Intra‐articular Orthobiologics Show Statistically but Not Clinically Meaningful Improvements Compared With Viscosupplementation in Knee Osteoarthritis: A Network Meta‐analysis of Randomized Controlled Trials

PURPOSE: To evaluate the comparative effectiveness of intra-articular platelet-rich plasma (PRP), stromal vascular fraction (SVF), bone marrow aspirate concentrate (BMAC), umbilical cord-derived mesenchymal stem cell (UC-MSC), and hyaluronic acid (HA) for pain relief and functional improvement in patients with knee osteoarthritis through network meta-analysis. METHODS: A systematic search was conducted using major biomedical databases to identify randomized controlled trials that compared the clinical efficacies of PRP, SVF, BMAC, UC-MSC, and HA. The clinical scores for pain and function were standardized for network meta-analysis based on minimal clinically important differences. RESULTS: Twenty-four studies, with 2960 patients, were included. SVF and BMAC showed significantly greater reductions in pain scores than HA at 3, 6, and 12 months (mean difference [MD], -0.7 to -1.1), whereas UC-MSC and PRP showed modest or nonsignificant effects (MD, -0.3 to -0.7). Functional outcomes showed a similar trend, with SVF and BMAC producing the greatest improvements (MD, -0.6 to -1.4), followed by UC-MSC and PRP (MD, -0.3 to -0.9). However, the magnitude of change in both pain and function did not exceed the minimal clinically important difference. At the final follow-up, SVF had the highest surface under the cumulative ranking curve, followed by BMAC and UC-MSC, with PRP ranking lower and HA showing the lowest value. The radiologic findings suggested potential cartilage repair benefits for orthobiologics; however, the results were inconsistent. No serious adverse events were reported, although procedure-specific complications were observed in some interventions. CONCLUSIONS: The improvements in pain and functional outcomes achieved by orthobiologic injections, including SVF, BMAC, UC-MSC, and PRP, did not exceed the minimal clinically important difference when compared with HA for knee osteoarthritis up to 12 months postinjection. Although some treatments showed statistically significant differences, these changes did not translate into clinically meaningful benefits. LEVEL OF EVIDENCE: Level I, network meta-analysis of randomized controlled trials.