骨质疏松性椎体骨折(OVF)约占全部骨折的50%[1]。初发椎体骨折可称为哨兵骨折,是骨质量严重下降的标志,患者初发椎体骨折后再骨折的发生率为27.4% ~ 38.0%[2-3]。椎体再骨折不仅增加了骨质疏松症患者的致残率和死亡风险[4],还给家庭和社会带来了巨大的经济负担。骨密度(BMD)下降是OVF及椎体再骨折发生的独立危险因素[5-6]。BMD评估在OVF的预防和诊疗中具有重要意义。目前最常用的BMD测量技术包括双能X线吸收法(DXA)和定量CT扫描技术(QCT),DXA易受脊柱退行性变的影响而不够精确,QCT易受设备及软件的限制而无法普及。
近年来,以CT值评估BMD的方法逐渐受到关注。CT值是人体某一局部组织密度值的相对量,其单位是HU,又称亨氏单位[7]。椎体内组织以松质骨为主,椎体CT值可反映松质骨骨量水平[8],其测量仅需在影像归档和通信系统(PACS)中完成CT图像的三维重建,在椎体松质骨区域放置一椭圆形的感兴趣区域(ROI),即可自动读取ROI内的平均CT值。目前,椎体CT值不仅可作为一种机会性临床筛查工具,提高骨质疏松症的诊断率[9],还可有效预测OVF[10]和椎体再骨折[11]的发生。本文总结了椎体CT值在OVF中的诊断价值及预测价值,旨在更好地推广椎体CT值在临床实践中的应用。
1 诊断价值 1.1 与BMD的相关性椎体CT值与DXA测量的BMD值显著相关,其随着年龄的增加而相应降低(约2 HU/年)[12-13]。Schreiber等[8]以聚氨酯模体为参照对椎体CT值的骨质量评估效能进行评价,证实椎体CT值与DXA测量的T值(r2=0.48)、BMD(r2=0.44)和椎体抗压强度均呈显著性正相关。一项基于人工智能技术测量椎体CT值的研究[14]发现,其诊断骨质疏松症和骨量减少症的受试者工作特征(ROC)曲线的曲线下面积(AUC)可高达0.831和0.972。但是,椎体CT值在腰椎退行性疾病患者骨质量评估中的应用尚存争议。在退行性脊柱侧凸患者的研究[15]中发现,L1~4平均CT值与DXA测量的腰椎及髋部的BMD和T值的相关性均较差(r < 0.5)。类似的研究[16]也发现,腰椎退行性变组患者L1~4的平均CT值与DXA测量的BMD和T值的相关系数显著低于非退行性变组,腰椎退行性变可能会影响相关性研究结果的准确性。
与DXA的测量原理不同,QCT和椎体CT值测量的均为椎体松质骨,因此,将QCT所测量的BMD作为参照标准更精确。Kim等[17]对180例接受腰椎内固定手术的患者进行研究发现,椎体CT值与QCT测量的BMD值的相关性(r=0.868)优于与DXA测量的BMD值的相关性(r=0.489),进一步证实了椎体CT值在评估OVF患者骨质量中的有效性。
1.2 骨质疏松症的诊断界值为进一步指导椎体CT值的临床应用,诸多学者对椎体CT值诊断骨质疏松症的界值及效能进行了分析和评价。借助机器学习算法的大样本研究[18]发现,椎体CT值诊断骨质疏松症与DXA诊断结果的一致性为82%。美国威斯康星医学院放射医学中心进行的回顾性研究[19]证实,L1 CT值低于135 HU是诊断骨质疏松症的最佳截断值;当界值为160 HU时诊断灵敏度为90.0%,适用于高风险人群以降低假阴性率,促进骨质疏松症的进一步准确筛查;当界值为110 HU时诊断特异度为91.3%,适用于低风险人群以降低假阳性率,提高诊断准确性。
其他研究[17, 20-26]提出骨质疏松症的诊断阈值为99 ~ 146 HU,各诊断实验的AUC基本均大于0.7,证明其诊断效能可靠。最新的一项荟萃分析[27]评估了界值分别为110 HU、135 HU、150 HU时椎体CT值的诊断效能,当界值为135 HU时具有最佳的灵敏度及特异度,其诊断试验的OR值为14.88(95%置信区间为7.521 ~ 29.44),ROC曲线的AUC为0.831。
1.3 优势及局限性椎体CT值在骨质疏松症的诊断及筛查中具有以下优势。①测量结果可靠。与DXA测量所用的平面投影技术不同,椎体CT值可直接测量椎体松质骨骨量水平,其结果可有效避免因骨质增生、脊柱退行性变等因素引起的误差[25]。②测量方法方便快捷。在设备条件不足的情况下,椎体CT值是代替其他骨密度检查的良好选择,专科医师可在不依靠额外检查和软件技术的前提下快速评估患者的骨质量。③无须额外辐射暴露。胸腰椎CT是脊柱疾病临床诊疗中最常用的评估工具,尤其是OVF患者,术前多已完成胸腰椎CT检查,因此,可在不产生额外辐射量的前提下快速准确地评估患者的骨质量。
虽然既往研究均证实了椎体CT值具有一定的临床应用潜力,但仍存在局限性。①诊断界值缺乏统一标准。椎体CT值的测量尚未执行BMD的标准化体模校准工作,因此,各项研究获得的椎体CT值的界值、灵敏度及特异度存在差异,限制了其在骨质疏松症筛查和诊断中的推广应用(表 1)。研究人群、参照标准及CT类型是各诊断实验产生差异的主要因素[28]。②测量结果缺乏代表性。与QCT测量的椎体三维体积BMD不同,椎体CT值所测量的是椎体单一层面的松质骨衰减系数,故其准确度及分辨率稍差。③测量技术缺乏标准化。与DXA类似,椎体CT值须完成流程规范、数据采集、数据分析和质量保证等标准化问题,才可确定骨质疏松症的诊断界值,并在临床推广应用[29]。
椎体CT值与椎体骨折及再骨折的发生密切相关[10, 32](表 2)。Lee等[33]的研究证实,L1 CT值每下降10 HU,未来5年内脆性骨折风险将增加47%。L1 CT值的下降是老年人群发生OVF的独立危险因素,L1 CT值< 90 HU时,65岁以上老年人群OVF的发生风险增加31.9倍[34]。在急性OVF的发生风险评估中,当L1 CT值界值为60 HU时,预测的特异度为90%;当界值为100 HU时,预测的灵敏度为90%[35]。
椎体CT值下降对OVF发生的影响与测量节段、脆性骨折史、初发OVF节段和骨折部位等因素均相关。L1作为胸腰椎CT扫描中第一个没有肋骨的椎体而便于识别,故既往常选用L1作为测量节段。有研究[36]证实,L4 CT值与OVF发生风险的相关性最强,因此,L4 CT值可作为评估OVF风险的最佳选择。椎体CT值下降合并既往椎体骨折史的患者发生OVF的风险将进一步增加,当患者椎体CT值< 133 HU且合并既往脆性骨折时,患者1年内和3年内新发椎体骨折的HR值分别为7.5和5.4[37]。发生多节段OVF的患者椎体CT值显著低于单节段OVF患者,并且当椎体CT值< 61 HU时,患者发生多节段OVF的风险将显著增加[36]。此外,椎体CT值每下降50 HU,少发OVF部位(T4~6,T9,10)的骨折风险增加2.2 ~ 3.4倍,多发OVF部位(T7,8,T11,12)的骨折风险增加1.4 ~ 1.8倍[38]。
2.2 预测椎体再骨折的发生风险初发OVF患者骨质量较差,椎体再骨折的风险显著增加而出现椎体级联骨折的现象[39]。椎体CT值下降是椎体强化术后椎体再骨折的独立危险因素[40],初发OVF合并椎体CT值降低的患者1年内和3年椎体再骨折的风险将增加1.38倍和1.25倍。一项对275例接受椎体强化术治疗的OVF患者的病例对照研究[41]发现,L1 CT值的下降与椎体再骨折及椎体级联骨折的发生密切相关,当L1 CT值< 61 HU时,患者椎体再骨折的风险增加7.6倍;当L1 CT值< 54 HU时,患者发生椎体级联骨折的风险增加9.8倍。Ji等[42]对317例行椎体强化术的OVF患者进行回顾性研究发现,椎体强化术后椎体再骨折的发生率为13.6%,既往脆性骨折史(OR=6.639)及L1 CT值下降(OR=15.260)均与椎体强化术后椎体再骨折的发生密切相关(表 2)。
本团队对近5年共515例行椎体强化术的OVF患者椎体再骨折的风险因素进行了回顾性研究[11],并分析了L1 CT值对骨质疏松症患者发生椎体再骨折的预测价值。OVF患者椎体强化术后椎体再骨折的发生率为32.2%,再骨折患者的L1 CT值显著低于无再骨折组。COX回归分析证实高龄、低体质量指数(BMI)、糖尿病病史、接受抗骨质疏松药物治疗及L1 CT值下降均与椎体再骨折密切相关。ROC提示L1 CT值预测椎体再骨折风险的截断值为95 HU(AUC为0.802;灵敏度为70.5%,特异度为9.9%),Kaplan-Meier生存曲线提示L1 CT值< 95 HU的患者5年内无再骨折生存率显著低于对照组(log-rank test,P < 0.001)。该研究证实椎体CT值可有效识别OVF椎体再骨折的高风险人群,初发OVF患者L1 CT值< 95 HU时椎体再骨折风险显著增加。
2.3 椎体CT值的优势及局限性与传统的骨质量评估工具相比,椎体CT值在预测OVF及椎体再骨折风险中具有以下优势。①敏感评估OVF的发生风险。松质骨代谢活性较皮质骨高8倍[44],椎体CT值所测量的松质骨BMD能更敏感地评估骨量丢失,可更早识别OVF高风险患者。②降低OVF的漏诊率。在完成椎体CT值测量的基础上,充分利用CT扫描的结构测量优势,通过半定量的方法尽早识别OVF。③指导OVF治疗方案的选择。对于因剧烈腰背痛不能配合完成DXA的急性OVF患者,椎体CT值可作为初步评估BMD的有效替代工具,有助于制订个性化的手术及抗骨质疏松治疗方案,降低椎体再骨折的发生风险。④提高OVF风险预测的准确率。肌肉CT值的减少反映了肌纤维数量的减少及脂肪物质的堆积,联合椎体CT值评估有助于提高OVF及椎体再骨折风险预测的准确率[45]。
椎体CT值在辅助预测OVF及椎体再骨折的发生风险的应用中仍存在一定的局限性。①椎体CT值的最佳预测阈值及最佳筛查椎体节段尚未明确,未来需要大样本的横断面研究或前瞻性研究来确定及验证。②忽略了椎体皮质骨质量对OVF发生风险的影响。除了骨小梁密度及强度的下降等因素外,椎体皮质骨的退行性变对OVF的发生也存在显著影响[46]。Yao等[47]的研究发现,L1 CT值及椎体骨皮质厚度均与BMD下降密切相关。椎体CT值联合椎体皮质骨厚度测量综合评估椎体骨强度,可更有效地预测OVF及椎体再骨折的发生风险。
3 结语与展望椎体骨折是骨质疏松症患者最严重的并发症之一,严重影响患者的生活质量和预期寿命。骨质量评估对椎体骨折患者的诊疗方案制订和再骨折的预防至关重要。椎体CT值可反映松质骨骨量水平,在患者BMD的评估及椎体骨折风险的预测中优势显著。在我国现有DXA仪器数量不能满足临床需求的背景下,椎体CT值的测量是一种快速、可重复的骨质量评估方法。椎体CT值测量简单、方便,不需要额外的扫描设备和软件,适用于基层医院的筛查工作。椎体CT值还可有效预测骨质疏松症患者OVF及椎体再骨折的发生风险,有助于实现对高危人群早期评估、早期诊断、早期干预的目标。但是,椎体CT值的应用须解决不同机器之间测量结果的差异问题。在CT扫描仪中添加标准化的体模校准是解决该问题的简单方法,但目前CT制造商对骨质疏松症筛查和诊断工作的关注仍有限。此外,将机器学习算法和人工智能技术与椎体CT值结合可实现高危人群的大规模筛查,对骨质疏松症诊断及OVF风险预测阈值的确立有重要意义。综上所述,椎体CT值是BMD测量工具的有益补充,临床应用潜力巨大,其在临床中进一步的推广仍需临床医师、影像科医师及专业技术人员的共同努力。
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