Abstract
BackgroundThe objectives are to compare the efficacy of intra-articular hyaluronic acid (IA-HA) alone and in combination with anti-inflammatory drugs (IA-HA + AI), corticosteroids (CS) or non-steroidal anti-inflammatory drugs (NSAIDs) in clinical trials and in vivo and in vitro studies of osteoarthritis (OA).MethodsData in the BIOSIS, CINAHL, Cochrane Library, EMBASE and Medline databases were collected and analyzed. Random effects models were used to compute the effect size (ES) of the mean difference in pain reduction scores from baseline and the relative risk (RR) of adverse events. The ES of histological scores in vivo and cartilage metabolism in vitro were also calculated. We conducted sensitivity analysis of blinding and intention-to-treat (ITT), compared IA-HA combined with CS vs. IA-HA alone in trials, and compared the effects of HA + AI vs. AI alone in vitro, including anabolic and catabolic gene expression.ResultsThirteen out of 382 papers were included for data analysis. In clinical trials, the ES of pain reduction scores within the 1st month was −4.24 (−6.19, −2.29); 2nd–12th month, −1.39 (−1.95, −0.82); and within one year, −1.63 (−2.19, −1.08), favoring IA-HA + AI (P < 0.001). The ES of RR was 1.08 (0.59, 1.98), and histological scores was 1.38 (−0.55, 3.31). The ES of anabolic gene expression was 1.22 (0.18, 2.25), favoring HA alone (P < 0.05); catabolic gene expression was 0.74 (−0.44, 1.53), favoring HA alone; and glycosaminoglycans remaining was −2.45 (−5.94, 1.03).ConclusionsIA-HA + AI had greater efficacy for pain relief than IA-HA alone within a one-year period. However, HA + AI down-regulated the ACAN gene when compared with HA alone in vitro.
Highlights
The objectives are to compare the efficacy of intra-articular hyaluronic acid (IA-Hyaluronic acid (HA)) alone and in combination with anti-inflammatory drugs (IA-HA + AI), corticosteroids (CS) or non-steroidal anti-inflammatory drugs (NSAIDs) in clinical trials and in vivo and in vitro studies of osteoarthritis (OA)
The following 51 papers were excluded for reasons of: (1) not using HA as a control (7 papers); (2) studies of HA compared with anti-inflammatory drugs (41 papers); and (3) insufficient data for pooling (3 papers)
The I2 value was 0% and the P value of heterogeneity was 0.29. These results suggest that using IA-HA + AI was a related factor in relative risk (RR), causing 8% more (1.08-fold) adverse events (AE) than IA-HA alone; this was not a significant difference
Summary
The objectives are to compare the efficacy of intra-articular hyaluronic acid (IA-HA) alone and in combination with anti-inflammatory drugs (IA-HA + AI), corticosteroids (CS) or non-steroidal anti-inflammatory drugs (NSAIDs) in clinical trials and in vivo and in vitro studies of osteoarthritis (OA). The cartilage cannot return to normal, some medications, such as corticosteroids (CS) and non-steroidal anti-inflammatory drugs (NSAIDs), are useful for relief of pain and inflammation in affected joints due to their inhibition of inflammatory cytokines [6, 7]. Corticosteroids have potent anti-inflammatory effects by inhibiting phospholipase A2, reducing pain and effusion to a comparatively greater extent than NSAIDs, but prolonged use of CS may result in negative effects and accelerate OA progression. Many recent reports have investigated the synergistic effects, drug interactions and decreased cytotoxicity of HA when combined with other drugs, in order to develop more effective OA treatments [21,22,23,24,25,26,27]
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