标准与规范 | 肌骨系统疾病临床研究方法专家共识

共识综合与多学科· 未分类与其他 · 中华医学会骨科学分会

标题: 标准与规范 | 肌骨系统疾病临床研究方法专家共识

作者: 中华医学杂志

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引用本文：中华医学会骨科学分会, 中国医师协会骨科医师分会, 国家老年疾病临床医学研究中心（湘雅医院）. 肌骨系统疾病临床研究方法专家共识 [J] . 中华医学杂志, 2024, 104(23) : 2123-2141. DOI: 10.3760/cma.j.cn112137-20231124-01181.

通信作者：雷光华，中南大学湘雅医院骨科，国家老年疾病临床医学研究中心（湘雅医院），长沙410008，Email：lei_guanghua@csu.edu.cn；张英泽，河北医科大学第三医院骨科，石家庄050051，Email：dryzzhang@126.com.

摘要

肌骨系统疾病的临床研究对明确该类疾病的危险因素、规范和创新诊疗方法十分重要，为进一步促进肌骨系统疾病临床研究规范化，满足当前临床研究实践需要，中华医学会骨科学分会、中国医师协会骨科医师分会及国家老年疾病临床医学研究中心（湘雅医院）组织专家基于国际权威肌骨系统疾病临床研究方法学标准和指南，结合我国医疗卫生实践，制订出符合我国国情的肌骨系统疾病临床研究方法专家共识，旨在促进肌骨系统疾病临床研究规范化、科学化。

肌骨系统疾病是指影响骨骼、关节、肌腱、韧带和肌肉等组织器官正常功能的一系列疾病的统称，主要包括创伤性疾病、退行性疾病、感染性疾病、代谢性疾病、先天发育性疾病、遗传性疾病和骨与软组织肿瘤等［1-4］。大部分肌骨系统疾病可导致疼痛和行动力丧失，是老年人致残的主要原因之一［5］。随着全球人口老龄化程度日益加剧，肌骨系统疾病给患者和社会带来了沉重负担［2］。然而，目前肌骨系统疾病的影响因素尚未完全阐明，有些治疗手段往往局限于对症治疗，疗效有限且安全性风险不明。

临床研究从具体临床问题出发，通过采用标准、严谨、合乎伦理要求的研究设计，以明确疾病的影响因素并评价治疗手段的有效性和安全性，从而针对性解决重要临床问题。开展肌骨系统疾病临床研究旨在：（1）明确疾病发生发展及预后的影响因素；（2）评价现有治疗手段的疗效与安全性；（3）探索更准确、更明确的诊断技术和方法；（4）探索安全有效的治疗新方法。综上，为进一步促进肌骨系统疾病临床研究规范化，满足当前临床研究实践需要，填补国内肌骨系统疾病领域临床研究方法学指导空白，中华医学会骨科学分会和中国医师协会骨科医师分会组织相关专家在国外肌骨系统疾病临床研究方法学标准和指南基础上，结合我国医疗卫生实践，制订符合国情的肌骨系统疾病临床研究方法专家共识，为临床研究的研究设计、数据管理和质量控制等方面提供方法学指导，对中国肌骨健康促进和疾病防治具有重要临床意义。

第一部分本共识制订方法学

一、共识发起机构与专家组成员

本共识由国家老年疾病临床医学研究中心（湘雅医院）发起，中华医学会骨科学分会和中国医师协会骨科医师分会批准制订。由国家老年疾病临床医学研究中心（湘雅医院）组织骨科、运动医学科和流行病与卫生统计学领域的59名资深专家成立工作组。本共识启动时间为2023年1月，定稿时间为2024年2月。

二、共识使用者与应用目标人群

本共识使用者与应用目标人群包括但不限于各级医疗机构、医学院校及科研机构从事肌骨系统疾病临床研究相关的医务人员、科研工作者和医学生。

第二部分研究方案制订

一、研究问题的确定

临床研究选题要基于临床实践中亟待解决的、关键的、重要的临床问题，经过严格、全面的文献检索与总结以及向相关领域内专家咨询，遵循重要性、创新性、科学性、实用性和可行性的基本原则，明确研究对象、研究的干预措施或暴露因素、研究的对照人群、主要和次要的结局指标，最终将重要的临床问题转化为研究问题。

二、研究设计

研究设计是指根据研究问题和研究目的所制订的研究方案，旨在回答特定的研究问题或者检验特定的研究假设。一项考虑周密、合理、全面与可行的流行病学研究设计，能够很好地指导流行病学研究有序开展，对获得真实可靠的研究证据具有重要意义。开展研究前，研究者需明确研究目的，选择样本量足够、具有良好代表性的研究对象，选择合适的研究设计类型，研究变量要求客观、灵敏和特异，需应用正确的统计分析方法分析数据［6］。本共识将重点阐述随机对照试验和观察性研究两大类流行病学研究设计。

（一）随机对照试验

随机对照试验是指将研究对象随机分配到两组（或多组），分别接受不同干预的临床试验研究，通常被认为是研究治疗措施疗效和安全性的最佳方案。例如，最新研究发现：关节腔注射富血小板血浆对轻中度膝骨关节炎患者的症状与结构无明显改善作用［7］；低剂量白细胞介素-2可安全有效缓解类风湿关节炎病情进展［8］，这两项研究便是采用的随机对照试验设计。其优点是用随机的方式将研究对象进行分组，使比较组之间的背景因素可达到均衡分布，彼此几乎完全可比，控制了混杂偏倚；但由于伦理的限制，随机对照试验只能用于检验对健康有益的因素或措施的作用。

1. 根据研究假设撰写研究方案（protocol）：开展随机对照试验之前应根据已有的研究假设，确定并撰写研究方案。研究方案可经过同行评审的评议，由经验丰富的研究人员组成的学术委员会针对研究方案的研究设计提出建议，并通过伦理审查，对于涉及人类遗传样本采集、检测等的，按《中华人民共和国人类遗传资源管理条例》在科技部进行备案。研究方案还需线上注册（https：//clinicaltrials.gov/或https：//www.chictr.org.cn/），以便于后续研究的开展和发表。

2. 选择符合要求的研究对象：研究对象的选择需考虑是否能代表目标人群，从而使研究结果具有普遍外推性；干预组和对照组应为同一来源的人群；应制订合理的纳入和排除标准，使研究对象具有更好的内部一致性。样本量计算和预试验的开展有利于研究者对后续正式试验进行人力、财力及研究时间上的规划［9］。

3. 随机化、分配隐藏和盲法：随机化指所有研究对象有同等的概率被分配到干预组或对照组，有效的随机可实现比较组间预后因素的可比性，从而消除潜在的混杂偏倚。分配隐藏是指为了防止随机分组方案提前解密采用的一种方法，例如将随机分配方案密封在按顺序编号的不透明信封或外形相同的药物容器中进行递送。盲法是指为了避免干预实施、数据收集和评价过程中研究对象和研究者的主观因素带来的偏倚，使研究对象和研究者都不知道干预措施分组情况（双盲设计）。如果由于客观条件限制（如手术、针灸等干预）无法对研究对象和研究者实施盲法，可采用单盲设计（即仅对研究对象实施盲法）和其他方法减少偏倚的产生［10］。

4. 确定结局变量及测量方法：结局变量包括主要结局变量和次要结局变量。选择结局变量时需明确测量结局的时间及方法，以避免产生信息偏倚。结局变量应能确切反映研究目的和干预效应，具有可行性、客观性以及较高的灵敏性和特异性，测量方式应能被研究对象所接受。常见肌骨系统疾病科学研究常用结局指标举例如表1。

5.分析策略：数据分析时可采用不同的分析策略：（1）意向性治疗分析：指参与随机分组的研究对象，无论其是否真实接受该分组的治疗方案，最终都被纳入所分配组进行统计分析。该分析策略可保留随机化的优势，但可能低估干预措施效果或高估安全性风险［83］。（2）遵循研究方案分析［84］：即只对完成随机分组时所指定的治疗方案的研究对象进行分析。该分析策略能反映试验药物的生物效应，但可能产生选择偏倚，高估干预效果或低估安全性风险。（3）接受实际治疗分析［85］：指根据研究对象实际接受的治疗而不是随机分配的治疗进行分析。由于比较的对象非随机分组，该分析策略可能存在选择偏倚。在评价随机对照试验的干预措施的效应时，可同时使用以上3种分析策略，以获得更全面的信息。

等效性检验：研究目的：检验试验药物A的有效性或安全性是否与对照药B无差异；假设检验：A.无效假设：A-B≤-Δ或A-B≥Δ；B.备择假设：-Δ<a-b<Δ；结论：a药与b药差异的置信区间落在设定的界值（-Δ，Δ）范围内时，可认为a药与b药等效；适用范围：常用于对同一活性成分的药物之间的比较。

优效性检验：研究目的：检验试验药物A的有效性或安全性是否优于对照药B；假设检验：A.无效假设：A-B≤Δ；B.备择假设：A-B>Δ；结论：A药与B药差异的置信区间下限大于设定的界值Δ时，可认为A药优于B药；适用范围：常用于以安慰剂为对照的试验。

（2）统计分析方法选择：临床研究中的统计分析方法包括统计描述和统计推断。统计描述是对资料的数量特征及其分布规律进行测定和描述，统计推断则是由样本信息推断总体特征。临床研究数据类型主要分为计量、计数和等级数据等，不同类型的数据要合理选择相应的统计分析方法［203］。选择统计分析方法可按照以下思路进行：①因变量是单变量、双变量还是多变量；②结局指标属于三种数据类型中的哪一种（连续资料、分类资料或等级资料）；③暴露因素为单因素还是多因素；④样本分组为单样本、两样本或多样本；⑤研究设计为独立设计还是配对或配伍设计；⑥是否满足检验方法所需的前提条件。经典统计分析方法如t检验、方差分析、χ2检验等通常不涉及时间变量，而现代高级统计方法是经典统计分析方法的延伸和发展，表现在空间的广度和时间的深度上，如重复测量设计资料的分析、生存分析、判别分析等。

第三部分研究方案实施

一、研究伦理及知情同意

临床研究的对象是人，应当尊重受试者的自主意愿，遵循有益、不伤害、公正和保护隐私的原则，同时参照国家卫生健康委员会《涉及人的生物医学研究伦理审查办法》相关规定，经伦理审查委员会审批后方可开展研究，正式开始前还需按照“完全告知”的原则，由研究对象本人或其监护人签署知情同意。研究负责人在申请伦理审查时应当向伦理审查委员会提交以下材料：（1）研究材料诚信承诺书；（2）伦理审查申请表；（3）研究人员信息、研究项目所涉及的相关机构的合法资质证明以及研究项目经费来源说明；（4）研究项目方案、相关资料；（5）受试者知情同意书或样本、信息的来源证明等；（6）科学性论证意见；（7）利益冲突声明；（8）受试者招募广告及其发布形式；（9）科研成果的发布形式说明；（10）伦理审查委员会认为需要提交的其他相关材料。经伦理审查委员会批准后的项目在实施前应当将项目相关信息、伦理审查意见和机构审核意见等按国家医学研究登记备案信息系统要求上传，并根据研究进展及时更新信息。若研究涉及基因、器官、组织等人类遗传资源，需按照有关管理条例提前报备。

二、现场数据收集

现场调查实施前应取得有关部门的支持；制订现场工作手册，内容主要包括课题研究的背景、研究的组织机构、研究目的、研究设计、研究的实施步骤、调查方法及调查问卷条目的解释等，用于指导现场工作的开展。现场调查过程中需要的物品和设备应提前准备好，并在调查过程中注意校准，以减少系统误差。调查前准备工作完成后，则可进行预调查，充分动员调查对象。调查正式开始后，应规划好每天的工作量，在现场设立不同的功能分区，逐一核查研究对象是否完成研究项目，若有遗漏要及时补查。完成每天的调查工作后，还需要对当天的现场工作进行审查、总结，保证调查有序、高质量地完成。

病例报告表（CRF）是临床研究中数据收集的一种常用手段，在提高临床研究数据质量以及统计分析的质量和效率、方便数据的交流与汇总分析等方面发挥重要作用。目前临床数据获取协调标准（CDASH）［210］被监管部门推荐作为CRF设计的基本标准，其组成部分包括CDASH模型、实施指南和相关元数据表。CRF设计应由研究方案设计者、数据录入人员、统计分析人员、数据管理及质控人员、临床医师及伦理委员会等多方面人员参与，在设计中应注意遵循方案、内容完整，符合法规及相关标准，易于理解、有标准操作规程，简明扼要、避免重复、布局合理等。

三、质量控制与数据管理

质量控制是临床研究的一个关键环节。质量控制应在临床研究的研究设计阶段、数据收集阶段、结果评价阶段以及数据分析阶段的全过程中实施。研究方案中应根据已有的知识，分析可能出现的影响研究精确性与真实性的问题，并针对各类问题制订详细的质量控制措施。例如，研究开始前应对研究参与者进行责任分工和指导培训，提供标准化的操作手册以及标准化操作培训，考核合格后方能正式参与工作；要严格确保研究对象符合纳入排除标准，采用规范合理的研究方法、技术、标准的问卷，所有的仪器设备应经过计量认证，以确保研究过程中的每一个环节和数据正确无误；问卷调查时要记录好问卷开始和结束的时间，评估问卷的准确度和完成度；主观评价指标需要进行信效度的检验；实验室检测中通过设计标准对照和平行样本，监控实验质量。另外，应尽量避免在研究开始后修改研究方案，如果必须修改方案应标注具体原因和时间。

研究数据收集完成后应安排专人负责管理，防止数据的丢失、泄露、破坏或误用等。纸质型数据需进行扫描和电子存档，与扫描电子数据完全核对一致后，将纸质型数据进行销毁；电子数据中的隐私数据需匿名化处理后保存；存放数据的计算机系统必须有全面、规范、严格的用户管理办法；数据管理负责人严格遵守数据备份要求，及时做好数据的备份工作。

四、数据分析结果解读

P值是指从无效假设所规定的总体做随机抽样，获得等于及大于（或等于及小于）现有样本的检验统计量值的概率，被广泛用于临床研究数据分析结果解读，P<0.05成为差异具有统计学意义的判断标准。然而，研究中常存在对P值解读错误或进行人为操纵、基于P值是否<0.05进行一刀切等问题，近年来对P<0.05这一法则存在着种种质疑与批评［211］。研究人员进行临床研究数据分析结果解读时应避免追求单纯的“统计学”差异。例如，不能以P<0.05来断定整个研究的结论，而应该综合研究设计、样本量大小与样本代表性、数据质量、统计分析方法等多维度来思考研究变量之间是否存在真实的关联；应关注效应点估计值与区间估计值（如95%CI）；研究的汇报结果应与临床实际相结合，譬如与具有临床显著性的最小差值进行比较，以辅助判断研究结论可能的临床或公共卫生意义。

第四部分研究报告撰写

一、随机对照试验

随机对照试验应该按照CONSORT声明进行报告撰写［212］。该声明包含25个条目组成的清单和一个流程图。清单对论文的标题摘要到讨论部分的写作进行了规定，并对试验注册、试验方案和资助情况的说明做出了要求。流程图则要求研究者对研究对象的登记、分配、随访和分析阶段的流动情况以流程图的形式表现出来。

二、观察性研究

观察性研究应该按照STROBE声明进行报告撰写［213］。STROBE清单覆盖观察性研究的三种主要研究设计——横断面研究、病例对照研究和队列研究，包括标题和摘要、引言、方法、结果、讨论和其他信息六大部分共22个条目的撰写要求，以为更好地报告观察性研究提供指导。

综上，临床研究的研究设计、数据管理与质量控制应该渗透在整个临床研究过程中，数据收集、数据库搭建、数据录入、数据整理与数据分析方案制订等环节都极大影响了临床研究的质量。肌骨系统疾病临床研究方法专家共识的制订有助于促进肌骨系统疾病临床研究规范化，保障临床研究的顺利开展，提升临床研究的质量，为我国肌骨系统疾病的临床研究和实践提供科学指导和帮助。

本专家共识制订委员会名单

项目负责人：雷光华［中南大学湘雅医院骨科，国家老年疾病临床医学研究中心（湘雅医院）］；张英泽（河北医科大学第三医院骨科）

指导专家组：邱贵兴（北京协和医院骨科）；姜保国（北京大学人民医院创伤骨科）；唐佩福（解放军总医院第四医学中心骨科医学部）；王坤正（西安交通大学第二附属医院骨科）

编写专家组（按姓氏汉语拼音排序）：敖英芳（北京大学第三医院运动医学科）；白晓春（南方医科大学附属第三医院骨科）；曹力（新疆医科大学第一附属医院骨科）；曾超（中南大学湘雅医院骨科）；陈廖斌（武汉大学中南医院关节与运动医学科）；陈世益（复旦大学附属华山医院运动医学科）；范存义（上海交通大学附属第六人民医院骨科）；冯世庆（天津医科大学总医院骨科）；高曙光（中南大学湘雅医院骨科）；郝定均（西安交通大学医学院附属红会医院脊柱外科）；侯志勇（河北医科大学第三医院骨科）；胡懿郃（浙江大学医学院附属第一医院骨科）；胡永成（天津骨科医院骨肿瘤科）；姜建元（复旦大学附属华山医院骨科）；蒋青（南京大学医学院附属鼓楼医院骨科）；寇玉辉（北京大学人民医院创伤骨科）；李辉（中南大学湘雅医院骨科）；李宇晟（中南大学湘雅医院骨科）；林剑浩（北京大学人民医院骨关节科）；刘璠（南通大学附属医院骨科）；罗卓荆（第四军医大学附属西京医院骨科）；马信龙（天津医科大学总医院骨科）；裴福兴（四川大学华西医院骨科）；裴国献（南方科技大学医院骨科）；秦彦国（吉林大学第二医院骨科）；邵增务（华中科技大学同济医学院附属协和医院骨科）；苏佳灿（海军军医大学长海医院创伤骨科）；谭明生（中日友好医院脊柱外科）；王娟（河北医科大学第三医院关节外科）；王伊伦（中南大学湘雅医院骨科）；王拥军（上海中医药大学附属龙华医院脊柱病研究所）；翁习生（北京协和医院骨科）；肖建如（海军军医大学长征医院骨科）；肖文峰（中南大学湘雅医院骨科）；谢东兴（中南大学湘雅医院骨科）；熊依林（中南大学湘雅医院骨科）；徐卫东（长海医院关节骨病外科）；徐文东（复旦大学附属华山医院手外科）；许建中（陆军军医大学第一附属医院骨科）；阎作勤（复旦大学附属中山医院骨科）；杨惠林（苏州大学附属第一医院骨科）；杨柳（陆军军医大学第一附属医院关节外科）；殷国勇（南京医科大学第一附属医院骨科）；余斌（南方医科大学南方医院骨科）；余家阔（北京大学第三医院运动医学科）；张长青（上海第六人民医院骨科）；赵德伟（大连大学附属中山医院骨科）；周跃（陆军军医大学第二附属医院骨科）

方法学及流行病学专家组：张余庆（哈佛医学院马塞诸塞州总医院风湿免疫科临床研究中心）；魏捷（老年骨关节疾病防治教育部重点实验室中南大学湘雅公共卫生学院）；吴心音（中南大学湘雅公共卫生学院）；杨子丹（老年骨关节疾病防治教育部重点实验室骨关节退变与损伤湖南省重点实验室）；王昊晨（中南大学湘雅医院骨科）

执笔者：魏捷（老年骨关节疾病防治教育部重点实验室中南大学湘雅公共卫生学院）；曾超（中南大学湘雅医院骨科）；王伊伦（中南大学湘雅医院骨科）

利益冲突

所有作者声明不存在利益冲突

参考文献（下滑查看）：

[1]GwinnuttJM, WieczorekM, BalanescuA, et al. 2021 EULAR recommendations regarding lifestyle behaviours and work participation to prevent progression of rheumatic and musculoskeletal diseases[J]. Ann Rheum Dis, 2023, 82(1):48-56. DOI: 10.1136/annrheumdis-2021-222020.

[2]SebbagE, FeltenR, SagezF, et al. The world-wide burden of musculoskeletal diseases: a systematic analysis of the World Health Organization Burden of Diseases Database[J]. Ann Rheum Dis, 2019, 78(6):844-848. DOI: 10.1136/annrheumdis-2019-215142.

[3]BairMJ, KrebsEE. Fibromyalgia[J]. Ann Intern Med, 2020, 172(5):ITC33-ITC48. DOI: 10.7326/AITC202003030.

[4]HamermanD. Aging and the musculoskeletal system[J]. Ann Rheum Dis, 1997, 56(10): 578-585.

[32]LiY, SamartzisD, CampbellDD, et al. Two subtypes of intervertebral disc degeneration distinguished by large-scale population-based study[J]. Spine J, 2016, 16(9):1079-1089. DOI: 10.1016/j.spinee.2016.04.020.

[33]DelamarterR, ZiglerJE, BalderstonRA, et al. Prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement compared with circumferential arthrodesis for the treatment of two-level lumbar degenerative disc disease: results at twenty-four months[J]. J Bone Joint Surg Am, 2011, 93(8):705-715. DOI: 10.2106/JBJS.I.00680.

[34]NguyenC, BoutronI, BaronG, et al. Intradiscal glucocorticoid injection for patients with chronic low back pain associated with active discopathy: a randomized trial[J]. Ann Intern Med, 2017, 166(8):547-556. DOI: 10.7326/M16-1700.

[49]GenslerLS, WardMM, ReveilleJD, et al. Clinical, radiographic and functional differences between juvenile-onset and adult-onset ankylosing spondylitis: results from the PSOAS cohort[J]. Ann Rheum Dis, 2008, 67(2):233-237. DOI: 10.1136/ard.2007.072512.

[50]JaakkolaE, HerzbergI, LaihoK, et al. Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis[J]. Ann Rheum Dis, 2006, 65(6):775-780. DOI: 10.1136/ard.2005.041103.

[51]BraunJ, BrandtJ, ListingJ, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial[J]. Lancet, 2002, 359(9313):1187-1193. DOI: 10.1016/s0140-6736(02)08215-6.

三、证据检索

共识制订工作组成立了证据检索与评价小组，根据我国临床研究过程中的关键方法学问题，通过检索肌骨系统疾病临床研究方法学指南、共识、综述类文献及高质量临床研究文章，确定共识的初步框架。经共识制订专家组讨论评估和反馈意见，进一步明确本共识的关注方向。

四、推荐意见形成

共识制订专家组基于证据评估小组提供的国内外证据及自身的临床研究经验，同时考虑我国肌骨系统临床研究开展的真实情况及特点，初步拟定了共识推荐。共识制订工作组所有专家于2023年6至10月对推荐意见初稿进行了反复讨论、反馈及修改，最终达成共识。

本共识不具备强制性，不作为医疗事故鉴定和医学责任认定依据，仅供各级医疗机构、医学院校及科研机构从事肌骨系统疾病临床研究相关的医务人员、科研工作者和医学生参考。

图1 观察性研究流程图

1.基于已有数据集的可行性评价：观察性研究中的已有数据集主要包括电子病历、电子健康档案和医保数据等。由于这些已有数据集的数据采集并不针对某个特定研究目的，因此，此类数据集的完整性和准确性常常存在一系列问题。利用已有数据集开展临床研究前需进行可行性评估，主要包括以下几个方面：暴露变量和结局变量的测量是否准确、研究对象的关键基本信息是否记录准确（包括年龄、性别、身高、体重与合并症等）、数据清理方案是否合理、缺失值的数量和类型是否会对研究产生重大影响等。

2.数据收集的可行性评价：观察性研究常根据特定的研究目的开展数据收集。数据收集类型主要包括：自然人群队列的建立和随访、疾病注册登记和随访、公共健康监测等。此类数据集在建立之前已确定了具体的研究目的，需要收集的条目和数据也较为明确，因此数据的完整性和准确性均较好。但开展数据收集需要花费大量的人力和财力，其样本量常受到限制。开展数据收集工作前，研究者需要预先制订好数据收集方案，主要包括以下几个方面：确定潜在研究对象、样本量大小、数据条目和类型、抽样方案（招募方案）与质控方案等。

3.观察性研究的研究设计：观察性研究的主要研究类型为观察性研究，包括队列研究、病例-对照研究、自身对照研究和横断面研究等（表2）。

（1）队列研究：队列研究以研究开始时是否暴露于某因素或不同暴露程度将人群划分为不同组，随访一定时间后，通过比较各组结局发生率的差异，确定暴露因素与结局的联系，达到检验病因假设的目的。例如，既往研究采用前瞻性队列研究发现口服曲马多的骨关节炎患者的全因死亡率显著高于口服非甾体抗炎药的患者，表明曲马多可能升高骨关节炎患者的全因死亡率［86］；另有研究发现骨关节炎患者与对照组相比，其静脉血栓栓塞发生风险显著升高［87］。队列研究的优点是能明确提出暴露与结局时间先后的关系，可直接获得发生率等绝对指标，暴露资料都是在疾病发生之前收集，资料相对可靠等；其局限性在于耗费的人力、物力、财力和时间较多，实施难度较大，不适用于发病率很低的疾病的病因研究，易产生失访偏倚等［88］。

（2）病例对照研究：病例对照研究以确诊某特定疾病的一组患者作为病例组，以不患有该病但具有可比性的一组个体作为对照组，通过收集既往各种可能的危险因素的暴露史，测量并比较病例组与对照组中各因素的暴露比例，达到检验病因假设的目的［89］。例如，既往研究开展病例对照研究发现纤维肌痛患者相比对照组出现中枢痛觉敏化的风险显著升高［90］；另有研究发现骨肉瘤患者与对照组的氟化水饮用情况无显著差异，即饮用氟化水不会增加骨肉瘤的发生风险［91］。病例对照研究适用于罕见病和诱导期长的疾病，相对于队列研究更节省人力、物力、财力和时间，且较易组织实施。此研究类型的局限性在于不适用于研究极端罕见的暴露、容易受到回忆偏倚的影响、不能获得发病率等绝对指标等。

（3）自身对照研究：自身对照研究以自身为对照，经过一段时间的随访，按照是否暴露于某种因素分为暴露期和对照期，通过比较研究对象自身暴露期与对照期的疾病或其他结局的发生或进展的比例情况，推断暴露因素与疾病的因果关系；或者将研究对象分为患病期和对照期，回顾性寻找自身暴露情况，比较患病期与对照期的暴露比例，推断暴露因素与疾病的因果关系。例如，既往研究通过回顾性比较痛风患者在痛风发作前两天（风险期）和无痛风发作期（对照期）的樱桃食用情况，发现食用樱桃可显著降低痛风发作的风险［92］；另有研究通过比较成人在阿片类药物服用期间与未服用期间的骨折发生率，发现服用阿片类药物可升高骨折发生风险［93］。由于自身对照研究中的对比均发生于同一研究对象的不同时期，大部分潜在的混杂因素是保持稳定不变的（例如遗传因素），故该研究设计的最大优点是可避免大量未知或无法测量的混杂因素对研究结论的影响［94］。

（4）横断面研究：横断面研究是在某一人群中应用普查或抽样调查的方法收集特定时间内特定人群中疾病和相关因素的分布情况的一种研究类型，研究目的主要为描述疾病或健康状况在特定人群中的分布，或观察某些因素与疾病之间的关联，为病因研究提出初步线索或研究假设［95］。例如，既往横断面研究发现，高龄、超重及跌倒史与骨折风险升高之间存在显著正相关［96］；另有研究发现高龄、女性、营养不良、居住在农村地区和正在使用的药物数量与肌少症患病之间存在显著性关联［97］。横断面研究的优点是其是寻找病因或危险因素线索的最常用和最简单的方法，但难以确定暴露与结局之间的前后时序关系、不能获得发病率资料等。

4.暴露和结局：暴露变量是指影响疾病的发生进展或健康状况分布的变量；结局变量是指在暴露变量的作用下产生反应的变量，包括疾病状态（发病或进展）、健康状况、健康相关事件和死亡等。常见暴露变量的选择包括人口学基本特征、行为生活方式、社会经济状态、精神心理状态、膳食营养摄入、体力活动水平、家族遗传因素以及生理、生化和分子生物学标志物与治疗方式等。不同的研究课题和研究目的其结局变量不同，可通过定期问卷或电话随访来确定研究对象是否发生结局事件及其健康状况，或定期进行临床检查来获得生物学测量和影像学检查等结局指标，也可从医院记录、疾病登记系统和死亡监测系统等获取［98］。根据研究类型及研究目的不同，应选择合适的相应肌骨系统疾病结局指标（表1）。

[5]RobertsS, ColombierP, SowmanA, et al. Ageing in the musculoskeletal system[J]. Acta Orthop, 2016, 87(sup363):15-25. DOI: 10.1080/17453674.2016.1244750.

[6]詹思延. 流行病学[M]. 北京:人民卫生出版社, 2018.

[7]BennellKL, PatersonKL, MetcalfBR, et al. Effect of intra-articular platelet-rich plasma vs placebo injection on pain and medial tibial cartilage volume in patients with knee osteoarthritis: the RESTORE randomized clinical trial[J]. JAMA, 2021, 326(20):2021-2030. DOI: 10.1001/jama.2021.19415.

[8]ZhangX, MiaoM, ZhangR, et al. Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis: a randomized, double-blind, placebo-controlled phase 2 trial[J]. Signal Transduct Target Ther, 2022, 7(1):67. DOI: 10.1038/s41392-022-00887-2.

[9]BowlingA. Researching methods in health: investigating health and health services[M]. Buckingham: Open University Press, 1997.

[10]AltmanDG. Randomisation[J]. BMJ, 1991, 303(6799): 415-416.

[11]BradleyJD, BrandtKD, KatzBP, et al. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee[J]. N Engl J Med, 1991, 325(2):87-91. DOI: 10.1056/NEJM199107113250203.

[12]EttingerWH, BurnsR, MessierSP, et al. A randomized trial comparing aerobic exercise and resistance exercise with a health education program in older adults with knee osteoarthritis. The Fitness Arthritis and Seniors Trial (FAST)[J]. JAMA, 1997, 277(1):25-31.

[13]Paula DakinP, DiMartinoSJ, GaoH, et al. The efficacy, tolerability, and joint safety of fasinumab in osteoarthritis pain: a phase Ⅱb/Ⅲ double-blind, placebo-controlled, randomized clinical trial[J]. Arthritis Rheumatol, 2019, 71(11):1824-1834. DOI: 10.1002/art.41012.

[14]WangN, XieM, LeiG, et al. A cross-sectional study of association between plasma selenium levels and the prevalence of osteoarthritis: data from the Xiangya Osteoarthritis Study[J]. J Nutr Health Aging, 2022, 26(2):197-202. DOI: 10.1007/s12603-022-1739-2.

[15]JiangT, YangT, ZhangW, et al. Prevalence of ultrasound-detected knee synovial abnormalities in a middle-aged and older general population-the Xiangya Osteoarthritis Study[J]. Arthritis Res Ther, 2021, 23(1):156. DOI: 10.1186/s13075-021-02539-2.

[16]BeckerMA, BarafHS, YoodRA, et al. Long-term safety of pegloticase in chronic gout refractory to conventional treatment[J]. Ann Rheum Dis, 2013, 72(9):1469-1474. DOI: 10.1136/annrheumdis-2012-201795.

[17]SundyJS, BarafHS, YoodRA, et al. Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials[J]. JAMA, 2011, 306(7):711-720. DOI: 10.1001/jama.2011.1169.

[18]JanssensHJ, JanssenM, van de LisdonkEH, et al. Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial[J]. Lancet, 2008, 371(9627):1854-1860. DOI: 10.1016/S0140-6736(08)60799-0.

[19]KimSC, LiuJ, SolomonDH. Risk of incident atrial fibrillation in gout: a cohort study[J]. Ann Rheum Dis, 2016, 75(8):1473-1478. DOI: 10.1136/annrheumdis-2015-208161.

[20]LieblingMR, LeibE, McLaughlinK, et al. Pulse methylprednisolone in rheumatoid arthritis: a double-blind cross-over trial[J]. Ann Intern Med, 1981, 94(1):21-26. DOI: 10.7326/0003-4819-94-1-21.

[21]SköldstamL, HagforsL, JohanssonG. An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis[J]. Ann Rheum Dis, 2003, 62(3):208-214. DOI: 10.1136/ard.62.3.208.

[22]VanagsD, WilliamsB, JohnsonB, et al. Therapeutic efficacy and safety of chaperonin 10 in patients with rheumatoid arthritis: a double-blind randomised trial[J]. Lancet, 2006, 368(9538):855-863. DOI: 10.1016/S0140-6736(06)69210-6.

[23]MacholdKP, NeumannK, SmolenJS. Recombinant human interferon gamma in the treatment of rheumatoid arthritis: double blind placebo controlled study[J]. Ann Rheum Dis, 1992, 51(9):1039-1043. DOI: 10.1136/ard.51.9.1039.

[24]CordtzRL, ZobbeK, HøjgaardP, et al. Predictors of revision, prosthetic joint infection and mortality following total hip or total knee arthroplasty in patients with rheumatoid arthritis: a nationwide cohort study using Danish healthcare registers[J]. Ann Rheum Dis, 2018, 77(2):281-288. DOI: 10.1136/annrheumdis-2017-212339.

[25]HewettTE, TorgJS, BodenBP. Video analysis of trunk and knee motion during non-contact anterior cruciate ligament injury in female athletes: lateral trunk and knee abduction motion are combined components of the injury mechanism[J]. Br J Sports Med, 2009, 43(6):417-422. DOI: 10.1136/bjsm.2009.059162.

[26]ParkSK, StefanyshynDJ, RamageB, et al. Relationship between knee joint laxity and knee joint mechanics during the menstrual cycle[J]. Br J Sports Med, 2009, 43(3):174-179. DOI: 10.1136/bjsm.2008.049270.

[27]RoemerFW, LohmanderLS, EnglundM, et al. Development of MRI-defined structural tissue damage after anterior cruciate ligament injury over 5 years: the KANON Study[J]. Radiology, 2021, 299(2):383-393. DOI: 10.1148/radiol.2021202954.

[28]FrobellRB, RoosEM, RoosHP, et al. A randomized trial of treatment for acute anterior cruciate ligament tears[J]. N Engl J Med, 2010, 363(4):331-342. DOI: 10.1056/NEJMoa0907797.

[29]KatzJN, BrophyRH, ChaissonCE, et al. Surgery versus physical therapy for a meniscal tear and osteoarthritis[J]. N Engl J Med, 2013, 368(18):1675-1684. DOI: 10.1056/NEJMoa1301408.

[30]SihvonenR, PaavolaM, MalmivaaraA, et al. Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear[J]. N Engl J Med, 2013, 369(26):2515-2524. DOI: 10.1056/NEJMoa1305189.

[31]LiX, HuZ, CuiJ, et al. Percutaneous endoscopic lumbar discectomy for recurrent lumbar disc herniation[J]. Int J Surg, 2016, 27:8-16. DOI: 10.1016/j.ijsu.2016.01.034.

[35]BråtenL, RolfsenMP, EspelandA, et al. Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial[J]. BMJ, 2019, 367:l5654. DOI: 10.1136/bmj.l5654.

[36]OosterhuisT, OsteloRW, van DongenJM, et al. Early rehabilitation after lumbar disc surgery is not effective or cost-effective compared to no referral: a randomised trial and economic evaluation[J]. J Physiother, 2017, 63(3):144-153. DOI: 10.1016/j.jphys.2017.05.016.

[37]LiaoJC, ChenWJ. Surgical outcomes in the elderly with degenerative spondylolisthesis: comparative study between patients over 80 years of age and under 80 years-a gender-, diagnosis-, and surgical method-matched two-cohort analyses[J]. Spine J, 2018, 18(5):734-739. DOI: 10.1016/j.spinee.2017.08.250.

[38]GhogawalaZ, DziuraJ, ButlerWE, et al. Laminectomy plus fusion versus laminectomy alone for lumbar spondylolisthesis[J]. N Engl J Med, 2016, 374(15):1424-1434. DOI: 10.1056/NEJMoa1508788.

[39]WeinsteinJN, LurieJD, TostesonTD, et al. Surgical versus nonsurgical treatment for lumbar degenerative spondylolisthesis[J]. N Engl J Med, 2007, 356(22):2257-2270. DOI: 10.1056/NEJMoa070302.

[40]AustevollIM, HermansenE, FagerlandMW, et al. Decompression with or without Fusion in Degenerative Lumbar Spondylolisthesis[J]. N Engl J Med, 2021, 385(6):526-538. DOI: 10.1056/NEJMoa2100990.

[41]WeinsteinJN, LurieJD, TostesonTD, et al. Surgical compared with nonoperative treatment for lumbar degenerative spondylolisthesis. four-year results in the Spine Patient Outcomes Research Trial (SPORT) randomized and observational cohorts[J]. J Bone Joint Surg Am, 2009, 91(6):1295-1304. DOI: 10.2106/JBJS.H.00913.

[42]IshimotoY, YoshimuraN, MurakiS, et al. Associations between radiographic lumbar spinal stenosis and clinical symptoms in the general population: the Wakayama Spine Study[J]. Osteoarthritis Cartilage, 2013, 21(6):783-788. DOI: 10.1016/j.joca.2013.02.656.

[43]KatzJN, HarrisMB. Clinical practice. Lumbar spinal stenosis[J]. N Engl J Med, 2008, 358(8):818-825. DOI: 10.1056/NEJMcp0708097.

[44]MinetamaM, KawakamiM, TeraguchiM, et al. Supervised physical therapy vs. home exercise for patients with lumbar spinal stenosis: a randomized controlled trial[J]. Spine J, 2019, 19(8):1310-1318. DOI: 10.1016/j.spinee.2019.04.009.

[45]MoojenWA, ArtsMP, JacobsWC, et al. Interspinous process device versus standard conventional surgical decompression for lumbar spinal stenosis: randomized controlled trial[J]. BMJ, 2013, 347:f6415. DOI: 10.1136/bmj.f6415.

[46]WeinsteinJN, TostesonTD, LurieJD, et al. Surgical versus nonsurgical therapy for lumbar spinal stenosis[J]. N Engl J Med, 2008, 358(8):794-810. DOI: 10.1056/NEJMoa0707136.

[47]FörsthP, ÓlafssonG, CarlssonT, et al. A randomized, controlled trial of fusion surgery for lumbar spinal stenosis[J]. N Engl J Med, 2016, 374(15):1413-1423. DOI: 10.1056/NEJMoa1513721.

[48]HermansenE, AustevollIM, HellumC, et al. Comparison of 3 different minimally invasive surgical techniques for lumbar spinal stenosis: a randomized clinical trial[J]. JAMA Netw Open, 2022, 5(3):e224291. DOI: 10.1001/jamanetworkopen.2022.4291.

[52]BaetenD, BaraliakosX, BraunJ, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial[J]. Lancet, 2013, 382(9906):1705-1713. DOI: 10.1016/S0140-6736(13)61134-4.

[53]van der HeijdeD, SongIH, PanganAL, et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial[J]. Lancet, 2019, 394(10214):2108-2117. DOI: 10.1016/S0140-6736(19)32534-6.

[54]PassiasPG, KrolO, PassfallL, et al. Three-column osteotomy in adult spinal deformity: an analysis of temporal trends in usage and outcomes[J]. J Bone Joint Surg Am, 2022, 104(21):1895-1904. DOI: 10.2106/JBJS.21.01172.

[55]BessS, LineB, AmesC, et al. Would you do it again? Discrepancies between patient and surgeon perceptions following adult spine deformity surgery[J]. Spine J, 2023, 23(8):1115-1126. DOI: 10.1016/j.spinee.2023.04.018.

[56]TetreaultL, KopjarB, NouriA, et al. The modified Japanese Orthopaedic Association scale: establishing criteria for mild, moderate and severe impairment in patients with degenerative cervical myelopathy[J]. Eur Spine J, 2017, 26(1):78-84. DOI: 10.1007/s00586-016-4660-8.

[57]GhogawalaZ, TerrinN, DunbarMR, et al. Effect of ventral vs dorsal spinal surgery on patient-reported physical functioning in patients with cervical spondylotic myelopathy: a randomized clinical trial[J]. JAMA, 2021, 325(10):942-951. DOI: 10.1001/jama.2021.1233.

[58]FehlingsMG, WilsonJR, KopjarB, et al. Efficacy and safety of surgical decompression in patients with cervical spondylotic myelopathy: results of the AOSpine North America prospective multi-center study[J]. J Bone Joint Surg Am, 2013, 95(18):1651-1658. DOI: 10.2106/JBJS.L.00589.

[59]CheungCL, TanCB, KungWC. Cohort profile: the Hong Kong Osteoporosis Study and the follow-up study[J]. Int J Epidemiol, 2018, 47(2):397-398. DOI: 10.1093/ije/dyx172.

[60]WarensjöE, BybergL, MelhusH, et al. Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study[J]. BMJ, 2011, 342:d1473. DOI: 10.1136/bmj.d1473.

[63]NeerRM, ArnaudCD, ZanchettaJR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis[J]. N Engl J Med, 2001, 344(19):1434-1441. DOI: 10.1056/NEJM200105103441904.

[64]KendlerDL, MarinF, ZerbiniC, et al. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial[J]. Lancet, 2018, 391(10117):230-240. DOI: 10.1016/S0140-6736(17)32137-2.

[65]VestergaardP, MollerupCL, FrøkjaerVG, et al. Cohort study of risk of fracture before and after surgery for primary hyperparathyroidism[J]. BMJ, 2000, 321(7261):598-602. DOI: 10.1136/bmj.321.7261.598.

[66]WoltzS, StegemanSA, KrijnenP, et al. Plate fixation compared with nonoperative treatment for displaced midshaft clavicular fractures: a multicenter randomized controlled trial[J]. J Bone Joint Surg Am, 2017, 99(2):106-112. DOI: 10.2106/JBJS.15.01394.

[72]KimM, WonCW. Prevalence of sarcopenia in community-dwelling older adults using the definition of the European Working Group on Sarcopenia in Older People 2: findings from the Korean Frailty and Aging Cohort Study[J]. Age Ageing, 2019, 48(6):910-916. DOI: 10.1093/ageing/afz091.

[73]BernabeiR, LandiF, CalvaniR, et al. Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project)[J]. BMJ, 2022, 377:e068788. DOI: 10.1136/bmj-2021-068788.

[74]LuYX, NitiM, YapKB, et al. Assessment of sarcopenia among community-dwelling at-risk frail adults aged 65 years and older who received multidomain lifestyle interventions: a secondary analysis of a randomized clinical trial[J]. JAMA Netw Open, 2019, 2(10):e1913346. DOI: 10.1001/jamanetworkopen.2019.13346.

[75]RooksD, SwanT, GoswamiB, et al. Bimagrumab vs optimized standard of care for treatment of sarcopenia in community-dwelling older adults: a randomized clinical trial[J]. JAMA Netw Open, 2020, 3(10):e2020836. DOI: 10.1001/jamanetworkopen.2020.20836.

[76]HopewellS, KeeneDJ, MarianIR, et al. Progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of patients with rotator cuff disorders (GRASP): a multicentre, pragmatic, 2 × 2 factorial, randomised controlled trial[J]. Lancet, 2021, 398(10298):416-428. DOI: 10.1016/S0140-6736(21)00846-1.

[78]CederqvistS, FlinkkiläT, SormaalaM, et al. Non-surgical and surgical treatments for rotator cuff disease: a pragmatic randomised clinical trial with 2-year follow-up after initial rehabilitation[J]. Ann Rheum Dis, 2021, 80(6):796-802. DOI: 10.1136/annrheumdis-2020-219099.

[79]BrummettCM, UrquhartAG, HassettAL, et al. Characteristics of fibromyalgia independently predict poorer long-term analgesic outcomes following total knee and hip arthroplasty[J]. Arthritis Rheumatol, 2015, 67(5):1386-1394. DOI: 10.1002/art.39051.

[80]MawlaI, IchescoE, ZöllnerHJ, et al. Greater somatosensory afference with acupuncture increases primary somatosensory connectivity and alleviates fibromyalgia pain via insular γ-aminobutyric acid: a randomized neuroimaging trial[J]. Arthritis Rheumatol, 2021, 73(7):1318-1328. DOI: 10.1002/art.41620.

[81]RichardsSC, ScottDL. Prescribed exercise in people with fibromyalgia: parallel group randomised controlled trial[J]. BMJ, 2002, 325(7357):185. DOI: 10.1136/bmj.325.7357.185.

[82]WangC, SchmidCH, RonesR, et al. A randomized trial of tai chi for fibromyalgia[J]. N Engl J Med, 2010, 363(8):743-754. DOI: 10.1056/NEJMoa0912611.

[83]EllenbergJH. Intention-to Treat Analysis[M]. New Jersey: John Wiley & Sons, 2001.

[84]SedgwickP. Intention to treat analysis versus per protocol analysis of trial data[J]. BMJ, 2015, 350:h681. DOI: 10.1136/bmj.h681.

[85]SmithVA, CoffmanCJ, HudgensMG. Interpreting the results of intention-to-treat, per-protocol, and as-treated analyses of clinical trials[J]. JAMA, 2021, 326(5):433-434. DOI: 10.1001/jama.2021.2825.

[86]ZengC, DubreuilM, LaRochelleMR, et al. Association of tramadol with all-cause mortality among patients with osteoarthritis[J]. JAMA, 2019, 321(10):969-982. DOI: 10.1001/jama.2019.1347.

[87]ZengC, BennellK, YangZ, et al. Risk of venous thromboembolism in knee, hip and hand osteoarthritis: a general population-based cohort study[J]. Ann Rheum Dis, 2020, 79(12):1616-1624. DOI: 10.1136/annrheumdis-2020-217782.

[88]HulleySB, CummingsSR, BrownerWS, et al. Designing clinical research: an epidemiologic approach[M]. 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2001.

[89]SchulzKF, GrimesDA. Case-control studies: research in reverse[J]. Lancet, 2002, 359(9304):431-434. DOI: 10.1016/S0140-6736(02)07605-5.

[90]BourkeJH, WodehouseT, ClarkLV, et al. Central sensitisation in chronic fatigue syndrome and fibromyalgia; a case control study[J]. J Psychosom Res, 2021, 150:110624. DOI: 10.1016/j.jpsychores.2021.110624.

[91]KimFM, HayesC, BurgardSL, et al. A case-control study of fluoridation and qsteosarcoma[J]. J Dent Res, 2020, 99(10):1157-1164. DOI: 10.1177/0022034520919385.

[92]ZhangY, NeogiT, ChenC, et al. Cherry consumption and decreased risk of recurrent gout attacks[J]. Arthritis Rheum, 2012, 64(12):4004-4011. DOI: 10.1002/art.34677.

[93]PeachEJ, PearceFA, GibsonJ, et al. Opioids and the risk of fracture: a self-controlled case series study in the clinical practice research datalink[J]. Am J Epidemiol, 2021, 190(7):1324-1331. DOI: 10.1093/aje/kwab042.

[94]HallasJ, PottegårdA. Use of self-controlled designs in pharmacoepidemiology[J]. J Intern Med, 2014, 275(6):581-589. DOI: 10.1111/joim.12186.

[95]HennekensCH, BuringJE. Epidemiology in Medicine[M]. Philadelphia: Lippincott Williams & Wilkins, 1987.

[96]ClarkEM, GouldVC, MorrisonL, et al. Determinants of fracture risk in a UK-population-based cohort of older women: a cross-sectional analysis of the Cohort for Skeletal Health in Bristol and Avon (COSHIBA)[J]. Age Ageing, 2012, 41(1):46-52. DOI: 10.1093/ageing/afr132.

[97]GaoL, JiangJ, YangM, et al. Prevalence of sarcopenia and associated factors in Chinese community-dwelling elderly: comparison between rural and urban areas[J]. J Am Med Dir Assoc, 2015, 16(11):1003.e1-e6. DOI: 10.1016/j.jamda.2015.07.020.

[98]YucesoyC, GencG, BalA, et al. Ultrasonographic assessment of knee in patients with rheumatoid arthritis: is it an effective imaging method for initial evaluation?[J]. Turk J Rheumatol, 2011, 26(2): 120.

[99]RothmanKJ, GreenlandS, LashTL. Modern epidemiology[M]. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2008.

[100]LipskyAM, GreenlandS. Causal directed acyclic graphs[J]. JAMA, 2022, 327(11):1083-1084. DOI: 10.1001/jama.2022.1816.

[101]BakerMC, ShethK, LuR, et al. Increased risk of osteoarthritis in patients with atopic disease[J]. Ann Rheum Dis, 2023, 82(6):866-872. DOI: 10.1136/ard-2022-223640.

[102]BoerCG, SzilagyiI, NguyenNL, et al. Vitamin K antagonist anticoagulant usage is associated with increased incidence and progression of osteoarthritis[J]. Ann Rheum Dis, 2021, 80(5):598-604. DOI: 10.1136/annrheumdis-2020-219483.

[103]BucciJ, ChenX, LaValleyM, et al. Progression of knee osteoarthritis with use of intraarticular glucocorticoids versus hyaluronic acid[J]. Arthritis Rheumatol, 2022, 74(2):223-226. DOI: 10.1002/art.42031.

[104]DubreuilM, Louie-GaoQ, PeloquinCE, et al. Risk of myocardial infarction with use of selected non-steroidal anti-inflammatory drugs in patients with spondyloarthritis and osteoarthritis[J]. Ann Rheum Dis, 2018, 77(8):1137-1142. DOI: 10.1136/annrheumdis-2018-213089.

[105]LatourteA, RatAC, Ngueyon SimeW, et al. Chondrocalcinosis of the knee and the risk of osteoarthritis progression: data from the knee and hip osteoarthritis long-term assessment cohort[J]. Arthritis Rheumatol, 2020, 72(5):726-732. DOI: 10.1002/art.41186.

[106]MisraD, FieldingRA, FelsonDT, et al. Risk of knee osteoarthritis with obesity, sarcopenic obesity, and sarcopenia[J]. Arthritis Rheumatol, 2019, 71(2):232-237. DOI: 10.1002/art.40692.

[107]MohajerB, DolatshahiM, MoradiK, et al. Role of thigh muscle changes in knee osteoarthritis outcomes: osteoarthritis initiative data[J]. Radiology, 2022, 305(1):169-178. DOI: 10.1148/radiol.212771.

[108]NguyenUS, ZhangY, ZhuY, et al. Increasing prevalence of knee pain and symptomatic knee osteoarthritis: survey and cohort data[J]. Ann Intern Med, 2011, 155(11):725-732. DOI: 10.7326/0003-4819-155-11-201112060-00004.

[109]SharmaL, SongJ, DunlopD, et al. Varus and valgus alignment and incident and progressive knee osteoarthritis[J]. Ann Rheum Dis, 2010, 69(11):1940-1945. DOI: 10.1136/ard.2010.129742.

[110]SnoekerB, TurkiewiczA, MagnussonK, et al. Risk of knee osteoarthritis after different types of knee injuries in young adults: a population-based cohort study[J]. Br J Sports Med, 2020, 54(12):725-730. DOI: 10.1136/bjsports-2019-100959.

[111]KotoR, NakajimaA, HoriuchiH, et al. Serum uric acid control for prevention of gout flare in patients with asymptomatic hyperuricaemia: a retrospective cohort study of health insurance claims and medical check-up data in Japan[J]. Ann Rheum Dis, 2021, 80(11):1483-1490. DOI: 10.1136/annrheumdis-2021-220439.

[112]Vargas-SantosAB, PeloquinCE, ZhangY, et al. Association of chronic kidney disease with allopurinol use in gout treatment[J]. JAMA Intern Med, 2018, 178(11):1526-1533. DOI: 10.1001/jamainternmed.2018.4463.

[113]McCormickN, YokoseC, LuN, et al. Impact of adiposity on risk of female gout among those genetically predisposed: sex-specific prospective cohort study findings over>32 years[J]. Ann Rheum Dis, 2022, 81(4):556-563. DOI: 10.1136/annrheumdis-2021-221635.

[114]YokoseC, McCormickN, LuN, et al. Adherence to 2020 to 2025 dietary guidelines for Americans and the risk of new-onset female gout[J]. JAMA Intern Med, 2022, 182(3):254-264. DOI: 10.1001/jamainternmed.2021.7419.

[115]McCormickN, YokoseC, WeiJ, et al. Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors for recurrent gout flares and gout-primary emergency department visits and hospitalizations: a general population cohort study[J]. Ann Intern Med, 2023, 176(8):1067-1080. DOI: 10.7326/M23-0724.

[116]ChoiHK, HernánMA, SeegerJD, et al. Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study[J]. Lancet, 2002, 359(9313):1173-1177. DOI: 10.1016/S0140-6736(02)08213-2.

[117]WaskoMC, HubertHB, LingalaVB, et al. Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis[J]. JAMA, 2007, 298(2):187-193. DOI: 10.1001/jama.298.2.187.

[118]LindhardsenJ, AhlehoffO, GislasonGH, et al. Risk of atrial fibrillation and stroke in rheumatoid arthritis: danish nationwide cohort study[J]. BMJ, 2012, 344:e1257. DOI: 10.1136/bmj.e1257.

[119]Di GiuseppeD, AlfredssonL, BottaiM, et al. Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study[J]. BMJ, 2012, 345:e4230. DOI: 10.1136/bmj.e4230.

[120]MolanderV, BowerH, FrisellT, et al. Risk of venous thromboembolism in rheumatoid arthritis, and its association with disease activity: a nationwide cohort study from Sweden[J]. Ann Rheum Dis, 2021, 80(2):169-175. DOI: 10.1136/annrheumdis-2020-218419.

[121]NguyenY, SalliotC, GelotA, et al. Mediterranean diet and risk of rheumatoid arthritis: findings from the French E3N-EPIC cohort study[J]. Arthritis Rheumatol, 2021, 73(1):69-77. DOI: 10.1002/art.41487.

[122]BugattiS, De StefanoL, D′OnofrioB, et al. Inflammatory correlates of the Patient Global Assessment of Disease Activity vary in relation to disease duration and autoantibody status in patients with rheumatoid arthritis[J]. Ann Rheum Dis, 2022, 81(9):1206-1213. DOI: 10.1136/annrheumdis-2022-222436.

[123]LinSH, WangTC, LaiCF, et al. Association of anterior cruciate ligament injury with knee osteoarthritis and total knee replacement: a retrospective cohort study from the Taiwan National Health Insurance Database[J]. PLoS One, 2017, 12(5):e0178292. DOI: 10.1371/journal.pone.0178292.

[124]FaleideA, MagnussenLH, StrandT, et al. The role of psychological readiness in return to sport assessment after anterior cruciate ligament reconstruction[J]. Am J Sports Med, 2021, 49(5):1236-1243. DOI: 10.1177/0363546521991924.

[125]McPhersonAL, ShirleyMB, SchilatyND, et al. Effect of a concussion on anterior cruciate ligament injury risk in a general population[J]. Sports Med, 2020, 50(6):1203-1210. DOI: 10.1007/s40279-020-01262-3.

[126]ZebisMK, AagaardP, AndersenLL, et al. First-time anterior cruciate ligament injury in adolescent female elite athletes: a prospective cohort study to identify modifiable risk factors[J]. Knee Surg Sports Traumatol Arthrosc, 2022, 30(4):1341-1351. DOI: 10.1007/s00167-021-06595-8.

[127]PattersonBE, EmeryC, CrossleyKM, et al. Knee-and overall health-related quality of life following anterior cruciate ligament injury: a cross-sectional analysis of Australian and Canadian cohorts[J]. J Orthop Sports Phys Ther, 2023, 53(7):402-413. DOI: 10.2519/jospt.2023.11838.

[128]UlsteinS, ÅrøenA, EngebretsenL, et al. Effect of concomitant cartilage lesions on patient-reported outcomes after anterior cruciate ligament reconstruction: a nationwide cohort study from Norway and Sweden of 8 470 patients with 5-year follow-up[J]. Orthop J Sports Med, 2018, 6(7):2325967118786219. DOI: 10.1177/2325967118786219.

[129]BeynnonBD, VacekPM, NewellMK, et al. The effects of level of competition, sport, and sex on the incidence of first-time noncontact anterior cruciate ligament injury[J]. Am J Sports Med, 2014, 42(8):1806-1812. DOI: 10.1177/0363546514540862.

[130]ParkkariJ, PasanenK, MattilaVM, et al. The risk for a cruciate ligament injury of the knee in adolescents and young adults: a population-based cohort study of 46 500 people with a 9 year follow-up[J]. Br J Sports Med, 2008, 42(6):422-426. DOI: 10.1136/bjsm.2008.046185.

[131]JurgensmeierK, TillSE, LuY, et al. Risk factors for secondary meniscus tears can be accurately predicted through machine learning, creating a resource for patient education and intervention[J]. Knee Surg Sports Traumatol Arthrosc, 2023, 31(2):518-529. DOI: 10.1007/s00167-022-07117-w.

[132]SulaimanY, LiJ, ChenG, et al. The relationship between a Segond fracture and meniscus injury in patients with anterior cruciate ligament tears[J]. Knee, 2021, 33:193-199. DOI: 10.1016/j.knee.2021.09.008.

[133]TeraguchiM, YoshimuraN, HashizumeH, et al. Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study[J]. Osteoarthritis Cartilage, 2014, 22(1):104-110. DOI: 10.1016/j.joca.2013.10.019.

[134]MaurerE, KlingerC, LorbeerR, et al. Long-term effect of physical inactivity on thoracic and lumbar disc degeneration-an MRI-based analysis of 385 individuals from the general population[J]. Spine J, 2020, 20(9):1386-1396. DOI: 10.1016/j.spinee.2020.04.016.

[135]TeraguchiM, YoshimuraN, HashizumeH, et al. Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study[J]. Osteoarthritis Cartilage, 2017, 25(7):1122-1131. DOI: 10.1016/j.joca.2017.01.001.

[136]SaloS, HurriH, RikkonenT, et al. Association between severe lumbar disc degeneration and self-reported occupational physical loading[J]. J Occup Health, 2022, 64(1):e12316. DOI: 10.1002/1348-9585.12316.

[137]DialloTD, RospleszczS, FabianJ, et al. Associations of myosteatosis with disc degeneration: a 3T magnetic resonance imaging study in individuals with impaired glycaemia[J]. J Cachexia Sarcopenia Muscle, 2023, 14(3):1249-1258. DOI: 10.1002/jcsm.13192.

[138]JungM, RospleszczS, LöfflerMT, et al. Association of lumbar vertebral bone marrow and paraspinal muscle fat composition with intervertebral disc degeneration: 3T quantitative MRI findings from the population-based KORA study[J]. Eur Radiol, 2023, 33(3):1501-1512. DOI: 10.1007/s00330-022-09140-4.

[139]IshimotoY, YoshimuraN, MurakiS, et al. Association of lumbar spondylolisthesis with low back pain and symptomatic lumbar spinal stenosis in a population-based cohort: the Wakayama Spine Study[J]. Spine (Phila Pa 1976), 2017, 42(11):E666-E671. DOI: 10.1097/BRS.0000000000001960.

[140]AzadTD, VailD, O′ConnellC, et al. Geographic variation in the surgical management of lumbar spondylolisthesis: characterizing practice patterns and outcomes[J]. Spine J, 2018, 18(12):2232-2238. DOI: 10.1016/j.spinee.2018.05.008.

[141]ChenJC, ChanWP, KatzJN, et al. Occupational and personal factors associated with acquired lumbar spondylolisthesis of urban taxi drivers[J]. Occup Environ Med, 2004, 61(12):992-998. DOI: 10.1136/oem.2003.011775.

[142]ShintoK, MinamideA, HashizumeH, et al. Prevalence of facet effusion and its relationship with lumbar spondylolisthesis and low back pain: the Wakayama Spine Study[J]. J Pain Res, 2019, 12:3521-3528. DOI: 10.2147/JPR.S227153.

[143]ThornleyP, UrquhartJC, GlennieA, et al. Functional outcomes correlate with sagittal spinal balance in degenerative lumbar spondylolisthesis surgery[J]. Spine J, 2023, 23(10):1512-1521. DOI: 10.1016/j.spinee.2023.06.004.

[144]IshimotoY, YoshimuraN, MurakiS, et al. Associations between radiographic lumbar spinal stenosis and clinical symptoms in the general population: the Wakayama Spine Study[J]. Osteoarthritis Cartilage, 2013, 21(6):783-788. DOI: 10.1016/j.joca.2013.02.656.

[145]KnutssonB, MukkaS, WahlströmJ, et al. The association between tobacco smoking and surgical intervention for lumbar spinal stenosis: cohort study of 331, 941 workers[J]. Spine J, 2018, 18(8):1313-1317. DOI: 10.1016/j.spinee.2017.11.018.

[146]BattiéMC, JonesCA, SchopflocherDP, et al. Health-related quality of life and comorbidities associated with lumbar spinal stenosis[J]. Spine J, 2012, 12(3):189-195. DOI: 10.1016/j.spinee.2011.11.009.

[147]HeldU, BurgstallerJM, DeforthM, et al. Association between depression and anxiety on symptom and function after surgery for lumbar spinal stenosis[J]. Sci Rep, 2022, 12(1):2821. DOI: 10.1038/s41598-022-06797-1.

[148]KobayashiH, TominagaR, OtaniK, et al. Lumbar spinal stenosis is a risk factor for the development of dementia: locomotive syndrome and health outcomes in the Aizu cohort study[J]. Eur Spine J, 2023, 32(2):488-494. DOI: 10.1007/s00586-022-07318-4.

[149]PoddubnyyD, RudwaleitM, HaibelH, et al. Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort[J]. Ann Rheum Dis, 2012, 71(10):1616-1622. DOI: 10.1136/annrheumdis-2011-201252.

[150]VosseD, LandewéR, van der HeijdeD, et al. Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case-control study[J]. Ann Rheum Dis, 2009, 68(12):1839-1842. DOI: 10.1136/ard.2008.100503.

[151]StolwijkC, EssersI, van TubergenA, et al. The epidemiology of extra-articular manifestations in ankylosing spondylitis: a population-based matched cohort study[J]. Ann Rheum Dis, 2015, 74(7):1373-1378. DOI: 10.1136/annrheumdis-2014-205253.

[152]WeiCY, LinJY, WangYT, et al. Risk of ankylosing spondylitis following human papillomavirus infection: a nationwide, population-based, cohort study[J]. J Autoimmun, 2020, 113:102482. DOI: 10.1016/j.jaut.2020.102482.

[153]HuangYF, ChangCT, MuoCH, et al. Bidirectional relationship between temporomandibular disorder and ankylosing spondylitis: a population-based cohort study[J]. Clin Oral Investig, 2021, 25(11):6377-6384. DOI: 10.1007/s00784-021-03938-0.

[154]TsurAM, DavidP, WatadA, et al. Ankylosing spondylitis and the risk of hip fractures: a matched cohort study[J]. J Gen Intern Med, 2022, 37(13):3283-3288. DOI: 10.1007/s11606-021-07241-2.

[155]ClarkEM, TaylorHJ, HardingI, et al. Association between components of body composition and scoliosis: a prospective cohort study reporting differences identifiable before the onset of scoliosis[J]. J Bone Miner Res, 2014, 29(8):1729-1736. DOI: 10.1002/jbmr.2207.

[156]TobiasJH, FairbankJ, HardingI, et al. Association between physical activity and scoliosis: a prospective cohort study[J]. Int J Epidemiol, 2019, 48(4):1152-1160. DOI: 10.1093/ije/dyy268.

[157]YongJH, HongJP, LeeYH, et al. Association and risk of axial spondyloarthritis of scoliosis patients: a database study[J]. Spine (Phila Pa 1976), 2022, 47(5):438-443. DOI: 10.1097/BRS.0000000000004248.

[158]KaushalN, OrlandKJ, SchwartzAM, et al. Effects of race on blood loss in spinal fusions for adolescent idiopathic scoliosis[J]. J Neurosurg Pediatr, 2020, 27(2):213-217. DOI: 10.3171/2020.7.PEDS2049.

[159]ZhuL, RuS, WangW, et al. Associations of physical activity and screen time with adolescent idiopathic scoliosis[J]. Environ Health Prev Med, 2023, 28:55. DOI: 10.1265/ehpm.23-00004.

[160]WatanabeK, MichikawaT, YonezawaI, et al. Physical activities and lifestyle factors related to adolescent idiopathic scoliosis[J]. J Bone Joint Surg Am, 2017, 99(4):284-294. DOI: 10.2106/JBJS.16.00459.

[161]EvaniewN, Charest-MorinR, JacobsWB, et al. Cervical sagittal alignment in patients with cervical spondylotic myelopathy: an observational study from the Canadian Spine Outcomes and Research Network[J]. Spine (Phila Pa 1976), 2022, 47(5):E177-E186. DOI: 10.1097/BRS.0000000000004296.

[162]LinSY, LinCL, ChenDC, et al. Risk of posterior circulation stroke in patients with cervical spondylosis: a nationwide, population-based study[J]. Atherosclerosis, 2018, 277:42-46. DOI: 10.1016/j.atherosclerosis.2018.08.006.

[163]LinWS, HuangTF, ChuangTY, et al. Association between cervical spondylosis and migraine: a nationwide retrospective cohort study[J]. Int J Environ Res Public Health, 2018, 15(4):587. DOI: 10.3390/ijerph15040587.

[164]LyuH, YoshidaK, ZhaoSS, et al. Delayed denosumab injections and fracture risk among patients with osteoporosis: a population-based cohort study[J]. Ann Intern Med, 2020, 173(7):516-526. DOI: 10.7326/M20-0882.

[165]ChalitsiosCV, McKeeverTM, ShawDE. Incidence of osteoporosis and fragility fractures in asthma: a UK population-based matched cohort study[J]. Eur Respir J, 2021, 57(1):2001251. DOI: 10.1183/13993003.01251-2020.

[166]AbtahiS, DriessenJ, BurdenAM, et al. Concomitant use of oral glucocorticoids and proton pump inhibitors and risk of osteoporotic fractures among patients with rheumatoid arthritis: a population-based cohort study[J]. Ann Rheum Dis, 2021, 80(4):423-431. DOI: 10.1136/annrheumdis-2020-218758.

[167]BliucD, TranT, ChenW, et al. The association between multimorbidity and osteoporosis investigation and treatment in high-risk fracture patients in Australia: a prospective cohort study[J]. PLoS Med, 2023, 20(1):e1004142. DOI: 10.1371/journal.pmed.1004142.

[168]JosephsonCB, Gonzalez-IzquierdoA, DenaxasS, et al. Independent associations of incident epilepsy and enzyme-inducing and non-enzyme-inducing antiseizure medications with the development of osteoporosis[J]. JAMA Neurol, 2023, 80(8):843-850. DOI: 10.1001/jamaneurol.2023.1580.

[169]LyuH, ZhaoSS, ZhangL, et al. Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study[J]. BMJ, 2023, 381:e073435. DOI: 10.1136/bmj-2022-073435.

[170]PincusD, RaviB, WassersteinD, et al. Association between wait time and 30-day mortality in adults undergoing hip fracture surgery[J]. JAMA, 2017, 318(20):1994-2003. DOI: 10.1001/jama.2017.17606.

[171]SamelsonEJ, BroeKE, XuHF, et al. Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study[J]. Lancet Diabetes Endocrinol, 2019, 7(1):34-43. DOI: 10.1016/S2213-8587(18)30308-5.

[172]CrandallCJ, LarsonJC, LaCroixAZ, et al. Risk of subsequent fractures in postmenopausal women after nontraumatic vs traumatic fractures[J]. JAMA Intern Med, 2021, 181(8):1055-1063. DOI: 10.1001/jamainternmed.2021.2617.

[173]HussainSM, EbelingPR, BarkerAL, et al. Association of plasma high-density lipoprotein cholesterol level with risk of fractures in healthy older adults[J]. JAMA Cardiol, 2023, 8(3):268-272. DOI: 10.1001/jamacardio.2022.5124.

[174]SwayambunathanJ, DasguptaA, RosenbergPS, et al. Incidence of hip fracture over 4 decades in the framingham heart study[J]. JAMA Intern Med, 2020, 180(9):1225-1231. DOI: 10.1001/jamainternmed.2020.2975.

[175]AbrahamsenB, EikenP, Prieto-AlhambraD, et al. Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study[J]. BMJ, 2016, 353:i3365. DOI: 10.1136/bmj.i3365.

[176]KhaliliH, HuangES, JacobsonBC, et al. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study[J]. BMJ, 2012, 344:e372. DOI: 10.1136/bmj.e372.

[177]MorsethB, AhmedLA, BjørneremÅ, et al. Leisure time physical activity and risk of non-vertebral fracture in men and women aged 55 years and older: the Tromsø Study[J]. Eur J Epidemiol, 2012, 27(6):463-471. DOI: 10.1007/s10654-012-9665-y.

[178]BruyereO, VarelaAR, AdamiS, et al. Loss of hip bone mineral density over time is associated with spine and hip fracture incidence in osteoporotic postmenopausal women[J]. Eur J Epidemiol, 2009, 24(11):707-712. DOI: 10.1007/s10654-009-9381-4.

[179]DaneseMD, KimJ, DoanQV, et al. PTH and the risks for hip, vertebral, and pelvic fractures among patients on dialysis[J]. Am J Kidney Dis, 2006, 47(1):149-156. DOI: 10.1053/j.ajkd.2005.09.024.

[180]ZhangSB, ChenH, XuHW, et al. Association between handgrip strength and subsequent vertebral-fracture risk following percutaneous vertebral augmentation[J]. J Bone Miner Metab, 2021, 39(2):186-192. DOI: 10.1007/s00774-020-01131-z.

[181]KadoDM, LuiLY, EnsrudKE, et al. Hyperkyphosis predicts mortality independent of vertebral osteoporosis in older women[J]. Ann Intern Med, 2009, 150(10):681-687. DOI: 10.7326/0003-4819-150-10-200905190-00005.

[182]ChunHS, LeeM, LeeHA, et al. Association of physical activity with risk of liver fibrosis, sarcopenia, and cardiovascular disease in nonalcoholic fatty liver disease[J]. Clin Gastroenterol Hepatol, 2023, 21(2):358-369.e12. DOI: 10.1016/j.cgh.2021.12.043.

[183]KitamuraA, SeinoS, AbeT, et al. Sarcopenia: prevalence, associated factors, and the risk of mortality and disability in Japanese older adults[J]. J Cachexia Sarcopenia Muscle, 2021, 12(1):30-38. DOI: 10.1002/jcsm.12651.

[184]HongHC, HwangSY, ChoiHY, et al. Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean Sarcopenic Obesity Study[J]. Hepatology, 2014, 59(5):1772-1778. DOI: 10.1002/hep.26716.

[185]WilliamsGR, ChenY, KenzikKM, et al. Assessment of sarcopenia measures, survival, and disability in older adults before and after diagnosis with cancer[J]. JAMA Netw Open, 2020, 3(5):e204783. DOI: 10.1001/jamanetworkopen.2020.4783.

[186]WangY, ZhangY, LaneNE, et al. Population-based metagenomics analysis reveals altered gut microbiome in sarcopenia: data from the Xiangya Sarcopenia Study[J]. J Cachexia Sarcopenia Muscle, 2022, 13(5):2340-2351. DOI: 10.1002/jcsm.13037.

[187]GruskyAZ, SongA, KimP, et al. Factors associated with symptomatic rotator cuff tears: the rotator cuff outcomes workgroup cohort study[J]. Am J Phys Med Rehabil, 2021, 100(4):331-336. DOI: 10.1097/PHM.0000000000001684.

[188]KijowskiR, ThurlowP, BlankenbakerD, et al. Preoperative MRI shoulder findings associated with clinical outcome 1 year after rotator cuff repair[J]. Radiology, 2019, 291(3):722-729. DOI: 10.1148/radiol.2019181718.

[189]LongoUG, FranceschiF, SpieziaF, et al. Triglycerides and total serum cholesterol in rotator cuff tears: do they matter?[J]. Br J Sports Med, 2010, 44(13):948-951. DOI: 10.1136/bjsm.2008.056440.

[190]ChouWY, WangCJ, WuKT, et al. Comparative outcomes of extracorporeal shockwave therapy for shoulder tendinitis or partial tears of the rotator cuff in athletes and non-athletes: retrospective study[J]. Int J Surg, 2018, 51:184-190. DOI: 10.1016/j.ijsu.2018.01.036.

[191]HinsleyH, GandertonC, ArdenNK, et al. Relationship between shoulder abduction strength and rotator cuff tear in elderly women: a general population study[J]. BMJ Open, 2023, 13(7):e071908. DOI: 10.1136/bmjopen-2023-071908.

[192]WangJY, LinYR, LiawCK, et al. Cervical spine pathology increases the risk of rotator cuff tear: a population-based cohort study[J]. Orthop J Sports Med, 2021, 9(12):23259671211058726. DOI: 10.1177/23259671211058726.

[193]HinsleyH, GandertonC, ArdenNK, et al. Prevalence of rotator cuff tendon tears and symptoms in a Chingford general population cohort, and the resultant impact on UK health services: a cross-sectional observational study[J]. BMJ Open, 2022, 12(9):e059175. DOI: 10.1136/bmjopen-2021-059175.

[194]KuoLT, ChenHM, YuPA, et al. Depression increases the risk of rotator cuff tear and rotator cuff repair surgery: a nationwide population-based study[J]. PLoS One, 2019, 14(11):e0225778. DOI: 10.1371/journal.pone.0225778.

[195]LongoUG, FranceschiF, RuzziniL, et al. Higher fasting plasma glucose levels within the normoglycaemic range and rotator cuff tears[J]. Br J Sports Med, 2009, 43(4):284-287. DOI: 10.1136/bjsm.2008.049320.

[196]GrovenN, ForsEA, ReitanSK. Patients with fibromyalgia and chronic fatigue syndrome show increased hsCRP compared to healthy controls[J]. Brain Behav Immun, 2019, 81:172-177. DOI: 10.1016/j.bbi.2019.06.010.

[197]TzengNS, ChungCH, LiuFC, et al. Fibromyalgia and risk of dementia-a nationwide, population-based, cohort study[J]. Am J Med Sci, 2018, 355(2):153-161. DOI: 10.1016/j.amjms.2017.09.002.

[198]KivimäkiM, Leino-ArjasP, Kaila-KangasL, et al. Increased absence due to sickness among employees with fibromyalgia[J]. Ann Rheum Dis, 2007, 66(1):65-69. DOI: 10.1136/ard.2006.053819.

[199]MoltóA, EtchetoA, GossecL, et al. Evaluation of the impact of concomitant fibromyalgia on TNF alpha blockers′ effectiveness in axial spondyloarthritis: results of a prospective, multicentre study[J]. Ann Rheum Dis, 2018, 77(4):533-540. DOI: 10.1136/annrheumdis-2017-212378.

[200]LeeYC, LuB, BoireG, et al. Incidence and predictors of secondary fibromyalgia in an early arthritis cohort[J]. Ann Rheum Dis, 2013, 72(6):949-954. DOI: 10.1136/annrheumdis-2012-201506.

[201]VarinenA, KosunenE, MattilaK, et al. The association between bullying victimization in childhood and fibromyalgia. Data from the nationwide Finnish health and social support (HeSSup) study based on a sample of 64, 797 individuals[J]. J Psychosom Res, 2019, 117:48-53. DOI: 10.1016/j.jpsychores.2018.12.003.

[202]HernánMA, Hernández-DíazS, RobinsJM. A structural approach to selection bias[J]. Epidemiology, 2004, 15(5):615-625. DOI: 10.1097/01.ede.0000135174.63482.43.

[203]谭红专. 现代流行病学[M]. 3版. 北京:人民卫生出版社, 2019.

[204]ColeSR, PlattRW, SchistermanEF, et al. Illustrating bias due to conditioning on a collider[J]. Int J Epidemiol, 2010, 39(2):417-420. DOI: 10.1093/ije/dyp334.

[205]SuissaS. Immortal time bias in pharmaco-epidemiology[J]. Am J Epidemiol, 2008, 167(4):492-499. DOI: 10.1093/aje/kwm324.

[206]ZhouZ, RahmeE, AbrahamowiczM, et al. Survival bias associated with time-to-treatment initiation in drug effectiveness evaluation: a comparison of methods[J]. Am J Epidemiol, 2005, 162(10):1016-1023. DOI: 10.1093/aje/kwi307.

[207]AlthubaitiA. Information bias in health research: definition, pitfalls, and adjustment methods[J]. J Multidiscip Healthc, 2016, 9:211-217. DOI: 10.2147/JMDH.S104807.

[208]FaillieJL. Indication bias or protopathic bias?[J]. Br J Clin Pharmacol, 2015, 80(4):779-780. DOI: 10.1111/bcp.12705.

[209]StürmerT, RothmanKJ, AvornJ, et al. Treatment effects in the presence of unmeasured confounding: dealing with observations in the tails of the propensity score distribution--a simulation study[J]. Am J Epidemiol, 2010, 172(7):843-854. DOI: 10.1093/aje/kwq198.

[210]IagnoccoA, MeenaghG, RienteL, et al. Ultrasound imaging for the rheumatologist XXIX. Sonographic assessment of the knee in patients with osteoarthritis[J]. Clin Exp Rheumatol, 2010, 28(5):643-646.

[211]IoannidisJ. The importance of predefined rules and prespecified statistical analyses: do not abandon significance[J]. JAMA, 2019, 321(21):2067-2068. DOI: 10.1001/jama.2019.4582.

[212]SchulzKF, AltmanDG, MoherD. CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials[J]. BMJ, 2010, 340:c332. DOI: 10.1136/bmj.c332.

[213]von ElmE, AltmanDG, EggerM, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies[J]. BMJ, 2007, 335(7624):806-808. DOI: 10.1136/bmj.39335.541782.AD.

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[61]GuJM, WangL, LinH, et al. The efficacy and safety of weekly 35-mg risedronate dosing regimen for Chinese postmenopausal women with osteoporosis or osteopenia: 1-year data[J]. Acta Pharmacol Sin, 2015, 36(7):841-846. DOI: 10.1038/aps.2015.30.

[62]LibermanUA, WeissSR, BröllJ, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase Ⅲ Osteoporosis Treatment Study Group[J]. N Engl J Med, 1995, 333(22):1437-1443. DOI: 10.1056/NEJM199511303332201.

[67]MillerL, CrosbieJ, WajonA, et al. No difference between two types of exercise after proximal phalangeal fracture fixation: a randomised trial[J]. J Physiother, 2016, 62(1):12-19. DOI: 10.1016/j.jphys.2015.11.006.

[68]GriffinD, ParsonsN, ShawE, et al. Operative versus non-operative treatment for closed, displaced, intra-articular fractures of the calcaneus: randomised controlled trial[J]. BMJ, 2014, 349:g4483. DOI: 10.1136/bmj.g4483.

[69]CarliD, VenmansA, LodderP, et al. Vertebroplasty versus active control intervention for chronic osteoporotic vertebral compression fractures: the VERTOS V randomized controlled trial[J]. Radiology, 2023, 308(1):e222535. DOI: 10.1148/radiol.222535.

[70]BurkhartK, AllaireB, AndersonDE, et al. Effects of long-duration spaceflight on vertebral strength and risk of spine fracture[J]. J Bone Miner Res, 2020, 35(2):269-276. DOI: 10.1002/jbmr.3881.

[71]中国康复医学会骨质疏松预防与康复专业委员会. 骨质疏松性椎体压缩骨折诊治专家共识(2021版)[J]. 中华医学杂志, 2021, 101(41):3371-3379. DOI: 10.3760/cma.j.cn112137-20210625-01436.

[77]MetcalfeA, ParsonsH, ParsonsN, et al. Subacromial balloon spacer for irreparable rotator cuff tears of the shoulder (START:REACTS): a group-sequential, double-blind, multicentre randomised controlled trial[J]. Lancet, 2022, 399(10339):1954-1963. DOI: 10.1016/S0140-6736(22)00652-3.

引用 / 出处

中华医学会骨科学分会. 标准与规范 | 肌骨系统疾病临床研究方法专家共识[S/OL]. .