The promising potential of polynucleotide injections for knee osteoarthritis: A systematic review of literature and meta-analysis of randomized control trials

IF 2.7 Q2 ORTHOPEDICS

Journal of Experimental Orthopaedics Pub Date : 2025-09-15 DOI:10.1002/jeo2.70428

Joseph Elphingstone, Michael Bowler, Pietro Conte, Giuseppe Anzillotti, Elizaveta Kon

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Abstract

Purpose

The present study aims to synthesize and evaluate the evidence on the effectiveness of intra-articular polynucleotides (PNs) for knee osteoarthritis (OA).

Methods

In March 2024, we searched MEDLINE, Emcare, Web of Science and Cochrane Library for studies involving PNs for knee OA in human subjects. Inclusion criteria consisted of human subjects with knee OA and the use of intra-articular PNs. Studies were excluded if they were basic science, included non-knee OA pathology, did not use PNs, were case reports, or if there was no available full-text article. The primary outcome was pain, and secondary measures were functional outcome scores and adverse events. Risk of bias was analyzed using Cochrane's Risk of Bias Tool for randomized controlled trials and ROBINS-I for non-randomized studies.

Results

Twelve studies were included for systematic review and five for meta-analysis. Two studies evaluated a combined treatment of PN and HA (PNHA) to HA but were included only for qualitative analysis. Meta-analysis demonstrated significantly better pain improvement in PN than HA at 2 months (mean difference [MD] = −1.04 [−1.63 to −0.45], p = 0.0006) and four months (MD = −0.84 [−1.45 to −0.24], p = 0.006). Functional outcomes also favoured PNs at 2 months (standardized mean difference [SMD] = 0.46 [0.17–0.74], p = 0.002) and 4 months (SMD = 0.25 [0.00–0.50], p = 0.05) over HA. Data from PNHA studies suggested better pain and functional outcomes than those from HA. Adverse events with PNs were not significantly different from those receiving HA (RR = 1.97 [0.72–5.37], p = 0.187).

Conclusion

PN injections are a safe and more effective option for treating knee OA than conventional HA. Treatments combining PN and HA also appear to be a promising therapeutic option. However, limited statistical power and potential publication bias warrant further research to enhance confidence in these findings.

Level of Evidence

Level IV, systematic review of Levels II–IV studies. Level I, meta-analysis of Level I studies.

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多核苷酸注射治疗膝关节骨性关节炎的潜力：一项随机对照试验的系统文献综述和荟萃分析

目的综合评价关节内多核苷酸（PNs）治疗膝关节骨性关节炎（OA）的疗效。方法于2024年3月检索MEDLINE、Emcare、Web of Science和Cochrane Library，检索涉及人类膝关节OA患者PNs的研究。纳入标准包括患有膝关节OA和使用关节内PNs的人类受试者。如果研究是基础科学，包括非膝关节OA病理，没有使用PNs，是病例报告，或者没有可用的全文文章，则排除研究。主要结果是疼痛，次要指标是功能结果评分和不良事件。随机对照试验使用Cochrane偏倚风险分析工具，非随机对照试验使用ROBINS-I分析偏倚风险。结果系统评价纳入12项研究，meta分析纳入5项研究。两项研究评估了PN和HA （PNHA）对HA的联合治疗，但仅用于定性分析。meta分析显示，在2个月和4个月（MD = - 0.84[- 1.45至- 0.24],p = 0.006）， PN组疼痛改善明显优于HA组（平均差异[MD] = - 1.04[- 1.63至- 0.45],p = 0.0006）。与HA相比，功能结果在2个月时（标准化平均差[SMD] = 0.46 [0.17-0.74], p = 0.002）和4个月时（SMD = 0.25 [0.00-0.50], p = 0.05）也有利于PNs。来自PNHA研究的数据表明，与HA相比，PNHA的疼痛和功能预后更好。PNs组不良事件与HA组无显著性差异（RR = 1.97 [0.72-5.37], p = 0.187）。结论PN注射治疗膝关节OA比常规HA安全、有效。PN和HA联合治疗似乎也是一种很有前途的治疗选择。然而，有限的统计能力和潜在的发表偏倚需要进一步的研究来增强对这些发现的信心。证据等级IV级，II-IV级研究的系统评价。一级，一级研究的荟萃分析。

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