孫文婷,鄭丹妮,楊愛(ài)娟,胡麗芳,穆聞君,李孟霞,羅靜,陶慶文,閻小萍,孔維萍
男性強(qiáng)直性脊柱炎患者中醫(yī)證型與骨密度關(guān)系及低骨密度危險(xiǎn)因素分析
孫文婷1,2,鄭丹妮1,2,楊愛(ài)娟1,2,胡麗芳1,2,穆聞君1,2,李孟霞1,2,羅靜2,3,陶慶文2,3,閻小萍2,3,孔維萍2,3
1.北京中醫(yī)藥大學(xué)研究生院,北京 100029;2.中日友好醫(yī)院,北京 100029;3.免疫炎性疾病北京市重點(diǎn)實(shí)驗(yàn)室,北京 100029
分析男性強(qiáng)直性脊柱炎(AS)中醫(yī)證型與骨密度的關(guān)系及低骨密度發(fā)生的危險(xiǎn)因素。收集2013年9月-2018年9月中日友好醫(yī)院中醫(yī)風(fēng)濕科男性AS患者192例,其中腎虛督寒證106例、腎虛濕熱證86例,分析不同證型、不同骨密度患者的臨床資料,采用Logistic回歸模型分析患者低骨密度危險(xiǎn)因素及不同中醫(yī)證型患者低骨密度危險(xiǎn)因素。腎虛濕熱證患者全髖骨密度顯著低于腎虛督寒證患者,腎虛濕熱證患者病程、紅細(xì)胞沉降率(ESR)、C-反應(yīng)蛋白(CRP)、AS疾病活動(dòng)評(píng)分(ASDAS-CRP)、Bath AS測(cè)量指數(shù)(BASMI)、改良Stoke AS脊柱評(píng)分(mSASSS)顯著高于腎虛督寒證患者(<0.05)。Logistic回歸分析顯示,腎虛濕熱證型、病程、ESR、ASDAS-CRP、mSASSS、Bath AS功能指數(shù)(BASFI)、BASMI與全髖低骨密度的發(fā)生顯著相關(guān),腎虛督寒證患者疾病活動(dòng)指標(biāo)ESR、ASDAS-CRP是全髖低骨密度的危險(xiǎn)因素,腎虛濕熱證患者病程、ASDAS-CRP、mSASSS、BASFI是全髖低骨密度的危險(xiǎn)因素(<0.05)。腎虛濕熱證患者全髖骨密度低于腎虛督寒證患者,腎虛濕熱證型、病程、ESR、ASDAS-CRP、mSASSS、BASFI、BASMI是男性AS患者低骨密度發(fā)生危險(xiǎn)因素。
強(qiáng)直性脊柱炎;腎虛督寒證;腎虛濕熱證;低骨密度
強(qiáng)直性脊柱炎(ankylosing spondylitis,AS)是一種主要影響中軸骨骼的慢性炎癥性疾病,該病以骨質(zhì)破壞及韌帶、附著點(diǎn)部位的新骨形成為特征,可導(dǎo)致骶髂、脊柱關(guān)節(jié)等關(guān)節(jié)間隙變窄、融合和關(guān)節(jié)強(qiáng)直[1]。因骨質(zhì)破壞的發(fā)生可造成骨密度下降,AS患者低骨密度的發(fā)生率在50%以上[2]。然而AS患者低骨密度的危險(xiǎn)因素尚不完全清楚[3-4]。AS在男性人群中的發(fā)病率較女性高2~3倍,男性較女性病情重、預(yù)后差,低骨密度發(fā)生率也顯著高于女性患者[5]。低骨密度可導(dǎo)致脊柱壓縮性骨折,發(fā)病隱匿,病死率較高,影響AS預(yù)后[6]。因此,檢測(cè)男性AS患者骨密度并對(duì)低骨密度危險(xiǎn)因素進(jìn)行評(píng)估尤為重要。AS屬中醫(yī)學(xué)“痹證”范疇,閻小萍教授在繼承全國(guó)首批名中醫(yī)焦樹(shù)德教授學(xué)術(shù)思想基礎(chǔ)上,提出AS的中醫(yī)病名為“大僂”,并將AS分為腎虛督寒證、腎虛濕熱證,該辨證體系已被國(guó)家中醫(yī)藥管理局牽頭制定的大僂(強(qiáng)直性脊柱炎)臨床診療方案、臨床路徑采納[7]。前期研究表明,腎虛濕熱證患者較腎虛督寒證患者具有更高的疾病活動(dòng)度,且不同證型患者的骨密度水平存在差異[8]。本研究在前期研究基礎(chǔ)上進(jìn)一步探討男性AS患者骨密度與中醫(yī)證型的關(guān)系,以及低骨密度的危險(xiǎn)因素,以期更好地指導(dǎo)臨床治療。
選擇2013年9月-2018年9月中日友好醫(yī)院中醫(yī)風(fēng)濕病科門(mén)診及住院男性AS患者192例,其中腎虛督寒證106人,腎虛濕熱證86人,平均年齡(35±11)歲,平均病程(7±6)年。將患者按照全髖骨密度水平分為正常骨密度組(T值≥-1)和低骨密度組(包括骨量減少及骨質(zhì)疏松,T值<-1),2組年齡及人類白細(xì)胞抗原(HLA)-B27陽(yáng)性率比較差異無(wú)統(tǒng)計(jì)學(xué)意義(>0.05),具有可比性。本研究經(jīng)中日友好醫(yī)院倫理委員會(huì)審查批準(zhǔn)(2017-68)。
參照美國(guó)風(fēng)濕病學(xué)會(huì)1984年修訂的AS紐約分類標(biāo)準(zhǔn)[9]制定西醫(yī)診斷標(biāo)準(zhǔn)。
參照世界衛(wèi)生組織推薦的基于雙能X線吸收法制定低骨密度診斷標(biāo)準(zhǔn)[10]。骨密度值低于同性別、同種族正常成人的骨峰值不足1個(gè)標(biāo)準(zhǔn)差為正常,降低1~2.5個(gè)標(biāo)準(zhǔn)差為骨量減少,減低≥2.5個(gè)標(biāo)準(zhǔn)差為骨質(zhì)疏松;T值=(測(cè)定值-骨峰值)÷正常成人骨密度標(biāo)準(zhǔn)差。
參照《中藥新藥臨床研究指導(dǎo)原則(試行)》[11],結(jié)合閻小萍教授經(jīng)驗(yàn)[7]制定中醫(yī)辨證標(biāo)準(zhǔn)。腎虛督寒證:腰、臀、胯疼痛,僵硬不舒,伴膝腿痛,肩、肘、踝等不舒,畏寒喜暖,遇寒加重,得熱則緩,俯仰受限,活動(dòng)不利,甚或脊柱僵直、側(cè)彎、變形,行走坐臥受限,可兼陰囊濕冷,舌苔薄白或白厚,脈沉弦或沉弦細(xì)。腎虛濕熱證:腰骶及脊背疼痛,活動(dòng)受限,晨僵,發(fā)熱,四肢關(guān)節(jié)紅腫熱痛或伴屈伸不利,目赤腫痛,口渴口苦黏膩或口干不欲飲,脘悶納呆,肢體困重,身熱不揚(yáng),綿綿不解,大便干或溏軟,或黏滯不爽,溲黃,舌紅,苔黃或黃厚膩,脈沉滑、弦滑或弦細(xì)數(shù)。
①符合上述AS西醫(yī)診斷標(biāo)準(zhǔn)及中醫(yī)辨證標(biāo)準(zhǔn);②男性,年齡<60歲;③患者對(duì)本研究知情,并簽署知情同意書(shū)。
①合并銀屑病、炎癥性腸病、甲狀旁腺功能亢進(jìn)及內(nèi)分泌疾病者;②合并有其他風(fēng)濕病者;③服用糖皮質(zhì)激素等影響骨代謝藥物者;④合并重度營(yíng)養(yǎng)不良,或有心、腦、腎造血系統(tǒng)嚴(yán)重?fù)p害者;⑤有嗜酒病史;⑥妊娠期婦女;⑦改良Stoke AS脊柱評(píng)分(mSASSS)>60分,骨化嚴(yán)重者;⑧骨密度、一般資料及實(shí)驗(yàn)室檢查不全者。
1.6.1 一般資料
記錄患者年齡、癥狀首發(fā)年齡、病程、身高、體質(zhì)量、體質(zhì)量指數(shù)(BMI)、規(guī)律運(yùn)動(dòng)情況,應(yīng)用腫瘤壞死因子(TNF)-α拮抗劑、傳統(tǒng)改善病情藥物(cDMARDs)、非甾體類抗炎藥(NSAIDs)使用情況及AS家族史。
1.6.2 疾病活動(dòng)性及功能評(píng)估
記錄患者Bath AS功能指數(shù)(BASFI)[12]、Bath AS活動(dòng)指數(shù)(BASDAI)[13]、Bath AS測(cè)量指數(shù)(BASMI)[14]和AS疾病活動(dòng)評(píng)分(ASDAS-CRP)[15]。
1.6.3 實(shí)驗(yàn)室檢查
檢測(cè)患者HLA-B27、紅細(xì)胞沉降率(ESR)、C-反應(yīng)蛋白(CRP)、血尿酸及血鈣水平。
1.6.4 放射學(xué)檢查
由2位具有5年以上影像學(xué)診斷工作經(jīng)驗(yàn)者評(píng)估患者頸椎、腰椎側(cè)位X線,進(jìn)行mSASSS評(píng)分[16],包括椎體前角C2~T1、T12~S1。錐體角0分為正常,1分為侵蝕、硬化或變形,2分為骨贅,3分為骨橋。
1.6.5 骨密度檢查
采用雙能X線法檢測(cè)AS患者腰椎、股骨頸、股骨粗隆、全髖骨密度,使用美國(guó)LUNAR公司IDXA型骨密度儀,腰椎精確度誤差<1/1000,股骨頸精確度誤差<3/1000,其中腰椎骨密度取L1~L4平均值。
腎虛督寒證與腎虛濕熱證男性AS患者病程、ESR、CRP、ASDAS-CRP、BASMI、mSASSS及全髖骨密度比較差異有統(tǒng)計(jì)學(xué)意義(<0.05)。腎虛濕熱證患者病程、ESR、CRP、ASDAS-CRP、BASMI、mSASSS顯著高于腎虛督寒證患者,全髖骨密度顯著低于腎虛督寒證患者(<0.05)。腎虛督寒證與腎虛濕熱證男性AS患者年齡、BMI、規(guī)律運(yùn)動(dòng)情況、HLA-B27+、用藥史比較差異無(wú)統(tǒng)計(jì)學(xué)意義(>0.05)。詳見(jiàn)表1。
表1 男性AS不同證型患者一般資料比較
項(xiàng)目腎虛督寒證 (106例)腎虛濕熱證 (86例)Z值χ2值P值 特征 年齡(±s,歲)32.19±10.11 35.01±10.96-1.828 0.068 BMI(±s,kg/m2)23.81±3.2821.92±3.720.121 0.903 病程(±s,年) 5.65±4.30 9.60±7.24-4.304 <0.001 規(guī)律運(yùn)動(dòng)[例(%)] 17(16.04) 10(11.63) 0.7640.382 HLA-B27+[例(%)] 95(89.62) 81(94.19) 1.2940.256 BASDAI(±s,分) 3.11±1.173.14±1.300.093 0.926 BASFI(±s,分) 1.45±1.731.60±1.60-1.209 0.223 BASMI(±s,分) 1.31±1.592.98±2.07-5.582 <0.001 mSASSS(±s,分) 6.75±13.1814.31±18.51-2.731 <0.001 ASDAS-CRP(±s,分) 1.60±0.601.86±0.68-2.595 0.010 用藥史[例(%)] TNF-α抑制劑 21(19.81) 13(15.12) 0.7180.397 cDMARDs 62(58.49) 46(53.49) 0.4830.487 NSAIDs 58(54.72) 44(51.16) 0.2410.624 實(shí)驗(yàn)室指標(biāo)(±s) ESR/(mm/h)12.70±12.55 23.12±14.29-5.819 <0.001 CRP/(mg/L) 1.50±1.37 2.46±2.45-3.160 0.002 血尿酸/(mg/dL)340.15±83.73333.74±87.950.432 0.665 血鈣/(mmol/L) 2.41±0.79 2.39±0.851.201 0.230 骨密度(±s,g/cm2) 全髖 0.99±0.13 0.89±0.174.542 <0.001 腰椎 1.09±0.17 1.09±0.250.780 0.436 股骨頸 0.96±0.13 0.93±0.171.921 0.055 股骨粗隆 0.81±0.12 0.79±0.141.350 0.177
腎虛督寒證AS患者低骨密度組ASDAS-CRP、ESR顯著高于正常骨密度組(<0.05)。腎虛濕熱證AS患者低骨密度組病程、BASFI、mSASSS、ASDAS-CRP顯著高于正常骨密度組(<0.05)。見(jiàn)表2、表3。
單因素Logistic回歸分析顯示,病程、ESR、ASDAS-CRP、mSASSS、BASFI、BASMI、腎虛濕熱證型作為危險(xiǎn)因素,與全髖低骨密度發(fā)生顯著相關(guān)(<0.05)。調(diào)整年齡、BMI后上述各因素與全髖低骨密度仍顯著相關(guān)(<0.05)。見(jiàn)表4。
表2 腎虛督寒證男性AS患者病程、Bath指數(shù)、椎體損傷程度及實(shí)驗(yàn)室指標(biāo)不同骨密度組比較(±s)
表3 腎虛濕熱證男性AS患者病程、Bath指數(shù)、椎體損傷程度及實(shí)驗(yàn)室指標(biāo)不同骨密度組比較(±s)
表4 男性AS患者全髖低骨密度相關(guān)因素Logistic回歸分析
項(xiàng)目單因素 調(diào)整年齡、BMI OR95%CIP值 OR95%CIP值 病程1.1671.092,1.247<0.001 1.1781.099,1.262<0.001 ESR1.0531.028,1.078<0.001 1.0511.025,1.077<0.001 CRP1.1590.994,1.3490.059 1.1720.999,1.3740.051 ASDAS-CRP2.8891.656,5.035<0.001 3.5311.932,6.454<0.001 mSASSS1.0331.013,1.0530.001 1.0411.020,1.063<0.001 BASDAI1.1600.890,1.5120.271 1.1690.890,1.5360.262 BASFI1.4331.180,1.740<0.001 1.3971.145,1.7060.001 BASMI1.1961.018,1.4050.029 1.2031.016,1.4240.032 腎虛濕熱證型3.5951.786,7.237<0.001 3.9701.916,8.227<0.001
腎虛督寒證男性AS患者全髖低骨密度的單因素Logistic回歸分析顯示,ESR、ASDAS-CRP與全髖低骨密度的發(fā)生顯著相關(guān)(<0.05)。調(diào)整年齡、BMI后上述各因素與全髖的低骨密度仍顯著相關(guān)(<0.05)。
腎虛濕熱證男性AS患者全髖骨密度的單因素Logistic回歸分析顯示,病程、ASDAS-CRP、mSASSS、BASFI作為危險(xiǎn)因素與全髖低骨密度發(fā)生顯著相關(guān)(<0.05)。調(diào)整年齡、BMI后,各因素與全髖低骨密度發(fā)生仍顯著相關(guān)(<0.05)。見(jiàn)表5。
表5 不同證型男性AS患者全髖低骨密度相關(guān)因素的Logistic回歸分析
項(xiàng)目單因素 調(diào)整年齡、BMI 腎虛督寒證 腎虛濕熱證 腎虛督寒證 腎虛濕熱證 OR95%CIP值 OR95%CIP值 OR95%CIP值 OR95%CIP值 病程1.0740.953,1.2100.241 1.1891.080,1.309<0.001 1.1200.981, 1.2790.095 1.1921.079,1.3170.001 ESR1.0681.025,1.1140.002 1.0260.993,1.0580.115 1.0731.026, 1.1240.002 1.0210.988,1.0540.211 CRP1.2810.917,1.7890.146 1.0440.875,1.2450.631 1.2730.897,1.8070.175 1.0650.885,1.2820.504 ASDAS-CRP3.6831.347,10.0670.011 2.0901.051,4.1570.036 4.2191.478,12.0450.007 2.4541.123,5.3540.024 mSASSS1.0210.986,1.0560.243 1.0311.006,1.0570.016 1.0280.990,1.0670.147 1.0441.014,1.0740.004 BASDAI1.1740.743,1.8530.492 1.1560.825,1.6190.400 1.2530.776,2.0240.356 1.1120.770,1.6060.570 BASFI1.2300.933,1.6220.141 1.8671.312,2.6580.001 1.2500.935,1.6720.133 1.7791.245,2.5420.002 BASMI1.0100.718,1.4220.954 1.0950.885,1.3550.404 1.0010.706,1.4200.994 1.1040.883,1.3800.383
AS患者低骨密度發(fā)生率較高,對(duì)疾病預(yù)后造成不良影響。本研究中男性患者低骨密度發(fā)生率為56%,其中骨量減少發(fā)生率為46%,骨質(zhì)疏松發(fā)生率為10%,與文獻(xiàn)報(bào)道[2]基本相符。AS的病因病機(jī)主要為腎督正氣虧虛,風(fēng)寒濕熱諸邪深侵腎督而致[17]。腎精不足則髓無(wú)以化生,髓不足則骨失其養(yǎng);腎陽(yáng)不足,腎失溫煦,骨之生長(zhǎng)失其動(dòng)力;腎陰不足,骨失濡養(yǎng),而質(zhì)松質(zhì)脆,以骨量減少、骨質(zhì)疏松為特點(diǎn)的低骨密度是腎虛骨失所養(yǎng)的外在表現(xiàn)。
本研究顯示,腎虛濕熱證患者全髖骨密度低于腎虛督寒證患者(<0.05)。腎虛濕熱證患者由于感受風(fēng)濕熱邪或風(fēng)寒濕邪日久,郁而化熱,濕熱壅滯經(jīng)絡(luò),流注關(guān)節(jié),臨床表現(xiàn)除腰脊背疼痛之外,還可有關(guān)節(jié)紅熱、腫脹、活動(dòng)受限等表現(xiàn)。既往研究表明,腎虛濕熱證疾病活動(dòng)性指標(biāo)ESR、CRP等較腎虛督寒證高,病程也較長(zhǎng)[8]。本研究顯示,腎虛濕熱證患者疾病活動(dòng)度指標(biāo)ESR、CRP、ASDAS-CRP顯著高于腎虛督寒證患者,mSASSS、BASMI、病程均大于腎虛督寒證組(<0.05),表明腎虛濕熱證患者疾病活動(dòng)性高、脊柱結(jié)構(gòu)損傷較重、病程長(zhǎng)。研究表明,AS患者骨密度與病程、疾病活動(dòng)度、脊柱功能、椎體結(jié)構(gòu)結(jié)構(gòu)損傷呈負(fù)相關(guān)[18-20]。中醫(yī)認(rèn)為濕熱之邪交結(jié),阻滯氣血,導(dǎo)致陽(yáng)之布化受抑,陰之營(yíng)榮乏源,加之大僂以腎督虧虛為本,腎虛濕熱證患者腎陰相對(duì)不足,熱灼津液,則筋脈攣廢、精血虧虛,可致骨失濡養(yǎng),骨質(zhì)愈發(fā)松脆。髖部又稱“髀樞”,為足太陽(yáng)膀胱經(jīng)、足少陽(yáng)膽經(jīng)循行所過(guò),足厥陰肝經(jīng)亦分布其周,為全身氣機(jī)活動(dòng)之樞[21],腎虛濕熱證患者腎水不足,不能生肝木,導(dǎo)致肝筋失養(yǎng),經(jīng)氣流轉(zhuǎn)不通,亦加重全髖部位骨量流失,導(dǎo)致腎虛濕熱證患者全髖骨密度更低。
通過(guò)構(gòu)建Logistic回歸模型發(fā)現(xiàn),病程、ESR、ASDAS-CRP、mSASSS、BASFI、BASMI是男性AS患者低骨密度危險(xiǎn)因素,表明病程長(zhǎng)、疾病活動(dòng)性高、脊柱功能減退及椎體結(jié)構(gòu)損傷重更容易導(dǎo)致男性AS患者低骨密度的發(fā)生,與既往研究結(jié)果相符[22]。此外,腎虛濕熱證型是男性AS患者低骨密度發(fā)生的危險(xiǎn)因素,表明腎虛濕熱證型可增加AS男性低骨密度風(fēng)險(xiǎn)。進(jìn)一步分析顯示,ESR、ASDAS-CRP為腎虛督寒證患者低骨密度危險(xiǎn)因素,病程、ASDAS-CRP、mSASSS、BASFI為腎虛濕熱證患者低骨密度危險(xiǎn)因素,表明腎虛督寒證患者低骨密度與疾病活動(dòng)度關(guān)系密切,而腎虛濕熱證患者低骨密度不僅與疾病活動(dòng)度關(guān)系密切,還與椎體結(jié)構(gòu)損傷、脊柱活動(dòng)功能關(guān)系密切。由此可見(jiàn),對(duì)于高疾病活動(dòng)度AS患者,應(yīng)關(guān)注骨量并及時(shí)檢測(cè)骨密度。對(duì)于椎體結(jié)構(gòu)損傷程度高、脊柱活動(dòng)功能差的腎虛濕熱證患者尤應(yīng)重視骨密度檢測(cè),提早預(yù)防和治療低骨密度。
AS患者存在許多導(dǎo)致低骨密度的危險(xiǎn)因素,高疾病活動(dòng)度患者存在較高水平的致炎因子會(huì)加重骨質(zhì)的破壞,引起低骨密度[23];疼痛僵硬等癥狀、椎體結(jié)構(gòu)損傷加劇、脊柱骨化強(qiáng)直等均可導(dǎo)致患者關(guān)節(jié)活動(dòng)功能降低、活動(dòng)受限,加重低骨密度發(fā)生[24-25]。研究顯示,AS患者脊柱骨贅形成和全髖低骨密度具有相關(guān)性[19],mSASSS較高的患者椎體結(jié)構(gòu)損傷較重,加重活動(dòng)受限,促進(jìn)AS患者低骨密度進(jìn)展[26]。疼痛及脊柱活動(dòng)受限會(huì)導(dǎo)致BASMI、BASFI升高,使低骨密度的發(fā)生風(fēng)險(xiǎn)更高[20,27]。此外,病程也會(huì)對(duì)AS患者骨密度產(chǎn)生影響,有研究報(bào)道,病程5年內(nèi)的AS患者,全髖骨質(zhì)疏松癥患病率為11%,病程超過(guò)10年患者為30%[18]。本研究顯示,病程、疾病活動(dòng)度(ESR、ASDAS-CRP)、脊柱功能(BASFI、BASMI)、椎體結(jié)構(gòu)損傷(mSASSS)均為男性AS患者低骨密度危險(xiǎn)因素,表明在疾病發(fā)生早期,控制疾病活動(dòng)度、提高脊柱功能、改善椎體結(jié)構(gòu)損傷是預(yù)防男性AS患者低骨密度重要手段。
綜上所述,本研究揭示了不同中醫(yī)證型與男性AS患者骨密度的關(guān)系,對(duì)低骨密度發(fā)生的危險(xiǎn)因素進(jìn)行探究,為不同證型AS患者低骨密度防治及預(yù)后判斷提供依據(jù)。腎虛濕熱證患者全髖骨密度低于腎虛督寒證患者,腎虛濕熱證型、病程、ESR、ASDAS-CRP、mSASSS、BASFI、BASMI是男性AS患者低骨密度發(fā)生危險(xiǎn)因素,提示男性AS患者應(yīng)注重在早期控制疾病活動(dòng)度,減少低骨密度的發(fā)生。腎虛濕熱證者尤應(yīng)注重控制疾病活動(dòng)度,提高脊柱功能,延緩椎體結(jié)構(gòu)損傷,延緩低骨密度的發(fā)生。本研究尚存在一定局限性,單中心入組患者可能存在一定偏倚。由于AS患者慢性炎癥部位出現(xiàn)新骨形成可造成脊柱韌帶骨化[28],腰椎前后位骨密度的測(cè)量可能出現(xiàn)假性增高,對(duì)危險(xiǎn)因素分析造成一定影響。因此,今后研究中應(yīng)盡可能采用定量CT方法進(jìn)行腰椎骨密度檢測(cè)[29],并進(jìn)一步擴(kuò)大樣本量以提高準(zhǔn)確性。
[1] WARD M M, DEODHAR A, GENSLER L S, et al. 2019 update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis[J]. Arthritis Rheumatol, 2019,71(10):1599-1613.
[2] MALOCHET-GUINAMAND S, PEREIRA B, TATAR Z, et al. Prevalence and risk factors of low bone mineral density in spondyloarthritis and prevalence of vertebral fractures[J]. BMC Musculoskelet Disord, 2017,18(1):357.
[3] HU L Y, LU T, CHEN P M, et al. Should clinicians pay more attention to the potential underdiagnosis of osteoporosis in patients with ankylosing spondylitis? A national population-based study in Taiwan[J]. PLoS One,2019,14(2):e0211835.
[4] ULU M A, BATMAZ ?, DILEK B, et al. Prevalence of osteoporosis and vertebral fractures and related factors in patients with ankylosing spondylitis[J]. Chin Med J (Engl),2014,127(15):2740-2747.
[5] VAN DER WEIJDEN M A, VAN DENDEREN J C, LEMS W F, et al. Low bone mineral density is related to male gender and decreased functional capacity in early spondylarthropathies[J]. Clin Rheumatol,2011, 30(4):497-503.
[6] PRAY C, FEROZ N I, NIGIL H N. Bone mineral density and fracture risk in ankylosing spondylitis:a meta-analysis[J]. Calcif Tissue Int,2017,101(2):182-192.
[7] 陶慶文,徐愿,孔維萍,等.基于名老中醫(yī)經(jīng)驗(yàn)傳承寒熱辨治強(qiáng)直性脊柱炎的臨床研究[J].世界中西醫(yī)結(jié)合雜志,2013,8(7):730-733.
[8] 孔維萍,朱笑夏,金玥,等.強(qiáng)直性脊柱炎寒、熱不同證型的骨密度與疾病活動(dòng)度特點(diǎn)[J].中日友好醫(yī)院學(xué)報(bào),2015,29(3):151-153,157.
[9] VAN DER LINDEN S, VALKENBURG H A, CATS A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria[J]. Arthritis Rheum,1984, 27(4):361-368.
[10] 中華醫(yī)學(xué)會(huì)骨質(zhì)疏松和骨礦鹽疾病分會(huì).原發(fā)性骨質(zhì)疏松癥診治指南(2011年)[J].中華骨質(zhì)疏松和骨礦鹽疾病雜志,2011,4(1):2-17.
[11] 鄭筱萸.中藥新藥臨床研究指導(dǎo)原則(試行)[M].北京:中國(guó)醫(yī)藥科技出版社,2002:119-123.
[12] CALIN A, GARRETT S, WHITELOCK H, et al. A new approach to defining functional ability in ankylosing spondylitis:the development of the Bath ankylosing spondylitis functional index[J]. J Rheumatol,1994,21(12):2281-2285.
[13] GARRETT S, JENKINSON T, KENNEDY L G, et al. A new approach to defining disease status in ankylosing spondylitis:the Bath ankylosing spondylitis disease activity index[J]. J Rheumatol, 1994,21(12):2286-2291.
[14] JENKINSON T R, MALLORIE P A, WHITELOCK H C, et al. Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS metrology index[J]. J Rheumatol,1994,21(9):1694-1698.
[15] MACHADO P, NAVARRO-COMPáN V, LANDEWé R, et al. Calculating the ankylosing spondylitis disease activity score if the conventional c-reactive protein level is below the limit of detection or if high-sensitivity c-reactive protein is used:an analysis in the DESIR cohort[J]. Arthritis Rheumatol,2015,67(2):408-413.
[16] CREEMERS M C, FRANSSEN M J, VAN'T HMA, et al. Assessment of outcome in ankylosing spondylitis:an extended radiographic scoring system[J]. Ann Rheum Dis,2005,64(1):127-129.
[17] 閻小萍,朱俊嶺,顏玨,等.補(bǔ)腎強(qiáng)督方治療強(qiáng)直性脊柱炎骨質(zhì)疏松、骨量減少102例臨床觀察[J].中華中醫(yī)藥雜志,2007,22(8):571-573.
[18] BRIOT K, ROUX C. Inflammation, bone loss and fracture risk in spondyloarthritis[J]. RMD Open,2015,1(1):e000052.
[19] KARBERG K, ZOCHLING J, SIEPER J, et al. Bone loss is detected more frequently in patients with ankylosing spondylitis with syndesmophytes[J]. J Rheumatol,2005,32(7):1290-1298.
[20] ULU MA, ?EVIK R, DILEK B. Comparison of PA spine, lateral spine, and femoral BMD measurements to determine bone loss in ankylosing spondylitis[J]. Rheumatol Int,2013,33(7):1705-1711.
[21] 甘曉維,陶慶文,王建明,等.閻小萍辨治強(qiáng)直性脊柱炎髖關(guān)節(jié)受累用藥規(guī)律探析[J].北京中醫(yī)藥,2018,37(11):1039-1042.
[22] WANG D, HOU Z, GONG Y, et al. Bone edema on magnetic resonance imaging is highly associated with low bone mineral density in patients with ankylosing spondylitis[J]. PLoS One,2017,12(12):e0189569.
[23] BEEK K J, RUSMAN T, VAN DER WEIJDEN MAC, et al. Long-term treatment with TNF-alpha inhibitors improves bone mineral density but not vertebral fracture progression in ankylosing spondylitis[J]. J Bone Miner Res,2019,34(6):1041-1048.
[24] KLINGBERG E, LORENTZON M, MELLSTR?M D, et al. Osteoporosis in ankylosing spondylitis - prevalence, risk factors and methods of assessment[J]. Arthritis Res Ther,2012,14(3):R108.
[25] WARD M M, DEODHAR A, AKL E A, et al. American College of Rheumatology/Spondylitis Association of America/ Spondyloarthritis Research and Treatment Network 2015 recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis[J]. Arthritis Rheumatol,2016,68(2):282-298.
[26] KIM H R, HONG Y S, PARK S H, et al. Low bone mineral density predicts the formation of new syndesmophytes in patients with axial spondyloarthritis[J]. Arthritis Res Ther,2018,20(1):231.
[27] ETF C, HHL T, LEE K H, et al. MRI inflammation of facet and costovertebral joints is associated with restricted spinal mobility and worsened functional status[J]. Rheumatology (Oxford), 2020. https://doi.org/10.1093/rheumatology/kez649.
[28] WANG R, WARD M M. Epidemiology of axial spondyloarthritis:an update[J]. Curr Opin Rheumatol,2018,30(2):137-143.
[29] CAPARBO V F, FURLAM P, CGS S, et al. Assessing bone impairment in ankylosing spondylitis (AS) using the trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT)[J]. Bone,2019,122:8-13.
Relationship Between TCM Syndromes and Bone Mineral Density in Male Patients with Ankylosing Spondylitis and Analysis on Risk Factors of Low Bone Mineral Density
SUN Wenting1,2, ZHENG Danni1,2, YANG Aijuan1,2, HU Lifang1,2, MU Wenjun1,2, LI Mengxia1,2,LUO Jing2,3, TAO Qingwen2,3, YAN Xiaoping2,3, KONG Weiping2,3
To analyze the relationship between TCM syndromes and bone mineral density in male patients with ankylosing spondylitis (AS) and the risk factors of low bone mineral density.Totally 192 male AS patients in Department of TCM Rheumatology in China-Japan Friendship Hospital from September 2013 to September 2018 were collected, among which there were 106 cases with kidney deficiency and cold syndrome and 86 cases with kidney deficiency and dampness heat syndrome. Clinical data of patients with different syndrome types and bone mineral density were analyzed. The risk factors of low bone mineral density and the factors in different TCM syndrome types in male AS patients were analyzed by Logistic regression model.The total hip bone mineral density of the patients with kidney deficiency and dampness heat syndrome was significantly lower than that of the patients with kidney deficiency and cold syndrome. The duration of disease, ESR, CRP, ASDAS-CRP, Bath ankylosing spondylitis metrology index (BASMI) and modified Stoke ankylosing spondylitis spine score (mSASSS) of the patients with kidney deficiency and dampness heat syndrome were significantly higher than those of the patients with kidney deficiency and cold syndrome (<0.05). According to the Logistic regression analysis of the related factors of low bone mineral density in male AS patients, it was found as for that kidney deficiency and dampness heat syndrome, duration of disease, ESR, ASDAS-CRP, mSASSS, Bath ankylosing spondylitis function index (BASFI) and BASMI were significantly related to the occurrence of low bone mineral density in the total hip; ESR and ASDAS-CRP were risk factors of low bone mineral density in the total hip in the patients with kidney deficiency and cold syndrome; the duration of disease, ASDAS-CRP, mSASSS and BASFI were risk factors of low bone mineral density in the total hip in the patients with kidney deficiency and dampness heat syndrome (<0.05).Patients with kidney deficiency and dampness heat syndrome have lower total hip bone mineral density than those with kidney deficiency and cold syndrome. Kidney deficiency and dampness heat syndrome, duration of disease, ASDAS-CRP, mSASSS, BASFI and BASMI are the risk factors of low bone mass in male AS patients.
ankylosing spondylitis; kidney deficiency and dampness heat syndrome; kidney deficiency and cold syndrome; low bone mineral density
R259.932.3
A
1005-5304(2020)09-0035-06
10.3969/j.issn.1005-5304.202005066
國(guó)家自然科學(xué)基金青年基金(81403378);北京市自然科學(xué)基金(7182148);中日友好醫(yī)院青年科技英才培養(yǎng)計(jì)劃(2014-QNYC-B-02)
孔維萍,E-mail:kongweiping75@126.com
(2020-02-20)
(2020-05-13;編輯:季巍?。?/p>