CI: @ESD XD@ R 3N @RRDRR RDBTK@ S DMCR HM E @BST D HMBHCDMBD @S @KK RJDKDS@K RHSDR VD BNLO@ DC O@ SHBHO@MSR @S @M @FD NE XD@ R @B NRR SVN SHLD OD HNCR
M VNLDM @MC M VNLDM @MC
found no statistically signi cant di erence (p < 0.05) between fracture incidence rates H D HMBHCDMBD NE MNM UD SDA @K E @BST DR NE OD /8 (
ADSVDDM @MC @MC NE OD /8 ( ADSVDDM
@MC (M BNMBKTRHNM !,# HR RSHKK O DCHBSHUD NE ETST D E @BST D NUD @ KNMF OD HNC NE SHLD 6GHKD MN RDBTK@ BG@MFDR HM E @BST DR @SDR RDDL SN AD NARD UDC @ESD @ CDB@CD SGD L@IN HSX NE E @BST DR RSHKK NBBT @ANUD SGD NRSDNON NRHR SG DRGNKC DLOG@RHYHMF SGD MDDC SN HLO NUD SGD RB DDMHMF NE NRSDNODMHB O@SHDMSR
5 785 ,1 , 1 1 75 1 6
,1752 8 7,21
% @BST DR NE SGD GHO V HRS @MC ODKUHR @ D @LNMF SGD LNRS BNLLNM NRSDNON NSHB E @B ST DR a ecting hundreds of millions of people worldwide. In the European Union, SGD @MMT@K BNRSR NE @KK NRSDNON NSHB E @BST DR G@UD ADDM DRSHL@SDC @S AHKKHNM HM NE VGHBG NE SGD BNRSR @ D @SS HATSDC SN GHO E @BST DR #TD SN SGD @FHMF NE HMCTRS H@KHYDC RNBHDSHDR SGD HMBHCDMBD NE NRSDNON NRHR @MC E @FHKHSX E @BST DR HR DWODBSDC SN HMB D@RD HM SGD XD@ R SN BNLD
'NVDUD MNS @KK RSTCHDR RGNV @ BKD@ HMB D@RD NE E @BST DR @SDR %N HMRS@MBD O D vious studies have yielded con icting perspectives indicating that the incidence of GHO E @BST D G@R DHSGD HMB D@RDC OK@SD@TDC N DUDM CDB D@RDC HM SGD K@RS CDB@CDR 2TBG CHRB DO@MBHDR L@X AD DWOK@HMDC AX LTKSHOKD E@BSN R HMBKTCHMF RDBTK@ OD HNCR HM VGHBG SGD E @BST DR NBBT BG@MFDR HM BKHMHB@K O @BSHBD @MC C TF O DRB HOSHNM N BNLOKH @MBD CHRS HATSHNM NE @FD @MC CDLNF @OGHBR VHSGHM @FD @MC RDW RS @S@ LHF @SHNMR @MC N FDNF @OGHB@K N HFHM NE SGD DON S %N DW@LOKD RSTCHDR OD EN LDC HM SGD 42 G@UD
DON SDC @ CDBKHMD HM SGD HMBHCDMBD NE GHO E @BST DR ADSVDDM @MC (M BNMS @RS HM SGD -DSGD K@MCR @M HMHSH@K KHMD@ HMB D@RD HM GHO E @BST D HMBHCDMBD CT HMF SGD OD HNC ADSVDDM @MC HR MNV O NONRDC SN G@UD OK@SD@TDC CT HMF SGD ENKKNVHMF CDB@CDR ,N DNUD DBDMS HMEN L@SHNM NM HMBHCDMBD @SDR @MC S DMCR EN NSGD RHSDR NE MNM UD SDA @K E @BST DR HR BT DMSKX K@BJHMF CDROHSD SG@S MNM GHO E @B ST DR @ D @KRN @RRNBH@SDC VHSG GHFGD CHR@AHKHSX @MC LN S@KHSX @SDR #DOHBSHNM NE robustly-assessed overall and site-speci c fracture trends is important to estimate the burden of osteoporosis and to establish proper and cost-e ective prevention RS @SDFHDR
Part of delineating cost-e ective prevention strategies involves determining the O DCHBSHUD @AHKHSX NE E @BST D HRJ E@BSN R HM SHLD KSGNTFG E @BST DR G@UD @ LTKSHE@BSN
H@K A@BJF NTMC @O@ S E NL @FD KNV !,( @MC E@KKR @ KNV ANMD LHMD @K CDMRHSX !,# DL@HMR NMD NE SGD LNRS HLON S@MS HRJ E@BSN R 2STCHDR G@UD RGNVM SG@S SGD DCTB SHNM NE EDLN @K MDBJ %- !,# HR DRRDMSH@KKX KHMD@ NUD SHLD BNLO HRHMF ] NE A@RDKHMD !,# OD XD@ (S HR VDKK DRS@AKHRGDC SG@S !,# B@M O DCHBS E @BST D HRJ NUD @ OD HNC NE XD@ R ATS KHSSKD HR JMNVM @ANTS SGD O DCHBSHUD U@KTD NE !,# NUD KNMFD OD HNCR
KSNFDSGD NT @HLR VD D SN DU@KT@SD SGD @RRNBH@SHNM ADSVDDM !,# @S A@RDKHMD (both continuously and using clinical cut-o s) and fracture risk over a long time pe riod, 2) estimate the incidence of non-vertebral fractures (overall and site-speci c) CT HMF XD@ R NE ENKKNV TO @MC DU@KT@SD VGDSGD HMBHCDMBD @SDR G@UD BG@MFDC CT HMF SVN RTARDPTDMS RDBTK@ ENKKNV TO OD HNCR KK @M@KXRDR VD D OD EN LDC EN SGD total group and strati ed by sex, considering the well-established sexual di erences HM E @BST D @SD
37 5
0 7(5, /6 1 0(7 2 6
6WxG 3RSxODWLRq
.T RSTCX HMBKTCDC O@ SHBHO@MSR E NL SGD 1NSSD C@L 2STCX @M NMFNHMF ONOTK@SHNM A@RDC O NRODBSHUD BNGN S BNLO HRHMF #TSBG HMCHUHCT@KR @FDC XD@ R @MC NKCD DW@LHMDC @B NRR SG DD ONOTK@SHNM RDSR S HSR RS@ S HM @ SNS@K NE O@ SHBHO@MSR @FDC XD@ R @MC NKCD VD D HMBKTCDC HM SGD HMHSH@K RSTCX V@UD 12( 3GD BNGN S V@R DWO@MCDC HM VHSG O@ SHBHO@MSR 12(( @FDC XD@ R @MC NKCD @MC HM VHSG O@ SHBHO@MSR 12((( @FDC XD@ R @MC NKCD N VGN G@C LNUDC HMSN SGD RSTCX @ D@ KK O@ SHBHO@MSR TMCD VDMS @M DWSDMRHUD GNLD HMSD UHDV ENKKNVDC AX @ UHRHS SN SGD DRD@ BG BDMSD VGD D U@ HNTR OGXRHB@K @MC K@AN @SN X DW@LHM@SHNMR SNNJ OK@BD 3GD 1NSSD C@L 2STCX V@R @OO NUDC AX SGD ,DCHB@K SGHBR NLLHSSDD NE SGD @RLTR , @MC AX SGD ,HMHRS X NE 'D@KSG 6DKE@ D @MC 2ON S NE SGD -DSGD K@MCR HLOKDLDMSHMF SGD 6DS !DUNKJHMFRNMCD YNDJ 1&. /NOTK@SHNM 2STCHDR BS 1NS SD C@L 2STCX KK O@ SHBHO@MSR O NUHCDC V HSSDM HMEN LDC BNMRDMS SN O@ SHBHO@SD HM SGD RSTCX @MC SN NAS@HM HMEN L@SHNM E NL SGDH S D@SHMF OGXRHBH@MR % NL SGD
O@ SHBHO@MSR O NUHCDC HMEN LDC BNMRDMS SN TMCD FN ENKKNV TO @RRDRRLDMSR @MC VD D HMBKTCDC HM SGD E @BST D @M@KXRDR %N SGD !,# @M@KXRHR O@ SHBHO@MSR CHC MNS TMCD FN #7 KD@UHMF O@ SHBHO@MSR EN SGD !,# @M@KXRDR
%RqH 0LqHuDO HqVLW 0HDVxuHPHqWV
%- !,# F BL V@R LD@RT DC HM 12( @MC 12(( TRHMF CT@K DMD FX 7 @X @ARN OSHNLDS X #7 @BPTH DC VHSG @ +TM@ #/7 + CDMRHSNLDSD ,@CHRNM 6( 42 (M 12((( %- !,# V@R LD@RT DC TRHMF @ & +TM@ Prodigy bone densitometer. All scans and analyses were performed and veri ed by a trained technician who applied adjustments when necessary. Sex-speci c T-scores %- !,# VGDM BNLO@ DC SN SGD XNTMF MN L@K DED DMBD LD@M VD D B@KBTK@SDC TRHMF SGD -' - 2 ((( DED DMBD ONOTK@SHNM Osteoporosis was de ned according to WHO B HSD H@ @R @ 3 RBN D ADKNV N DPT@K SN @MC NRSDNODMH@ @R @ 3 RBN D ADSVDDM @MC 3N AD @AKD SN BNLO@ D !,# KDUDKR VHSG O DUHNTR DON SR di erences in mean BMD across software versions in RSI-1 (DPX-L and DPX-IQ) for the calculation NE 3 RBN DR VD D S@JDM HMSN @BBNTMS SN B D@SD @ TMHEN L C@S@RDS NE HMCHUHCT@KR !,# obtained from the DPX-IQ software was recalculated using the following conversionEN LTK@R !,# ∗ DPX-IQ BMD in women and BMD = 0.01588 +
∗ DPX-IQ BMD in men. The intercept and slope values were obtained from regressing BMD DPX-IQ values on the BMD DPX-L values across the same individuals (very similar estimates were obtained when employing di erent sampling sets of size
5 785 ,1 , 1 1 75 1 6
,qfLGHqW )uDfWxuH ROOHfWLRq
3GD O DRDMS @M@KXRDR @ D A@RDC NM ENKKNV TO C@S@ BNKKDBSDC E NL A@RDKHMD
for the rst cohort, 2000–2001 for the second cohort and 2006-2008 for the third co GN S TMSHK #DBDLAD %NKKNV TO SHLD V@R B@KBTK@SDC @R SHLD E NL A@RDKHMD to rst fracture, death or end of follow-up period (or loss to follow-up), whichever occurred rst. All fracture events were reported either by general practitioners (GPs) HM SGD DRD@ BG @ D@ AX LD@MR NE BNLOTSD HYDC RXRSDLR N SG NTFG GNROHS@K DBN CR 1DRD@ BG OGXRHBH@MR N S @HMDC MT RDR VGN BGDBJDC O@SHDMS DBN CR DFTK@ KX D S HDUDC HMEN L@SHNM E NL &/R NTSRHCD SGD DRD@ BG @ D@ KK DUDMSR DON SDC VD D UD H ed by research physicians who independently reviewed and coded the information. Subsequently, a medical expert reviewed all inconsistencies in coded events for nal classi cation. For the current study only non-vertebral fractures were considered, as SHLD NE DUDMS B@MMNS @BBT @SDKX AD @RRDC EN SGD U@RS L@IN HSX NE UD SDA @K E @BST DR
67 7,67,
/ 1 /<6(6
All analyses were performed for the total group of participants and strati ed by sex, considering the well-established sex di erences in fracture risk. %H RS NW O NON SHNM@K G@Y@ C LNCDKR @CITRSDC EN @FD @S A@RDKHMD @MC BNGN S VD D TRDC SN DRSHL@SD the hazard ratio (HR) of rst fracture associated with 1 SD decrease in FN-BMD across 1) all non-vertebral fractures, 2) for speci c types of fractures and 3) all non-vertebral fractures in groups of subjects classi ed by WHO-based BMD cut-o s. The latter @M@KXRDR VD D CNMD HM SG DD @FD F NTOR ADKNV XD@ R XD@ R @MC XD@ R and older. Subjects classi ed as having BMD in the normal range (T-score > 1.0) were TRDC @R SGD DED DMBD F NTO (M N CD SN ADSSD DW@LHMD SGD E @BST D O DCHBSHNM VD performed sensitivity analyses in which the follow-up time was strati ed by 5-years categories: 0-5; 5-10; 10-15; 15-20; and > 20 years. The proportionality of hazards as RTLOSHNM NE NW LNCDKR V@R BGDBJDC TRHMF BN DK@SHNM SDRSR NE 2BGNDMEDKC DRHCT@KR For the non-vertebral fractures analysis, we used natural splines to t a proportional hazards model in order to smooth the nonlinear e ect of age. Second, fracture inci CDMBD @SDR VD D B@KBTK@SDC @BBN CHMF SN E @BST D RHSD @MC @CCHSHNM@KKX RTACHUHCDC HMSN SG DD L@HM B@SDFN HDR TOOD DWS DLHSX KNVD DWS DLHSX @MC NSGD E @BST DR (M BHCDMBD @SDR VD D DWO DRRDC @R MTLAD NE E @BST DR OD OD RNM XD@ R /8 VHSG 95% con dence intervals, estimated using the exact Poisson formula. 3GH C SN C @V
SGD BNLO@ HRNM ADSVDDM RDBTK@ OD HNCR :- @MC
:-HMBHCDMBD @SDR VD D B@KBTK@SDC EN LDM @MC VNLDM VGN VD D XD@ R NKC @S SGD RS@ S NE SGD DRODBSHUD ENKKNV TO OD HNC 6D TRDC @ CHRSHMBS @FD B@SDFN X in order to avoid bias due to di erent age distribution among the follow-ups. The
37 5
XD@ R NE @FD B@SDFN X V@R TRDC @R HS BNLO HRDR SGD OD HNC HM KHED VHSG F D@SDRS DWONMDMSH@K HMB D@RD HM E @BST D @SDR NE LNRS KHJDKX NRSDNON NSHB DSHNKNFX /NHRRNM DW@BS SDRS V@R TRDC SN SDRS SGD MTKK GXONSGDRHR SG@S SGD @SHN ADSVDDM SGD @SDR V@R DPT@K SN 3GD S DMC O U@KTD V@R @CITRSDC EN LTKSHOKD SDRSHMF KK @M@KXRDR VD D OD EN LDC TRHMF SGD RS@SHRSHB@K O@BJ@FD 5 yHuVLRq
5(68/76
KDuDfWHuLVWLfV RI WKH 6WxG 3RSxODWLRq
)LjxuH is a ow diagram describing the selection of study participants. At baseline, SGD LD@M o 2# @FD NE SGD O@ SHBHO@MSR V@R o XD@ R EN LDM @MC o
5 785 ,1 , 1 1 75 1 6
years for women. The prevalence of osteoporosis (BMD T-score < -2.5) was 10.8% in VNLDM @MC HM LDM 3GD O DU@KDMBD HMB D@RDC DWONMDMSH@KKX VHSG @FD EN @KK SXODR NE E @BST DR ATS SGHR DK@SHNM HR KDRR O NLHMDMS EN V HRS E @BST DR )LjxuH ANUD SGD @FD NE XD@ R NE SGD VNLDM @MC NE SGD LDM G@C NRSDNON
NRHR -D@ KX NE @KK MNM UD SDA @K E @BST DR NBBT DC HM VNLDM VHSG NRSDNON NRHR @MC HM NRSDNON NSHB LDM )LjxuH @MC 6xSSOHPHqWDu 7DEOH (M VNLDM @MC LDM VHSG NRSDNON NRHR GHO E @BST DR VD D SGD LNRS BNLLNM SXOD NE E @BST DR women and 29% men). Overall, the highest fraction of all and -site-speci c fractures
@ANUD NBBT DC HM LDM @MC VNLDM VHSG NRSDNODMH@
VVRfLDWLRq EHWZHHq %0 DqG ,qfLGHqW )uDfWxuH
RRNBH@SHNMR NE %- !,# VHSG MNM UD SDA @K E @BST DR @ D RGNVM HM 3@AKD %N DUD X 2# CDB D@RD HM !,# @ : ( SHLDR HMB D@RDC HRJ HM MNM UD SDA @K E @BST D HRJ V@R NARD UDC 3GD @RRNBH@SHNMR NE !,# VHSG E @BST D HRJ VD D RHLHK@
HM VNLDM : ( @MC LDM : ( +NV !,#
(T-score < 1) was strongly associated with increases site-speci c fracture risk at the hip, wrist and proximal humerus, with similar e ects seen in women and men (7DEOH (MCHUHCT@KR VHSG NRSDNODMH@ N NRSDNON NRHR G@C SN SHLDR GHFGD HRJ NE MNM UD SDA @K E @BST D SG@M HMCHUHCT@KR VHSG MN L@K !,# )LjxuH 6NLDM @ANUD SGD @FD NE VHSG NRSDNON NRHR G@C SHLDR HMB D@RDC HRJ SN CDUDKNO E @BST DR VGHKD SGD HRJ HM NKCD VNLDM VHSG NRSDNODMH@ V@R SHLDR GHFGD SG@M NKCD VNLDM VHSGNTS
)LjxuH _ Prevalence of osteoporosis and osteopenia in men and women by gender-speci c
T-RBN DR 'HO E @BST DR NBBT DC LN D NESDM HM LDM @MC VNLDM @ANUD SGD @FD NE XD@ R .UD @KK
@B NRR SGD @FD CHRS HATSHNM GHO E @BST D HMBHCDMBD @SDR HM LDM VD D RHLHK@ SN SGD @SDR NE VNLDM XD@ XNTMFD %T SGD LN D VNLDM G@C GHFGD HMBHCDMBD @SDR SG@M LDM HM SGD R@LD @FD B@SDFN X EN @MX SXOD NE E @BST D
37 5
)LjxuH _ /D BDMS@FDR NE MNM UD SDA @K GHO O NWHL@K GTLD TR @MC V HRS E @BST DR SG@S NBBT DC in men and women with osteoporosis, osteopenia or normal BMD using gender-speci c T-scores.
5 785 ,1 , 1 1 75 1 6
7DEOH _ FD @CITRSDC G@Y@ C @SHN ( EN SGD O DCHBSHUD U@KTD NE EDLN @K MDBJ !,# F BL
OD NMD 2# CDB D@RD 7 SH RI IuDfWxuH 7RWDO q 0Hq q :RPHq q 1xPEHu D]DuG uDWLR , 1xPEHu D]DuG 5DWLR , 1xPEHu D]DuG uDWLR , 8SSHU H[WUHPLWLHV / NWHL@K GTLD TR 6 HRS '@MC .SGD O NWHL@K @ L@ .SGD CHRS@K @ LA /RZHU H[WUHPLWLHV /DKUHR 'HO MJKD ,DS@S@ R@K .SGD ENNSB .SGD O NWHL@K KDFC .SGD CHRS@K KDFD 2WKHUI OO QRQ YHUWHEUDO @NSGD O NWHL@K @ L E @BST DR HMBKTCD E @BST DR NE SGD RB@OTK@ BK@UHBTK@ @MC MNM O NWHL@K E @B ST DR NE SGD GTLD TR ANSGD CHRS@K @ L E @BST DR NE SGD NSGD O@ SR NE SGD @CHTR @MC N TKM@ BNSGD ENNS E @BST DR HMBKTCD MNM LDS@S@ R@K ENNS E @BST DR
CNSGD O NWHL@K KDF E @BST DR HMBKTCD MNM GHO E @BST DR NE SGD EDLT @MC O@SDKK@
Dother distal leg fractures include non-ankle fractures of the tibia and/ or bula
ENSGD E @BST DR HMBKTCD RJTKK HA @MC RSD MTL
)LjxuH _ 1DK@SHUD E @BST D HRJ BNLO@ HMF RTAIDBSR VHSG NRSDNODMH@ N NRSDNON NRHR VHSG MN L@K bone subjects strati ed by sex and age.
37 5
osteopenia/osteoporosis. The analysis of fracture risk over di erent follow-up peri ods con rms that BMD remains a good predictor of hip and non-vertebral fractures in time. In the rst 5 years the fracture HR per SD decrease in BMD was 2.5 (95%CI:
2.0-VGHKD @ESD XD@ R SGD '1 V@R ( 6xSSOHPHqWDu 7DEOH
)uDfWxuH ,qfLGHqfH 5DWHV
#T HMF SGD XD@ R NE ENKKNV TO NUD @KK LD@M o 12( 12((
12((( XD@ R O@ SHBHO@MSR RTRS@HMDC @S KD@RS NMD MNM UD SDA @K E @BST D NE VGNL VD D VNLDM 7DEOH RGNVR SGD E @BST D HMBHCDMBD @SDR AX RHSD @MC RDW .UD @KK SGD HMBHCDMBD NE MNM UD SDA @K E @BST DR V@R : (
7DEOH _ Gender and site-speci c incidence rates of rst non-vertebral fractures per 1000 person XD@ R 7 SH RI IuDfWxuH 7RWDO q 0Hq q :RPHq q 1xP EHu ,qfL GHqfH uDWH , 1xP EHu ,qfL GHqfH uDWH , 1xP EHu ,qfL GHqfH uDWH , 8SSHU H[WUHPLWLHV / NWHL@K GTLD TR 6 HRS '@MC .SGD O NWHL@K @ L@ .SGD CHRS@K @ LA /RZHU H[WUHPLWLHV /DKUHR 'HO MJKD ,DS@S@ R@K .SGD ENNSB .SGD O NWHL@K KDFC .SGD CHRS@K KDFD 2WKHUI OO QRQ YHUWHEUDO @NSGD O NWHL@K @ L E @BST DR HMBKTCD E @BST DR NE SGD RB@OTK@ BK@UHBTK@ @MC MNM O NWHL@K E @B ST DR NE SGD GTLD TR ANSGD CHRS@K @ L E @BST DR NE SGD NSGD O@ SR NE SGD @CHTR @MC N TKM@ BNSGD ENNS E @BST DR HMBKTCD MNM LDS@S@ R@K ENNS E @BST DR
CNSGD O NWHL@K KDF E @BST DR HMBKTCD MNM GHO E @BST DR NE SGD EDLT @MC O@SDKK@
Dother distal leg fractures include non-ankle fractures of the tibia and/ or bula
5 785 ,1 , 1 1 75 1 6
OD /8 HM LDM @MC : ( OD /8 HM VNLDM
(M ANSG LDM @MC VNLDM SGD LNRS O DCNLHM@MS E @BST D RHSDR VD D SGD V HRS G@MC O NWHL@K GTLD TR @MC GHO O@ S E NL SGD E @BST D @SDR NE SGD O NWHL@K GTLD TR HM men, all other non- vertebral and site-speci c fracture rates increased exponentially VHSG @FD )LjxuH
RPSDuLqj )uDfWxuH 5DWH EHWZHHq
DqG
DqG
3GD NUD @KK HMBHCDMBD NE MNM UD SDA @K E @BST DR HM SGD OD HNC ADSVDDM @MC
OD /8 : ( V@R RHLHK@ SN SGNRD NARD UDC HM SGD
OD HNC ADSVDDM @MC OD /8 : ( 6xSSOHPHq
WDu 7DEOH DqG %). There was no signi cant change in site-speci c fracture trends, VHSG SGD DWBDOSHNM NE @M HMB D@RDC CHRS@K KDF E @BST D HMBHCDMBD O HM LDM )LjxuH ). However, this trend is not signi cant (0.05/14, P= 0.004) after taking LTKSHOKD SDRSHMF HMSN @BBNTMS
)LjxuH _ FD DK@SDC HMBHCDMBD NE @KK MNM UD SDA @K GHO V HRS @MC O NWHL@K GTLD TR E @BST DR HM LDM @MC VNLDM
37 5
,6 866,21
(M SGHR ONOTK@SHNM A@RDC O NRODBSHUD BNGN S @ RHMFKD %- !,# LD@RT DLDMS @S A@RD KHMD DL@HMR @ RS NMF O DCHBSN NE HMBHCDMS MNM UD SDA @K E @FHKHSX E @BST DR NUD @ period of 20 years. The overall incidence rate of su ering non-vertebral fractures was
OD /8 : ( VHSG @ GHFGD HMBHCDMBD @SD HM VNLDM SG@M HM
LDM 3GD LNRS E DPTDMS MNM UD SDA @K E @BST DR HM DKCD KX LDM @MC VNLDM BNMSHMTDR SN AD E @BST DR NE SGD GHO V HRS O NWHL@K GTLD TR @MC G@MC VHSG LNRS DUDMSR NB BT HMF @ANUD SGD NRSDNON NRHR CH@FMNRSHB @MC HMSD UDMSHNM SG DRGNKC 3 RBN D @ANUD
)LjxuH _ Incidence of site-speci c fractures in 1989 to 2001 compared with 2001 to 2013 (70–80 years old) strati ed by sex
5 785 ,1 , 1 1 75 1 6
6D NARD UDC MN RDBTK@ S DMC BG@MFDR HM E @BST D HMBHCDMBD ADSVDDM @MC @MC
In an earlier e ort in the Rotterdam Study, VD RGNVDC @M HM UD RD @RRNBH@SHNM ADSVDDM %- !,# @MC SGD HRJ NE @KK MNM UD SDA @K E @BST DR CT HMF @ LD@M XD@ ENKKNV TO OD HNC ESD DWSDMCHMF SGHR ENKKNV TO OD HNC HM SGD BT DMS RSTCX AX LN D XD@ R NM @UD @FD VD BNMBKTCD SG@S TRHMF NMD RHMFKD !,# LD@RT DLDMS HR RSHKK a good predictor for fracture risk even up to 20 years after. This nding reinforces the central role of BMD in fracture etiology and prediction. Our ndings corroborate with ndings recently reported by Black and colleagues @LNMF VNLDM NE SGD 2STCX NE .RSDNON NSHB % @BST DR RGNVHMF SG@S @ RHMFKD %- !,# LD@RT DLDMS RS NMFKX O DCHBSR long-term hip fracture up to 23 years. The fracture risk in the rst ve years (0–5 y) V@R BNLO@ @AKD SN SGD HRJ @ESD XD@ R X CCHSHNM@KKX VD RGNVDC SG@S KNV !,# HR MNS NMKX @RRNBH@SDC VHSG GHO E @BST DR ATS @KRN VHSG E @BST DR @S NSGD RJDKDS@K RHSDR @LNMF NSGD OD HOGD @K RHSDR 'NVDUD !,# CHC MNS G@UD @MX O DCHBSHUD U@KTD EN @MJKD @MC ENNS E @BST DR %T SGD LN D HMCHUHCT@KR VHSG NRSDNON NRHR !,# 3 RBN D < -2.5) fractured two to three times more often than individuals with normal BMD E NL SGD R@LD RDW @MC @FD F NTO (M @CCHSHNM HM NT RSTCX VNLDM VHSG NRSDNON NRHR E @BST DC LN D NESDM SG@M LDM VGHKD SGD O NON SHNM NE E @BST DR HM SGD NRSDNODMH@ F NTO HR RHLHK@ HM LDM @MC VNLDM KSGNTFG !,# HR @M HLON S@MS O DCHBSN NE E @B ture risk, the treatment indication based on T-score cut-o s alone it is not sufficient. As in our previous work, we still see that if we use a T-score of −2.5 as a diagnostic and treatment threshold, a very large proportion (> 50%) of the individuals who E @BST D VHKK DL@HM TMS D@SDC ETDKKHMF @CCHSHNM@KKX SGD DWHRSHMF B HRHR HM NRSDNON NRHR S D@SLDMS KSGNTFG SGD D HR @ BNMRDMRTR SN S D@S NRSDNODMHB O@SHDMSR O DRDMSHMF VHSG O DU@KDMS KNV DMD FX E @BST DR SGD S D@SLDMS NE NRSDNODMH@ VHSGNTS @ E @BST D DL@HMR BNMS NUD RH@K 1HRJ @RRDRRLDMSR SNNKR KHJD %1 7 @MC & 15 - G@UD ADDM CDUDKNODC HM SGD K@RS CDB@CD VGHBG S@JD HMSN @BBNTMS NSGD SHLD CDODMCDMS BKHMHB@K HRJ E@BSN R VGHBG L@X DRS@AKHRG HMCHB@SHNM EN OG@ L@BNSGD @OX %N DW@LOKD @FD HR @M HLON S@MS HRJ E@BSN @MC RSTCHDR G@UD ENTMC SG@S C TF A@RDC HMSD UDMSHNMR @LNMF elderly (≥65 years) women with osteopenia are cost-e ective. 'NVDUD S D@SLDMS NE DKCD KX VNLDM VHSG NRSDNODMH@ HR RSHKK MNS O@ S NE BT DMS BKHMHB@K O @BSHBD DBNL LDMC@SHNMR @MC LNRS FTHCDKHMDR EN NRSDNODMHB O@SHDMSR DLOG@RHYD KHEDRSXKD BG@MFDR Nevertheless, our ndings encountering no signi cant change in the secular trends of E @BST D HRJ @B NRR OD HNCR RTFFDRS SG@S @S KD@RS HM SGD -DSGD K@MCR @CCHSHNM@K RSDOR are required to improve fracture risk prediction. Rede ning intervention thresholds @MC S@ FDSHMF RS @SDFHDR SN HLO NUD @CGD DMBD SN FTHCDKHMDR @MC C TF BNLOKH@MBD @ D RNLD NE SGD V@XR SN @BGHDUD SGHR HLO NUDLDMS
R DON SDC HM O DUHNTR RSTCHDR VD NARD UDC SG@S V HRS @MC GHO E @BST DR NBBT LN D E DPTDMSKX HM VNLDM SG@M HM LDM VHSG @ @SHN NE @MC EN GHO @MC
37 5
wrist fractures, respectively. The sex-speci c incidence of hip fractures was similar SN @ O DUHNTR DON S HM SGD #TSBG ONOTK@SHNM OD EN LDC HM 4RHMF SGD #TSBG LDCHB@K DFHRSD SGDX NARD UDC SG@S EN DUD X HMG@AHS@MSR VNLDM @MC 308 men su ered a hip fracture. The observed sexual dimorphism in fracture risk has ADDM L@HMKX @SS HATSDC SN SGD @OHC ONRSLDMNO@TR@K ANMD KNRR HM VNLDM @BBNTMSHMF EN KNRR HM B@MBDKKNTR ANMD @MC KNRR HM BN SHB@K ANMD CCHSHNM@KKX GHFGD OD@J ANMD L@RR @MC RS NMFD ANMD FDNLDS X O@ @LDSD R HM LDM BNMS HATSD SN the sex di erences.
Beside the di erences in sex, large variation in hip fracture rates (up to 7-fold) G@R ADDM NARD UDC @B NRR BNTMS HDR (RL@HK @MC BNKKD@FTDR estimated site-speci c fracture incidence rates across Europe and found di erences in rates by sex and re gion. In line with our study they have reported similar sex-speci c hip fracture rates in 2B@MCHM@UH@ @MC KNVD HM 2NTSGD M @RSD M @MC 6DRSD M T NOD ,N DNUD HM VNLDM SGD HMBHCDMBD @SD NE GTLD TR E @BST DR ENKKNVDC SGD R@LD BNTMS X O@SSD M @R GHO E @BST D VGHKD HM LDM SGD HMBHCDMBD @SD NE NT RSTCX V@R NMKX GHFGD SG@M HM @RSD M Europe and similar to the other countries. No di erences in wrist fracture incidence @SDR VD D MNSHBDC ADSVDDM DFHNMR !DRHCD E@KKR @MC GHFGD K@SHSTCD NSGD DMUH NM LDMS@K E@BSN R SNFDSGD VHSG FDMDSHB E@BSN R BNTKC KD@C SN FDNF @OGHB@K U@ H@SHNMR HM HMBHCDMBD @SDR 2SHKK CH DBS BNLO@ HRNM NE @SDR @B NRR RSTCHDR RGNTKC AD L@CD VHSG caution given di erences in age and sex distribution, methods for age standardiza SHNM E @BST D @RBD S@HMLDMS @MC DFHNM@K U@ H@SHNM HM FDMD @K GD@KSG
In our study we provided incidence rates for di erent site-speci c fractures. KSGNTFG SGD L@IN NRSDNON NSHB E @BST DR GHO ROHMD @MC EN D@ L @ D BNMRHCD DC the most important and prominent ones, other site-speci c fractures also contribute BNMRHCD @AKX SN SGD AT CDM NE NRSDNON NRHR 3GDRD NSGD E @BST DR @BBNTMS EN
NE @KK GD@KSG B@ D DWODMCHST D VGHKD HS G@R @KRN ADDM RGNVM SG@S VNLDM VHSG NSGD SXODR NE E @BST D MNM GHO TSHKHYD LN D GD@KSGB@ D DRNT BDR BNLO@ DC SN VNLDM VHSG GHO E @BST D KSNFDSGD F@HMHMF @CCHSHNM@K HMRHFGS @MC JMNVKDCFD @ANTS SGD incidence of site-speci c fractures and trends in time might help in establishing bet SD O DUDMSHNM RS @SDFHDR
Studies in di erent countries have shown a steady increase in the incidence of GHO E @BST DR HM SGD R @MC D@ KX R !TS DBDMSKX HS G@R ADDM O NONRDC SG@S SGD HMBHCDMBD NE E @BST D G@R DL@HMDC @SGD RS@AKD N BNTKC G@UD DUDM CDB D@RDC HM RNLD BNTMS HDR 42 @M@C@ TRS @KH@ @MC 2VHSYD K@MC (M NT RSTCX @KSGNTFG there was a positive non-signi cant fracture trend for the majority of site-speci c E @BST DR SGD HMBHCDMBD @SDR G@UD DL@HMDC @SGD RS@AKD NUD SGD O@RS XD@ R LHM @MC BNKKD@FTDR G@UD @KRN DON SDC RS@AHKHY@SHNM NE SGD E @BST D HMBHCDMBD @SDR @S many skeletal sites in the past two decades in the U.S. This is in contrast with ndings E NL @ DBDMS M@SHNM@K DFHRS X A@RDC RSTCX HM SGD -DSGD K@MCR VGHBG NARD UDC
5 785 ,1 , 1 1 75 1 6
increased incidence rates for wrist, hand/ nger, hip/proximal leg, ankle and foot/toe E @BST DR ,N DNUD -@MMHF@ @MC BNKKD@FTDR G@UD DON SDC HMB D@RDC HMBHCDMBD rate of pelvic fractures in the Netherlands. The di erent ndings from the latter two RSTCHDR L@X AD @SS HATSDC SN @ BNTOKD NE E@BSN R %H RSKX SGD RSTCHDR TRDC GNROHS@K DBN CR SN DWS @ONK@SDC C@S@ VGHKD VD TRDC ANSG GNROHS@K @MC &/ DBN CR -DWS HM SGD RSTCX AX !DD DJ@LO DS @K the age range was wide and included patients ≥16 years NKC (M @CCHSHNM SGDH ONOTK@SHNM LD@M @FD HMB D@RDC E NL SN VGHBG BNTKC AD NMD D@RNM EN SGD HMB D@RD HM SGD @ARNKTSD MTLAD NE E @BST DR 1D@RNM VGX HM our study we chose a xed age category of 70-80 years to compare between two time OD HNCR %T SGD SGDX G@C LHRRHMF C@S@ NM HM DKCD KX @ANUD XD@ R VGHBG BNTKC have in uenced the fracture numbers. Although all events were ICD10 or ICD9 codes di erent group-classi cations applied between the studies might have impacted the rates. Finally, our study is a cohort study and the ndings might be speci c for our ONOTK@SHNM NMKX .UD @KK U@ H@SHNM HM E @BST D @SDR HM SHLD B@M AD CTD SN AH SG BNGN S e ects resulting from changes in early life risk factors such as perinatal nutrition, ADG@UHN @K BG@MFDR HM RLNJHMF @MC @KBNGNK BNMRTLOSHNM !,( S D@SLDMS NE NRSDNON
NRHR :AHROGNROGNM@SDR B@KBHTL UHS@LHM # N TRD NE DRS NFDM SGD @OX M@KXRHR NE SGD trends can help us identify the main factors leading to di erences between countries. .T RSTCX G@R RDUD @K RS DMFSGR 6D VD D @AKD SN DRSHL@SD SGD HMBHCDMBD @MC incidence trends of site-speci c fractures in both men and women from the same ONOTK@SHNM @ESD @ O NKNMFDC ENKKNV TO (M @CCHSHNM HM SGD -DSGD K@MCR SGD NMKX V@X to access specialist and hospital care is consulting a GP. Therefore, checking the GPs’ LDCHB@K DBN CR NE @KK O@ SHBHO@MSR RGNTKC G@UD DRTKSDC HM @ LN D BNLO DGDMRHUD ENKKNV TO .MD HLON S@MS KHLHS@SHNM HR SG@S NT RSTCX L@X AD RTAIDBS SN RDKDBSHNM AH@R @S A@RDKHMD CTD SN MNM DRONMRD NE RTAIDBSR VHSG HLO@H DC LNAHKHSX @MC SGHR BNTKC G@UD KDC SN @M TMCD DRSHL@SHNM NE SGD HMBHCDMBD @SDR +NRR SN ENKKNV TO @MC LN S@KHSX B@M @KRN B@TRD KNVD HMBHCDMBD @SDR FHUDM SG@S TRT@KKX SGDRD HMCHUHCT@KR @ D NKCD @MC LN D RTRBDOSHAKD SN ANMD KNRR NLODSHMF HRJ NE CD@SG BG@MFDR HM BKHMHB@K O @BSHBD and bisphosphonates use could have in uenced the fracture rates in both follow-up OD HNCR 'NVDUD VD @ D MNS @AKD SN @BBNTMS EN SGDRD BG@MFDR HM NT RSTCX ,N DNUD we were not able to use repeated BMD measures due to di erences in densitometer OD ENKKNV TO KSGNTFG RHMFKD !,# LD@RT DLDMS HR @RRNBH@SDC VHSG E @BST D HRJ NUD KNMFD OD HNC HM SGD ONOTK@SHNM DOD@SDC !,# LD@RT DR L@X RSHKK AD MDBDRR@ X SN HLO NUD SGD O DCHBSHNM NE E @BST D EN @M HMCHUHCT@K
(M BNMBKTRHNM !,# DL@HMR @ RS NMF O DCHBSN NE GHO @MC MNM UD SDA @K E @BST DR NUD XD@ R HM ANSG LDM @MC VNLDM 3GD L@IN HSX NE E @BST DR BNMSHMTD SN NBBT @ANUD SGD NRSDNON NRHR SG DRGNKC DLOG@RHYHMF SGD MDDC SN HLO NUD SGD RB DDMHMF of osteopenic patients. Most importantly, we established there are no di erence in
37 5
@BSHNMR RDDJHMF SN HLO NUD SGD CH@FMNRDR S D@SLDMS @MC O DUDMSHNM RS @SDFHDR SN SGHR BNRSKX CHRD@RD
HWDLOHG DfNqRZOHGjPHqWV DqG RqOLqH uHVRxufHV fDq EH IRxqG Lq WKH
SxEOLVKHG DuWLfOH RqOLqH
GSSOR VVV RBHDMBDCH DBS BNL RBH DMBD @ SHBKD OHH 2 UH@ #HGTA
5 785 ,1 , 1 1 75 1 6
5()(5(1 (6
A. Litwic, M. Edwards, C. Cooper, E. Dennison, Geographic di erences in fractures among women, Women’s Health (Lond. Engl.) 8 (2012) 673–684, http://dx.doi. org/10.2217/ VGD
'D MKTMC 2UDCANL , (UD F C ) NLORSNM NNOD ) 2SDML@ J DS @K .RSDNON
NRHR HM SGD T NOD@M 4MHNM LDCHB@K L@M@FDLDMS DOHCDLHNKNFX @MC DBNMNLHB AT CDM DON S O DO@ DC HM BNKK@AN @SHNM VHSG SGD (MSD M@SHNM@K .RSDNON NRHR %NTMC@SHNM (.% @MC SGD T NOD@M %DCD @SHNM NE /G@ L@BDTSHB@K (MCTRS X RRNBH@SHNMR %/( BG .R
SDNON NR GSSO CW CNH N F R
! &TKKAD F . )NGMDKK ) *@MHR 6N KC VHCD O NIDBSHNMR EN GHO E @BST D .RSDNON NR (MS 1 !T FD ! #@VRNM 'TFGDR # ' 2NKNLNM ) ! 6NMF *HMF 3NRSDRNM (MBHCDMBD @MC DBNMNLHB AT CDM NE NRSDNON NRHR DK@SDC E @BST DR HM SGD 4MHSDC 2S@SDR ) !NMD ,HMD 1DR GSSO CW CNH N F IAL , ) /TDXN 2 MBGDY , +@ NR@ 7 2T HR @R@CN ) TKDC@ ) %TRS DS @K 2DBTK@ S DMC HM SGD HMBHCDMBD NE GHO E @BST D HM @S@KNMH@ 2O@HM FD FDHMF GSSO CW CNH N F @FDHMF @EV
) 2 F@@ C * 'NKUHJ ' ,DXD & 2 3DKK & &IDRC@K - L@TR DS @K NMSHMTDC CD
BKHMD HM GHO E @BST D HMBHCDMBD HM -N V@X @ -.1 /.2 RSTCX .RSDNON NR (MS
GSSO CW CNH N F R
2 1 TLLHMFR + ) ,DKSNM OHCDLHNKNFX @MC NTSBNLDR NE NRSDNON NSHB E @BST DR +@MBDS
GSSO CW CNH N F 2
R. Hiebert, G.B. Aharono , E.L. Capla, K.A. Egol, J.D. Zuckerman, K.J. Koval, Temporal and
FDNF @OGHB U@ H@SHNM HM GHO E @BST D @SDR EN ODNOKD @FDC N NKCD -DV 8N J 2S@SD
L ) . SGNO !DKKD ,D@C -)
# 9HMFLNMC + ) ,DKSNM 2 2HKUD L@M (MB D@RHMF GHO E @BST D HMBHCDMBD HM @KHEN MH@ 'HR
O@MHBR SN .RSDNON NR (MS GSSO CW CNH N F
R
% 3 !ND DANNL 1 1 CD & NNS ) 1@XL@JD R 2 #TT RL@ 3GD HMBHCDMBD NE GHO E @BST DR HM 3GD -DSGD K@MCR -DSG ) ,DC
6 & &NDSSRBG 1 ! CD )NMF / * @L@ Y 1 , 'D HMFR #DUDKNOLDMSR NE SGD HMBHCDMBD
NE NRSDNON NRHR HM 3GD -DSGD K@MCR @ /' 1,. RSTCX /G@ L@BNDOHCDLHNK # TF 2@E
GSSO CW CNH N F OCR
' %HMJ * MR TC # ! -DKRNM 1 / *D @MH %N LD KX /HDOD / ) 2BG DHMD 8 9G@N
DS @K #HR@AHKHSX @ESD BKHMHB@K E @BST D HM ONRSLDMNO@TR@K VNLDM VHSG KNV ANMD CDM
RHSX SGD E @BST D HMSD UDMSHNM S H@K %(3 .RSDNON NR (MS GSSO CW CNH
N F R X
3 3 @M # !KHTB 3 U@M &DDK ) # C@BGH !D FD ) U@M CDM !D FG DS @K /NOTK@SHNM VHCD
HLO@BS NE MNM GHO MNM UD SDA @K E @BST DR NM LN S@KHSX ) !NMD ,HMD 1DR
GSSO CW CNH N F IAL
L.J. Melton, E.J. Atkinson, M.K. O’Connor, W.M. O’Fallon, B.L. Riggs, Determinants of bone loss from the femoral neck in women of di erent ages, J. Bone Miner. Res. 15 (2000)
37 5
2 2BGTHS , U@M CD *KHES , 6DDK # ' CD +@DS ' !T FD 2DDL@M DS @K
% @BST D HMBHCDMBD @MC @RRNBH@SHNM VHSG ANMD LHMD @K CDMRHSX HM DKCD KX LDM @MC VNLDM SGD 1NSSD C@L 2STCX !NMD
L.J. Melton, C.S. Crowson, W.M. O’Fallon, H.W. Wahner, B.L. Riggs, Relative con-tributions NE ANMD CDMRHSX ANMD ST MNUD @MC BKHMHB@K HRJ E@BSN R SN KNMF SD L E @BST D O DCHBSHNM
) !NMD ,HMD 1DR GSSO CW CNH N F IAL # , !K@BJ ) @TKDX 1 6@FL@M * MR TC ' %HMJ 3 'HKKHD DS @K 3GD @AHKHSX NE @ RHMFKD !,# @MC E @BST D GHRSN X @RRDRRLDMS SN O DCHBS E @BST D NUD XD@ R HM ONRS LDMNO@TR@K VNLDM SGD RSTCX NE NRSDNON NSHB E @BST DR ) !NMD ,HMD 1DR GSSO CW CNH N F IAL 2N M@X 1DMCT % #TANDTE 2 !NTS NX 1 # G@OT K@S 'NV SN O DCHBS E @FHKHSX E @BST D ADXNMC XD@ R 3GD .% +8 RSTCX ) KHM MCNB HMNK ,DS@A GSSO CW CNH N F IB
, (J @L & & . ! TRRDKKD 2 # ,T @C , U@M #THIM . ' % @MBN &NDCDFDAT D
DS @K 3GD 1NSSD C@L 2STCX TOC@SD NM NAIDBSHUDR CDRHFM @MC L@HM DRTKSR T )
OHCDLHNK GSSO CW CNH N F R
+NNJD ' 6 6@GMD 6 + #TMM , 2 @KUN 3 ! '@ HR 2 / 'DXRD DS @K 4OC@SDC C@S@ NM O NWHL@K EDLT ANMD LHMD @K KDUDKR NE 42 @CTKSR .RSDNON NR (MS
) *@MHR RRDRRLDMS NE E @BST D HRJ @MC HSR @OOKHB@SHNM SN RB DDMHMF EN ONRS LDMNO@TR @K NRSDNON NRHR RXMNORHR NE @ 6'. DON S 6'. 2STCX & NTO .RSDNON NR (MS
+NAN & ,@ BNR ) 2@MS@A A@ @ ' 2@KU@CN 1NR R + +NAN RBNK@ #D K@ L@ @
et al., Gender di erences in the incidence of and risk factors for hip fracture: a 16-year
KNMFHSTCHM@K RSTCX HM @ RNTSGD M T NOD@M ONOTK@SHNM ,@ST HS@R GSSO
CW CNH N F I L@ST HS@R
- # -FTXDM ' & GKAN F ) 1 DMSD ) HRL@M 3 5 -FTXDM 1DRHCT@K KHED SHLD HRJ
NE E @BST DR HM VNLDM @MC LDM ) !NMD ,HMD 1DR GSSO CW CNH
N F IAL
P.M. Cawthon, Gender di erences in osteoporosis and fractures, Clin. Orthop. Relat. Res.
GSSO CW CNH N F R
K. Ulm, A simple method to calculate the con dence interval of a standardized mortality @SHN 2,1 L ) OHCDLHNK
- !HMJKDX 1 # !K@MJ 6 # +DRKHD , +DVHDBJH ) HRL@M ) / !HKDYHJH@M .RSDNON NRHR
in crisis: it’s time to focus on fracture, J. Bone Miner. Res. 32 (2017) 1391–1394, http://
CW CNH N F IAL 2 *GNRK@ 2G@MD B HRHR HM SGD S D@SLDMS NE NRSDNON NRHR ) !NMD ,HMD 1DR GSSO CW CNH N F IAL ) *@MHR # '@MR NNOD 2 !@HL ) / !HKDYHJH@M - !HMJKDX DS @K (MSD O DS@SHNM @MC TRD NE %1 7 HM BKHMHB@K O @BSHBD .RSDNON NR (MS GSSO CW CNH N F R Y - # -FTXDM 2 % NRS ) 1 DMSD ) HRL@M 3 5 -FTXDM #DUDKNOLDMS NE O NFMNRSHB MNLNF @LR EN HMCHUHCT@KHYHMF XD@ @MC XD@ E @BST D HRJR .RSDNON NR (MS GSSO CW CNH N F R 2 ,D@CNVR 1 *KDHM , # 1NTRBTKO + 2LNKDM 1 + .GREDKCS ) )NGMRSNM NRS
e ectiveness of preventative therapies for postmenopausal women with osteopenia,
5 785 ,1 , 1 1 75 1 6
! 1 2HMFD & ) ,BK@TBGK@M , 1NAHMRNM ) G HRSHD OHCDLHNKNFX NE E @BST DR HM
adults: the in uence of age and gender, J. Bone Joint Surg. (Br.) 8080 (1998) 243–248. J.A. Baron, M. Karagas, J. Barrett, W. Kniffin, D. Malenka, M. Mayor, et al., Basic epidemi
NKNFX NE E @BST DR NE SGD TOOD @MC KNVD KHLA @LNMF LD HB@MR NUD XD@ R NE @FD
OHCDLHNKNFX
) 1NRDM LD HB@M 2NBHDSX EN !NMD @MC ,HMD @K 1DRD@ BG / HLD NM SGD ,DS@ANKHB !NMD #HRD@RDR @MC #HRN CD R NE ,HMD @K ,DS@ANKHRL LD HB@M 2NBHDSX EN !NMD @MC ,HMD @K 1DRD@ BG
(RL@HK 2 1 /XD 6 NBJD HKK , +TMS ) 2HKL@M ) 1DDUD DS @K (MBHCDMBD NE KHLA
E @BST D @B NRR T NOD DRTKSR E NL SGD T NOD@M / NRODBSHUD .RSDNON NRHR 2STCX /.2
.RSDNON NR (MS GSSO CW CNH N F R
/ # #DKL@R % ,@ HM 1 ,@ BTR # ,HRT RJH ! ' ,HSK@J !DXNMC GHO HL ON S@MBD NE
NSGD MNMROHM@K E @BST DR L ) ,DC GSSO CW CNH N F I
@LILDC
& (N@MMHCHR ) %K@GHUD + /HBJ@ C /@O@HN@MMNT 1 # G@OT K@S * & 2@@F DS @K -NM GHO MNM ROHMD E @BST DR C HUD GD@KSGB@ D TSHKHY@SHNM ENKKNVHMF @ E @BST D 3GD &KNA@K +NMFHST
CHM@K 2STCX NE .RSDNON NRHR HM 6NLDM &+.6 .RSDNON NR (MS GSSO
CW CNH N F R Y
J. Joseph Melton, W.M. O’Fallon, B.L. Riggs, Secular trends in the incidence of hip fractures,
@KBHE 3HRRTD (MS GSSO CW CNH N F !%
NNOD 9 NKD 1 'NK NXC 2 @ K - '@ UDX , #DMMHRNM DS @K 2DBTK@
S DMCR HM SGD HMBHCDMBD NE GHO @MC NSGD NRSDNON NSHB E @BST DR .RSDNON NR (MS
GSSO CW CNH N F R
L.J. Melton, P.C. Amadio, C.S. Crowson, W.M. O’Fallon, Long-term trends in the incidence of
CHRS@K EN D@ L E @BST DR .RSDNON NR (MS GSSO CW CNH N F
2
) 2SDUDMR 1 MMD 1TCC #DBKHMHMF GHO E @BST D @SDR HM SGD 4MHSDC 2S@SDR FD FDHMF
GSSO CW CNH N F @FDHMF @EP
* / G@MF ) 1 DMSD 3 5 -FTXDM ) HRL@M (MBHCDMBD NE GHO @MC NSGD NR SDNON NSHB E @BST DR HM DKCD KX LDM @MC VNLDM #TAAN .RSDNON NRHR OHCDLHNKNFX 2STCX ) !NMD
,HMD 1DR GSSO CW CNH N F )!,1
6 # +DRKHD , 2@C@SR@E@UH + , +HW , YHL@DD 2 ,N HM ) ,DSFD DS @K 2DBTK@ CD
B D@RDR HM E @BST D @SDR EN ,@MHSNA@ @M@C@ @ ONOTK@SHNM A@RDC @M@KXRHR
.RSDNON NR (MS GSSO CW CNH N F R
2 , LHM 2 ) BGDMA@BG ) SJHMRNM 2 *GNRK@ + ) ,DKSNM (HH 3 DMCR HM E @BST D HM
BHCDMBD @ ONOTK@SHNM A@RDC RSTCX NUD XD@ R ) !NMD ,HMD 1DR
GSSO CW CNH N F IAL
, 2 ' !DD DJ@LO 1 ) . CD ,THMBJ *DHYD - 6 + 2BGDO # 3 4AAHMJ , ) , /@MMDL@M
) &NRKHMFR OHCDLHNKNFX NE DWS DLHSX E @BST DR HM SGD -DSGD K@MCR (MIT X
GSSO CW CNH N F I HMIT X
& + -@MMHMF@ * CD +DT , ) , /@MMDL@M , U@M CD KRS * '@ SGNKS (MB D@RHMF @SDR NE ODKUHB E @BST DR @LNMF NKCD @CTKSR SGD -DSGD K@MCR
FD FDHMF GSSO CW CNH N F @FDHMF @ES
3 5 -FTXDM ) HRL@M RRDRRLDMS NE E @BST D HRJ ONOTK@SHNM @RRNBH@SHNM UD RTR HMCH
The Association between
Metabolic Syndrome, Bone
Mineral Density, Hip Bone
Geometry and Fracture Risk:
The Rotterdam Study
Taulant Muka, Katerina Trajanoska, Jessica C. Kiefte-de Jong, Ling
Oei, André G Uitterlinden, Albert Hofman, Abbas Dehghan, M. Carola
Zillikens, Oscar H. Franco, Fernando Rivadeneira
37 5
%675 7
3GD @RRNBH@SHNM ADSVDDM LDS@ANKHB RXMC NLD ,2 @MC ANMD GD@KSG DL@HMR TMBKD@ 6D @HLDC SN RSTCX SGD @RRNBH@SHNM ADSVDDM ,2 @MC GHO ANMD FDNLDS X '!& EDLN @K MDBJ ANMD LHMD @K CDMRHSX %- !,# @MC SGD HRJ NE NRSDNON NRHR @MC HMBHCDMS E @B ST DR #@S@ NE VNLDM @MC LDM O@ SHBHO@MSR HM SGD SGH C UHRHS
NE SGD 1NSSD C@L 2STCX 12( @ O NRODBSHUD ONOTK@SHNM A@RDC BNGN S VD D @U@HK able (mean follow-up 6.7 years). MS was de ned according to the recent harmonized de nition. HBG parameters were measured at the third-round visit whereas FN-BMD was assessed at the third round and 5 years later. Incident fractures were identi ed E NL LDCHB@K DFHRS X C@S@ ESD BN DBSHMF EN @FD ANCX L@RR HMCDW !,( KHEDRSXKD E@BSN R @MC LDCHB@SHNM TRD HMCHUHCT@KR VHSG ,2 G@C KNVD ANMD VHCSG β / KNVD BN SHB@K ATBJKHMF @SHN β / @MC KNVD NCCR NE G@UHMF NRSDNON NRHR NCCR @SHN / HM VNLDM ATS MNS HM LDM 2HLHK@ KX ,2 V@R @RRNBH@SDC VHSG GHFGD %- !,# NMKX HM VNLDM β / (M SGD @M@KXRDR NE ,2 BNLONMDMSR SGD FKTBNRD BNLONMDMS TM DK@SDC SN CH@ADSDR RS@STR V@R ONRHSHUDKX @RRNBH@SDC VHSG %- !,# HM ANSG FDMCD R β / EN VNLDM @MCβ / EN LDM (M LDM V@HRS BH BTLED DMBD V@R HMUD RDKX @RRNBH@SDC VHSG %- !,# β / -N @RRNBH@SHNM V@R NARD UDC VHSG E @BST D HRJ HM DHSGD RDW (M BNMBKTRHNM VNLDM VHSG ,2 G@C GHFGD %- !,# HMCDODMCDMS NE !,( 3GD FKTBNRD BNLONMDMS NE ,2 V@R @RRNBH@SDC VHSG GHFG %- !,# HM ANSG FDMCD R GHFGKHFGSHMF SGD MDDC SN O DRD UD FKXBDLHB BNMS NK SN O DUDMS RJDKDS@K BNLOKHB@SHNMR
0 7 2 , 6 1 520 1 21 7
,1752 8 7,21
.RSDNON NRHR @ RXRSDLHB RJDKDS@K CHRD@RD HR @M HLON S@MS OTAKHB GD@KSG O NAKDL CTD to its in-creased risk for fractures, high morbidity and mortality and signi cant health B@ D BNRSR Di erent factors have been associated with osteoporosis including @ACNLHM@K NADRHSX GXOD SDMRHNM CXRKHOHCDLH@ @MC @AMN L@K FKTBNRD LDS@ANKHRL VGHBG @ D BNMRHCD DC BNLONMDMSR NE LDS@ANKHB RXMC NLD 3GDRD BNLONMDMSR LHFGS a ect bone di erently. Obesity may lead to increased bone mineral density (BMD) ADB@TRD HS HR @RRNBH@SDC VHSG GHFGD β DRS @CHNK KDUDKR @MC GHFGD LDBG@MHB@K KN@C VGHBG L@X O NSDBS ANMD 5HRBD @K E@S @BBTLTK@SHNM HR @RRNBH@SDC VHSG GHFGD KDUDKR of proin ammatory cytokines, which may upregulate receptor activators of nuclear J@OO@ ! KHF@MC KD@CHMF SN HMB D@RDC ANMD DRN OSHNM @MC SGD DEN D CDB D@RDC !,#
KRN @KSGNTFG GXOD FKXBDLH@ HR @ O DCHBSN NE NRSDNON NSHB E @BST DR SGD @RRNBH@ tion between high glucose levels or insulin resistance with BMD is not well de ned. %N DW@LOKD CH@ADSHB HMCHUHCT@KR G@UD GHFGD !,# ATS HMB D@RDC HRJ NE E @BST DR 2HLHK@ KX SGD DUHCDMBD EN @RRNBH@SHNMR ADSVDDM CXRKHOHCDLH@ @MC GXOD SDMRHNM VHSG ANMD LDS@ANKHRL HR RSHKK HMBNMBKTRHUD @MC SGD NUD @KK @RRNBH@SHNM ADSVDDM ,2 @MC ANMD GD@KSG DL@HMR TMBKD@ 3VN DBDMS LDS@ @M@KXRDR NM SGD @RRNBH@SHNM ADSVDDM ,2 @MC !,# @MC E @BST DR VD D MNS BNMBKTRHUD @MC VGDSGD LDS@ANKHB RXMC NLD LHFGS AD @RRNBH@SDC VHSG ANMD GD@KSG ADXNMC SGD BNMS HATSHNM NE SGD HMCHUHCT@K BNLONMDMSR DL@HMR TMBKD@ Moreover, sex-di erences have been suggested in this relation ship, mainly due to di erences in body fat distribution between men and women, but yet not clearly de ned. 1DBDMSKX @ MDV BKTRSD NE B HSD H@ EN CH@FMNRHR NE ,2 G@C been presented with an emphasis on gender and ethnic di erences in the measure of BDMS @K NADRHSX VGHBG G@R MNS ADDM @CDPT@SDKX RSTCHDC HM DK@SHNM SN ANMD
6D @HLDC SN RSTCX SGD @RRNBH@SHNM ADSVDDM ,2 EDLN @K MDBJ !,# %- !,# GHO ANMD FDNLDS X '!& NRSDNON NRHR @MC E @BST DR @LNMF DKCD KX #TSBG LDM @MC VNLDM O@ SHBHO@MSR NE SGD 1NSSD C@L 2STCX @MC HE SGDRD @RRNBH@SHNMR VD D HMCDODM CDMS NE ANCX L@RR HMCDW !,( 6D DW@LHMDC VGDSGD ,2 V@R @RRNBH@SDC VHSG %- !,# @MC '!& O@ @LDSD R HM EDL@KDR @MC L@KDR TRHMF @ B NRR RDBSHNM@K CDRHFM @MC SN CDSD LHMD VGDSGD ,2 O DCHBSR %- !,# @MC HMBHCDMS E @BST DR TRHMF @ KNMFHSTCHM@K CDRHFM
0 7(5, /6 1 0(7 2 6
6WxG 3RSxODWLRq
3GD RSTCX V@R OD EN LDC VHSGHM SGD E @LDVN J NE SGD 1NSSD C@L 2STCX @ ONOTK@SHNM based cohort among persons ≥ 55 years and older living in the Ommoord district NE 1NSSD C@L SGD -DSGD K@MCR 3GD @SHNM@KD @MC CDRHFM NE SGD 1NSSD C@L 2STCX HR37 5
CDRB HADC DKRDVGD D 3GD RSTCX V@R @OO NUDC AX SGD ,DCHB@K SGHB@K NLLHSSDD NE @RLTR 4MHUD RHSX @MC @KK O@ SHBHO@MSR F@UD HMEN LDC BNMRDMS 3GD O DRDMS RSTCX used data from the baseline examination of the third wave of the rst cohort (RS-I-3) HM VGHBG EDL@KDR @MC L@KDR O@ SHBHO@SDC @MC %- !,# V@R LD@RT DC @S SGD ENT SG NTMC 12(
3RSxODWLRq IRu qDO VLV
0HWDEROLF 6 QGURPH )1 0
LS RQH *HRPHWU DQG 2VWHRSRURVLV
LNMF EDL@KDR @MC L@KDR VNLDM @MC LDM CHC MNS G@UD E@RSHMF
R@LOKDR N LD@RT DR NE @S KD@RS NM BNLONMDMS NE ,2 @MC VD D SGD DEN D DWBKTCDC E NL SGD @M@KXRHR %T SGD LN D %- !,# @S 12( V@R MNS @RRDRRDC HM EDL@KDR @MC L@KDR KD@UHMF EDL@KDR @MC L@KDR EN SGD B NRR RDB SHNM@K @M@KXRHR DF@ CHMF ,2 %- !,# @MC NRSDNON NRHR %N SGD @M@KXRHR BNMBD MHMF ,2 @MC '!& EDL@KD @MC L@KDR VD D ET SGD DWBKTCDC ADB@TRD NE MN@U@HK@AKD HMEN L@SHNM NM '!& C@S@ 6xSSOHPHqWDu )LjxuH DqG
0HWDEROLF 6 QGURPH DQG )UDFWXUHV 5LVN
LNMF EDL@KDR @MC L@KDR VHSG HMEN L@SHNM @U@HK@AKD NM ,2 BNLONMDMSR @S 12( RTAIDBSR EDL@KDR @MC L@KDR VD D DWBKTCDC ADB@TRD SGD D V@R MN C@S@ NM E @BST D ENKKNV TO GDMBD KD@UHMF EDL@KDR @MC L@KDR EN SGD @M@KXRHR NM ,2 @MC E @BST D HRJ %T SGD LN D EN D@BG SXOD NE E @BST D O DU@KDMS B@RDR VD D DWBKTCDC E NL SGD @M@KXRHR 6xSSOHPHqWDu )LjxuH DqG
M
S d m D
MS was de ned according to the new criteria announced by a joint scienti c state LDMS E NL SGD (MSD M@SHNM@K #H@ADSDR %DCD @SHNM (#% SGD LD HB@M 'D@ S RRNBH@ SHNM -@SHNM@K 'D@ S +TMF @MC !KNNC (MRSHSTSD ' -'+!( 6N KC 'D@ S %DCD @SHNM (MSD M@SHNM@K SGD NRBKD NRHR 2NBHDSX @MC (MSD M@SHNM@K RRNBH@SHNM EN SGD 2STCX NE .ADRHSX /@ SHBHO@MSR VHSG SG DD N LN D NE SGD ENKKNVHMF BNLONMDMSR VD D BK@RRH
ed as having MS: (1) abdominal obesity (waist circumference (WC) ≥ 102 cm for men or ≥ 88 cm for women); (2) high triglycerides (TG) ( ≥ 150 mg/dL) (3) low HDL ( ≤ 40 mg/dL for men or ≤ 50 mg/dL for women) (4) elevated blood pressure (BP) (systolic BP ≥ 130 and/or diastolic BP ≤ 85 mmHg) or (5) high glucose (fasting glucose level ≥ 100 mg/dL). The criteria for abdominal obesity were adopted from the cut-o s for
T NOD@M ODNOKD DFHNM
6NHOHWDO VVHVVPHqWV
KK DUDMSR HMBKTCHMF HMBHCDMS E @BST DR @MC CD@SG VD D DON SDC AX FDMD @K O @BSH SHNMD R &/R HM SGD DRD@ BG @ D@ AX LD@MR NE @ BNLOTSD HYDC RXRSDL KK DON SDC
