降鈣的藥物治療

降鈣的藥物治療第一頁，共23頁。第二頁，共23頁。參考文獻(xiàn)14523秦華東,石臣磊,石鐵鋒,等.急性高血鈣危象6例臨床分析[J].醫(yī)學(xué)臨床研究,2008,25(10):1861-1863.KennethG.Saag,JoseR.Zanchetta,Jean-PierreDevogelaer,etal.EffectsofTeriparatideVersusAlendronateforTreatingGlucocorticoid-InducedOsteoporosis:Thirty-Six–MonthResultsofaRandomized,Double-Blind,Contro-lledTrial[J].ARTHRITIS&RHEUMATISM,2009,60(11):3346–3355.N.L.Gilchrist,C.M.Frampton,R.H.Acland,etal.AlendronatePreventsBoneLossinPatientswithAcuteSpinalCordInjury:ARandomized,Double-Blind,PlaceboControlledStudy[J].TheJournalofClinicalEndocrino-logy&Metabolism,2007,92(4):1385–1390.C.M.Weaver,B.R.Martin,G.S.Jackson.J,etal.AntiresorptiveEffectsofPhytoestro-genSupplementsComparedwithEstradiolorRisedronateinPostmenopausalWomenUsing41CaMethodology[J].ClinEndocrinol.Metab,2009,94(10):3798-3805.T.S.Tapaninen1,P.K.Venesmaa1,J.S.Jurvelin,Alendronatereducesperiprostheticbonelossafteruncementedprimarytotalhiparthroplasty—A5-yearfollow-upof16patients[J].ScandinavianJournalofSurgery,2010,99:32–37.第三頁，共23頁。第四頁，共23頁。降鈣的藥物治療Ⅰ1.補(bǔ)鈉利尿：補(bǔ)充0.9%氯化鈉注射液既擴(kuò)充了細(xì)胞外液又競爭性抑制了腎近曲小管對(duì)鈣的重吸收,多數(shù)情況下第1個(gè)24h輸注0.9%氯化鈉注射液3～4L,使每日尿量達(dá)到3～4L。待血容量恢復(fù)正常后,靜脈給予利尿劑,以袢利尿劑為主,因其可進(jìn)一步阻斷腎小管髓袢升支粗段對(duì)鈉和鈣的重吸收,促進(jìn)尿鈣排泄,常用呋塞米40～80mg靜脈注射,必要時(shí)重復(fù)用藥;而噻嗪類利尿劑應(yīng)避免使用,因其可減少腎臟鈣的排泄。秦華東,石臣磊,石鐵鋒,等.急性高血鈣危象6例臨床分析[J].醫(yī)學(xué)臨床研究,2008,25(10):1861-1863.第五頁，共23頁。降鈣的藥物治療Ⅱ2.應(yīng)用骨溶解抑制劑：降鈣素抑制破骨細(xì)胞對(duì)骨的吸收和腎小管對(duì)鈣的重吸收,有利于鈉和鈣的排泄,作用迅速。降鈣素100～400U,每6h靜脈或皮下注射1次,常用2～3次,但常于幾小時(shí)或幾天內(nèi)出現(xiàn)“脫逸”現(xiàn)象而失效。經(jīng)降鈣素治療的患者,約80%血鈣可降低,但難以恢復(fù)正常水平。二膦酸鹽類藥物的作用可能是對(duì)破骨細(xì)胞的直接毒性作用,尤其適用于高血鈣伴低血磷的患者,低磷可使骨吸收和腎臟合成活性維生素D3增強(qiáng),骨形成減少,高鈣血癥加重。秦華東,石臣磊,石鐵鋒,等.急性高血鈣危象6例臨床分析[J].醫(yī)學(xué)臨床研究,2008,25(10):1861-1863.第六頁，共23頁。降鈣的藥物治療Ⅲ二膦酸鹽類藥物依據(jù)時(shí)間先后和結(jié)構(gòu)特點(diǎn)分為3代,包括:第1代的依替膦酸鹽和氯甲雙膦酸鹽第2代的帕米膦酸鹽、阿侖膦酸鹽和利塞膦酸鹽)以及第3代的伊苯膦酸鹽、替魯膦酸鹽和唑來膦酸鹽。第2代和第3代屬于含氮原子的二膦酸鹽類藥物,其抗骨重吸收能力是第1代的100～10000倍。3.其他：如光輝霉素和甲狀旁腺激素衍生物特立帕肽等。4.糖皮質(zhì)激素：病情允許時(shí)可口服,緊急情況下可用氫化可的松或地塞米松靜滴、靜注。其雖有一定的降鈣療效,但起效慢,維持時(shí)間短。秦華東,石臣磊,石鐵鋒,等.急性高血鈣危象6例臨床分析[J].醫(yī)學(xué)臨床研究,2008,25(10):1861-1863.第七頁，共23頁。第八頁，共23頁。文獻(xiàn)二ⅠStudydesignandparticipants.Subjectswererandomlyassignedtoreceiveinjectableteriparatide(20μg/day)plusoralplaceboororalalendronate(10mg/day)plusinjectableplacebo.Supplementsofcalcium(1,000mg/day)andvitaminD(800IU/day)wereprovided.Serumcalciummeasurements.

Thenumberofsubjectswithelevatedtotalserumcalciumconcentrations(>10.5mg/dl[2.62mmoles/liter]wasdeterminedfromserumcollected>16hoursafteradministrationofstudydrugs.KennethG.Saag,JoseR.Zanchetta,Jean-PierreDevogelaer,etal.EffectsofTeriparatideVersusAlendronateforTreatingGlucocorticoid-InducedOsteoporosis:Thirty-Six–MonthResultsofaRandomized,Double-Blind,ControlledTrial[J].ARTHRITIS&RHEUMATISM,2009,60(11):3346–3355.第九頁，共23頁。文獻(xiàn)二ⅡTable1.predoseserumcalcium*SubjectstakingalendronateSubjectstakingteriparatideP(n=214)(n=214)Predosetotalcalcium?≥1serumcalcium?14(7)44(21)<0.001≥2serumcalcium§6(3)16(8)0.046≥1serumcalcium?3(1)9(4)0.140≥2serumcalcium§01(0.5)1.000*Predosewasdefinedas_16hoursafteradministrationofstudydrugs.?Toconvertserumcalciumconcentrationstommoles/litermultiplyby0.25.?Baselineand≥1postbaselineserumcalciummeasurementswereavailablefor209subjectsinthealendronategroupandfor211subjectsintheteriparatidegroup.§Baselineand≥2postbaselineserumcalciummeasurementswereavailablefor196subjectsineachgroup.KennethG.Saag,JoseR.Zanchetta,Jean-PierreDevogelaer,etal.EffectsofTeriparatideVersusAlendronateforTreatingGlucocorticoid-InducedOsteoporosis:Thirty-Six–MonthResultsofaRandomized,Double-Blind,ControlledTrial[J].ARTHRITIS&RHEUMATISM,2009,60(11):3346–3355.第十頁，共23頁。文獻(xiàn)三Ⅰ:SubjectsandMethods.Patientswereassignedtoactiveoralalendronateorplacebowithin10dofacuteSCI(SpinalCordAssociation).Onceweeklytheytookalendronate70mgormatchedplacebowithwaterwithinaperiodof30minwhilesittinguprightandafterovernightfasting.Nosupplementofdietarycalciumwastaken,butvitaminDwasadministeredtothosewithlowbaselineserumvitaminDlevels(25-hydroxyvitaminD<50nmol/liter).Treatmentwithalendronateandmatchedplacebowascontinuedfor12months,andpatientswerereviewedfinally6monthsaftercessationoftherapy.N.L.Gilchrist,C.M.Frampton,R.H.Acland,etal.AlendronatePreventsBoneLossinPatientswithAcuteSpinalCordInjury:ARandomized,Double-Blind,Placebo-ControlledStudy[J].TheJournalofClinicalEndocrinology&Metabolism,2007,92(4):1385–1390.第十一頁，共23頁。文獻(xiàn)三ⅡChangesinbiochemicalmarkersfrombaselineover18monthsfromalendronateorplacebo.N.L.Gilchrist,C.M.Frampton,R.H.Acland,etal.AlendronatePreventsBoneLossinPatientswithAcuteSpinalCordInjury:ARandomized,Double-Blind,Placebo-ControlledStudy[J].TheJournalofClinicalEndocrinology&Metabolism,2007,92(4):1385–1390.第十二頁，共23頁。文獻(xiàn)三ⅢTwenty-four-hoururinarycalciumexcretionwasinitiallyhighinbothgroups(6.79±0.9inthealendronategroupvs.8.78±0.8mmol/literintheplacebogroup,notsignificant)buthaddecreasedsignificantlyinthealendronategroupat3months(2.66±1.032vs.9.13±0.91mmol/liter;P<0.001)andwasstillsignificantlylessthantheplacebogroupat18months(2.89±0.074vs.3.9±0.65mmol/liter;P<0.001).N.L.Gilchrist,C.M.Frampton,R.H.Acland,etal.AlendronatePreventsBoneLossinPatientswithAcuteSpinalCordInjury:ARandomized,Double-Blind,Placebo-ControlledStudy[J].TheJournalofClinicalEndocrinology&Metabolism,2007,92(4):1385–1390.第十三頁，共23頁。文獻(xiàn)四ⅠSubjectsandMethods(1)C.M.Weaver,B.R.Martin,G.S.Jackson.J,etal.AntiresorptiveEffectsofPhytoestrogenSupplementsComparedwithEstradiolorRisedronateinPostmenopausalWomenUsing41CaMethodology[J].ClinEndocrinol.Metab,2009,94(10):3798-3805.第十四頁，共23頁。文獻(xiàn)四ⅠSubjectsandMethods(2)Theisoflavoneprofileofeachsupplementvariedwiththebotanicalsourceandthedose.Subjectswereaskedtotakeeachinterventionindivideddosesthroughoutthedaywithmealsbuttoconsumeallcapsules/tabletsbymidnight.Theywereadvisednottotakeextrapillsonanydaytocompen-sateforpreviouslymissedpills.Either1mgoralestradiol(Estrace)combinedwith2.5mgmedroxyprogesteronedailyor5mg/dofrisedronatewasusedasthepositivecontrolforcomparison.Participantswereinstructedtotakerisedronateonrisingatleast30minbeforeconsumingfoodorbeve-ragesandtotakeestrogenbeforebreakfast.C.M.Weaver,B.R.Martin,G.S.Jackson.J,etal.AntiresorptiveEffectsofPhytoestrogenSupplementsComparedwithEstradiolorRisedronateinPostmenopausalWomenUsing41CaMethodology[J].ClinEndocrinol.Metab,2009,94(10):3798-3805.第十五頁，共23頁。文獻(xiàn)四ⅠSubjectsandMethods(3)Althoughsubjectswerenottoldwhichinterventiontheywereon,theinterventionregimenvariedandtabletsandcapsulesvariedinnumberperdayandappearance.Subjectswereprovided500mg/dcalciumand500IU/dvitaminD3throughoutthestudybeginningatbaselinetominimizefluctuationsincalciumintakeandvitaminDstatus.Thesubjectscompleteda3-dfoodrecordbeforeandduringeachinterventionperiodtoassesstheirusualdietarypattern.C.M.Weaver,B.R.Martin,G.S.Jackson.J,etal.AntiresorptiveEffectsofPhytoestrogenSupplementsComparedwithEstradiolorRisedronateinPostmenopausalWomenUsing41CaMethodology[J].ClinEndocrinol.Metab,2009,94(10):3798-3805.第十六頁，共23頁。文獻(xiàn)四ⅠSubjectsandMethods(4)CalciumabsorptionAttheendofbaselineandeachinterventionperiod,acalciumabsorptiontestwith15.2mg44CaasCaCO3andtheassignedsupplementaspartofatestmealcontaining250mgCawasperformedaspreviouslydescribed.44Caenrichmentwasdeterminedinthe5-hbloodsamplebyInductivelyCoupledPlasmaandMassSpectrometryaspreviouslydescribed.Fractionalcalciumabsorptionwasdeterminedas:(5-hSSA0.92373)×[0.3537×(height[meters]0.52847)×(weight[kilograms]0.37213)]whereSSA=serum-specificactivity(fractiondosepergramCa).C.M.Weaver,B.R.Martin,G.S.Jackson.J,etal.AntiresorptiveEffectsofPhytoestrogenSupplementsComparedwithEstradiolorRisedronateinPostmenopausalWomenUsing41CaMethodology[J].ClinEndocrinol.Metab,2009,94(10):3798-3805.第十七頁，共23頁。文獻(xiàn)四ⅡFIG.2.Suppressionofboneresorption(RR)bycommercialisoflavonesupplementsandtraditionalpharmaceu-ticaltherapies,estra-diolorrisedronate.ThelineatRR=1.0isthepreinterventioncompar-ison.Theerrorbarsindicate95%confidenceintervalaboutthemean.C.M.Weaver,B.R.Martin,G.S.Jackson.J,etal.AntiresorptiveEffectsofPhytoestrogenSupplementsComparedwithEstradiolorRisedronateinPostmenopausalWomenUsing41CaMethodology[J].ClinEndocrinol.Metab,2009,94(10):3798-3805.第十八頁，共23頁。文獻(xiàn)四ⅢIntervention,mean±SD(minimum,maximum)VariableBaselineEstradiol/risedronateSoycotyledonUrinarycalcium,mmol/24h7.4±3.1(2.9,14.3)8.1±7.1(2.1,25.4)9.1±7.9(2.0,26.3)Urinaryphosphorous,mmol/24h40.2±12.9(23.0,68.9)43.0±28.1(15.8,114.2)55.3±27.1(30.0,101.7)SerumPTH,pg/ml40.0±23.7(15.8,95.8)45.6±17.5(28.5,78.5)41.5±26.7(10.7,104.2)Serum25(OH)D,ng/ml22.9±6.5(8.9,31.9)24.4±4.9(18.5,33.8)26.7±4.4(20,32.7)TABLE1.Biomarkersofboneturnoverandcalciumregulatinghormonesatbaselineandattheendofeachinterventionn.s.:notsignificant.Intervention,mean±SD(minimum,maximum)Variable

SoygermRedcloverKudzuPvalue

Urinarycalcium,mmol/24h

8.9±5.9(1.3,22.6)8.6±4.6(2.1,14.7)9.7±8.0(3.5,28.7)n.s.Urinaryphosphorous,mmol/24h43.4±19.5(22.0,71.1)41.8±15.8(22.7,74.6)48.5±27.2(14.9,99.2)n.s.SerumPTH,pg/ml40.5±20.6(14.9,82.4)43.9±28.3(11.5,114.6)35.3±26.2(11.2,102.4)n.s.

Serum25(OH)D,ng/ml24.2±5.1(17.6,33.0)24.3±5.0(17.3,35.2)25.9±6.0(19.3,37.3)n.s.C.M.Weaver,B.R.Martin,G.S.Jackson.J,etal.AntiresorptiveEffectsofPhytoestrogenSupplementsComparedwithEstradiolorRisedronateinPostmenopausalWomenUsing41CaMethodology[J].ClinEndocrinol.Metab,2009,94(10):3798-3805.第十九頁，共23頁。文獻(xiàn)四ⅣTABLE2.EstimatedRRduetointerventionsaInterventionRR95%ConfidenceintervalPvalueEstrogen0.7560.70–0.82<0.0001Risedronate0.7830.73–0.84<0.0001Soycotyledon0.9100.87–0.960.0002Soygerm0.9450.90–0.990.0312Redclover0.9580.91–1.100.0928Kudzu0.9750.93–1.020.3100an=11exceptsubjectseitheroptedforestrogen(n=4)orrisedronate(n=6)asapositivecontrol.C.M.Weaver,B.R.Martin,G.S.Jackson.J,etal.AntiresorptiveEffectsofPhytoestrogenSupplementsComparedwithEstradiolorRisedronateinPostmenopausalWomenUsing41CaMethodology[J].ClinEndocrinol.Metab,2009,94(10):3798-3805.第二十頁，共23頁。文獻(xiàn)五ⅠMATERIALSANDMETHODS(1)Sixteenpatientsparticipatedinthisprospectiverandomizedcontrolledst