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评估用于治疗股骨头缺血性坏死的骨髓干细胞疗法的最新进展:一项对随机对照试验研究的全面系统评价、荟萃分析和荟萃回归分析

Assessing the latest advances in bone marrow stem cell therapy for Avascular Necrosis hip: A comprehensive systematic review, meta-analysis, and meta-regression of randomized controlled trial studies.

作者信息

Novriansyah Robin, Kesoema Tanti Ajoe, Tjandra Kevin Christian, Sudiasa I Nyoman Sebastian, Amirah Shakira, Puling Imke Maria Del Rosario, Lucianus Prudence, Maharani Revina, Respati Danendra Rakha Putra, Nugraha Laksmana Adi Krista, Dilogo Ismail Hadisoebroto

机构信息

Department of Surgery, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia.

Kariadi General Hospital, Semarang, Indonesia.

出版信息

PLoS One. 2025 Jun 24;20(6):e0297319. doi: 10.1371/journal.pone.0297319. eCollection 2025.


DOI:10.1371/journal.pone.0297319
PMID:40554507
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12186972/
Abstract

BACKGROUND: Avascular necrosis (AVN) of the hip is a disease characterized by vascular disruptions, where 67% of untreated cases may lead to the collapse of the femoral head. None of the current approaches, such as core decompression (CD), vascularized bone grafting, osteotomy, tissue implantation, and other methods, have been proven fully effective in delaying the progression of osteonecrosis. Recent findings indicate that bone marrow stem cells (BMSCs) have significant potential to regenerate necrotic tissue and prevent the progression of AVN in the hip. This study aims to evaluate the efficacy, side effects, treatment failure rate, most effective treatment stage of AVN hip, and application technique to treat AVN hip. METHOD: We performed this systematic review and meta-analysis from randomized controlled trials (RCTs) and sources published between 2013 and 2023 from six databases. The literature searching method was based on predetermined PICOS, study eligibility criteria, and PRISMA guidelines. The extracted data were then assessed quantitatively using R Studio with Harris hip score (HHS), Visual analog scale (VAS), the collapse of the femoral head, and conversion of total hip arthroplasty (THA) as the outcomes of interest, then qualitatively using RoB Tool, the extracted data were analyzed using R Studio. RESULT: A total of 12,939 records were identified through database searching. After the removal of duplicates and non-randomized studies using automation tools, 4,846 articles were screened. Following title and abstract review, 10 studies met the eligibility criteria and were included in the systematic review and meta-analysis, comprising 593 patients and 779 hips. The included studies originated from China (n = 4), France (n = 1), South Korea (n = 1), Australia (n = 1), Iran (n = 1), India (n = 1), and Spain (n = 1). Risk of bias assessment using RoB 2.0 tool revealed 70% of the RCTs were rated as having a low risk of bias, while 30% were judged to have some concerns. Meta-analysis demonstrated that BMSC therapy significantly reduced the risk of femoral head collapse (OR = 0.15; 95% CI: 0.09-0.25; P < 0.00001; I² = 0%) and conversion to THA (OR = 0.20; 95% CI: 0.13-0.31; P < 0.00001; I² = 83%). Functional outcomes, as measured by the HHS, were significantly improved in the BMSC group (MD = 10.70; 95% CI: 9.70-11.69; P < 0.00001; I² = 51%). Pain reduction, assessed using the VAS, also favored BMSC therapy (MD = -8.04; 95% CI: -8.66 to -7.42; P < 0.00001; I² = 99%). Meta-regression analyses explored the influence of study-level covariates on outcomes. No predictor reached statistical significance for HHS or THA conversion. However, mean age showed a borderline significant association with VAS (coefficient = -0.8029; P = 0.065), suggesting a possible trend of more significant pain reduction in older patients. CONCLUSION: Currently established AVN hip treatments are proven to be less effective. The findings strongly support that giving a BMSC at the early-stage AVN hip could improve the patient's clinical outcome and have fewer side effects and treatment failure compared to conventional treatment.

摘要

背景:股骨头缺血性坏死(AVN)是一种以血管中断为特征的疾病,67%未经治疗的病例可能导致股骨头塌陷。目前的任何方法,如髓芯减压(CD)、带血管蒂骨移植、截骨术、组织植入等,均未被证明在延缓骨坏死进展方面完全有效。最近的研究结果表明,骨髓干细胞(BMSCs)在再生坏死组织和预防髋关节AVN进展方面具有巨大潜力。本研究旨在评估BMSCs治疗髋关节AVN的疗效、副作用、治疗失败率、最有效的治疗阶段以及应用技术。 方法:我们从六个数据库中检索了2013年至2023年间发表的随机对照试验(RCTs)及相关文献,进行了这项系统评价和荟萃分析。文献检索方法基于预先确定的PICOS、研究纳入标准和PRISMA指南。提取的数据随后使用R Studio进行定量评估,以Harris髋关节评分(HHS)、视觉模拟量表(VAS)、股骨头塌陷情况和全髋关节置换术(THA)的转换作为感兴趣的结局指标,然后使用RoB Tool进行定性评估,提取的数据使用R Studio进行分析。 结果:通过数据库检索共识别出12,939条记录。使用自动化工具去除重复和非随机研究后,筛选出4,846篇文章。经过标题和摘要审查,10项研究符合纳入标准,被纳入系统评价和荟萃分析,共包括593例患者和779个髋关节。纳入的研究分别来自中国(n = 4)、法国(n = 1)、韩国(n = 1)、澳大利亚(n = 1)、伊朗(n = 1)、印度(n = 1)和西班牙(n = 1)。使用RoB 2.0工具进行的偏倚风险评估显示,70%的RCTs被评为低偏倚风险,而30%被认为存在一些问题。荟萃分析表明,BMSCs治疗显著降低了股骨头塌陷的风险(OR = 0.15;95%CI:0.09 - 0.25;P < 0.00001;I² = 0%)和转换为THA的风险(OR = 0.20;95%CI:0.13 - 0.31;P < 0.00001;I² = 83%)。以HHS衡量的功能结局在BMSCs组中有显著改善(MD = 10.70;95%CI:9.70 - 11.69;P < 0.00001;I² = 51%)。使用VAS评估的疼痛减轻情况也有利于BMSCs治疗(MD = -8.04;95%CI:-8.66至-7.42;P < 0.00001;I² = 99%)。荟萃回归分析探讨了研究水平协变量对结局的影响。对于HHS或THA转换,没有预测因素达到统计学显著性。然而,平均年龄与VAS显示出临界显著关联(系数 = -0.8029;P = 0.065),表明老年患者可能有更显著的疼痛减轻趋势。 结论:目前已确立的髋关节AVN治疗方法被证明效果较差。研究结果有力地支持了在髋关节AVN早期给予BMSCs与传统治疗相比,可改善患者的临床结局,且副作用和治疗失败更少。

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本文引用的文献

[1]
Stem cell therapy combined with core decompression versus core decompression alone in the treatment of avascular necrosis of the femoral head: a systematic review and meta-analysis.

J Orthop Surg Res. 2023-8-2

[2]
Avascular Necrosis of Femoral Head-Overview and Current State of the Art.

Int J Environ Res Public Health. 2022-6-15

[3]
Treatment of non-traumatic avascular necrosis of the femoral head (Review).

Exp Ther Med. 2022-5

[4]
Efficacy of orthobiologic adjuvants to core decompression for hip preservation in avascular necrosis hip.

J Hip Preserv Surg. 2020-11-22

[5]
Expansion and characterization of bone marrow derived human mesenchymal stromal cells in serum-free conditions.

Sci Rep. 2021-2-9

[6]
Stem cell therapy for osteonecrosis of femoral head: Opportunities and challenges.

Regen Ther. 2020-11-28

[7]
Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials.

Stem Cell Res Ther. 2020-10-19

[8]
Identifying the Therapeutic Significance of Mesenchymal Stem Cells.

Cells. 2020-5-6

[9]
Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version).

J Orthop Translat. 2020-1-6

[10]
New Advances in Stem Cell Therapy for Osteonecrosis of the Femoral Head.

Curr Stem Cell Res Ther. 2019

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