Ozone Therapy versus Hyaluronic Acid Injections for Pain Relief in Patients with Knee Osteoarthritis: Preliminary Findings on Molecular and Clinical Outcomes from a Randomized Controlled Trial

Abstract

Ozone therapy (OT) is used for the treatment of multiple musculoskeletal disorders. In recent years, there has been a growing interest in its use for the treatment of osteoarthritis (OA). The aim of this double-blind randomized controlled trial was to evaluate the efficacy of OT compared with hyaluronic acid (HA) injections for pain relief in patients with knee OA. Patients with knee OA for at least three months were included and randomly assigned to receive three intra-articular injections of ozone or HA (once a week). Patients were assessed at baseline and at 1, 3, and 6 months after the injections for pain, stiffness, and function using the WOMAC LK 3.1, the NRS, and the KOOS questionnaire. Out of 55 patients assessed for eligibility, 52 participants were admitted to the study and randomly assigned into the 2 groups of treatment. During the study, eight patients dropped out. Thus, a total of 44 patients, reached the endpoint of the study at 6 months. Both Group A and B consisted of 22 patients. At 1-month follow-up after injections, both treatment groups improved statistically significantly from baseline in all outcomes measured. At 3 months, improvements remained similarly consistent for Group A and Group B. At 6-month follow-up, the outcomes were comparable between the 2 groups, showing only a worsening trend in pain. No significant differences were found between the two groups in pain scores. Both therapies have proven to be safe, with the few recorded adverse events being mild and self-limiting. OT has demonstrated similar results to HA injections, proving to be a safe approach with significant effects on pain control in patients affected by knee OA. Due to its anti-inflammatory and analgesic effects, ozone might be considered as a potential treatment for OA.

A pre-market interventional, single-arm clinical investigation of a new topical lotion based on hyaluronic acid and peptides, EGYFILTM, for the treatment of pain and stiffness in soft tissues

“…Hyaluronic acid has been used successfully for the treatment of pain in a variety of pathologies, most notably in osteoarthritis and joint pain via intra-articular injection [ 19 , 21 , 60 – 63 ], however, based on our knowledge, no other clinical trial reports the usefulness of topical HA and peptides lotion to relieve muscle tension and pain. Puhl et al .…”

Role of the Gut Microbiota in Osteoarthritis, Rheumatoid Arthritis, and Spondylarthritis: An Update on the Gut–Joint Axis

“…The treatment of OA can include non-surgical treatments, such as changes in lifestyle (e.g., encompassing education, self-management, physical activity, weight reduction), pharmacological therapy (paracetamol, topical or oral NSAIDs, intra-articular injections of corticosteroids and hyaluronic acid), nutraceuticals, physical therapy, oxygen–ozone therapy, rehabilitation, and also some new therapies such as mesenchymal stem cell injections, nerve blocks, and platelet-rich plasma injections [ 75 , 76 , 77 , 78 , 79 ]. On the other hand, these actions merely decrease the symptoms of OA in patients, leading inevitably to surgery [ 80 , 81 ].…”

Efficacy and safety of ozone therapy for knee osteoarthritis: an umbrella review of systematic reviews

“…Injured chondrocytes release pro-inflammatory cytokines and damage their own DNA. Ozone therapy (OT) reduces inflammation and oxidative stress that induces organ damage in chronic diseases ( Davies et al, 2008 ; de Sire et al, 2022 ; Sconza et al, 2023 ). Like physical exercise, ozone induces low–moderate level oxidative stress and triggers a series of intracellular metabolic processes that improve cell functionality.…”

“…Thus, repeated exposure to OT may cause resistance against oxidative stress ( Bocci and Valacchi, 2015 ; de Sire et al, 2022 ; Serra et al, 2023 ). In a similar pattern, intra-articular ozone is able to induce the generation of reactive species of oxygen (ROS) and lipid oxygen products (LOPs), stimulating the antioxidant system and creating an environment that counteracts the proinflammatory and pro-oxidative circuits present in knee OA ( Davies et al, 2008 ; Borrelli et al, 2015 ; Sconza et al, 2023 ). In this scenario, OT becomes a low-cost therapeutic candidate for the management of KOA.…”

“…This variability may stem from differences in treatment protocols and administration methods, such as variations in the injected ozone’s volume and concentration, the number of therapy sessions, and the choice of substances used as a control. These disparities highlight the need for standardization and consistency in research methodologies to better understand the true impact of OT on KOA ( Giombini et al, 2016 ; Duymus et al, 2017 ; Lopes de Jesus et al, 2017 ; Babaei-Ghazani et al, 2018 ; de Sire et al, 2022 ; Aliyev et al, 2023 ; Sconza et al, 2023 ) The intervention seems to be a safe approach ( Hashemi et al, 2015 ; Chansoria et al, 2016 ; Lopes de Jesus et al, 2017 ; de Sire et al, 2022 ; Serra et al, 2023 ). Several systematic reviews (SRs) summarize the available evidence on the efficacy of OT in KOA pain and joint function, but the lack of a standardized protocol limits us from drawing conclusions on the efficacy of OT ( Raeissadat et al, 2018a ; Costa et al, 2018 ; Li et al, 2018 ; Arias-Vázquez et al, 2019a ; Oliviero et al, 2019 ; Sconza et al, 2020 ).…”