08鲑鱼降钙素治疗骨质疏松骨折专家共识解读-黄公怡教授

鲑鱼降钙素（密盖息?）治疗骨质疏松骨折专家共识解读骨质疏松骨折的临床特点骨质疏松性骨折属脆性骨折，为完全性骨折，是骨质疏松最严重的后果。由同时，应积极治疗骨质疏松(1)骨折后急性骨丢失的发生机制及危害目前多数学者比较一致地认为，运动及肢体生理负荷减少是急性制动后骨丢失的始动因素。制动或卧床使患者的肢体和躯干骨处于非承重状态，同时四肢及躯干运动量明显减少，肌肉收缩频率及幅度减少。肢体骨骼的负荷下降首先影响骨的重建系统，进而影响钙的内环境调节系统，乃至自律神经系统，最终再次影响骨的重建过程，力学与生物学双重影响导致了废用性骨质疏松的发生与发展(2)。骨质疏松骨折手术内固定最主要的并发症是植入物与假体的松动和脱落。而且这种情况可以发生在手术过程中或之后的康复过程中。严重者导致手术失败需再次手术。总之，急性骨丢失继发废用性骨质疏松，是导致下列并发症发生率进一步增高的主要原因之一：骨质量降低导致骨折愈合延迟；植入物周围骨溶解加剧导致植入物松动；延长卧床期，并发症发生率、死亡率增高；术中医源性骨折；术后骨折再发生率增高。鲑鱼降钙素治疗骨质疏松骨折中的应用鲑鱼降钙素能够逆转骨折制动后的急性骨丢失证据一：制动后急性骨丢失具有大量、快速和持续等特点。据资料统计，患1%，该数值相当于正常情况下一个人一年的“生理性骨丢失量”。6~125~10%，5PetersenX36和健侧腿等部位的骨密度和骨矿含量。结果显示，39.6%（CR：-10.2%~-3.5%)，614322%，619%。这一研究结果充分证明了骨折后急性骨丢失的存在。证据二：TsakalakosN(4)401其中治疗组患者从入院后立即进行围手术期治疗，即开始接受每日鲑鱼降钙素100IU21,200mg1,200mg证据三：T.karachalios5070~80A200IU3B1545低。证据四：是反映骨吸收的重要生化指标。LyritisHOP/Cr4对抗制动后骨吸收。鲑鱼降钙素有效控制骨折后疼痛，提高康复水平鲑鱼降钙素作用于中枢及外周神经系统，有效地缓解骨折造成的急性疼痛。临床研究显示(5)：1~2VAS解患者的骨痛。3引起的废用性骨丢失，降低再发骨折的风险。鲑鱼降钙素改善骨密度和骨质量T.karachalios(2)33.14%，4.52%；122.04%，10.71%3BMD（p<0.03p<0.002）3BMD2.52%，123.63%BMD7.4%9.2%312p<0.05。鲑鱼降钙素可以降低骨折发生率与再骨折发生率PROOF(6)4251,255681~5100、2004001,000mgD400IU20329.6%，而在鲑鱼降钙素治疗组患者中，发生椎体骨折的百分比仅为19.3%。研究数据显示，对于1~536%。之后，PROOF707570238200IU19.4%33.7%的患者发生骨折，两组间具有显著统计学差异，P=0.012，200IU53%75105200IU40.4%，两组间同样具有显著性统计学差异，P=0.028，75，200IU62%。实验研究显示：鲑鱼降钙素可能有益于骨折愈合鲑鱼降钙素不仅能够抑制破骨细胞的活性，田庆显(7)等的动物试验证明，它还能够促进成骨细胞的增殖。李晓林等(8)的研究表明鲑鱼降钙素能够促进矿7证明鲑鱼降钙素可能有益于骨折的愈合。鲑鱼降钙素用于骨质疏松骨折治疗的推荐方案鲑鱼降钙素用于骨折急性期治疗的国外用药经验研究组织者病例数用药剂量给药方法用药时间N.tsakalakos(4)69人100IU/QD肌注14天Lyritis(5)100人200IU/QD鼻喷28天Lyritis(9)40人200IU/QD鼻喷28天鲑鱼降钙素用于骨折愈合期治疗的国外用药经验研究组织者研究组织者病例数用药剂量给药方法用药时间Huusko(9)229200IU/QD鼻喷3T.karachalios(2)50200IU/QD鼻喷3根据国内患者的实际情况，我们推荐的用法为：急性期：骨折后，50~100IU/d2~4骨折愈合期：鼻喷剂给药，200IU/QdQod,疗程３个月注：骨质疏松并发骨折往往提示骨质量下降的程度已经很严重，因此建议在骨折急性期治疗成功后，要积极的针对原发病制定长期规范的后续治疗方案，降低患者再次发生骨折的风险。总结质疏松骨折患者在急性期制动状态和手术后引起的进行性骨丢失统，有效的缓解骨折造成的急性疼痛。鲑鱼降钙素可以改善骨密度和骨质量鲑鱼降钙素可以降低骨折发生率与再骨折发生率鲑鱼降钙素可能有益骨折愈合参考文献中华医学会骨质疏松骨折诊疗指南2005.9T.karachaliosetal.Theeffectsofcalcitoninonacutebonelossafterpertrochantericfractures:APROSPECTIVE,RANDOMISEDTRIAL.BoneJointSurg(Br),2004;86-B:350-8Weinvestigatedtheeffectofcalcitonininthepreventionofacutebonelossafterapertrochantericfractureanditsabilitytoreducetheincidenceoffurtherfracturesinthesamepatient.Fiftywomenagedbetween70and80yearswhohadapertrochantericfractureofthehipwererandomlyallocatedtogroupA(200IUofnasalsalmoncalcitonindailyforthreemonths)orgroupB(placebo).PatientsingroupAshowedasignificantlyhigherleveloftotalalkalinephosphataseandosteocalcinonthe15thdayafterinjuryandasignificantlyhigherlevelofbonealkalinephosphataseonthe90thdayaftersurgery.ThesepatientsalsohadsignificantlylowerlevelsofurinaryC-telopeptide(CrossLaps)onthe15th,45thand90thdaysafterinjuryandlowerlevelsofurinaryhydroxyprolineonthe15thand45thdaysafterinjury.PatientsingroupAhadsignificantlyhigherbonemineraldensityatallrecordedsitesexceptthegreatertrochanteratthreemonthsandoneyearafteroperation.Afterafour-yearperiodofclinicalobservation,fivepatients(24%)ingroupBsustainedanewfracture,infourofwhom(20%)itwasofthecontralateralhip.Ourfindingsshowthatcalcitoninreducesacutebonelossinpatientswithpertrochantericfracturesandmaypreventtheoccurrenceofnewfracturesofthecontralateralhipintheelderly.PeichlP,GriesmacherA,etal. Clinicaloutcomeofsalmoncalcitoninnasalspraytreatmentinpostmenopausalwomenaftertotalarthroplasty.Gerontology.2005Jul-Aug;51(4):242-52.OBJECTIVE:Theincreasingrateofhipfracturesisgivingrisetoanumberofsocio-economicproblemsfortheagingcommunity.Inadditiontobeingunabletoresumetheirpreviouslivinghabits,manypatientsfailtoachievefullfunctionalrecoveryafterthefractures.Totalhiparthroplasty(THA)isasuccessfuloperationforthemajorityofpatientswithallformsofhipfractures,beingperformedincreasinglyoftenthroughouttheworld.RevisionratesforTHArangeupto20%peryear.Asepticlooseningisthereasonfor75%oftherevisions.Anadditionalproblempost-THAistherateofheterotopicsofttissuecalcificationafterTHA,resultinginseverelyimpairedfunction,pain,andareducedrangeofhipmovement.SUBJECTS:Inanopenstudy,37womenwhohadundergonecementlessTHAafteraccidentalhipfracturesweretreatedtwicedailywith200IUofsalmoncalcitoninnasalsprayfor12months.Simultaneouslythepatientsreceivedonebagof1,000mgcalciumplus880IUvitaminDdailythroughoutthetreatmentperiodofyear.Aparallelgroupof38womenwithasimilarclinicalstatusintermsofhipfracturesandcementlessTHAweretreatedwithonlyoneof1,000mgcalciumplus880IUvitaminDdailythroughthetreatmentperiod.RESULTS:Theresultsofthis12-monthclinicaltrialshowthat200IUofsalmoncalcitoninnasalsprayperdaysignificantlyimprovestheclinicaloutcomeofpostmenopausalelderlywomenfollowingTHA.Treatmentwithasalmoncalcitoninnasalspraysignificantlyreducesboneturnover,lossofbonedensity,andpain.Thefunctionalstatusofthepatientswasimprovedandtheriskoffallingreducedbyrehabilitationduringtheobservationperiodof12months.calcitoninpromotedtherepairofhipfracturesandwasassociatedwithasignificantlylesserrateofrefracturesaswellasperiprostheticossifications.CONCLUSION:TheincreasingrevisionrateforTHAduringthefirstyearandthepatient'sproblemofresumingtheirpreviouslivinghabitsarethemainfociofourstudy.Calcitoninnasalsprayseemstocausefewsideeffects.TheadditivetreatmentappearstoimprovetheclinicaloutcomeofTHAinelderlypostmenopausalwomen.TsakalakosN,MagiasisB,TsekouraM,LyritisG.Theeffectshort-termcalcitoninadministrationonbiochemicalbonemarkersinpatientswithacuteimmobilizationfollowinghipfracture.OsteoporosInt.1993Dec;3(6):337-40.Theeffectofsalmoncalcitoninonchangesinmineralmetabolismwasstudiedin40elderlypatientswithrecenthipfracture.Allpatientsunderwentsurgery(internalfixation)1weekafteradmissionandwererandomlydividedintotwoequalgroups:groupA,whichnotreatment,andgroupB,whichreceived100IU/daysalmoncalcitoninintramuscularlyfor2weeksstartingonadmission.Bloodand24-hurineparametersofmineralmetabolismweremeasuredonadmissionandattheendofweeks1and2.Nointra-orintergroupchangesinserumcalcium,phosphorusoralkalinephosphatasewereobserved.Attheendofweek2biochemicalmarkersofboneresorption(urinarycalciumandhydroxyproline)hadsignificantlyincreasedingroupAanddecreasedingroupB,indicatingareductioninboneresorptioninB.UrinaryphosphorushadalsoincreasedingroupB,possiblyduetophosphaturiceffectofcalcitonin.Itisconcludedthatimmobilizationresultingfromahipfracture,andpossiblysurgeryitself,causessignificantchangesinbiochemicalmarkersofboneresorption.Calcitoninsuccessfullyreversesthesechangesandmayalsobeeffectiveinpreventingsubsequentboneloss,particularlyinpatientswhocannotberemobilizedimmediately.LyritisGP,PaspatiI,etal.Painrelieffromnasalsalmoncalcitonininosteoporoticvertebralcrushfractures.Adoubleplacebo-controlledclinicalstudy.ActaOrthopScandSuppl.1997275:112-4.Weexaminedtheanalgesiceffectofnasalsalmoncalcitonininpatientswithacutepainduetorecent,nontraumaticosteoporoticvertebralcrushfractures.32menand68postmenopausalwomenwerestudiedusingaprospective,double-blind,placebo-controlledclinicaldesign.Menandwomentaking200IUofnasalsalmoncalcitonindailyaperiodof28dayshadadramaticdecreaseofspinalpain.Thisanalgesiceffectwasaccompaniedbyearlymobilizationandgradualrestorationofthelocomotorfunctions,suchassitting,standingandwalking.Patientsreceivingtheplacebonasalsprayremainedinbedforalmosttheentireperiodofobservation.Theconsumptionofhighdosesofparacetamoldidnothelpplacebopatientstogetoutofbedduringthe4weeksofhospitalization.Nasalsalmoncalcitoninandearlymobilizationalsoreducedhydroxyprolineexcretion,thuspreventingmassivebonelossduringtheperiodofbedrest.ChesnutCH3rd,SilvermanS,AndrianoK,etal.Arandomizedtrialofnasalspraysalmoncalcitonininpostmenopausalwomenwithestablishedosteoporosis:thepreventrecurrenceofosteoporoticfracturesstudy.AmJMed,2000,109:267-276.PURPOSE:Weconducteda5-year,double-blind,randomized,placebo-controlledstudytodeterminewhethersalmoncalcitoninnasalsprayreducedtheriskofnewvertebralfracturesinpostmenopausalwomenwithosteoporosis.SUBJECTSANDMETHODS:Atotalof1,255postmenopausalwomenwithestablishedosteoporosiswererandomlyassignedtoreceivesalmoncalcitoninnasalspray(100,200,or400IU)orplacebodaily.Allparticipantsreceivedelementalcalcium(1,000mg)andvitaminD(400IU)daily.Vertebralfractureswereassessedwithlateralradiographsofspine.Theprimaryefficacyendpointwastheriskofnewvertebralfracturesinthesalmoncalcitoninnasalspray200-IUgroupcomparedwiththeplacebogroup.RESULTS:During5years,1,108participantshadatleaston