Oxygen–Ozone Therapy in Tendinopathy Management: A Comprehensive Review

Background: Tendinopathy is a degenerative condition caused by mechanical overload, accounting for approximately 30% of musculoskeletal healthcare cases. It progresses through a process characterized by collagen disorganization, altered vascularization, and neuronal ingrowth. Traditional conservative treatments, such as therapeutic exercises, non-steroidal anti-inflammatory drugs, and physical therapies, are useful, but their effectiveness is sometimes only partial and there is a need to search for new potential solutions. Recent interest in oxygen–ozone (O2-O3) therapy stems from preliminary observations suggesting potential anti-inflammatory and regenerative effects. Nevertheless, its clinical role remains speculative and warrants thorough investigation beyond anecdotal evidence. Considering the heterogeneity of clinical presentations and treatment responses among patients, O2-O3 therapy has been proposed as a promising tool for tailoring personalized treatment strategies for tendinopathy. This review critically appraises the available literature concerning the mechanistic rationale and clinical applications of O2-O3 therapy in tendinopathy, with attention to both its theoretical underpinnings and the quality of empirical evidence. Methods: A literature search was conducted on O2-O3 therapy for tendinopathy using PubMed, Cochrane, and Embase, filtering for full-text articles published between 2004 and 2024. Recent clinical trials were included irrespective of evidence level, while excluding systematic reviews, duplicates, and irrelevant studies. Results: Ozone has been shown to modulate oxidative stress, promote neovascularization, and suppress pro-inflammatory cytokines. Both clinical and in vivo studies indicate that O2-O3 therapy relieves pain, enhances tendon healing, and improves biomechanical properties. Some comparative studies suggest that O2-O3 therapy might provide more sustained symptoms control than corticosteroids, but the heterogeneity of follow-up durations and outcome measures prevents definitive conclusions. Conclusions: O2-O3 therapy emerges as a potentially valuable adjunct in the management of chronic tendinopathy, particularly in cases unresponsive to conventional treatments. However, its clinical role remains to be clearly defined and its possible role in personalized medicine needs further exploration, particularly in relation to patient stratification and individualized treatment protocols. Further high-quality randomized controlled trials are warranted to validate its efficacy, determine long-term outcomes, and standardize treatment protocols to ensure safety and reproducibility.