Effects of flurbiprofen and tiaprofenic Acid on oxidative stress markers in osteoarthritis: A prospective, randomized, open-label, active- and placebo-controlled trial

Abstract

Background: The relationship between oxidative stress and osteoarthritis (OA) has been widely investigated. Serum malondialdehyde (MDA), nitric oxide (NO), and Cu/Zn superoxide dismutase (SOD) levels are useful markers of oxidative stress. Because of the importance of oxidative stress markers in the pathogenesis of OA, treatment might involve modification of these markers to control oxidative stress. Objective: The aim of this study was to compare the effects of 2 conventionalNSAIDs on markers of oxidative stress in patients with OA of the knee. Methods: This 3-week, prospective, randomized, open-label, active- and placebo-controlled study was conducted at the Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey. Adult patients with clinically and radiographically diagnosed moderate OA of the knee who were previously untreated were enrolled. Patients were randomly assigned to 1 of 3 treatment groups: flurbiprofen 100 mg PO (tablets) BID, tiaprofenic acid 300 mg PO (tablets) BID, or placebo tablets BID. Patients were evaluated using clinical assessment and laboratory testing before treatment (week 0; baseline) and at the end of week 3. The primary end points were the differences in serum MDA, NO, and SOD levels versus placebo. Clinical parameters-pain at rest and on motion-were evaluated using a 10-cm visual analog scale (0 = no pain to 10 = worst pain imaginable). The duration (in minutes) of morning stiffness was recorded by patients, using patient diaries. The differences between treatment groups were assessed using multivariate analysis. Results: Thirty-nine patients (20 women, 19 men; mean [SD] age, 59.0 [11.3]years) were included in the study. Mean serum MDA and NO levels were significantly decreased at 3 weeks compared with baseline in the 2 active-treatment groups (all, P < 0.001); these values remained statistically similar to baseline in the placebo group. Serum SOD levels were increased significantly from baseline in the 2 active-treatment groups (both, P < 0.001), but not in the placebo group. No significant differences in serum MDA and NO levels were found between the group receiving flurbiprofen and that receiving tiaprofenic acid. Serum SOD levels were significantly higher in the flurbiprofen group compared with the tiaprofenic acid and placebo groups (both, P < 0.01). The mean (SD) score for pain at rest was significantly lower at 3 weeks compared with baseline with flurbiprofen and tiaprofenic acid (both, P < 0.001), but not with placebo. The mean score for pain on motion was significantly reduced from baseline values only with tiaprofenic acid ( P < 0.001). The duration of morning stiffness was significantly shorter at 3 weeks compared with baseline in all 3 study groups (all, P < 0.001). The mean scores for pain on motion and duration of morning stiffness were significantly reduced with tiaprofenic acid compared with placebo (both, P < 0.05). The study had some limitations (ie, small sample size, no blinding, the short duration of the study, and the weak correlation between serum and synovial fluid levels of NO). Conclusions: In this comparison of the effects of 3 weeks of treatment withflurbiprofen 100 mg BID and tiaprofenic acid 300 mg BID in patients with knee OA, both treatments effectively reduced serum MDA and NO levels compared with placebo. Only tiaprofenic acid significantly improved pain at rest and on motion and duration of morning stiffness compared with placebo.