降钙的药物治疗课件

参考文献14523秦华东,石臣磊,石铁锋,等.急性高血钙危象6例临床分析[J].医学临床研究,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.Double-Blind,PlaceboControlledStudy[J].TheJournalofClinicalEndocrino-logy&Metabolism,2007,92(4):1385–1390.[J].ClinEndocrinol.Metab,2009,94(10):3798-3805.[J].ScandinavianJournalofSurgery,2010,99:32–37.降钙的药物治疗Ⅰ1.补钠利尿：补充0.9%氯化钠注射液既扩充了细胞外液又竞争性抑制了肾近曲小管对钙的重吸收,多数情况下第1个24h输注0.9%氯化钠注射液3～4L,使每日尿量达到3～4L。待血容量恢复正常后,静脉给予利尿剂,以袢利尿剂为主,因其可进一步阻断肾小管髓袢升支粗段对钠和钙的重吸收,促进尿钙排泄,常用呋塞米40～80mg静脉注射,必要时重复用药;而噻嗪类利尿剂应避免使用,因其可减少肾脏钙的排泄。秦华东,石臣磊,石铁锋,等.急性高血钙危象6例临床分析[J].医学临床研究,2008,25(10):1861-1863.降钙的药物治疗Ⅱ2.应用骨溶解抑制剂：降钙素抑制破骨细胞对骨的吸收和肾小管对钙的重吸收,有利于钠和钙的排泄,作用迅速。降钙素100～400U,每6h静脉或皮下注射1次,常用2～3次,但常于几小时或几天内出现“脱逸”现象而失效。经降钙素治疗的患者,约80%血钙可降低,但难以恢复正常水平。二膦酸盐类药物的作用可能是对破骨细胞的直接毒性作用,尤其适用于高血钙伴低血磷的患者,低磷可使骨吸收和肾脏合成活性维生素D3增强,骨形成减少,高钙血症加重。秦华东,石臣磊,石铁锋,等.急性高血钙危象6例临床分析[J].医学临床研究,2008,25(10):1861-1863.降钙的药物治疗Ⅲ二膦酸盐类药物依据时间先后和结构特点分为3代,包括:第1代的依替膦酸盐和氯甲双膦酸盐第2代的帕米膦酸盐、阿仑膦酸盐和利塞膦酸盐)以及第3代的伊苯膦酸盐、替鲁膦酸盐和唑来膦酸盐。第2代和第3代属于含氮原子的二膦酸盐类药物,其抗骨重吸收能力是第1代的100～10000倍。3.其他：如光辉霉素和甲状旁腺激素衍生物特立帕肽等。4.糖皮质激素：病情允许时可口服,紧急情况下可用氢化可的松或地塞米松静滴、静注。其虽有一定的降钙疗效,但起效慢,维持时间短。秦华东,石臣磊,石铁锋,等.急性高血钙危象6例临床分析[J].医学临床研究,2008,25(10):1861-1863.Calcium-onlygroup(n=9)Alendronate-treatedgroup(n=7)9750.SerumPTH,pg/ml40.§Baselineand≥2postbaselineserumcalciummeasurementswereavailablefor196subjectsineachgroup.a)Friedman’stest.predoseserumcalcium*文献四ⅠSubjectsandMethods(4)Suppressionofboneresorption(RR)bycommercialisoflavonesupplementsandtraditionalpharmaceu-ticaltherapies,estra-diolorrisedronate.Thepatientswererandomizedintotwostudygroupsfora5-yearfollow-upperiod.34)1.9inthealendronategroupvs.35)1.GruenZonePostoperative6-m5-ypvaluea)Postoperative6-m5-ypvaluea)91mmol/liter;P<0.Calcium-onlygroup(n=9)Alendronate-treatedgroup(n=7)0isthepreinterventioncompar-ison.82<0.8mmol/literintheplacebogroup,notsignificant)buthaddecreasedsignificantlyinthealendronategroupat3months(2.Serum25(OH)D,ng/ml22.文献三Ⅰ:SubjectsandMethods.文献二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.文献二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.文献三Ⅰ:SubjectsandMethods.Patientswereassignedtoactiveoralalendronateorplacebowithin10dofacuteSCI(SpinalCordAssociation).Onceweeklytheytookalendronate70mgormatchedplacebowithwaterwithinaperiodof30minwhilesittinguprightandafterovernightfasting.Nosupplementofdietarycalciumwastaken,butvitaminDwasadministeredtothosewithlowbaselineserumvitaminDlevels(25-hydroxyvitaminD<50nmol/liter).Treatmentwithalendronateandmatchedplacebowascontinuedfor12months,andpatientswerereviewedfinally6monthsaftercessationoftherapy.文献三ⅡChangesinbiochemicalmarkersfrombaselineover18monthsfromalendronateorplacebo.文献三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).文献四ⅠSubjectsandMethods(1)文献四ⅠSubjectsandMethods(2)Theisoflavoneprofileofeachsupplementvariedwiththebotanicalsourceandthedose.Subjectswereaskedtotakeeachinterventionindivideddosesthroughoutthedaywithmealsbuttoconsumeallcapsules/tabletsbymidnight.Theywereadvisednottotakeextrapillsonanydaytocompen-sateforpreviouslymissedpills.Either1mgoralestradiol(Estrace)combinedwith2.5mgmedroxyprogesteronedailyor5mg/dofrisedronatewasusedasthepositivecontrolforcomparison.Participantswereinstructedtotakerisedronateonrisingatleast30minbeforeconsumingfoodorbeve-ragesandtotakeestrogenbeforebreakfast.文献四ⅠSubjectsandMethods(3)Althoughsubjectswerenottoldwhichinterventiontheywereon,theinterventionregimenvariedandtabletsandcapsulesvariedinnumberperdayandappearance.Subjectswereprovided500mg/dcalciumand500IU/dvitaminD3throughoutthestudybeginningatbaselinetominimizefluctuationsincalciumintakeandvitaminDstatus.Thesubjectscompleteda3-dfoodrecordbeforeandduringeachinterventionperiodtoassesstheirusualdietarypattern.文献四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).文献四ⅡFIG.2.Suppressionofboneresorption(RR)bycommercialisoflavonesupplementsandtraditionalpharmaceu-ticaltherapies,estra-diolorrisedronate.ThelineatRR=1.0isthepreinterventioncompar-ison.Theerrorbarsindicate95%confidenceintervalaboutthemean.文献四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.文献四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.文献五ⅠMATERIALSANDMETHODS(1)Sixteenpatientsparticipatedinthisprospectiverandomizedcontrolledstudy.Forinclusiontointhisstudy,thepatientsneithersufferedfromanydiseasesaffectingbonemetabolismnorusedanybone-inducingmedicationpreviously.Moreover,thepatientsunderstoodnottouseotherbonegrowth-inducingmedicationduringthestudy.Thepatientsalsohadtobeabletocomplywithastandardpostoperativemobilizationschedule.文献五ⅠMATERIALSANDMETHODS(2)Thepatientswererandomizedintotwostudygroupsfora5-yearfollow-upperiod.Nine(fivemenandfourwomen)receivedonly500mgcalciumcarbonatedaily.Seven(twomenandfivewomen)received10mgalendronatesodium(Fosamax)supplementedby500mgcalciumcarbonatedaily.Alendronatetabletswereadministratedorally30minutesbeforethebreakfast,beginningthefirstdayaftersurgery.Thedurationofthetreatmentwas6months.Serumcalciummeasurements.0isthepreinterventioncompar-ison.≥1serumcalcium‡14(7)44(21)<0.26)1.9750.‡Baselineand≥1postbaselineserumcalciummeasurementswereavailablefor209subjectsinthealendronategroupandfor211subjectsintheteriparatidegroup.如光辉霉素和甲状旁腺激素衍生物特立帕肽等。ScandinavianJournalofSurgery,2010,99:32–37.Subjectswereaskedtotakeeachinterventionindivideddosesthroughoutthedaywithmealsbuttoconsumeallcapsules/tabletsbymidnight.文献四ⅠSubjectsandMethods(2)9450.41)NS1.9inthealendronategroupvs.an=11exceptsubjectseitheroptedforestrogen(n=4)orrisedronate(n=6)asapositivecontrol.Nosupplementofdietarycalciumwastaken,butvitaminDwasadministeredtothosewithlowbaselineserumvitaminDlevels(25-hydroxyvitaminD<50nmol/liter).38)NS1.Studydesignandparticipants.医学临床研究,2008,25(10):1861-1863.文献四ⅠSubjectsandMethods(2)Attheendofbaselineandeachinterventionperiod,acalciumabsorptiontestwith15.待血容量恢复正常后,静脉给予利尿剂,以袢利尿剂为主,因其可进一步阻断肾小管髓袢升支粗段对钠和钙的重吸收,促进尿钙排泄,常用呋塞米40～80mg静脉注射,必要时重复用药;而噻嗪类利尿剂应避免使用,因其可减少肾脏钙的排泄。文献五ⅡThemeanperiprostheticBMD(SD)intheCalcium-onlyandAlendronate-treatedgroupsduringthe5-yearfollow-uptime.Calcium-onlygroup(n=9)Alendronate-treatedgroup(n=7)GruenZonePostoperative6-m5-ypvaluea)Postoperative6-m5-ypvaluea)10.95(0.17)0.85(0.18)0.80(0.26)NS0.93(0.24)0.96(0.19)0.91(0.22)NS21.89(0.20)1.64(0.41)1.64(0.48)0.0451.81(0.25)1.72(0.32)1.72(0.29)NS32.02(0.27)1.94(0.35)1.91(0.49)NS1.86(0.35)1.81(0.36)1.84(0.37)NS41.81(0.26)1.74(0.28)1.71(0.41)NS1.72(0.34)1.67(0.35)1.67(0.40)NS52.00(0.25)1.92(0.27)1.98(0.38)NS1.88(0.26)1.85(0.22)1.88(0.28)NS61.55(0.30)1.43(0.30)1.45(0.38)NS1.56(0.08)1.54(0.21)1.58(0.18)NS71.10(0.15)0.91(0.16)0.79(0.22)0.0001.17(0.26)1.12(0.34)0.98(0.35)0.02totROI1.62(0.17)1.49(0.21)1.47(0.32)0.0041.56(0.23)1.52(0.25)1.50(0.27)NSprROI1.02(0.13)0.88(0.15)0.79(0.23)0.0011.05(0.24)1.04(0.24)0.90(0.25)0.05

a)Friedman’stest.NS=NotSignificant,prROI=theproximalpartofthefemur,totROI=totalfemoralregionsofinterest.参考文献14523秦华东,石臣磊,石铁锋,等.急性高血钙危象6例临床分析[J].医学临床研究,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.Double-Blind,PlaceboControlledStudy[J].TheJournalofClinicalEndocrino-logy&Metabolism,2007,92(4):1385–1390.[J].ClinEndocrinol.Metab,2009,94(10):3798-3805.[J].ScandinavianJournalofSurgery,2010,99:32–37.文献三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).文献四ⅠSubjectsandMethods(1)文献四ⅠSubjectsandMethods(3)Althoughsubjectswerenottoldwhichinterventiontheywereon,theinterventionregimenvariedandtabletsandcapsulesvariedinnumberperdayandappearance.Subjectswereprovided500mg/dcalciumand500IU/dvitaminD3throughoutthestudybeginningatbaselinetominimizefluctuationsincalciumintakeandvitaminDstatus.Thesubjectscompleteda3-dfoodrecordbeforeandduringeachinterventionperiodtoassesstheirusualdietarypattern.文献四ⅡFIG.2.Suppressionofboneresorption(RR)bycommercialisoflavonesupplementsandtraditionalpharmaceu-ticaltherapies,estra-diolorrisedronate.ThelineatRR=1.0isthepreinterventioncompar-ison.Theerrorbarsindicate95%confidenceintervalaboutthemean.Patientswereassignedtoactiveoralalendronateorplacebowithin10dofacuteSCI(SpinalCordAssociation).ThemeanperiprostheticBMD(SD)intheCalcium-onlyandAlendronate-treated‡Baselineand≥1postbaselineserumcalciummeasurementswereavailablefor209subjectsinthealendronategroupandfor211subjectsintheteriparatidegroup.38)NS1.ThemeanperiprostheticBMD(SD)intheCalcium-onlyandAlendronate-treated医学临床研究,2008,25(10):1861-1863.38)NS1.ARTHRITIS&RHEUMATISM,2009,60(11):3346–3355.Alendronatetabletswereadministratedorally30minutesbeforethebreakfast,beginningthefirstdayaftersurgery.9inthealendronategroupvs.TheJournalofClinicalEndocrino-logy&Metabolism,2007,92(4):1385–1390.41)NS1.groupsduringthe5-yearfollow-uptime.Saag,JoseR.Alendronatetabletswereadministratedorally30minutesbeforethebreakfast,beginningthefirstdayaftersurgery.Calcium-onlygroup(n=9)Alendronate-treatedgroup(n=7)二膦酸盐类药物的作用可能是对破骨细胞的直接毒性作用,尤其适用于高血钙伴低血磷的患者,低磷可使骨吸收和肾脏合成活性维生素D3增强,骨形成减少,高钙血症加重。100.62mmoles/liter]wasdeterminedfromserumcollected>16hoursafteradministrationofstudydrugs.Zanchetta,Jean-PierreDevogelaer,etal.Studydesignandparticipants.Redclover0.Suppressionofboneresorption(RR)bycommercialisoflavonesupplementsandtraditionalpharmaceu-ticaltherapies,estra-diolorrisedronate.100.降钙素抑制破骨细胞对骨的吸收和肾小管对钙的重吸收,有利于钠和钙的排泄,作用迅速。Fractionalcalciumabsorptionwasdeterminedas:(5-hSSA0.ClinEndocrinol.Urinarycalcium,mmol/24h8.Zanchetta,Jean-PierreDevogelaer,etal.49)NS1.Soycotyledon0.急性高血钙危象6例临床分析[J].990.91mmol/liter;P<0.EffectsofTeriparatideVersusAlendronateforTreatingGlucocorticoid-InducedOsteoporosis:Thirty-Six–MonthResultsofaRandomized,Double-Blind,ControlledTrial[J].25)1.待血容量恢复正常后,静脉给予利尿剂,以袢利尿剂为主,因其可进一步阻断肾小管髓袢升支粗段对钠和钙的重吸收,促进尿钙排泄,常用呋塞米40～80mg静脉注射,必要时重复用药;而噻嗪类利尿剂应避免使用,因其可减少肾脏钙的排泄。91mmol/liter;P<0.≥1serumcalcium‡3(1)9(4)0.an=11exceptsubjectseitheroptedforestrogen(n=4)orrisedronate(n=6)asapositivecontrol.Theerrorbarsindicate95%confidenceintervalaboutthemean.100.001)andwasstillsignificantlylessthantheplacebogroupat18months(2.NS=NotSignificant,prROI=theproximalpartofthefemur,totROI=totalfemoralregionsofinterest.34)1.降钙素抑制破骨细胞对骨的吸收和肾小管对钙的重吸收,有利于钠和钙的排泄,作用迅速。Intervention,mean±SD(minimum,maximum)SerumPTH,pg/ml40.23)1.35)1.≥1serumcalcium‡14(7)44(21)<0.26)1.38)NS1.文献四ⅠSubjectsandMethods(1)Theerrorbarsindicate95%confidenceintervalaboutthemean.Calciumabsorption24)0.急性高血钙危象6例临床分析[J].91mmol/liter;P<0.Serum25(OH)D,ng/ml22.≥1serumcalcium‡3(1)9(4)0.Saag,JoseR.急性高血钙危象6例临床分析[J].待血容量恢复正常后,静脉给予利尿剂,以袢利尿剂为主,因其可进一步阻断肾小管髓袢升支粗段对钠和钙