## 4 Discussion  
KOA is considered the tenth largest contributor to global years lived with disabilities [49; 50]. The prevalence of OA is very high, and it is expected to affect more than 50 million subjects in the US by 2020 and increase with the aging of the population [51]. Non-pharmacogic strategies are a first-line approach to managing symptoms such as exercise, weight loss, and patient education [52; 53]. Physical activity of 150 min/week consisting of moderate-intensity aerobic exercise or 2 days/week of moderate-to-vigorous physical activity in muscle-strengthening exercises is important in maintaining physical function in OA [52]. Pharmacological treatment options include simple analgesics, nonsteroidal NSAIDs, selective COX-2 inhibitors, intra-articular corticosteroid injections, VS, and surgery. However, NSAIDs can cause gastrointestinal problems, renal failure, hypertension, and have a thrombotic potential, especially at high doses [53]. For patients with joint effusions, corticosteroids are usually administered by an IA injection. Systemic administration of corticosteroids, due to severe side effects, is not recommended in OA. Additionally, there are possible adverse events following repeated administration of corticosteroids, such as local tissue atrophy, long-term joint damage due to reduced bone formation, and the risk of infection [54]. Corticoids may produce immunosuppressive and anti-inflammatory effects, reduce production of IL-1, prostaglandandins, and leukotriene, and increase joint mobility. IA corticosteroid injections provide a short-term reduction in OA pain and act as key therapy for moderate-to-severe pain relief in patients with OA [54]. For VS with HA, platelet-rich plasma (PRP) injections or combination products such as PRP + HA have been used to improve lubrication, modulate inflammation, and modify the catabolic micro-environment [55]. Contraindications to hyalurone injections include allergies, joint infections at the injection site, and pregnant and lactating women. Patients with venous or lymphatic stasis in the legs, bleeding disorders, or treatment with anticoagulants are generally contraindicated. Herein, a two-group parallel randomized trial design was used to evaluate the effectiveness of a single HA-based VS product in combination with PT over a 1-year period. In this study, the WOMAC score decreased for both groups of patients, with remarkable results obtained at 3 months in the PG followed at some distance by the CG. From this point of view, the PT consistently improved the quality of life of the patients. The decrease in the VAS pain scores achieved from 5.7 to 2 represents the most important outcome of the combination therapy with Kombihylan(r) and PT. A VAS value of six is a high value of pain intensity, which is difficult to tolerate by patients, and in \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Variable** & **Factor 1** & **Factor 2** & **Factor 3** & **Factor 4** & **Factor 5** & **Factor 6** \\ \hline Age & \(-0.066009\) & \(-0.856533\) & \(0.12279\) & \(-0.443203\) & \(0.111468\) & \(0.195097\) \\ \hline Weight & \(-0.564898\) & \(0.497323\) & \(-0.098491\) & \(-0.494398\) & \(-0.423191\) & \(0.018414\) \\ \hline Height & \(-0.509841\) & \(0.59758\) & \(0.248188\) & \(-0.342513\) & \(0.446991\) & \(-0.065168\) \\ \hline Initial muscle strength & \(0.774789\) & \(-0.430082\) & \(0.069126\) & \(-0.38836\) & \(-0.052896\) & \(-0.237342\) \\ \hline WOMAC test after 12 months & \(-0.851222\) & \(-0.46791\) & \(-0.205264\) & \(0.070895\) & \(0.016589\) & \(-0.095119\) \\ \hline VAS test after 12 months & \(-0.368794\) & \(-0.178153\) & \(0.878551\) & \(0.166963\) & \(-0.177382\) & \(-0.032566\) \\ \hline ROM flexion test after 12 months & \(-0.851222\) & \(-0.46791\) & \(-0.205264\) & \(0.070895\) & \(0.016589\) & \(-0.095119\) \\ \hline \hline \end{tabular}
\end{table} 
Table 17: Baseline characteristics of the \(t\)-test results and factor coordinates of the variables based on correlations with the control group (CG) after 12 months.