Yang Fei, Wen Lei, Chen Changshun, Zhao Qiao, Feng Zhiwei, Ran Bin, Luo Xuwei, Xiao Dongqin, Fang Qifan
Nanchong Central Hospital, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, China.
The Second Clinical Medical School, Lanzhou University, Lanzhou, China.
Front Pharmacol. 2025 May 21;16:1601349. doi: 10.3389/fphar.2025.1601349. eCollection 2025.
Heterotopic ossification (HO) involves the ectopic deposition of bone in soft tissues, frequently occurring as a complication post-hip trauma or surgery. To prevent HO following total hip arthroplasty (THA), irradiation has been extensively employed, alongside the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Given the extensive range of NSAIDs available, determining the most effective NSAID or irradiation protocol for prophylaxis continues to be a matter of debate.
Adhering to the PRISMA guidelines, a comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Web of Science to identify relevant randomized controlled trials. To minimize bias in literature evaluation, two authors independently searched and assessed the articles. In cases of disagreement, a third author was consulted. We strictly implement the inclusion and exclusion criteria. Using the criteria for assessing bias in the Cochrane Collaboration Network, two writers independently evaluated the quality of the included studies. We systematically extracted and assessed data according to the level of evidence presented in the articles. A Bayesian network meta-analysis (NMA) was implemented to evaluate and contrast the efficacy of irradiation and six distinct NSAIDs in preventing HO after THA. The results were computed using the GEMTC package in R (V.4.4.1). The consistency of the model was tested using nodal analysis. The priority of drug efficacy was comprehensively evaluated using rank probability and the surface under the cumulative ranking curve (SUCRA). Stata 16 was used to assess publication bias, and sensitivity analysis was performed using the one-by-one elimination method. The protocol for this study was officially registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY).
A total of 461 studies were identified, and 17 studies were finally included in the analysis. The meta-analysis incorporated data from 3,014 patients: 629 administered ibuprofen, 54 with naproxen, 117 receiving celecoxib, 426 on indomethacin, 295 treated with diclofenac, 45 on etoricoxib, 522 subjected to irradiation, and 926 serving as controls. These trials reported an average age ranging from 59 to 75 years, with males comprising 31.2%-63% of subjects. The total incidence rate of HO in all control groups was 55.2%. In terms of effectiveness, compared with the control, four strategies showed a low incidence of HO, including naproxen (OR = 0.08, 95% CrI 0.01-0.60), indomethacin (OR = 0.13, 95% CrI 0.04-0.41), diclofenac (OR = 0.06, 95% CrI 0.01-0.29), and irradiation (OR = 0.08, 95% CrI 0.02-0.3). Diclofenac was more beneficial than ibuprofen (OR = 0.10, 95% CrI 0.01-0.97). The probabilities derived from the surface under the cumulative ranking curve (SUCRA) algorithm are as follows: Diclofenac (78.0%), etoricoxib (71.6%), irradiation (67.3%), naproxen (66.7%), indomethacin (53.2%), celecoxib (38.8%), ibuprofen (18.6%), and a control group (6.8%). Because stronger evidence supports the efficacy of diclofenac. The most likely ranking for the effectiveness of preventing HO after THA is as follows: Diclofenac > etoricoxib > irradiation > naproxen > indomethacin > celecoxib > ibuprofen.
In terms of preventive efficacy, diclofenac and etoricoxib demonstrated the most favorable performance in preventing HO after THA within this network meta-analysis. Irradiation, naproxen, and indomethacin are also satisfactory options, while ibuprofen is ineffective. Given the advantages shown by etoricoxib and celecoxib, further randomized controlled trials are recommended to clarify their effects. Our conclusions require confirmation through additional high-quality studies.
异位骨化(HO)是指骨在软组织中的异位沉积,常作为髋部创伤或手术后的并发症出现。为预防全髋关节置换术(THA)后发生HO,除使用非甾体类抗炎药(NSAIDs)外,放疗也已被广泛应用。鉴于有多种NSAIDs可供选择,确定预防HO最有效的NSAID或放疗方案仍是一个有争议的问题。
遵循PRISMA指南,在PubMed、Embase、Cochrane图书馆和Web of Science中进行全面检索,以识别相关的随机对照试验。为尽量减少文献评估中的偏倚,由两位作者独立检索和评估文章。如有分歧,则咨询第三位作者。我们严格执行纳入和排除标准。使用Cochrane协作网评估偏倚的标准,两位作者独立评估纳入研究的质量。我们根据文章中呈现的证据水平系统地提取和评估数据。实施贝叶斯网络荟萃分析(NMA)以评估和对比放疗及六种不同NSAIDs预防THA后HO的疗效。结果使用R(V.4.4.1)中的GEMTC软件包计算。使用节点分析测试模型的一致性。使用秩概率和累积排名曲线下面积(SUCRA)综合评估药物疗效的优先级。使用Stata 16评估发表偏倚,并使用逐一排除法进行敏感性分析。本研究方案已在国际注册系统评价和荟萃分析方案平台(INPLASY)正式注册。
共识别出461项研究,最终17项研究纳入分析。荟萃分析纳入了3014例患者的数据:629例使用布洛芬,54例使用萘普生,117例接受塞来昔布,426例使用吲哚美辛,295例使用双氯芬酸,45例使用依托考昔,522例接受放疗,926例作为对照。这些试验报告的平均年龄在59至75岁之间,男性占受试者的31.2% - 63%。所有对照组中HO的总发生率为55.2%。在有效性方面,与对照组相比,四种策略显示HO发生率较低,包括萘普生(OR = 0.08,95% CrI 0.01 - 0.60)、吲哚美辛(OR = 0.13,95% CrI 0.04 - 0.41)、双氯芬酸(OR = 0.06,95% CrI 0.01 - 0.29)和放疗(OR = 0.08,95% CrI 0.02 - 0.3)。双氯芬酸比布洛芬更有益(OR = 0.10,95% CrI 0.01 - 0.97)。累积排名曲线下面积(SUCRA)算法得出的概率如下:双氯芬酸(78.0%)、依托考昔(71.6%)、放疗(67.3%)、萘普生(66.7%)、吲哚美辛(53.2%)、塞来昔布(38.8%)、布洛芬(18.6%)和对照组(6.8%)。因为有更强的证据支持双氯芬酸的疗效。THA后预防HO有效性的最可能排名如下:双氯芬酸>依托考昔>放疗>萘普生>吲哚美辛>塞来昔布>布洛芬。
在预防效果方面,在该网络荟萃分析中,双氯芬酸和依托考昔在预防THA后HO方面表现最为良好。放疗、萘普生和吲哚美辛也是令人满意的选择,而布洛芬无效。鉴于依托考昔和塞来昔布显示出的优势,建议进一步进行随机对照试验以阐明其效果。我们的结论需要通过更多高质量研究来证实。