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Musculoskeletal and Sports Medicine

Polynucleotide Injections for Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Friday, October 24, 2025
9:15 AM - 10:30 AM MT
Location: Session Room - 250 DEF
Disclosure(s):
Michael Bowler, Other: No financial relationships to disclose
Joseph Elphingstone, MD: No financial relationships to disclose
Giuseppe Anzillotti, MD: No financial relationships to disclose
Background and/or Objectives: Knee osteoarthritis is one of the most prevalent and debilitating medical conditions, affecting more than 650 million patients worldwide. In recent years, polynucleotides (PNs) have emerged as a promising alternative to hyaluronic acid (HA) for viscosupplementation. The present study aims to synthesize and evaluate the evidence on the effectiveness of intra-articular polynucleotides for knee osteoarthritis (OA).

Design: PubMed, Emcare, Web of Science, and Cochrane Library were queried for studies involving PNs for knee OA in human subjects as of March 2024, in accordance with PRISMA 2020 guidelines. Inclusion criteria consisted of human subjects with knee osteoarthritis receiving intra-articular PN injections. Studies were excluded if they were basic science, included non-knee osteoarthritis pathology, did not use polynucleotides, were not prospective randomized controlled trials, or had no available full-text article. Risk of bias was analyzed using Cochrane’s Risk of Bias Tool.

Setting : Not applicable

Participants : 281 patients from five RCTs

Interventions: Intra-articular Polynucleotides or Hyaluronic Acid

Main Outcome Measures: The primary outcome was pain, and secondary measures were functional outcome scores and adverse events.

Results: 1172 papers were initially queried. After review, five randomized controlled trials (RCTs) met inclusion criteria. Meta-analysis demonstrated significantly better pain improvement (VAS) in PNs than HA at two months (MD -1.04 (-1.63, -0.45) p=0.0006) and four months (MD -0.84 (-1.45, -0.24) p=0.006). Functional outcomes also favored PNs at two months (SMD 0.46 (0.17, 0.74) p=0.002) and four months (SMD 0.25 (0.00, 0.50) p=0.05). Adverse events were slightly higher in patients treated with PNs but not significantly different from those receiving HA (RR=1.97 (0.72-5.37) p=0.187).

Conclusions: Intra-articular PN injections are a safe and more effective option for treating knee OA than conventional HA. However, limited statistical power and potential publication bias warrant further research to enhance the confidence in these findings.