## 4 Discussion  
The authors conducted a prospective trial to investigate the efficacy of HA hybrid Sinovial(r) H-L viscosupplementation in overweight/obese patients suffering from knee OA. Knee OA is one of the leading causes of disability worldwide and the most common cause of difficulty in walking. This chronic condition has an inestimable impact on quality of life, especially in terms of pain and functional disability [2]. Overweight and obesity are well known to increase the risk of knee OA by mechanical load on weight-bearing joints and by fueling the proinflammatory milieu associated with metabolic syndrome. With advancing age, a proinflammatory picture is established, related to the increase in proinflammatory cytokines and the alteration of protein synthesis. This, especially in obese patients, has a negative impact on skeletal muscle, resulting in muscle weakness and subsequent muscle atrophy [26]. All of this can contribute to the onset of sarcopenia obesity, an increasingly common condition among obese patients, associated with greater difficulty in maintaining body weight, various comorbidities, and a higher risk of mortality [27]. The functional limitation resulting from knee OA is a pejorative factor in such patients' already-limited physical activity level. The latter contributes to the worsening of OA, causing weakness of \begin{table}
\begin{tabular}{c c c c} \hline \hline  & **T0** & **T1** & \(p\)**-Value** \\ \hline SF-12 & 25 (4) & 28 (8) & \textless{}0.05 \\ (median (IQR)) & & & \\ \hline Muscle mass & 36.1 \(\pm\) 4.5 & 37.0 \(\pm\) 3.8 & 0.62 \\ (mean \(\pm\) SD) & 35 \(\pm\) 3.6 & 34.5 \(\pm\) 3.6 & 0.54 \\ \hline \multirow{2}{*}{Number of days taking analgesics (median (IQR))} & 0 & 0 (0) & 21 (56.8) \\ \cline{2-4}  & 1–2 & 19 (51.4) & 16 (43.2) \\ \cline{2-4}  & \textgreater{}2 & 18 (48.6) & 0 (0) \\ \hline \end{tabular} Legend: T0: baseline timepoint; T1: timepoint 3 months after treatment; IQR: interquartile range; SD: standard deviation; SF-12: 12-Item Short-Form Survey.  
\end{table} 
Table 2: Analyses of secondary variables. Figure 1: Boxplot analyses of primary variables. Legend: T0: baseline timepoint; T1: timepoint 3 months after treatment; WOMAC: Western Ontario and McMaster Universities Arthritis Index; VAS: Visual Analog Scale. the knee extensor muscles, which predisposes to damage to the knee due to less stable and weaker joints [28]. A certainly important role in the prevention and treatment of OA sequelae is played by physical exercise, especially in those patients at high risk of developing OA, such as obese people. A program of physical exercises, based on muscle reinforcement of the quadriceps, muscle stretching, and aerobic activity, is safe and effective in reducing pain and disability related to OA. Physical exercise would appear to play a chondrocyte role as it increases the expression levels of the cartilage synthesis markers, in addition to improving antioxidant defenses and lowering lipid peroxidation levels. However, it is important to consider that excessive or incorrect exercise could adversely affect the course of OA [12]. In patients with KOA, a first approach with conservative treatment is always preferable. For example, intra-articular oxygen-ozone therapy (O\({}_{2}\)-O\({}_{3}\)) has recently proven effective in patients with KOA in terms of pain reduction and improvement of function and quality of life. Its painkiller action is due to the intrinsic chemical properties of O\({}_{3}\) and its anti-inflammatory activity. O\({}_{2}\)-O\({}_{3}\) showed a high safety profile and results almost identical to those of hyaluronic acid in patients with KOA [29]. An additional conservative treatment option for patients with KOA is whole-body vibration (WBV). This type of treatment consists of performing static and dynamic exercises on a vibrating platform, with consequent reinforcement of the quadriceps muscles and improvement of the balance of the patients [30].