as与骨代谢-课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,骨,代谢异常是,强直性脊柱炎进展的关键环节,高冠民,郑州大学一附,院,风湿免疫科,主要内容,什么是强直性脊柱炎？,强直性脊柱炎发生骨代谢异常的机制,骨代谢异常对强直性脊柱炎的影响,骨代谢干预,AS,的实质,-,附着点,炎,炎症,-,侵蚀,-,骨化,再侵蚀骨化,.,强直性的髋关节关节囊内和关节内骨化遗留部分腔结构,常见症状,腰痛，臀区痛，肩痛，足跟痛,(,情人踵,),，前胸痛,竹节样改变的腰椎,垂直关节的破坏,骶髂关节、耻骨联合、胸锁关节、椎小关节、髋关节等,诊断强直性脊柱炎的纽约标准,（1966年）,临床标准：,1.腰椎在所有3个平面的活动均受限：前屈、侧屈、背伸,2.腰骶结合部或腰椎疼痛,3.在第4肋间隙水平测量的扩胸度,2.5cm,肯定AS：,至少1条临床标准+3级以上双侧骶髂关节炎；或3级以上单侧骶髂关节炎/双侧2级骶髂关节炎+临床标准第1条或同时具备临床标准第2，3条,可能AS：,3级以上双侧骶髂关节炎不具备临床标准,骨代谢异常,是,AS,进展,的关键,环节,遗传,-,免疫,-,炎症,-,代谢轴线,2000,年,Arron,和,Choi,首先提出“骨免疫学”的概念，免疫和炎症是,AS,及其骨代谢异常发生和发展的重要方面,Arron JR,Choi Y.Bone versus immune system.Nature,2000;408(6812):535-536,骨代谢异常既是造成,AS,不良预后的重要原因（机制）又是结果（骨松）,免疫和炎症,代谢异常,骨性强直,AS,发生骨松的概况,发生率,18.7%,到,62,%,男性更多见，随着病人年龄和患病时间而增加,Bessant R and Keat,AJ,Rheumatol.2019 Jul;29(7):1511-9,AS,发生骨松的概况,骨内分泌学,骨内分泌学,钙调节相关激素,维生素,D,，,降钙素，甲状旁腺素，甲状旁腺激素,相关蛋白,糖皮质激素,性激素,甲状腺激素,内分泌异常是,AS,重要特征,维生素,D,与,AS,选取,2019,年,10,月,2019,年,12,月至郑州大学第一附属医院住院,AS,患者,147,例，同期就诊的健康体检者,65,例,AS,患者,25,（,OH,）,D=,17.68,8.83,与,健康对照,组差异,无统计学意义（,t=-0.231,P=0.817,）,AS,组,男性高于,女性，差异有统计学意义（,P=0.038,）,与,病程、血红蛋白,、,BASFI,呈正,相关,Vitamin D,水平参考值,25(OH)D Level,ng/ml,nMol/L,缺乏,less than 8,less than 20,不足,8-20,20-50,正常,20-60,50-150,过高,60-90,150-225,中毒,greater than 90,greater than 225,相关性,年龄,r=0.019，P=0.818,病程,r=0.216，p=0.009,WBC,r=0.031，p=0.716,RBC,r=0.355，p=0.000,HGB,r=0.173，p=0.038,PLT,r=-0.172，p=0.040,血小板压积,r=-0.173，p=0.042,平均血小板分布体积,r=0.073，p=0.394,平均血小板分布宽度,r=-0.177，,p=0.039,ESR r=0.140，,p=0.095,CRP r=-0.071，p=0.407,碱性磷酸酶,r=0,134，p=0.137,甲状旁腺素,r=0,077，,p=0.355,总,型胶原氨基酸端,延,r=0,059，p=0.475,骨钙素,r=0,111，p=0.184,胶原特殊序列测定,r=-0.030，,p=0.716,BASDAI,r=0.085,p=0.312,BASFI r=0.220,P=0.008,骶髂关节分级,r=0.092,p=0.271,HIP,分级,r=-0.020,p=0.813,ASDAS-CRP,r=0.017,p=0.839,ASDAS-ESR,r=-0.71,P=0.393,25OHD,水平,与,临床、,实验室各项指标,的,相关性,细胞：,35%,有机成分：,65%,无机物 钙磷镁,少量糖蛋白，骨磷蛋白和,-,羟化蛋白,主要为,型胶原,骨基质,骨质,成骨细胞 破骨细胞 骨细胞 骨原细胞,骨组织结构异常与,AS,破骨细胞与免疫细胞存在共同的细胞起源,International Journal of Medical Sciences,2019;9(9):825-832.doi:10.7150/ijms.5180,Schett G.Arthritis Res Ther.2009;11(1):210.,炎症活动的程度与骨吸收程度存在线性关系,Marhoffer W,Stracker H,Masoud I,et al.Ann Rheum Dis,2019,54:5567.,路平，阎小萍 中华骨质疏松和骨矿盐疾病杂志,.2019,（,5,）,:1,陈丽华 中国骨质疏松杂志,2019,7(4),AS,疾病活动期，尿,D-Pyr,明显升高，骨吸收明显增加；血沉高的患者组的腰椎正位骨密度低于血沉低的患者组，统计学处理结果有明显差异，,AS,疾病越严重，骨损伤也越严重。,尿,D-Pyr,（,nmol,）,红细胞沉降速率（,mm/1st h,）,C,反应蛋白（,mg/l),尿,D-Pyr,（,nmol,）,炎症活动标志物：红细胞沉降速率，,C,反应蛋白；,骨吸收标志物：尿,D-Pyr,反应骨代谢异常的主要,标志,物,形成指标,PINP,完整,/N-MID,骨钙素,PICP,碱性磷酸酶,骨碱性磷酸酶,吸收指标,血清,-crosslaps,尿,I,型胶原,C/N,端肽,血清抗酒石酸酸性磷酸酶,尿吡啶啉,尿脱氧吡啶啉,AS,病人骨代谢指标的变化,骨转化指标影响,AS,的结局,药物治疗,NSAIDs,：迅速控制症状,肾上腺皮质激素,改善病情药,生物制剂,2019 ACR SpA,共识,活动期,AS,NSAIDs,非首选药物,连续使用,持续活动,TNFi,非首选药物,慢作用药（柳氮磺胺吡啶，帕米,膦,酸二钠）,当周围关节病变或,TNFi,禁忌时考虑,TNFi,禁忌,非,TNFi,生物制剂,物理疗法,主动好于被动,陆上好于水上,全身糖皮质激素,当有周围炎症爆发，怀孕，炎性肠病时考虑,持续活动,使用英夫利昔单抗或阿达木单抗,使用,TNFi,单抗,局部激素,局部激素,局部激素,复发虹膜炎,炎性肠病,单独的骶髂关节炎,外周关节炎,起止点炎,备选,TNFi,2,个关节时考虑；尽少使用,避开跟腱、膝、四头肌,自主的背部训练，正规组织或个人的自我管理教育，配合评估,/,咨询,规律监测经过验证的,AS,疾病活动度指标、,CRP,或,ESR,强烈推荐,有条件的推荐,有条件的不建议,强烈不建议,备注信息,图例,ASAS/EULAR关于AS的治疗无明显改变,Zochling J,et al.Ann Rheum Dis 2019;65:442-452.,教育指导,运动,物理治疗,康复治疗,患者协会,自助组织,NSAIDs,中轴疾病,外周疾病,镇痛药,手术,柳氮磺吡啶,局部皮质激素,TNF,抑制剂,29,被忽略的研究保泰松能抑制,AS,的骨赘生长,40,例,AS,的回顾性研究,A,组,(,持续用保泰松,):,无脊柱骨化,如已在进展中,则发展停止或大大延迟,B,组,(,间断用保泰松,),C,组,(,不用保泰松,):,骨化快速进展,早期或较早期,AS,持续用保泰松能完全或大部分控制椎体骨化,Boersma JW.Scand J Rheumatol,1976,5(1):60-4.,30年后NSAIDs在,AS,中的疗效,2,年后,NSAIDs,持续治疗组的影像学进展,(mSASSS),小于按需治疗组,(n=150),NSAIDs,持续治疗组,NSAIDs,按需治疗组,影像学进展,(,平均值,),*,得分为盲法评分结果,Ann Rheum Dis,(2019).doi:10.1136/annrheumdis-2019-201970,CRP,升高者,NSAIDs,连续治疗获益更好,又过了大概十年非甾体抗炎药治疗强柱无可替代,33,Renaissance of the selectiveCOX-2 inhibitors(coxibes)?,又过了大概十年,非甾体抗炎药治疗,AS,的体会,2019,年,10,月至,2019,年,9,月,郑大一附院门诊或住院病人,采用,随机、双盲、平行对照的方法,艾瑞昔布或塞来昔布治疗,3,个,月,非甾体抗炎药治疗,AS,的体会,艾瑞昔布组,塞来昔布组,所有入组患者,ESR,治疗前,治疗后,12,周,差值,P,20.5818.90,14.8514.67,-5.7319.08,0.027,16.8115.04,9.58.44,-7.3111.18,0.000,18.6617.071,12.1212.16,-6.5415.52,0.000,两组间比较的,P,值,0.705,CRP,治疗前,治疗后,12,周,差值,P,14.8516.78,12.9714.64,-1.8813.87,0.312,13.5114.39,7.978.98,-5.5411.41,0.000,14.1715.56,10.4312.3,-3.7412.76,0.002,两组间比较的,P,值,0.063,BASDAI,治疗前,治疗后,12,周,差值,P,4.101.71,3.101.65,-1.01.85,0.000,4.011.77,3.221.80,-0.792.09,0.006,4.191.66,2.981.49,-1.211.57,0.000,两组间比较的,P,值,0.274,BASFI,治疗前,治疗后,12,周,差值,P,2.092.27,1.871.91,-0.221.82,0.355,1.992.07,1.851.82,-0.141.81,0.558,2.042.16,1.861.86,-0.181.81,0.283,两组间比较的,P,值,0.719,两组间比较的,P,值,0.473,总体评估,治疗前,治疗后,12,周,差值,P,5.282.30,3.672.07,-1.612.34,0.000,5.552.00,3.762.08,-1.782.01,0.000,5.412.15,3.722.07,-1.692.17,0.000,两组间比较的,P,值,0.354,SPARCC,治疗前,治疗后,12,周,差值,P,13.6714.02,9.0411.03,-4.629.68,0.001,9.2011.29,4.235.66,-4.979.75,0.000,11.4012.85,6.609.01,-4.809.67,0.000,两组间比较的,P,值,0.728,0.000,VEGF,治疗前,治疗后,12,周,差值,P,247.5218.77,203.0212.08,-44.5015.80,0.038,234.4916.70,171.5310.63,-62.9712.78,0.000,240.8917.68,187.0011.42,-53.89614.31,0.000,两组间比较的,P,值,0.328,BMP-2,治疗前,治疗后,12,周,差值,P,210.5693.01,204.4596.95,-6.1289.12,0.606,252.19111.40,248.41129.46,-3.7849.83,0.562,231.74104.44,226.80116.26,-4.9371.56,0.460,治疗前,治疗后,12,周,差值,t,P,SOST，,pg/ml,38.93418.925,57.00536.460,18,07133.477,5.814,.000,DKK，,pg/ml,393.460136.810,542.