骨折风险评价工具(FRAX®)研究及应用
313100 湖州，浙江大学医学院第二附属医院长兴院区(长兴人民医院)骨科
摘要：脆性骨折是骨质疏松症(osteoporosis，OP)的常见并发症，为了评估该类骨折的发生风险，最终达到预防的目的，世界卫生组织(World Health Organization，WHO)推荐使用骨折风险评价工具(fracture risk assessment tool，FRAX®)对目标人群进行评价，即通过利用计算机软件综合分析受试者临床骨折危险因素，评价其未来10年骨折发生概率。FRAX®在制定过程中，排除了部分常见的骨折危险因素，使预测具有一定特异性，然而区域差异等因素导致无法形成统一的FRAX®干预阈值供临床医生直接使用，所以要真正发挥该评价工具的作用，需根据各地区人群特点建立符合当地特征的模型。另外随着对该评价工具认识的逐步深入，其使用范围也在不断扩大，针对特殊疾病患者的临床应用也在逐渐受到关注。鉴于该工具较高的实用性，国内已逐渐接受并将其付诸实践，并取得一定成果。FRAX®从诞生之初至广泛应用，研究与探讨从未停息，本文就近年来的进展做一综述。
关键词：脆性骨折 骨折风险评价工具 骨质疏松症
Research and application of the fracture risk assessment tool(FRAX®)
Department of Orthopedics, the Second Affiliated Hospital of Medical College of Zhejiang University Changxing Campus (Changxing People's Hospital), Huzhou 313100, Zhejiang, China
Abstract: Fragile fracture is a common complication of osteoporosis (OP). In order to assess the risk of such fracture and achieve the goal of prevention, the World Health Organization (WHO) recommends the use of fracture risk assessment tool (FRAX®) to evaluate the target population, that is, to comprehensively analyze the risk factors of clinical fracture in subjects by using computer software. To evaluate the incidence of fracture in the next 10 years. In the process of FRAX® formulation, some common fracture risk factors were excluded and the prediction specific was made. However, regional differences and other factors lead to the failure to form a unified FRAX® intervention threshold for clinicians to use directly. Therefore, in order to play the role of the evaluation tool, it is necessary to establish a model according to the local characteristics of the population. In addition, with the gradual deepen understanding of the evaluation tool. The use of FRAX®and the clinical application for special diseases is also gradually attracting attention. In view of its high practicability, FRAX® has been gradually accepted and put into practice in China. This paper reviews the status of the researches and application of FRAX® in recent years.
Key words:
fragility fractures fracture risk assessment tool osteoporosis
骨折风险评价工具(fracture risk assessment tool，FRAX®)是世界卫生组织(World Health Organization，WHO)推荐的评价骨质疏松症(osteoporosis，OP)患者骨折风险的计算机软件，临床用于协助识别脆性骨折风险较高的患者，并指导适当干预。脆性骨折的多发性和后果的严重性，促使该工具在世界范围内受到广泛研究和应用，现将其进展做一综述。
FRAX®的基本情况FRAX®工具收录了患者的性别、年龄、体质量指数及其他7个独立的临床危险因素, 包括既往脆性骨折史、父母髋部骨折史、长期糖皮质激素使用史、类风湿关节炎史、大量饮酒史、吸烟以及是否患有其他导致继发性OP的疾病，股骨颈骨密度(bone mineral density，BMD)列为可选因素, 在线打开该软件，根据要求选择是或否，即可得出未来10年髋部及主要OP骨折部位(包括髋部、脊椎、桡骨远端和肱骨)发生骨折风险的概率。基于超过25年大量的队列研究结果支持FRAX®所使用的算法来估计髋部骨折和主要骨折的发生率[1]。临床实践表明，FRAX®应用于门诊患者或社区居民的筛查或诊断，可以减少不必要的BMD检查的数量，以及盲目的OP治疗[2]。
FRAX®与其他评价工具对比BMD测定、亚洲人骨质疏松自我筛查工具(osteoporosis self-assessment tool for Asian, OSTA)[3]、定量CT扫描、GARVAN-NO MOGRAM评估法、有限元分析[4]等也可以用于评价骨折风险，但对客观条件要求较高, 而且对于BMD来说也有其局限性[5]。澳大利亚的研究认为OSTA在识别低骨折风险人群时与不包含BMD的FRAX®相似[6]。但另有研究表明，OSTA对高龄人群评价的敏感性没有FRAX®好[7]。FRAX®和澳大利亚GARVAN-NOMOGRAM评估法在髋部骨折预测的一致性在以前是被接受的, 但前者的应用范围更广[8]。
FRAX®关联因素选择FRAX®所选择的骨折危险因素均经过验证，除此之外的常见因素也受到广泛研究和讨论。
BMD是受到关注最多的危险因素。澳大利亚等地区的研究认为对于低风险人群不包含BMD的FRAX®也可以给出不逊于其他工具的的阈值[9-10]，尤其在年轻人群，单独的FRAX®可以提供与包含BMD的FRAX®相同的预测结果[11]。研究表明在无症状的绝经后女性，不参考BMD的FRAX®已较腰椎和股骨颈T值更能准确的预测常见的脊柱骨折[12]。英国的研究甚至认为，可以先行FRAX®评价，再根据结果决定是否检查BMD[13]。也有特殊情况需要注意，当预测时间超过10年时，通过BMD的预测好于通过临床风险因素评估FRAX®[14]，而且针对特殊人群的试验结果认为不包含BMD的10年骨折风险测算会轻度高估骨折风险[15]，欧洲的研究认为当选择BMD时FRAX®预测脊柱骨折的能力即被改善[16]，但是随意选择BMD检查的部位对于接近临界值的患者的骨折风险评价会产生较大影响[17]。西班牙的研究认为不选择BMD的FRAX®目前针对女性髋部骨折的预测效果尚可，但是对于预测主要部位骨折的能力有限[18]。
另外一些未入选因素也受到关注。骨小梁评分可以描述骨骼微结构，实验表明将其纳入FRAX®后可能提高骨折预测水平[19]。老年人脊柱的形态特征如胸椎曲度、腰椎曲度及坐立时的倾斜角与通过FRAX®计算得出脆性骨折的概率有确定关系[20]。血糖水平对于糖尿病患者是独立于BMD和FRAX®之外的髋部和主要骨折的预测指标[21]，但加拿大的研究认为，糖尿病是主要骨折的独立危险因素，但不会明显影响FRAX®的效果或骨折的高发部位[22]。研究认为炎性肠病不会使整体骨折风险升高，但是可能使髋部骨折风险升高[23]。跌倒是发生骨折的重要危险因素，但其干扰因素较多且难以量化，所以在FRAX®计算中没有被涉及。澳大利亚的研究表明，社会经济状况也可能是独立的骨折危险因素，虽然FRAX®提供了骨折评价和修正，但是没有把它考虑在内[24]。
FRAX®相关资料的获得对FRAX®表现的系统分析认为，可能因为评价因素获得的难度及准确度的差异，导致往往只在某一群体去评估FRAX®的性能并进行校正，而没在总体环境下进行[25]。FRAX®中使用的很多临床危险因素可以在电子病历中获得，但是与现有文献报道的研究相比，利用电子病历数据库做的研究得出的结果很有可能偏低[26]。
FRAX®在不同人群的使用 FRAX®适用对象FRAX®适用于未发生过骨折的骨量低下人群(T值＞-2.5)。不同年龄段使用的效果不同。针对≥85岁老年人的研究发现，FRAX®对该人群预测值偏低[27]，但是罗马尼亚的研究认为，骨折概率的干预阈值能够捕获高骨折风险患者，且不受年龄因素干扰[28]，尤其筛查年轻的患者，可降低不必要的检查，同时还提高发现需要接受干预患者的概率[29]。美国的研究认为FRAX®应该被推荐用来筛选高骨折风险的老年人[30]。加拿大的研究表明，FRAX®严重低估了年龄＜65岁并且发生过一次脆性骨折患者再骨折风险[31]。有数据表明性别因素也可导致偏倚，FRAX®可以被单独用来识别高风险女性，但是对男性的研究却很少，而且在整体骨折发生率方面仅有的研究结果认为评价能力仍不满意[32-33]。美国的一项研究也认为，把FRAX®应用在男性患者，其价值仍存在不确定性[34]。
FRAX®在不同国家的使用芬兰的研究表明，利用当地居民中绝经后妇女对修正后的芬兰FRAX®模型进行评估，提示芬兰的FRAX®工具能够恰当的反映髋部骨折风险状况[35]。波兰版本的FRAX®通过与实际的骨折发生率进行对比，其可信度得以验证[36]。欧洲的诸多研究表明，尽管FRAX®预测能力久经证实，但是作为金标准来实施干预仍然存在局限性，因为其敏感度较低、混杂因素的影响以及缺乏确能达标的证据[37]，类似的研究表明，FRAX®评分的改变无法独立地预测骨折可能性的改变，其反应程度不足以被当作治疗结果的评估工具[38]。英国国家健康研究院和国家OP指南小组认可FRAX®能够识别80%骨折人数作为中位或者更高风险的骨折[39]。加拿大指南推荐FRAX®来报告10年骨折风险，FRAX®报告被家庭医生优先选用并且产生了更好的骨折后随访及更接近专家的治疗策略[40]。在日本，FRAX®最近也被用来确定是否对骨量减少患者开始药物治疗的标准[41]。韩国针对类风湿关节炎患者的研究表明，符合FRAX®标准的患者发生新骨折的概率同根据BMD诊断的OP患者的发生概率一样，并据此进行药物干预[42]。在新加坡，FRAX®被用来指导减少风险因子或其他因素，如跌倒、补充钙和维生素D等[43]。爱尔兰的FRAX®模型是第一个使用国家髋部骨折概率数据和爱尔兰病死率修正过的骨折预测模型[44]。FRAX®工具已经被葡萄牙成功地修正到适合葡萄牙人的程度，现在就能够被用来计算10年OP性骨折的风险[45]。在马来西亚，FRAX®已部分代替最初的基于BMD的诊治[46]。根据总体罗马尼亚人进行修订的FRAX®模型在2011年6月发布，并且阐述了其不同于其他国家模型的特征[47]。哥伦比亚的FRAX®模型于2010年6月30日发布，FRAX®工具成为哥伦比亚临床使用较好的方法[48]。在沙特阿拉伯，使用FRAX®评估10年与OP相关的骨折概率，并从初级预防的人群中发现需要及时干预的患者[49]。斯里兰卡FRAX®模型与非洲的其他国家模型表现一致[50]。在墨西哥以及巴勒斯坦地区，使用FRAX®可帮助在巴勒斯坦的初级预防中心筛查出存在高骨折风险的人群[51]。
FRAX®在实际运用中出现的问题在瑞士，研究发现他们目前提出的FRAX®阈值不能把50%~70%的研究人群在骨折以前就将他们归类到高风险行列[52]，需要及时修正。在意大利，WHO推荐的FRAX®对于全科医师来说使用起来存在一定障碍[53]。在韩国，有88%的人知道FRAX®，其中只有19.3%的人使用[54]。很多国家缺少流行病学资料，对FRAX®评价效果的评估带来影响[55]。
FRAX®在不同学科领域的使用OP性骨折继发于很多疾病。溃疡性结肠炎患者是得OP的高危人群，FRAX®评价骨折风险指导干预[56]。肌少症患者，联合四肢骨骼肌质量、握力、步行速度能够提高FRAX®预测中国老年男性骨折发生率的能力[57]。对于肥胖人群，FRAX®已被证实有预测价值[58]。富马酸替诺福韦酯治疗艾滋病及慢性肝炎患者时可使其骨矿物质流失，研究表明，FRAX®对其预测结果与BMD检测结果一致[59]。口腔科方面，FRAX®评价提示高骨折风险的绝经后妇女已经患有严重到难以治疗的牙周疾病，提示牙科医生在处理患有牙周病的绝经后女性的时候，应该关注到他们的FRAX®评估值可能预示着较高的骨折风险[60]。FRAX®把大部分接受肾移植的患者分类为低骨折风险组，但是临床医生在接受肾移植手术的患者人群中常规使用FRAX®之前，仍建议逐个患者确认[61]。患有慢性肾病的患者的骨折风险升高，FRAX®能够判断其骨折概况，研究结果表明其表现与BMD相当[62]。前列腺癌患者接受雄激素阻断治疗时的骨丢失，FRAX®也可对其进行评估[63]。研究者建议在所有库欣综合征患者中使用FRAX®评估，并采用17%作为干预阈值，尽可能逆转OP和骨折风险[64]。俄罗斯针对100个长期吸烟的患有COPD的男性进行的研究表明，FRAX®的应用揭示患有COPD的患者存在OP性骨折风险成为可能[65]。
FRAX®的应用前景统计发现，FRAX®在非洲和部分南亚国家使用相对较少[66]，在我国也尚未被广泛接受。Wang等[67]利用FRAX®进行脆性骨折风险评估的效果较为满意，所以虽然该工具并非WHO推荐的官方工具，且近年来也没有对其再进行充分的评估[68]，相信随着社会需求的不断增大，大家根据各地人群的特点进行修正和正确使用，其应用也将会得到不断发展。
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| (收稿日期：2017-11-07) |