Medical ozone is a molecule composed of three oxygen atoms with anti-inflammatory, analgesic, and antioxidant functions. Ozone therapy (O3 or O2– O3) for knee osteoarthritis has gradually received increasing attention from researchers in recent years. Here, we discuss the research hotspots and development trends of ozone therapy for knee osteoarthritis through literature visualization and analysis. (1) From 2012 to the present, the overall trend of publications on ozone treatment for knee osteoarthritis has been increasing annually, and it has received widespread attention, especially in Iran and China. (2) Keyword analysis revealed that the keywords with the greatest number of citations for ozone treatment of knee osteoarthritis are “osteoarthritis,” “ozone,” “knee osteoarthritis,” “ozone therapy,” and “hyaluronic acid.” (3) The results of the cocitation analysis revealed that the themes of the cocited literature are concentrated in 11 directions: intra-articular injections, intra-articular oxygen ozone, treatment of knee osteoarthritis, rehabilitation studies, time effects, pain function, comprehensive review, growth factors, rheumatic diseases, ultrasound-guided corticosteroid injections, and placebo. (4) The hotspots of the available highly cited literature have focused mainly on the efficacy and safety of ozone or growth factors alone in the treatment of knee osteoarthritis. Most of the literature suggests that intra-articular injections are the most common form of ozone therapy, and the accuracy and safety of ozone injections can be ensured using ultrasound-guided techniques. Ozone therapy has a positive short-term effect on pain control and functional recovery within 6 months after injection, but how to maintain the long-term efficacy of ozone therapy has rarely been described. It is hypothesized that the combination of ozone and growth factors may be beneficial for prolonging the efficacy of ozone therapy. (5) Ozone therapy has no advantages over other therapies in terms of therapeutic efficacy. Compared with ozone therapy, platelet-rich plasma and growth factor-rich plasma have better long-term outcomes in the treatment of knee osteoarthritis, whereas stromal vascular components have the best effects on pain relief and functional improvement. Few studies address the combination of ozone and growth factors for the treatment of knee osteoarthritis, and a few clinical studies registered have explored other treatments (e.g., corticosteroids). (6) Future studies could further explore the specific mechanisms and optimal dosing regimens of ozone combined with different growth factors in the treatment of knee osteoarthritis to compensate for the short-term efficacy of ozone therapy and to validate the long-term efficacy and safety of this combination therapy. It is also imperative to develop international guidelines for ozone therapy for osteoarthritis of the knee as soon as possible.
