Iacopo Pecchi: Gestire i multi magazzini nelle strategie di vendita multi e omnichannel
Valen&na Morelli, Cris&na Eller-Vainicher, Iacopo Chiodini, · 2017. 9. 6. · Crisna Eller-...
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PROPOSAL: Study on the effect of the shi6 from classic glucocor<coid (GC) replacement therapy (CGR-T) to dual-release hydrocor<sone replacement therapy (DRHC-T) on bone turnover, bone mineral density and bone quality in pa<ents with Addison disease Valen&na Morelli, Cris&na Eller-Vainicher, Iacopo Chiodini, Unit of Endocrinology, Fondazione IRCCS Cà Granda, Milan Dpt. of Medical Sciences and Community Health, University of Milan, Milan
Transcript of Valen&na Morelli, Cris&na Eller-Vainicher, Iacopo Chiodini, · 2017. 9. 6. · Crisna Eller-...
PROPOSAL:Studyontheeffectoftheshi6fromclassicglucocor<coid(GC)replacementtherapy(CGR-T)todual-releasehydrocor<sonereplacementtherapy(DRHC-T)onbone
turnover,bonemineraldensityandbonequalityinpa<entswithAddisondisease
Valen&naMorelli,Cris&naEller-Vainicher,IacopoChiodini,
UnitofEndocrinology,FondazioneIRCCSCàGranda,MilanDpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan
AnnInternMed.1994;120:207-210
JClinEndocrinolMetab.2012;97:85-92
EurJEndocrinol.2014;170;141–150
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
THEEFFECTSOFCLASSICGCREPLACEMENTTHERAPYONBONE
Dual-releasehydrocor&sonereplacementtherapyandbone
DESIGN• Prospec<verandomizedstudy• InclusionCriteria:eugonadalpa<ents,age20-50years,withAddisonDisease,
BMI19-30kg/m2,treatedwithcor<soneacetateorhydrocor<sonewithgoodclinicalandmetaboliccontrol.
• ExclusionCriteria:hyperthyroidism,notcontrolledhypothyroidism,hypoparathyroidism,hypercalciuria,type1diabetes,rheuma<cdiseases,chronicinflammatoryboweldiseases,coeliacdisease,renaland/orliverdiseases,drugsinfluencingbone,historyofseverehypovitaminosisD
• Samplesize:Priordata(BehanLAetal,EJE2014)suggestthatthedifferenceintheresponseofmatchedpairsisabout30%(30%SD).Wewillneedtostudy13pairsofsubjectstobeabletorejectthenullhypothesisthatthisresponsedifferenceiszerowithprobability(power)0.9andTypeIerror0.05.
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
AIM• Effectoftheshi6fromCGR-TtoDRHC-Tinpa<entswithAddison
diseaseonboneturnover,bonemineraldensity,bonequalityandincidentvertebralfractures
Dual-releasehydrocor&sonereplacementtherapyandbone
Subjects• 60consecu&vepa&entswillberandomizedto- Con&nuecor&soneacetatetherapy(GroupA,n=15)- Con&nuehydrocor&sonetherapy(GroupB,n=15)- ShiRfromcor&soneacetatetoDRHC-T(GroupC,n=15)- ShiRfromhydrocor&sonetoDRHC-T(GroupD,n=15)- 30age-BMI-gendermatchedcontrols• Atenrolmenttwooralbolusofcholecalciferol100.000U(every15day)willbegiventoall
subjects,andpa&entswithanes&matecalciumintakebelow500mg/daywillbesupplementedwithcalciumcarbonate500mg/day
• Thestudybegins15daysaRerthesecondcholecalciferolsupplementa&on
MethodsBaselineandat6,12and18months• Electrolytes,aldosterone,renin,bonealkalinephosphatase(bALP),albumin-adjusted
calcium(aCa),phosphate(P),parathyroidhormone(PTH),25hydroxyvitaminD(25OHD),N-terminalpropep&deoftype1collagen(PINP),osteocalcin(OC),C-terminaltelopep&deoftype1collagen(CTX),β-catenin,scleros&n(SS),dickkopf-relatedprotein1(Dkk1)
• 24hurinarycalciumexcre&on,crea&nineclearance,3hmorningfas&ngurinaryphosphate,calciumandcrea&nine
Baselineanda6er18months• BMDspineandfemur,TBS,spinalX-rayA6er1and3monthssincebaseline• OC,CTX,PINP,β-catenin,SS,Dkk1
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
Dual-releasehydrocor&sonereplacementtherapyandbone
ExpectedResults:Pa<entsshi6ingfromCGR-TtoDRHC-Tcouldhave- Increaseinboneturnovermarkers(OCandbALP>CTX)- Increaseinβ-cateninlevelsanddecreaseinSSandDkk-1levels- IncreaseornodecreaseofTBSand,possibly,ofBMDlevels
- NoincreaseofincidentvertebralfracturesStateoftheartandtransferability:• PreviousdatasuggestthatlowdoseCGR-TisnotassociatedwithaBMDdecrease.However,the
GC-relatedfractureriskislargelyindependentofBMD.Reducedbonequality(indirectlymeasuredbyTBS)mayaccountforthisBMD-independentincreasefracturerisk.
• PreviousdataalsosuggestthatlowdoseGCR-Timprovesboneremodelling.However,lowdoseCGR-Tiso6enhardlyobtainableinthemajorityofpa<ents.
• ThestudycoulddemonstratethatDRHC-Timprovesboneturnoverandbonequalityandthatitmayhaveaposi<veeffectonbonebyac<va<ngtheosteoblastsignaling.
• Therefore,ifthishypothesiswillbeconfirmed,thefractureriskprofileshouldbeincludedamongthecriteriaforaddressingtheGCtherapyofchoiceinpa<entswithAddisondisease.
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
Dual-releasehydrocor&sonereplacementtherapyandbone
PROPOSAL:Studyontheeffectoftheshi6fromclassicglucocor<coid(GC)replacementtherapy(CGR-T)todual-releasehydrocor<sonereplacementtherapy(DRHC-T)onbone
turnover,bonemineraldensityandbonequalityinpa<entswithAddisondisease
Forpar<cipa<ngcontact:Valen<naMorelli:[email protected];Cris<naEller-Vainicher:[email protected];IacopoChiodini:[email protected];
UnitofEndocrinology,FondazioneIRCCSCàGranda,MilanDpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
Dual-releasehydrocor&sonereplacementtherapyandbone
BoneMineralDensityIsNotSignificantlyReducedinAdultPa<entsonLow-DoseGlucocor<coidReplacementTherapy
K.R.Koetzetal,JClinEndocrinolMetab2012
Adultpa<entswithprimaryadrenalinsufficiencyandcongenitaladrenalhyperplasiaonlowglucocor<coiddosesshowednormalBMDwithinthenormalreferencerange.
Theuseoflongerac<ngprednisoloneresultedinsignificantlylowerBMDinpa<entswithprimaryadrenalinsufficiency.
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
EurJEndocrinol.2014;170;141–150
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
AnnInternMed.1994;120:207-210
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
AIM:Effectoftheshi6fromCGR-TtoDRHC-Tinpa<entswithAddisondiseaseon- boneturnover- bonemineraldensity- bonequality
Methods
Anamnesipersonaleefamiliareeques&onarisucaduteeconsumodicalcio.Baselineedopo6,12e18mesi:• emocromo,uricemia,transaminasi,elebroli&,colesterolototale,trigliceridi,colesterolo-HDL,colesterolo-LDL,• glicemiabasaleadigiuno,emoglobinaglicata,insulina,C-pep&de,• fosfatasialcalinaeisoenzimaosseodellaALP(bALP),calciocorreboperalbumina,fosforo,paratormone,25OHvitaminaD,propep&deN-terminaledelcollagenedi&poI,osteocalcina(OC),telopep&deC-terminaledelcollagenedi&poI(CTX),WNT,β-catenina,scleros&na,dickkopf-relatedprotein1(Dkk1),glucagon-likepep&de1(GLP1),glucagon-likepep&de2(GLP2),glucose-dependentinsulinotropicpolypep&de(GIP)• esamedelleurine,microalbuminuria,calciuria24ore,clearancecrea&nina,calcio,• fosforo(P)ecrea&nina(Cr)nellasecondaminzionedelmadnoBaselineando18mesi• proteinetotali,elebroforesisiero-proteica• BMDspineandfemur,TBSDopo15,45,180,365,giornidall’arruolamentoOC,CTX,WNT,β-catenina,scleros&na,Dkk1,GLP1,GLP2eGIPBaselinee24mesiRxlateraledorso-lombare(T4-L4)permorfometriavertebrale.
ChiodiniI.UnitofEndocrinologyandMetabolicDiseases,FondazioneIRCCSCàGranda–Dpt.ofMedicalSciencesandCommunityHealth,UniversityofMilan,Milan,Italy
