Witteveen Angelique G H, Hofstad Cheriel J, Kerkhoffs Gino M M J
Department of Orthopaedic Surgery, St Maartenskliniek, Hengstdal 3, Nijmegen, Netherlands, 6522JV.
Cochrane Database Syst Rev. 2015 Oct 17;2015(10):CD010643. doi: 10.1002/14651858.CD010643.pub2.
BACKGROUND: The cause of ankle osteoarthritis (OA) is usually trauma. Patients are relatively young, since ankle trauma occurs at a relatively young age. Several conservative treatment options are available, evidence of the benefits and harms of these options are lacking. OBJECTIVES: To assess the benefits and harms of any conservative treatment for ankle OA in adults in order to provide a synthesis of the evidence as a base for future treatment guidelines. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2014, issue 9), MEDLINE (Ovid) (1946 up to 11 September 2014), EMBASE (1947 to September 2014), PsycINFO (1806 to September 2014), CINAHL (1985 to September 2014), PEDro (all years till September 2014), AMED until September 2014, ClinicalTrials.gov, Current Controlled Trials, The Dutch Register. To identify potentially relevant studies we screened reference lists in retrieved review articles and trials. SELECTION CRITERIA: We considered randomised or controlled clinical trials investigating any non-surgical intervention for ankle OA for inclusion. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: No other RCT concerning any other conservative treatment besides the use of hyaluronic acid (HA) for ankle OA was identified. Six randomised controlled trials (RCTs) were included.A total of 240 participants diagnosed with ankle OA were included in this review. The primary analysis included three RCTs (109 participants) which compared HA to placebo. One study compared HA to exercise therapy, one compared HA combined with exercise therapy to an intra-articular injection of botulinum toxin and one compared four different dosages of HA.Primary analysis: a pooled analysis of two trials (45 participants) found that the Ankle Osteoarthritis Scale (AOS) total score (measuring pain and physical function) was reduced by 12% (95% CI -24% to -1%) at six months (mean difference (MD) -12.53 (95% CI -23.84 to -1.22) on a scale of 0 to 100; number needed to treat for an additional beneficial outcome (NNTB) = 4 (95% CI 2 to 205); this evidence was graded as low quality, due to limitations in study design (unclear risk of selection bias for two studies and unclear risk for attrition bias for one study) and imprecision of results: a small population size (45 participants). It is not known if a mean difference of 12.53 points on a 100 point scale is clinically relevant. No minimal important clinical difference is known for this score. Pain and function outcomes were not reported separately. Radiographic joint structure changes were not investigated. For the mean quality of life at six months (two trials; 45 participants) no meta-analysis could be performed due to missing data. No serious adverse events (SAEs) were noted and no participants withdrew because of an adverse event. There were a few adverse events (AEs) 5/63 (8%) in the HA group and 2/46 (4%) in the placebo group. The Peto odds ratio (Peto OR) to have an adverse event was 2.34 higher compared to the control group (95% CI 0.45 to 12.11). This evidence is inconclusive because of a wide CI and a small number of events.For comparing HA to exercise therapy (30 participants) the results for pain on a Visual Analogue Scale (VAS 0 to 10) at 12 months are inconclusive (MD 0.70, 95% CI -2.54 to 1.14). The American Orthopedic Foot and Ankle Society score (AOFAS score) was 13.10 points (MD) higher in favour of HA (95% CI 2.97 to 23.23) on a scale of 0 to 100. The evidence was graded as low. No adverse events were found. Radiographic structure changes were not measured; no participants withdrew due to AEs; no SAEs were found.For the comparison of HA injection combined with exercise therapy to an intra-articular injection of botulinum toxin A (BoNT-A) (75 participants), the outcome of the AOS pain score of the affected joint at six months is inconclusive (MD 0.10, 95% CI -0.42 to 0.62). The physical function (the AOS disability score) at six months is inconclusive (MD 0.20, 95% CI -0.34 to 0.74). The same number of AEs were found in both groups; HA 2/37 (5.9%), BoNT-A 2/38 (5.8%) (risk ratio (RR) 1.03, 95% CI 0.15 to 6.91). Radiographic changes were not examined, no SAEs were found and no participants withdrew because of an AE. The evidence was graded as low.The RCT comparing four different dosing schedules for HA (26 participants) showed the best median decrease in pain on walking VAS (on a scale of 0 to 100) for 3 x 1 ml at 27 weeks with a median decrease of 30. Physical function, radiographic changes and quality of life were not measured.Twenty-seven percent of all participants had AEs, most of them in the 2ml group (57% in this group). No participants withdrew due to an AE and no SAEs were noted.Overall the quality of the evidence showed some serious limitations. The evidence was graded low for the primary analysis comparing HA to placebo. This was based on a limitation in design and implementation: sample sizes were small (45 to 92 participants) and and imprecision in results: there was an unclear risk of bias for several items concerning the three studies used in the meta analysis. AUTHORS' CONCLUSIONS: Currently, there is insufficient data to create a synthesis of the evidence as a base for future guidelines for ankle OA. Since the aetiology of ankle OA is different, guidelines that are currently used for hip and knee OA may not be applicable for ankle OA. Simple analgesics as recommended for hip and knee OA seem however a reasonable first step to treat ankle OA. It is unclear if there is a benefit or harm for HA as treatment for ankle OA compared to placebo at six months based on a low quality of evidence. Inconclusive results were found comparing HA to other treatments. HA can be conditionally recommended if patients have an inadequate response to simple analgesics. It remains unclear which patients (age, grade of ankle OA) benefit the most from HA injections and which dosage schedule should be used.
背景:踝关节骨关节炎(OA)的病因通常是创伤。由于踝关节创伤多发生在相对年轻的年龄,因此患者相对年轻。有几种保守治疗方法可供选择,但缺乏这些方法利弊的证据。 目的:评估成人踝关节OA任何保守治疗的利弊,以便综合证据为未来治疗指南提供依据。 检索方法:我们检索了Cochrane对照试验中心注册库(CENTRAL 2014年第9期)、MEDLINE(Ovid)(1946年至2014年9月11日)、EMBASE(1947年至2014年9月)、PsycINFO(1806年至2014年9月)、CINAHL(1985年至2014年9月)、PEDro(截至2014年9月的所有年份)、AMED截至2014年9月、ClinicalTrials.gov、当前对照试验、荷兰注册库。为识别潜在相关研究,我们筛选了检索到的综述文章和试验中的参考文献列表。 选择标准:我们纳入了调查踝关节OA任何非手术干预的随机或对照临床试验。 数据收集与分析:我们采用了Cochrane预期的标准方法程序。 主要结果:除了使用透明质酸(HA)治疗踝关节OA外,未发现其他关于任何其他保守治疗的随机对照试验。纳入了六项随机对照试验(RCT)。本综述共纳入240名被诊断为踝关节OA的参与者。主要分析包括三项RCT(109名参与者),将HA与安慰剂进行比较。一项研究将HA与运动疗法进行比较,一项将HA联合运动疗法与关节内注射肉毒杆菌毒素进行比较,一项将四种不同剂量的HA进行比较。 主要分析:两项试验(45名参与者)的汇总分析发现,在六个月时,踝关节骨关节炎量表(AOS)总分(测量疼痛和身体功能)降低了12%(95%CI -24%至-1%)(平均差(MD)-12.53(95%CI -23.84至-1.22),范围为0至100;额外有益结果的治疗所需人数(NNTB)=4(95%CI 2至205);由于研究设计的局限性(两项研究的选择偏倚风险不明确,一项研究的失访偏倚风险不明确)和结果的不精确性:样本量小(45名参与者),该证据质量等级为低。尚不清楚在100分制上12.53分的平均差是否具有临床相关性。该评分尚无最小重要临床差异。疼痛和功能结果未分别报告。未调查影像学关节结构变化。由于数据缺失,对于六个月时的平均生活质量(两项试验;45名参与者)无法进行荟萃分析。未观察到严重不良事件(SAE),也没有参与者因不良事件退出。HA组有一些不良事件(AE)5/63(8%),安慰剂组有2/46(4%)。发生不良事件的Peto比值比(Peto OR)比对照组高2.34(95%CI 0.45至12.11)。由于置信区间宽且事件数量少
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