系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性課件

1、系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性GC induced osteoporosis 北京協(xié)和醫(yī)院風(fēng)濕(fn sh)免疫科 張 烜第一頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性IntroductionnGCs are effective in many rheumatic diseases nBut GC induced OP is a common side effectnTrabecular rich sites eg spine & ribs are especially at risknEffective Rx can prevent or reverse

2、GC bone loss 第二頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性O(shè)P in RA on GC Rxn多因素 RA Osteoclast 活化 ( TNFa，RANK) Physical inactivity GC Rx Menopausen 不同部位(bwi)骨丟失不同 Hand Femur Spine 腰椎骨丟失與GC強(qiáng)相關(guān)第三頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性PathophysiologynMost of the biological activities mediated via Passage across cell membrane a

3、ttachment to cytosolic GC receptor binding to GC response element & regulating gene transcriptionnMay act via other transcription factors: activated protein (AP)-1 NFB第四頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性GC receptor & binding第五頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Effects of GC on bone metabolismn Bone for

4、mation Most important n Bone resorbtion Probably only during 1st 6 12 months of Rx OC production & postponed apoptosis Longterm, bone turnovern Intestinal absorbtion of calciumn Urinary phosphate & calcium loss Direct effect on kidneynSecondary Hyperparathyroidism Bone loss Early but tempora

5、ry 第六頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性 Bone formationnMost important nDirect effects on osteoblasts cell replication osteocyte apoptosis type 1 collagen gene expressionnIndirect effects synthesis, release, receptor binding or binding proteins of growth factors eg IGF I & II related to sex steroid pr

6、oduction第七頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Effects of GC on bone metabolism第八頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性EpidemiologynCommonnFirst recognised by CushingnRisk of OP with GC Rx unclear Reported in up to 50% on longterm RxnFracture riskProspective data lacking Retrospective cohort study 244 236 pts on GC

7、Rx vs 244 235 control pts ( UK GP registry)RR of vertebral # 2.6, hip # 1.6, nonvertebral # 1.3 Estimated vertebral fracture incidence13 22% in first yr of Rxfrom calcium treated control arms of recent randomised control trials Cumulative prevalence of vertebral fractures : Up to 28% (cross sectiona

8、l studies) 第九頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Factors associated with fracture risk with GC RxnAgenBMD Initial & subsequent to GC Rx Postmenopausal women highest risknGlucorticoid dose Cumulative & mean daily dosenDuration of exposurenUnderlying disease第十頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Relative Ris

9、k of Fracture第十一頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Risk factors for bone loss & fracturenRisk varies according to age, dose & underlying diseasenThe case for primary prevention is strongest for postmenopausal women & older men with low BMD第十二頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Bone Density & Frac

10、ture RisknIn postmenopausal women a in 1 SD in BMD is associated with 2 x # risknIn pts on GC Rx risk may be greater at lower BMD第十三頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Dose, duration & formulation of Rx & Bone Lossn dose GC Rx ( 10mg/yr) vertebral bone loss 5- 10 % / yrn dose lower rate of bone los

11、snBone loss most rapid in 1st 6 12 months of RxnGC bone loss appears reversible Rx of CushingsnInhaled steroids less likely to have systemic effects except at high doses第十四頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性InvestigationsnDEXA scannBiochemical markers Bone formation eg osteocalcin Fall within a few hours

12、of Rx Bone resorption Rise after acute administration第十五頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Treatment of GC OPnPrimary prevention Most rapid bone loss within 1st 6 12 months of RxnSecondary prevention第十六頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Prevention of GC-induced bone lossnUse lowest dose GC possiblenMinimise lif

13、estyle risk factors smokingnIndividualised exercise programmesnDrug Rx Calcium Vitamin D & metabolites HRT Bisphosphonates PTH Calcitonin第十七頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Drug RxnBeneficial effects in spine & hip demonstrated in spine & hip by several interventionsnPost hoc/ safety analysi

14、s of trials of etidronate, alendronate & residronate vertebral fractures第十八頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性CalciumnGC intestinal calcium absorbtion & urinary calcium excretionnConflicting data on efficacy in primary preventionnACR : Calcium intake (diet/ suppl) 1000 1500 mg/d第十九頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的

15、骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Vitamin D active - metabolitesnCalcitriol (1,25 dihydroxy vitamin D)nAlfacalcidiol (1 vitamin D)n1o prevention : BMD vs placebon2o prevention : active vit D metabolites better than simple vit D BMD/ fracture/ painRisk : hypercalcaemia & hypercalcuria第二十頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性H

16、RTn1 controlled trial in men BMD with testosterone vs calciumn1 randomised control trial in postmenopausal women BMD with oestrogen vs calciumnNo trials in premenopausal womennNo fracture datanReserved for pts with hormone deficiency第二十一頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Bisphosphonatesn bone resorbtionnM

17、ay GC induced apoptosis of osteoblasts 第二十二頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性AlendronatenCombined analysis of trials (477 pts) vertebral/ femoral neck/ trochanter & whole body BMD Post hoc analysis of vertebral fractures favoured Alendronate in postmenopausal women第二十三頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性第二十

18、四頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性RisedronatenPrimary prevention trial (224 pts) Placebo + calcium vs Risedronate After 1 yr, BMD on Risedronate unchanged but with placebo Incidence of vertebral fractures 17% with calcium vs 5.7% with Risedronate 5mg (p=0.072) Vertebral fractures seen only in postmenopa

19、usal women & men, not premenopausal womennStudy of 290 pts L spine & femoral neck BMD vs Ca + Vit D Not powered to show fracture efficacy Vertebral fractures: 15% controls; 5% Risedronate Suggested 70% fracture risk第二十五頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性PTHn lifespan on osteoclasts & osteoblas

20、tsn osteoblast no.n BMD in postmenopausal women with GC induced OPnStudy not powered to determine effect on fracture rate第二十六頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性CalcitoninnVariable data on effect on BMDn Bone pain induced by fractures第二十七頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Thiazide diuretics & salt restrictio

21、nn urinary calcium excretionnEffect on BMD & fracture risk uncertainnIn general population, chronic thiazide Rx is associated with BMD nIn elderly pts Rx for 2 yrs hip fractures第二十八頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性GIOPGIOP干預(yù)措施干預(yù)措施(cush)(cush)實(shí)施時(shí)機(jī)實(shí)施時(shí)機(jī)分為三個(gè)時(shí)機(jī)：分為三個(gè)時(shí)機(jī)：第一時(shí)機(jī)第一時(shí)機(jī) 無(wú)論無(wú)論BMD多少，一開(kāi)始用糖皮多少，一開(kāi)始用糖皮 質(zhì)

22、激素就實(shí)施干預(yù)質(zhì)激素就實(shí)施干預(yù)第二時(shí)機(jī)第二時(shí)機(jī) 激素治療前發(fā)現(xiàn)激素治療前發(fā)現(xiàn)BMD低時(shí)或治低時(shí)或治 療后出現(xiàn)療后出現(xiàn)BMD降低降低(jingd)時(shí)時(shí)第三時(shí)機(jī)第三時(shí)機(jī) 糖皮質(zhì)激素治療過(guò)程中發(fā)生骨折糖皮質(zhì)激素治療過(guò)程中發(fā)生骨折 后才實(shí)施干預(yù)后才實(shí)施干預(yù) 第二十九頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性GIOP-ACR Guideline(1)Patient begining therapy with GC ( 5 mg/day) of 3 m: 糾正對(duì)OP不良的生活習(xí)慣 停止或少吸煙 減少過(guò)度飲酒負(fù)重體育鍛煉指導(dǎo) 開(kāi)始補(bǔ)鈣 開(kāi)始補(bǔ)充VitD (plain or activated

23、 form). Bisphosphonate處方 (絕經(jīng)期前婦女使用小心).第三十頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性 long-term GC (equivalent of 5 mg/day): 糾正對(duì)OP不良的生活習(xí)慣 停止或少吸煙 減少過(guò)度飲酒負(fù)重體育鍛煉指導(dǎo) 開(kāi)始補(bǔ)鈣 開(kāi)始補(bǔ)充(bchng)VitD (plain or activated form). 如缺乏或有臨床指征-HRT 測(cè)定腰椎和/或髖關(guān)節(jié)BMD. If BMD abnormal (i.e., T-score below -1)BPT (絕經(jīng)期前婦女使用小心). BPT有禁忌或不能耐受calcitoni

24、n If BMD is normal隨診，每年或每?jī)赡陱?fù)查BMD.GIOP-ACR Guideline (2)第三十一頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Guideline英國(guó)英國(guó)(yn u)（Bone and Tooth Society of Great Britain, the National Osteoporosis Society and the Royal College of Physicians）n口服 GC可引起髖關(guān)節(jié)和脊柱骨折危險(xiǎn)增加(zngji)(Level Ia). 盡管大劑量風(fēng)險(xiǎn)最大，但每天小于7.5 mg也會(huì)引起風(fēng)險(xiǎn)增加 (Level III)

25、.n治療開(kāi)始骨折風(fēng)險(xiǎn)迅速增加，停藥后骨折風(fēng)險(xiǎn)迅速下降(Level III). 口服GC頭幾個(gè)月BMD丟失最大(Level IIa). nThe effects of inhaled GCs on BMDare less certain, although some studies report increased bone loss with high doses (Level IIa) and long-term use of lower doses may result in significant deficits of BMD(Level III).第三十二頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼

26、瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性第三十三頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Guideline英國(guó)英國(guó)(yn u)（Bone and Tooth Society of Great Britain, the National Osteoporosis Society and the Royal College of Physicians）nGC對(duì)骨折風(fēng)險(xiǎn)增加的影響較低BMD更顯著(Level Ia).對(duì)特定BMD,GIOP較絕經(jīng)后OP更易引起骨折。n有高風(fēng)險(xiǎn)患者，如65歲，或有骨折史，在開(kāi)始用GC時(shí)即應(yīng)該(ynggi)用保護(hù)骨治療(Grade A). 此時(shí)不一定要測(cè)骨密度n對(duì)

27、其它患者，在開(kāi)始用GC 時(shí)應(yīng)該用DEXA測(cè)定BMD評(píng)價(jià)骨折風(fēng)險(xiǎn)(Grade C). 對(duì)有骨折史患者應(yīng)該排除其它繼發(fā)OP原因 (Grade C).第三十四頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Guideline英國(guó)英國(guó)(yn u)（Bone and Tooth Society of Great Britain, the National Osteoporosis Society and the Royal College of Physicians） n一般原則包括盡量少用GC,使用不同劑型或方法，盡量用其它IC替代 (Grade C). 營(yíng)養(yǎng)，充足鈣吸收，必要體育鍛煉，減少

28、吸煙和酗酒 (Grade C).n不同治療在預(yù)防和治療GIOP及對(duì)脊柱和髖關(guān)節(jié)BMD的影響(yngxing)見(jiàn)表 1(Level Ia).盡管骨折并不是這些研究的原發(fā)終點(diǎn)，etidronate, alendronate and risedronate可減少骨折 (Level Ib).第三十五頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Drug Rx第三十六頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性Guideline英國(guó)英國(guó)(yn u)（Bone and Tooth Society of Great Britain, the National Osteoporosi

29、s Society and the Royal College of Physicians） n口服GC3月以上，應(yīng)進(jìn)行(jnxng)BMD測(cè)定 (Grade C). T score1.5應(yīng)行治療 (Level IV), 在治療時(shí)應(yīng)考慮年齡對(duì)骨折影響 (Grade C).n盡管GIOP治療療效如何監(jiān)測(cè)意見(jiàn)不一，但有些患者在治療1-2年后通過(guò)脊柱BMD測(cè)定提示有顯著反應(yīng) (Level IV).第三十七頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性第三十八頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性GIOP-Belgium Guidelinen所有患者補(bǔ) Ca and V

30、it D. n規(guī)律鍛煉， No煙酒 n像絕經(jīng)婦女(fn)和雄激素水平低男性一樣，對(duì)年輕絕經(jīng)婦女(fn)也考慮HRT. n長(zhǎng)期GC加用BPT 第三十九頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性GIOP-Belgium Guideline Ca and VitDn一線治療: GC減少腸鈣吸收(xshu) n不需聯(lián)合其它7.5 mg/D and/or3mn其它情況與其它有效藥物聯(lián)合.第四十頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性GIOP-Belgium Guideline Ca and VitD 在服用GC過(guò)程中可作為維持治療 停用激素可終止(zhngzh)補(bǔ)充:

31、停用激素BMD可恢復(fù) 第四十一頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性系統(tǒng)性紅斑狼瘡系統(tǒng)性紅斑狼瘡(hn bn ln chun)的骨質(zhì)疏的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性松與皮質(zhì)激素的相關(guān)性-北京協(xié)和醫(yī)院風(fēng)濕(fn sh)免疫科資料 第四十二頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性研究(ynji)對(duì)象n1998年3月到1999年1月北京協(xié)和醫(yī)院風(fēng)濕免疫科SLEn58例，男性3例，女性55例n平均年齡(33.89.5)歲，病程(76.685.8)個(gè)月，激素治療時(shí)間(39.253.7)個(gè)月，激素累積量（按潑尼松折算(sh sun)）(21.125.0)g。n研究階段還符合：（1）年齡45歲；（2）能自由活動(dòng)；（3）腎功能正常；（4）無(wú)其他代謝性骨病或股骨頭壞死。第四十三頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性骨質(zhì)疏松的診斷按世界衛(wèi)生組織1994年提出的標(biāo)準(zhǔn)(biozhn)：（1）骨密度值低于正常年輕人峰值2.5個(gè)標(biāo)準(zhǔn)差（s）為骨質(zhì)疏松；（2）骨密度值在正常年輕人峰值以下1.02.5 s 之間為骨量減少。第四十四頁(yè)，共五十一頁(yè)。系統(tǒng)性紅斑狼瘡的骨質(zhì)疏松與皮質(zhì)激素的相關(guān)性方法(fngf)（1）患者均有詳細(xì)的病