Exercises plus intra-articular injection for knee osteoarthritis: a systematic review with meta-analysis

Abstract Objective To evaluate whether the combination of exercise and intra-articular injection (IAI) effectively improves pain, function, and quality of life in patients with knee osteoarthritis (OA) compared to any control group in the short, medium, and long term through a systematic review. Methods A comprehensive search strategy was applied in the databases Embase, PubMed, MEDLINE, CENTRAL, CINAHL, and PEDro. Inclusion criteria focused on randomized controlled trials examining the effects of exercise combined with IAI in patients with knee OA, with outcomes assessed at short-, medium-, and long-term follow-ups. The primary outcomes were pain and function. The quality of the evidence was evaluated using the GRADE system. Results Eleven studies, comprising 802 participants, were included. All studies investigated the combination of IAI and exercise. A statistically significant difference in pain was observed: in the short and medium term, the Botulinum toxin IAI group demonstrated superior pain reduction compared to the Hyaluronic acid IAI group (MD -1.32, 95% CI -2.20 to -0.44 and MD -9.09, 95% CI -13.16 to -5.01, respectively). In the medium term, Saline IAI was more effective than Corticosteroid IAI (MD 1.99, 95% CI 0.49 to 1.90). Regarding function, Saline IAI outperformed IAI with any medication in the short term (MD 0.50, 95% CI 0.20 to 0.79). In terms of quality of life, the Corticosteroid IAI group demonstrated superior physical function and mental health outcomes compared to the Saline IAI group in the medium term (MD -0.43, 95% CI -0.77 to -0.08 and MD -0.38, 95% CI -0.76 to -0.01, respectively). In the long term, physical function improved more with IAI combined with exercise compared to exercise alone. Conclusion Given the very low quality of the evidence, it is not possible to definitively conclude that the combination of IAI and exercise is more effective than IAI or exercise alone in patients with knee OA. Further high-quality studies are needed to establish more definitive conclusions. Registration The International Prospective Register of Systematic Reviews (PROSPERO): CRD42021277729. Clinical trial number Not applicable.