Ozone therapy for knee osteoarthritis: a literature visualization analysis of research hotspots and prospects

Qing Liu, Jian Liu, Guanglei Cao, Yuan Liu, Ye Huang, Xieyuan Jiang

Department of Knee Preservation Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China

Abstract

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.

摘要：医用臭氧是由三个氧原子组成的分子，具有抗炎、镇痛、抗氧化等功能。臭氧疗法（O3或O2 - O3）治疗膝关节骨性关节炎近年来逐渐受到研究者的重视。本文通过文献可视化和分析，探讨臭氧治疗膝关节骨性关节炎的研究热点和发展趋势。(1)从2012年至今，臭氧治疗膝关节骨性关节炎的出版物总体呈逐年增加的趋势，受到了广泛的关注，尤其是在伊朗和中国。(2)关键词分析显示，臭氧治疗膝关节骨性关节炎被引用次数最多的关键词是“骨关节炎”、“臭氧”、“膝关节骨性关节炎”、“臭氧治疗”和“透明质酸”。(3)共引文献的主题集中在11个方向：关节内注射、关节内氧臭氧、膝关节骨性关节炎的治疗、康复研究、时间效应、疼痛功能、综合综述、生长因子、风湿病、超声引导皮质类固醇注射、安慰剂。(4)现有高被引文献的热点主要集中在臭氧或生长因子单独治疗膝关节骨性关节炎的疗效和安全性。大多数文献表明，关节内注射是最常见的臭氧治疗形式，超声引导技术可以确保臭氧注射的准确性和安全性。臭氧治疗对注射后6个月内疼痛控制和功能恢复有积极的短期效果，但如何保持臭氧治疗的长期疗效鲜有报道。假设臭氧与生长因子联合使用可能有利于延长臭氧治疗的疗效。(5)臭氧疗法在治疗效果上没有其他疗法的优势。与臭氧治疗相比，富血小板血浆和富生长因子血浆治疗膝关节骨性关节炎的远期疗效更好，而间质血管成分治疗在缓解疼痛和功能改善方面效果最好。很少有研究涉及臭氧和生长因子联合治疗膝关节骨关节炎，少数临床研究已注册探索其他治疗方法（例如，皮质类固醇）。(6)未来的研究可以进一步探索臭氧联合不同生长因子治疗膝关节骨性关节炎的具体机制和最佳给药方案，弥补臭氧治疗的短期疗效，验证该联合治疗的长期疗效和安全性。尽快制定臭氧治疗膝关节骨关节炎的国际指南也是当务之急。