A Search for Factors that Predict the Efficacy of Viscosupplementation in Knee Osteoarthritis

Abstract Objective: Previous research demonstrates inconsistent effects of hyaluronate (HA) viscosupplementation on patients with knee osteoarthritis (OA). The purpose of this study was to evaluate factors that predict clinical response to a single intra-articular injection of Hylan GF-20. Methods: This was an observational study of 55 patients with knee OA, scheduled to receive intra-articular injections of Hylan GF-20. These patients met the institution's guidelines for use of viscosupplementation, which entails failure/intolerance of medical management of OA. At baseline, patients completed a series of questionnaires, including the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Patient Health Questionnaire (PHQ-9) depression score. Questionnaires were repeated at three months post-injection. A clinical responder was someone with a change in KOOS score which exceeded the mean minimal detectable change (MDC) values calculated based on test-retest reliability coefficients reported in four prior studies. Hypothesized predictors of response included PHQ-9 score, baseline visual analog scale (VAS) pain score, age, body mass index (BMI), and Kellgren score. Results: There were 35 responders and 20 non-responders. There were no statistically significant differences between responders and non-responders for any of the primary predictors. There were no differences for secondary predictors, including history of knee injury or smoking, prior HA injection, prior intra-articular corticosteroid injection, or location of OA. There was a moderate negative correlation between age and change in total KOOS score (r = −0.32, p = 0.01). Conclusions: Our research did not confirm previous predictors of response to hyaluronate injections, and highlighted the need for prospective studies in order to answer this question

Randomized double-blind crossover study of the efficacy of a tart cherry juice blend in treatment of osteoarthritis (OA) of the knee

SummaryObjectiveTo assess the efficacy of tart cherry juice in treating pain and other features of knee osteoarthritis (OA).Methods58 non-diabetic patients with Kellgren grade 2–3 OA were randomized to begin treatment with cherry juice or placebo. Two 8 oz bottles of tart cherry juice or placebo were consumed daily for 6 weeks with a 1 week washout period before switching treatments (crossover design). Western Ontario McMaster Osteoarthritis Index (WOMAC) scores and walking times were recorded prior to and after each treatment period. Additionally, plasma urate, creatinine and high sensitivity C-reactive protein (hsCRP) were recorded at baseline, after the first treatment period and after the second treatment period. Acetaminophen was allowed as a rescue drug and self reported after each treatment period. Treatment effect was examined with repeated measures analysis of variance (ANOVA) using an intention-to-treat (ITT) analysis.ResultsThere were five withdrawals during the cherry juice treatment (four adverse events (AEs)) and seven withdrawals during the placebo treatment (three AEs). WOMAC scores decreased significantly (P < 0.01) after the cherry juice treatment but not after the placebo treatment (P = 0.46); differences between treatments were not significant (P = 0.16). hsCRP declined during the cherry juice treatment vs placebo (P < 0.01). The decline in hsCRP was associated with WOMAC improvement (P < 0.01). Walking time, acetaminophen use, plasma urate and creatinine were unaffected by treatments.ConclusionsTart cherry juice provided symptom relief for patients with mild to moderate knee OA, but this effect was not significantly greater than placebo. Tart cherry juice lowered hsCRP levels and this effect was associated with improved WOMAC scores

Dihomo-γ-linolenic acid inhibits tumour necrosis factor-α production by human leucocytes independently of cyclooxygenase activity

Dietary oils (such as borage oil), which are rich in γ-linolenic acid (GLA), have been shown to be beneficial under inflammatory conditions. Dihomo-GLA (DGLA) is synthesized directly from GLA and forms a substrate for cyclooxygenase (COX) enzymes, resulting in the synthesis of lipid mediators (eicosanoids). In the present study, the immunomodulatory effects of DGLA were investigated and compared with those of other relevant fatty acids. Freshly isolated human peripheral blood mononuclear cells (PBMC) were cultured in fatty acid (100 µm)-enriched medium for 48 hr. Subsequently, cells were stimulated with lipopolysaccharide (LPS) for 20 hr and the cytokine levels were measured, in supernatants, by enzyme-linked immunosorbent assay (ELISA). Phospholipids were analysed by gas chromatography. Fatty acids were readily taken up, metabolized and incorporated into cellular phospholipids. Compared with the other fatty acids tested, DGLA exerted pronounced modulatory effects on cytokine production. Tumour necrosis factor-α (TNF-α) and interleukin (IL)-10 levels were reduced to 60% of control levels, whereas IL-6 levels were not affected by DGLA. Kinetic studies showed that peak levels of TNF-α, occurring early after LPS addition, were inhibited strongly, whereas IL-10 levels were not affected until 15 hr after stimulation. Both the reduction of cytokine levels and the decrease in arachidonic acid levels in these cells, induced by DGLA, were dose dependent, suggesting a shift in eicosanoid-subtype synthesis. However, although some DGLA-derived eicosanoids similarly reduced TNF-α levels, the effects of DGLA were probably not mediated by COX products, as the addition of indomethacin did not alter the effects of DGLA. In conclusion, these results suggest that DGLA affects cytokine production by human PBMC independently of COX activation