## 4 Discussion
However, there is no consensus in the studies regarding OT's injection side, volume, and concentration [33]. OT at the dose of 30 mcg/mL (20 mL) with the IA method effectively reduces the severity of pain in KOA patients [36]. Administration of OT at the dose of 30 mcg/mL (10 mL) with the IA method three times a week reduces pain intensity after 6 months. However, the decrease in pain intensity is not different from the decrease obtained with a home exercise program [37]. In several OT studies in KOA patients, VAS pain scores and WOMAC scores (pain, stiffness, physical function, and total) were improved significantly from baseline. The effect of three doses of OT was continued for 3 months [38] and for 6 months [37; 39], the effect of eight doses of OT was 3 months [40], the effect of four doses of OT was decreased at 3 months and disappeared in 6 months [41], the effect of four doses of OT continued to the follow-up after 4 weeks [42], and the effect of 15 sessions OT (two sessions in a week) was continued to the follow-up after 12 months [20]. The comparison of the long-term effectiveness of OT, PRP, and hyaluronic acid applications in KOA patients showed a significant decrease in pain intensity at the end of the 1 st month in the OT group, and the effects decreased at the 3 rd month. It disappeared at the 6 th month [41]. Therefore, the long-term effectiveness of ozone therapy is controversial. In the current study, ozone therapy continued its pain relieving effect (demonstrated with VAS-rest and VAS-movement) at the 12 th week. Further studies are needed for the effects of ozone therapy longer than 12 weeks. There is an only one available study in the literature comparing DPT and OT in the treatment of KOA. In the study mentioned above, KOA patients were divided into two groups, and IA 12.5% DPT was administered to one group and 15 g/mL of ozone/oxygen mixture (5-7 cm\({}^{3}\)) OT was administered to the other group three times with 10-day intervals. After 3 months, pain intensity decreased in both groups, but there was no significant difference between the groups [38]. In the current study, 12.5% DPT and OT were applied to the same 10 points with both IA and PA injections, and results were compared with the exercise group considered as a control group. Pain intensity and WOMAC scores were significantly reduced in both DPT and OT groups at weeks 6 and 12, consistent with the literature. The reduction in all VAS scores at weeks 6 and 12 was more effective with ozone therapy than with prolotherapy. Again, the decrease in WOMAC-stiffness scores and VAS scores was more effective in the ozone group at the 6 th and 12 th weeks. In our study, the significant superiority of OT over DPT in reducing pain intensity and stiffness is probably due to the combination of OT using IA and PA injections. The superiority of OT to DPT was shown with TUG scores. Both prolotherapy and ozone therapy decreased TUG scores at 6 and 12 weeks compared to baseline. When the difference between treatment groups was evaluated, it was seen that the therapeutic effect of ozone therapy on TUG scores was more effective than prolotherapy. Again, prolotherapy and OT improved ROM-active and ROM-passive scores, and prolotherapy and OT showed superiority over exercise therapy in improving ROM-active score. In one of the few studies in the literature evaluated with TUG, no difference was found between OT and placebo at week 12 [40]. Our findings are in line with this result. This study has a limitation: The patients were not blinded to which therapy they had been taken because we informed them of ethical issues.