# Viscosupplementation in the Therapy for Osteoarthritic Knee
## 2 Hyaluronic Acid
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline \begin{tabular}{c} **Publication** \\ **Year [Ref.]** \\ \end{tabular} & \begin{tabular}{c} **Study** \\ **Design** \\ \end{tabular} & \begin{tabular}{c} **Comparison** \\ **Agent** \\ \end{tabular} & \begin{tabular}{c} **Patients Number** \\ **(TreatControl)** \\ \end{tabular} & \
\begin{tabular}{c} **Injection** \\ **Times** \\ \end{tabular} &
\begin{tabular}{c} **Result** \\ \end{tabular} \\ \hline
1998 [14] & RCT & saline & 495(248/247) & 5 & HA group, VAS decreased by 2 or more (5–26 weeks). In the HA group about half of the group had mild pain or no pain at week 26 (about 30\% of the naporegon). There was also less pain when walking. \\ \hline
1999 [15] & RCT & saline & 50(25/25) & 5 & Pain during walking, VAS, LI. Proved that the HA group was superior with a significant difference at 5 weeks and 6 months F/U \\ \hline
2001 [16] & RCT & saline & 226(113/113) & 3 & WOMAC, pain on standing were improved from Weeks 7 to 27 \\ \hline
2002 [17] & RCT & saline, NSAID & 120(30/30/30/30) & 3 & IA HA + p.o. placebo vs. IA HA + p.o. NSAID vs. IA placebo + p.o. placebo: For resting pain relief, HA seems to be as effective as NSAIDs. For pain with physical activity and functional performance, HA may be superior to placebo alone or NSAIDs alone. \\ \hline
2003 [18] & RCT & saline & 408(204/204) & 3 & No superior effect compared to placebo group (in mean joint space width) \\ \hline
2004 [19] & RCT & saline & 240(120/120) & 5 & WOMAC pain, stiffness improved compared to placebo group \\ \hline
2005 [20] & RCT & arthrocentesis & 374(128/120/124) & 4 &
\begin{tabular}{c} HAX4 (O4), HAX3+ Arthrocentesis 1 time (O3A1), or 4 arthrocentesis \\ (control group, A4). More O4 patients improved their WOMAC pain scores by more than 40\% compared to A4. \\ \end{tabular} \\ \hline
2006 [21] & RCT & saline & 106(53/53) & 3 & WOMAC, VAS improved compared to placebo group \\ \hline
2007 [22] & Clinical study & Home exercise program & 60(20/20/20) & 5 & HA 5 times vs. HA 3 times vs. HA 3 times + exercise: HA 3 times + exercise group significantly faster onset of pain relief compared with other group: WOMAC, VAS improved in all groups \\ \hline
2008 [23] & RCT & saline & 20(10/10) & 8 & WOMAC, VAS improved compared to placebo group \\ \hline
2009 [24] & RCT & saline & 588(293/295) & 3 & WOMAC, pain, QOL improved compared to placebo group \\ \hline
2010 [25] & RCT & saline & 48(24/24) & 3 & WOMAC, VAS improved but there was no statistically significant difference in functional and symptom improvement with respect to placebo \\ \hline
2010 [26] & RCT & CS & 51(26/25) & 5 & VAS improved both groups; measured joint fluid levels of HA, biomarker. IA HA may have protective effects on the articular cartilage by increasing the HA concentration in synovial fluid, inhibitory effects on the catabolism \\ \hline
2011 [27] & RCT & saline & 306(153/153) & 5 &
\begin{tabular}{c} Received four cycles of five IA HA or placebo injections: repeated cycles of IA HA not only improve knee OA symptoms during the in-between cycle period but also exert a marked carry-over effect for at least 1 year after the last cycle. \\ \end{tabular} \\ \hline
2011 [28] & RCT & saline & 200(100/100) & 5 & WOMAC, pain 50-foot walking test improved compared to placebo group \\ \hline
2012 [29] & RCT & saline & 30(15/15) & 3 & Old age (mean age: 72), The overall effect of HA on gait velocity in older knee OA patients was not significant compared to placebo. \\ \hline
2012 [30] & RCT & MPA & 391(130/129/132) & 3 & HAX1 vs. HAX2 vs. MPS 40 mg 1 time: Both IA IA regimens were effective in nine relaying unit: did not show a difference vs. IA MPA \\ \hline
2014 [31] & Randomized, open-label & NSAID & 184(98/86) & 5 & HAX5 vs. NSAIDs 3 times per day for 5 weeks: early efficacy of IA HA is suggested to be not inferior to that of NSAIDs, and that the safety of the early phase of IA is superior to that of NSAIDs for patients with knee OA. \\ \hline
2015 [32] & RCT & saline & 196(98/98) & 3 & HA was not superior to placebo. \\ \hline
2019 [33] & RCT & HA + CS & 44(16/16/12) & 3 & In HA alone group, WOMAC, knee extensor and flexor strength improved, but not proprioception \\ \hline \end{tabular}
\end{table}