Efficacy and safety of collagen derivatives for osteoarthritis: A trial sequential meta-analysis

Objective: To investigate the efficacy and safety of collagen derivatives for osteoarthritis. Design: PubMed, Embase, and Cochrane Library were searched till June 2023 for randomized controlled trials (RCTs) investigating collagen derivatives for treating osteoarthritis. Data were independently extracted by two authors. The risk of bias was assessed using the RoB 2 tool. A random-effects meta-analysis was performed within a frequentist framework. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Results: A total of 35 RCTs involving 3165 patients were included. The main analysis of the primary outcome was based on 25 RCTs involving 2856 patients. Collagen derivatives exerted small-to-moderate effects on pain alleviation (standardized mean difference [SMD] −0.35, 95% confidence interval [CI] −0.48 to −0.22, moderate certainty) and function improvement (SMD −0.31, 95%CI −0.41 to −0.22, high certainty) compared with the control. Collagen derivatives were safe; they did not increase the risk of withdrawal or adverse events compared with the control. The trial sequential analyses indicated that this study had sufficient statistical power for deriving definitive conclusions, confirming the robustness of our findings. Conclusions: Strong evidence supports the efficacy and safety of collagen derivatives for osteoarthritis treatment.