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I}OPMy___PPT10Y+D=' = @B +"0 PT(  T T  p\0e0e?Title 1 `}  d SOsteoporosis vs. OsteopeniaN T   d0e0e?,Content Placeholder 2 ` d hNational Institutes of Health defined Osteoporosis A disease of increase skeletal fragility Low bone mineral density (a T-score below -2.5) Microarchitectural deterioration Osteopenia T-score between -1.0 and -2.5d3{ 3Cf$ f 8Xx6 T S ޽h ? I}OPMy___PPT10Y+D=' = @B +"0 `Xp( H1! X X  p(d0e0e?Title 1 `}  d KT-Score vs. Z-Score! X  l\0e0e?,Content Placeholder 2 ` d ;T-score: Number of SD the BMD is above or below the mean for young-normal bone density Z-score: Number of SD the BMD is above or below the mean for an age and sex specific reference group L> fP  f V]8Xx6 X S ޽h ? I}OPMy___PPT10Y+D=' = @B +"h0 p\t(  \ \  p<1d0e0e?Title 1 `}  d A Treatment / \  Ad0e0e?,Content Placeholder 2"PK!{[Content_Types].xml|AN0EH,BI F$- qڲAK{4fg`bhlz39,7U=DdQhVN9GLUHe2!gu]]k(#*kzky_O&鴷Vb\D:r g.dUg3Uc8O.͹᭜&9R~_,dgzjǎ?I'f#®Pb-\/Ƿ0Z]nLnp__3.iJV KQBiDžrL,Vʌ/7р4`ANar+m;E/'3U Aںv83/PK!k drs/downrev.xmlDMKADah5bk:!ԽDI"xmwz?tg!*^v>Nn'(ҙVjT$:'płrqk rBhbsCٰ0q=K*-}!mY6ӖZI iXM=̼x{A*j\?+B#style.visibility<*\3Z%(D' =+4 8?\CB#ppt_xBCB#ppt_xB*Y3>B ppt_x<*\3ZD' =+4 8?dCB1+#ppt_h/2BCB#ppt_yB*Y3>B ppt_y<*\3ZDn' =%(D' =%(D' =4BBB@B%(D' =1:Bvisible*o3>+B#style.visibility<*\Zx%(D' =+4 8?\CB#ppt_xBCB#ppt_xB*Y3>B ppt_x<*\ZxD' =+4 8?dCB1+#ppt_h/2BCB#ppt_yB*Y3>B ppt_y<*\ZxDn' =%(D' =%(D' =4BBB@B%(D' =1:Bvisible*o3>+B#style.visibility<*\x%(D' =+4 8?\CB#ppt_xBCB#ppt_xB*Y3>B ppt_x<*\xD' =+4 8?dCB1+#ppt_h/2BCB#ppt_yB*Y3>B ppt_y<*\xDn' =%(D' =%(D' =4BBB@B%(D' =1:Bvisible*o3>+B#style.visibility<*\%(D' =+4 8?\CB#ppt_xBCB#ppt_xB*Y3>B ppt_x<*\D' =+4 8?dCB1+#ppt_h/2BCB#ppt_yB*Y3>B ppt_y<*\+" 0 `S(  ` `  pKd0e0e?Title 1 `}  d A Mechanism  `  \Zd0e0e?,Content Placeholder 2"PK!{[Content_Types].xml|AN0EH,BI F$- qڲAK{4fg`bhlz39,7U=DdQhVN9GLUHe2!gu]]k(#*kzky_O&鴷Vb\D:r g.dUg3Uc8O.͹᭜&9R~_,dgzjǎ?I'f#®Pb-\/Ƿ0Z]nLnp__3.iJV KQBiDžrL,Vʌ/7р4`ANar+m;E/'3U Aںv83/PK!drs/downrev.xmlDj1!Bw5SKE^EYN$}.ty8MnęAx& VզDٯ' | .a>B)"TJWm&vuBQẑ$KM8?~5ʏ{56#ɷnj>;}ׯz+QBxQ|^V[BtPK-!{[Content_Types].xmlPK-!Z,[ _rels/.relsPK-!drs/downrev.xmlPK  `H$D 0 d The patient would like to know how the bisphosphonate meds work. What do you tell her? Bisphosphonates decrease bone resorption by interfering with cells responsible for bone turnover (osteoclast cells) V]8Xx6 ` S ޽h ? I}OPM___PPT10+qZD|' = @B D7' = @BA?%,( < +O%,( < +Dn' =%(D' =%(D' =4BBB@B%(D' =1:Bvisible*o3>+B#style.visibility<*`Y%(D' =+4 8?\CB#ppt_xBCB#ppt_xB*Y3>B ppt_x<*`YD' =+4 8?dCB1+#ppt_h/2BCB#ppt_yB*Y3>B ppt_y<*`Y+""0 d3(  d d  p0dd0e0e?Title 1 `}  d @Efficacy   d   {d0e0e?,Content Placeholder 2" PK! [Content_Types].xmlQN0 #QI!v:`|mDDq(n쀄8~ZQ̘_˕*@ou2x cX=\7v=r9iMf H']Hd.S#wQ_6gȋl;}tt)eU-!lT/STOl<9R~Q&4@Dƨ*j"t3D q>}-^p>rr‘ܼlb!\}PPK!1_a _rels/.relsj0 ѽqCNo^K [ILcX&m߾0XFo;>0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!slYI%drs/shapexml.xmlXn6}/ Zd}Y{Qˆϋ1EŬ)R )SO;Of tp8sf9mF:]3i͕y | Ff|'=xwWW T_PMz=/V$V`{UNzilTް+I~ Uf./c*{ rjMJ6$\:6VYHffڷ&?1)w<CA/әf`YܴZmG帕ma{kM t_n'buO韍`4BBCth&#41Ml+B~ZYT^浈8PNԡ}Xu zi Ʉ`EOл>3I3erV: ҏPs⁖fhH[IIKA/ܴX"F`A:󕘋6iĭ,^7Edov*!.vۄ^f8i$J%yU<Ѱsgmڹrbԗa%Aim)iF* xJ A`Jɢ"t3jvʤxP3t%LbB@;}oI7~?,L:cTcSg'ƾ clG#}hd[9:A5.$KG1.sc#ʿ}8GSX>/N㾜cX˿K܉׹8|fd"b;ܼ5܌F_Xr k'$MvK^6m6hSSXijQ"F$UN:=tt9@2*ISGbTz{lU934,W 3Kp\ +҅պRX'E䀋hشTUVHN$NKQaP;5G'pC+^UjЄeھ/A L 장-G(э.P)\,`A&ͽwdf~; [1PK!xOdrs/downrev.xmlDN0HHܨCQ.Tmy%@iҷьѷ\OWGsp=@Tt B$1;aXϖT7ʎبPBPh-XRW;o)m< n{=ϲ\[$=4sm6!8E}Qߖ( by|_* ;#$d,A~PK-! [Content_Types].xmlPK-!1_a /_rels/.relsPK-!slYI%*drs/shapexml.xmlPK-!xOdrs/downrev.xmlPK  `H$@0 d !The patients asks you what benefits the bisphosphonates have shown? Alendronate (Fosamax) Fracture Intervention Trial (FIT) Alendronate increased BMD femoral neck (4.1%) and spine (6.2%) Reduced risk of vertebral fx by ~50% Risedronate (Actonel) Increased BMD lumbar spine (5.4%), femoral neck (1.6%), trochanter (3.3) Reduced risk of vertebral fx (41%) and non-vertebral fx (39%) tZPPPPPZ 8Xx6 d S ޽h ? I}OPM___PPT10+D' d= @B DJ' = @BA?%,( < +O%,( < +D ' =%(D ' =%(DG' =4BBB @B%(D' =1:Bvisible*o3>+B#style.visibility<*dDZ%(D' =-6B'blinds(horizontal)*<3<*dDZDG' =4BBB @B%(D' =1:Bvisible*o3>+B#style.visibility<*dZ|%(D' =-6B'blinds(horizontal)*<3<*dZ|DG' =4BBB @B%(D' =1:Bvisible*o3>+B#style.visibility<*d|%(D' =-6B'blinds(horizontal)*<3<*d|DG' =4BBB @B%(D' =1:Bvisible*o3>+B#style.visibility<*d%(D' =-6B'blinds(horizontal)*<3<*dD' =%(D=' =%(DG' =4BBB @B%(D' =1:Bvisible*o3>+B#style.visibility<*d%(D' =-6B'blinds(horizontal)*<3<*dDG' =4BBB @B%(D' =1:Bvisible*o3>+B#style.visibility<*dA%(D' =-6B'blinds(horizontal)*<3<*dADG' =4BBB @B%(D' =1:Bvisible*o3>+B#style.visibility<*dA%(D' =-6B'blinds(horizontal)*<3<*dA+"0 hg(  h h  pdd0e0e?Title 1 `}  d SAlendronate vs. Risedronate h  d0e0e?,Content Placeholder 2 ` d *Compared in one prospective randomized trial Alendronate increased BMD more than Risedronate at all sites after 12 months and results persisted in 2nd year However, NO differences in incidence of fx21  V]8Xx6 h S ޽h ? I}OPMy___PPT10Y+D=' d= @B +"$0 /'l( x! l l  pd0e0e?Title 1 `}  d @Efficacy  l  d0e0e?,Content Placeholder 2 ` d [Ibandronate (Boniva) Increases in BMD at lumbar spine and hip Fracture data not reported \[ V]8Xx6 l S ޽h ? I}OPMy___PPT10Y+D=' d= @B +"0 p(  p  p  pܸd0e0e?Title 1 `}  d E HORIZON Study D p  .d0e0e?,Content Placeholder 2 ` d ^6Black D et al,  Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis,  NEJM 2007; 356 (18): 1809-1822. International, multi-center, 3889 patients Randomized, double-blind, placebo-controlled 15- min infusion of Zoledronic acid (5 mg) vs. placebo 3-year follow-up V]8Xx6 p S ޽h ? I}OPMy___PPT10Y+D=' d= @B +"0 "t( ! t  t  pd0e0e?Title 1 `}  d E HORIZON Study { t  d0e0e?,Content Placeholder 2 ` d IPostmenopausal women age 65-89 years BMD T-score of -2.5 or less at the femoral neck with or w/o evidence of existing vertebral fx OR BMD T-score -1.5 or less with radiologic evidence of at least 2 mild vertebral fxs or one moderate vertebral fx All patients received oral daily calcium (1000-1500 mg) and vitamin D (400-1200 IU)JI V]8Xx6 t S ޽h ? I}OPMy___PPT10Y+D=' d= @B +" 0   x (  x  x  p`d0e0e?Title 1 `}  d E HORIZON Study y  x  xd0e0e?,Content Placeholder 2"PK! [Content_Types].xmlQN0 #QI!v:`|mDDq(n쀄8~ZQ̘_˕*@ou2x cX=\7v=r9iMf H']Hd.S#wQ_6gȋl;}tt)eU-!lT/STOl<9R~Q&4@Dƨ*j"t3D q>}-^p>rr‘ܼlb!\}PPK!1_a _rels/.relsj0 ѽqCNo^K [ILcX&m߾0XFo;>0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!%Ov0uHdrs/shapexml.xmlWn8 v\@낦cHʵK!G1hS+ 0A{ծVd+F)~(۳(q)EAѫ.k4]{Lעfi2f[0hpB{qQݠfR)ea.,eAPY+gF{hb\*%#:IMb?bRi ў4 ¥ :]/޽]ͲIJO8-Sl t/1pGJG zq>#|>noߏ}ǫQ"l֛Jzwly.v UGtb8!@fvAh`rFO%2gSPQRꞭO:݄ R:0s:f h5%وf05|=2!0K܈XrgПJ50;58,]3PK!Wkdrs/downrev.xmlDN0HHܨCUh%hNEmy%@lӤo}omC~b)iFx?-@Hbs^]_-)7nV "!'&>: [ ׳rRLxvzesmPۆ˯E؆d~j=+*Y+*q7/0÷@!GHn4Y^PK-! [Content_Types].xmlPK-!1_a /_rels/.relsPK-!%Ov0uH*drs/shapexml.xmlPK-!Wkdrs/downrev.xmlPK ` d gPrevious use of oral bisphosphonates allowed but had to have a washout period based on duration of use (eg previous use of >=48 weeks required 2 years washout) Other osteoporosis meds allowed: hormone tx, raloxifene, calcitonin, tibolone, tamoxifen, DHEA, ipriflavone, medroxyprogesterone Pts stratified based on whether taking other osteoporosis meds or nothZh V]8Xx6 x S ޽h ? I}OPMy___PPT10Y+D=' d= @B +"0 !|( >! |  |  pdd0e0e?Title 1 `}  d E HORIZON Study z |  t e0e0e?,Content Placeholder 2 ` d @Primary Endpoints: new vertebral fx, hip fx Secondary Endpoints: non-vertebral fx, any clinical fx, clinical vertebral fx, BMD, changes in biochemical markers of bone resorption Results at 3 years follow-up Decreased risk of vertebral fx by 70% Decreased risk of hip fx by 41% Decreased risk of non-vertebral fx by 25%&pp 8Xx6 | S ޽h ? I}OPMy___PPT10Y+D=' d= @B +"0   b (     pe0e0e?Title 1 `}  e VHORIZON Study: Adverse Events    #e0e0e?,Content Placeholder 2" PK! [Content_Types].xmlQN0 #QI!v:`|mDDq(n쀄8~ZQ̘_˕*@ou2x cX=\7v=r9iMf H']Hd.S#wQ_6gȋl;}tt)eU-!lT/STOl<9R~Q&4@Dƨ*j"t3D q>}-^p>rr‘ܼlb!\}PPK!1_a _rels/.relsj0 ѽqCNo^K [ILcX&m߾0XFo;>0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK!t*6drs/shapexml.xmlWn8 x]v\7m(EbˆsAQ5E $9[%}$%Gͩ3CμGW"{a4:/ǔM!&go)q)EFwg&pnVgt}=ߊ؊y fT[cJ&ŨbRk,zeޯ,EF_QY-F{xb\l*%:j#C4Kw HHewmH_验}͆aO$MG>}T{3"~;1x\Rˎ0+4d2h#=p&q-m;a䐔taX>> U6bL*֟J(@t&o!ZfP $cүqev2d%xG-遇wVu/RTlx0,Y7bۙOU3VD8աT%lF(;쵹XGAq7:yp%KoW}r;sOB\׽s*AW "p DQ2@':#'ytE"}y`PF; d+omq}^Ӱic JFzűs1 Juʰ)!L8_/C1Rw‘᎐a:3|*d?PK!9drs/downrev.xmlDMO0DHkQ"*t[A%hNy7#$ь6>Ng(ҙVjT$:'pيrFpJ 9!41֡lR%ubӘ,[hKz6\~-6,fY<ͨo~xy1߁<_* jwS[2M?PK-! [Content_Types].xmlPK-!1_a /_rels/.relsPK-!t*6*drs/shapexml.xmlPK-!9drs/downrev.xmlPK ` e 5 most common sx within 3 days after infusion (post-dose sx): pyrexia, flu-like sx, myalgia, HA, arthralgia Chills, nausea, bone pain, back pain Renal safety: Transient increase in Cr Atrial fibrillation more common with Zoledronic Acid No spontaneous reports of osteonecrosis of jaw 6 Z5f/  V]8Xx6  S ޽h ? I}OPMy___PPT10Y+D=' d= @B +"0 #( !    p*e0e0e?Title 1 `}  e D Instructions }   ;e0e0e?,Content Placeholder 2"PK!{[Content_Types].xml|AN0EH,BI F$- qڲAK{4fg`bhlz39,7U=DdQhVN9GLUHe2!gu]]k(#*kzky_O&鴷Vb\D:r g.dUg3Uc8O.͹᭜&9R~_,dgzjǎ?I'f#®Pb-\/Ƿ0Z]nLnp__3.iJV KQBiDžrL,Vʌ/7р4`ANar+m;E/'3U Aںv83/PK!tqdrs/downrev.xmlDN0HH\u(jUTrjՖXבmzhF[G۩:10@Z |_BD!윰3XdϧCUH@ckʆ-YRW9o1kMf\[l%=4c lHbҠgEe |3f|~ycfw+/ <ϟ=@rKPK-!{[Content_Types].xmlPK-!Z,[ _rels/.relsPK-!tqdrs/downrev.xmlPK `H$D0 e 4What instructions should you give the patient about taking an oral bisphosphonate? Do not lie down or recline for at least 30 minutes after taking Do not eat or drink anything other than plain water Do not take any other medicines including vitamins, calcium, or antacids for at least 30 minutes after taking&SS 8Xx6  S ޽h ? I}OPMG ? ___PPT10 +)D ' d= @B D ' = @BA?%,( < +O%,( < +D' =%(D' =%(DG' =4BBB @B%(D' =1:Bvisible*o3>+B#style.visibility<*S%(D' =-6B'blinds(horizontal)*<3<*SD' =%(D' =%(DG' =4BBB @B%(D' =1:Bvisible*o3>+B#style.visibility<*%(D' =-6B'blinds(horizontal)*<3<*D' =%(D' =%(DG' =4BBB @B%(D' =1:Bvisible*o3>+B#style.visibility<*5%(D' =-6B'blinds(horizontal)*<3<*5+"0  ?(     pFe0e0e?Title 1 `}  e UBisphosphonate Therapy Timing   Qe0e0e?,Content Placeholder 2 ` e The patient states that she hates taking meds. How often does she have to take the bisphosphonate medication? For how long does she have to stay on the bisphosphonate medication? V]8Xx6  S ޽h ? 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[Content_Types].xmlPK-!1_a /_rels/.relsPK-!lU %*drs/shapexml.xmlPK-!W7ddrs/downrev.xmlPKg ` e !Alendronate (Fosamax) has been shown to be well-tolerated and effective (results in continued increases in BMD) for at least 10 years Risedronate (Actonel) is effective and well-tolerated for up to 7 years However, there is currently NO consensus on how long to continue bisphosphonate txt"Zfgf* f f)  V]8Xx6  S ޽h ? I}OPMy___PPT10Y+D=' d= @B +"0 P(     p0e0e?Title 1 `}   MDuration of TreatmentQ   e0e0e?,Content Placeholder 2 `  k5 years may be enough Fracture Intervention Trial Long-Term Extension (FLEX) 1099 post-menopausal women who received alendronate x 5 years in the Fracture Intervention Trial (FIT) Randomly assigned to an additional 5 years of alendronate vs. placebo Excluded pts at highest risk &MM 8Xx6  S ޽h ? I}OPMy___PPT10Y+D=' d= @B +"70 B:`( !    p"0e0e?Title 1 `}   MDuration of Treatment   4+0e0e?,Content Placeholder 2 `  EFLEX results for the placebo group Gradual decline in BMD but BMD remained at or higher than levels 10 years earlier Gradual rise in biochemical markers of bone turnover No significantly higher risk of fracture except for clinically detected vertebral fracture There may be a residual benefit on BMD and fx for up to 5 years :#A#A 8Xx6  S ޽h ? I}OPMy___PPT10Y+D=' d= @B +"0 p>(     p:0e0e?Title 1 `}   D Drug Holiday    8K0e0e?,Content Placeholder 2 `  Some MDs recommend a  drug holiday after 5 years of therapy (eg. Tx for 5 years, one year off, then tx for 5 more years) Attempt to reduce the risk of Osteonecrosis of the Jaw No data to suggest that drug holiday reduces risk V]8Xx6  S ޽h ? I}OPMy___PPT10Y+D=' d= @B +"\/0 d\( h!    pDQ0e0e?Title 1 `}   D Side Effects     ,W0e0e?,Content Placeholder 2", & PK! 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[Content_Types].xmlPK-!1_a /_rels/.relsPK-!k: //*drs/shapexml.xmlPK-!Ő5drs/downrev.xmlPK  `  XAn area of exposed bone in the mandible, maxilla, or palate that heals poorly or does not heal over 6-8 weeks First reported in connection with bisphosphonate tx in 2003 Most of reported cases (95%) have been assoc with Zoledronic acid or Pamidronate given IV for metastatic bone dz For oral bisphosphonates, >1 million pts tx and <50 cases ONJ"YZX V]8Xx6  S ޽h ? I}OPMy___PPT10Y+D=' = @B +"% 0 0 (  ( x!    p0e0e?Title 1 `}   ?Summary    0e0e?,Content Placeholder 2"PK! 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[Content_Types].xmlPK-!1_a /_rels/.relsPK-!xٙ *drs/shapexml.xmlPK-!Fdrs/downrev.xmlPK `  MBisphosphonates have been shown to increase BMD and decrease risk of vertebral and non-vertebral fractures in pts with osteoporosis Main side effect with oral bisphosphonate is GI side FX HORIZON study shows benefits from IV Zoledronic Acid once yearly but unexpected increased risk of a-fib Continue bisphosphonate tx for 5-10 years NM V]8Xx6  S ޽h ? I}OPMy___PPT10Y+D=' = @B +"\0 g _  (     p0e0e?Title 1 `}   D Bibliography     0e0e?,Content Placeholder 2"PK! [Content_Types].xmlQN0 #QI!v:`|mDDq(n쀄8~ZQ̘_˕*@ou2x cX=\7v=r9iMf H']Hd.S#wQ_6gȋl;}tt)eU-!lT/STOl<9R~Q&4@Dƨ*j"t3D q>}-^p>rr‘ܼlb!\}PPK!1_a _rels/.relsj0 ѽqCNo^K [ILcX&m߾0XFo;>0xM e`|X}đ I`߽N4aG2$RKIZ)4(M9`ctB{m:f@`3n|O,ܗr޾jxR0T ,0@}WBLǬ5vPK! =drs/shapexml.xmlXn7;dEIj඀Ps.F\ŊK.H*gIܕe6Bff>.wf[鼲I#lc?<]șdJȂwL|`l):f2x5Wʺq8 Q&eKYn93Tc˙5lIȵեtlv6$x3b;߸T:qC@qAwiGW㫷FWo:ݬpDhb6JͲlEI!G 2pEjMnAjrަH2%*GD9+e@Sc.dIss6$XRI&.tb<2!ЌF,D`[² c[Y)ƳMz뤫v.jOBaa *SjFĚ&-hgIϿb]$jCT5&ٴ*`\K15"lY-O 6eq.f2vHI'sK]8k/ 3- fFh]7NiMV2N&y'p?dkɪ"s%tTIG6:dt%$e';|(gey!M<"GNur)pf'!3SpMD>E ~Yxf^\=sWFaLoҔ r|-&s)kPK!-| drs/downrev.xmlDJAEДIc*AYஜytf&oB{9\SGup=@δR#B$19aXϖ7ȎXBckʆ-YRW9o)km< n;=ͲJzhM"l`ej=+*Yxw *oR>_Tan@Uϧߚ!%d zPK-! [Content_Types].xmlPK-!1_a /_rels/.relsPK-! =*drs/shapexml.xmlPK-!-| drs/downrev.xmlPK `  Bilezikian, J,  Osteonecrosis of the Jaw Do Bisphosphonates Pose a Risk?, NEJM 2006; 355 (22): 2278-2281. 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