Background: To evaluate the efficacy and safety of prolotherapy with hypertonic dextrose in patients with knee osteoarthritis. A systematic search was performed in electronic databases including PUBMED, SCIELO, DIALNET and Google Scholar. Main body:We searched for randomized clinical trials that evaluated therapeutic interventions in patients with knee osteoarthritis. These trials compared the effect of intra-articular and / or extra-articular infiltrations of hypertonic dextrose vs the effect of intra-articular and / or extra-articular infiltrations of other substances or some interventional procedure application, via assessing pain, physical function and secondary effects and / or adverse reactions. Ten randomized clinical trials were included in this systematic review, the total sample size comprised 328 patients treated with hypertonic dextrose (prolotherapy) vs 348 controls treated with other infiltrations such as local anesthetics, hyaluronic acid, ozone, platelet-rich plasma or interventional procedures like radiofrequency. Conclusions: In terms of pain reduction and function improvement, prolotherapy with hypertonic dextrose was more effective than infiltrations with local anesthetics, as effective as infiltrations with hyaluronic acid, ozone or radiofrequency and less effective than PRP and erythropoietin, with beneficial effect in the short, medium and long term. In addition, no side effects or serious adverse reactions were reported in patients treated with hypertonic dextrose. Although HDP seems to be a promising interventional treatment for knee OA, more studies with better methodological quality and low risk of bias are needed to confirm the efficacy and safety of this intervention.

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Intra-articular injections with hyaluronic acid are recommended in the treatment of knee osteoarthritis; however, hypertonic dextrose prolotherapy has been reported as effective and safe. The aim was to evaluate the effectiveness of hypertonic dextrose prolotherapy for pain reduction and improvement of function in individuals with knee osteoarthritis in comparison with hyaluronic acid by meta-analysis. The search was performed in electronic databases. Six studies were included (395 participants). No statistically significant differences were found between prolotherapy and hyaluronic acid in pain control in the short-term; however, in the subanalysis that included only the studies that used intra-articular injection within the prolotherapy scheme, an effect was found in favor of the prolotherapy groups (d = −1.33; 95% confidence interval, −2.50 to −0.16; P (z) = 0.03). Also, an effect was found in favor of the prolotherapy group in the improvement in function (d = −1.05; 95% confidence interval, −2.03 to −0.08; P (z) = 0.03). No major adverse reactions or side effects were reported in any of the studies. Hypertonic dextrose prolotherapy seems to be an effective intervention to decrease pain and improve function in knee osteoarthritis, with efficacy similar to intra-articular injections with hyaluronic acid in the short-term follow-up. Nonetheless, better-quality clinical trials are necessary.