Shen et al.2323 Shen L, Yuan T, Chen S, Xie X, Zhang C. The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials. J Orthop Surg Res. 2017;12(16):1-12.
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Meta-analysis. 1493 patients included in the randomization. Groups: PRP, control group including HA, placebo, ozone and corticosteroids, by intra-articular route. |
15mL Concentration not mentioned |
Pain Functional scores WOMAC |
The intra-articular PRP injections were more effective in the treatment of osteoarthrosis of the knee regarding pain, relief and self-reported function improvement at 3, 6 and 12 months of follow-up in comparison with other injections, including placebo with saline solution, HA, ozone and corticosteroids. |
Lopes de Jesus et al.1818 Lopes de Jesus CC, Dos Santos FC, de Jesus LM, Monteiro I, Sant'Ana MS, Trevisani VF. Comparison between intra-articular ozone and placebo in the treatment of knee osteoarthritis: a randomized, double-blinded, placebo-controlled study. PLoS One. 2017;12(7):e0179185.
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Randomized, double-blind, placebo-controlled clinical trial with 98 patients who with symptomatic osteoarthritis of the knee. Groups: Group 20 µg/mL ozone intra-articular or placebo for 8 weeks. |
20µg/mL |
Pain: (visual analog scale) - VAS, Lequesne Index, Timed Up and Go Test (TUG Test), SF-36, WOMAC and Geriatric Pain Measure (GPM). |
The study confirms the ozone efficacy regarding pain relief, functional improvement, and quality of life in patients with osteoarthritis of the knee |
Feng and Beiping2222 Feng X, Beiping L. Therapeutic efficacy of ozone injection into the knee for the osteoarthritis patient along with oral celecoxib and glucosamine. J Clin Diagn Res. 2017;11(9):UC01-UC03.
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76 patients randomly distributed into two groups. Group 1: Ozone: injection in the knee joint cavity, and oral celecoxib and glucosamine hydrochloride for 6 weeks; Group 2: Control: oral celecoxib and glucosamine hydrochloride for 6 weeks. |
20µg/mL |
Functional capacity (Lysholm knee score); Pain intensity (VAS) |
The ozone intra-articular injection plus oral celecoxib and glucosamine can significantly reduce pain intensity in patients with mild to moderate osteoarthritis and improve their functional state before oral celecoxib and only glucosamine. |
Duymus et al.2424 Duymus TM, Mutlu S, Dernek B, Komur B, Aydogmus S, Kesiktas FN. Choice of intra-articular injection in treatment of knee osteoarthritis: platelet-rich plasma, hyaluronic acid or ozone options. Knee Surg Sports Traumatol Arthrosc. 2017;25(2):485-92.
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102 patients divided into 3 groups: PRP Group: received 2 doses of PRP intra-articular injections HA group: received one single HA dose Ozone group: received 4 doses of ozone. Treatment time: 12 months. |
30µg/mL, 15mL |
Pain (WOMAC Scale2 and VAS) |
In the treatment of mild to moderate knee osteoarthrosis, the PRP presented better results than HA and ozone injections since the application was enough to provide at least 12 months of daily life activities without pain. |
León Fernández et al.1919 León Fernández OS, Viebahn-Haensler R, Cabreja GL, Espinosa IS, Matos YH, Roche LD, et al. Medical ozone increases methotrexate clinical response and improves cellular redox balance in patients with rheumatoid arthritis. Eur J Pharmacol. 2016;789:313-8.
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Randomized clinical trial with 60 patients. MTX Group: received MTX, folic acid and ibuprofen MTXbozone Group: received the same as the MTX group plus ozone by rectal insufflation. Treatment time: 21 days. |
25mg/L to 40mg/L in scaling dose and ascending order application. |
Disease activity, Health Assessment Questionnaire Disability Index (HAQ-DI) Biochemical markers of the oxidative stress before and after 20 days of treatment. |
MTXþozone increased the MTX clinical response in patients with rheumatoid arthritis. The results suggest that ozone can probably increase the MTX efficacy because both share common therapeutical targets. The treatment with ozone can be a complement in the treatment of rheumatoid arthritis. |
Hashemi et al.2626 Hashemi M, Jalili P, Mennati S, Koosha A, Rohanifar R, Madadi F, et al. The effects of prolotherapy with hypertonic dextrose versus prolozone (intraarticular ozone) in patients with knee osteoarthritis. Anesth Pain Med. 2015;5(5):e27585.
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Randomized clinical trial with 80 patients. Group 1: Dextrose, Group 2: Ozone therapy The injections were repeated three times at 10 days intervals. Pain was measured before treatment and 3 months after the intra-articular injections. |
15g/mL in the ozone therapy group and dextrose at 12.5% in the dextrose group. |
Pain (McMaster and VAS scales) |
The intra-articular injection of dextrose or ozone could significantly reduce the pain in patients with osteoarthrosis, improving their functional state. However, there was no significant difference between the groups regarding the results. |
Vaillant et al.2020 Vaillant JD, Fraga A, Díaz MT, Mallok A, Viebahn-Hänsler R, Fahmy Z, et al. Ozone oxidative postconditioning ameliorates joint damage and decreases pro-inflammatory cytokine levels and oxidative stress in PG/PS-induced arthritis in rats. Eur J Pharmacol. 2013;714(1-3):318-24.
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Study in rats divided into 4 groups of 45 animals each: Group 1: Control, only received the stress of the needle in the articular space 3 times/week; Group 2: received peptidoglycan-polysaccharide (PG/PS); Group 3: similar to group 2, but after 10 days of PG/PS they received a 0.2mL intra-articulate mixture of ozone/oxygen Group 4: similar to group 3, but the ozone therapy was replaced by oxygen. Treatment time: 24 days. |
The ozone dose was calculated based on the weight. The ozone concentration was 20 mg/mL and the total administered dose was 80 mg/kg. |
Cytokines, nitric oxide and levels of oxidative stress in spleen homogenates and inflammatory processes. |
The ozone effects reduce inflammation of the joints, the pro-inflammatory cytokines, TNF-a and the IL-1b transcriptions and the reestablishment of the redox cell balance. Group 4 (PG/PS+oxygen) did not show these effects. |
Mishra et al.2121 Mishra SK, Pramanik R, Das P, Das PP, Palit AK, Roy J, et al. Role of intra-articular ozone in osteo-arthritis of knee for functional and symptomatic improvement. IJPMR. 2011;22(2):65-9.
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Randomized clinical trial with 46 patients divided into 3 groups: Ozone intra-articular Group, Methylprednisolone Group and, Ozone Group when methylprednisolone failed. Treatment time: 3 months. |
30µg/mL, 10mL |
WOMAC scale MacNab Criterion |
The group that received ozone had a better result in the relief of pain, stiffness and physical disability in relation to the group that received methylprednisolone. |
Al-Jaziri and Mahmoodi33 Al-Jaziri AA, Mahmoodi SM. Efeito analgésico da injeção de oxigênio do ozônio na osteoartrite da coluna e da articulação. Saudi Med J. 2008;29(4):553-7.
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A prospective study with 220 patients treated during 3 years with ozone injections twice a week, with at least 12 sessions. |
20µg/mL |
Pain (6 faces VAS) |
The study validates the analgesic effect of the injection of the ozone-oxygen in the osteoarthritis of the joints and spine. |