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

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], 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.