Effect of atorvastatin on knee structure and pain in patients with knee osteoarthritis: a randomised controlled trial

Abstract

Purpose: Observational studies have shown an effect of oral statin on reducing structural progression of knee osteoarthritis. However, no randomised controlled trials have been performed. This study examined the effect of atorvastatin compared to placebo on reducing structural progression and improving symptoms in participants with symptomatic knee osteoarthritis. Methods: A multicentre, randomised, parallel-group, double-blind, placebo-controlled trial was conducted in Melbourne, Hobart, and Adelaide, Australia. Participants aged 40-70 years with symptomatic knee osteoarthritis assessed by the American College of Rheumatology criteria were randomly assigned in a 1:1 ratio to receive oral atorvastatin 40 mg (n=151) or inactive matching placebo (n=153) once daily over two years. The primary outcome was annual percentage change in tibial cartilage volume assessed using magnetic resonance imaging (MRI) over two years. Secondary outcomes were worsening of tibiofemoral cartilage defects and bone marrow lesions (BMLs) assessed using MRI and change in knee pain and function assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) over two years. Intention-to-treat analyses were performed. Analysis of intervention effects according to the absence or presence of BMLs at baseline was pre-specified. Results: Of 304 participants (mean age 55.7 years, 55.6% female), 248 (81.6%) completed the trial. Annual change in tibial cartilage volume was not significantly different between groups [atorvastatin: -0.26% (95% CI -0.92% to 0.41%) vs. placebo: -0.91% (95% CI -1.52% to -0.30%), p=0.15]. No significant between-group differences were observed in worsening of cartilage defects (atorvastatin: 59.6% vs. placebo: 63.4%, p=0.56) or BMLs (57.6% vs. 57.5%, p=0.99), or change in WOMAC pain (-35.9 vs. -31.6, p=0.78) or function score (-90.7 vs. -92.8, p=0.97). In those without BMLs at baseline (n=105), annual change in tibial cartilage volume was significantly different between the atorvastatin and placebo groups [0.50% (95% CI -0.88% to 1.87%) vs. -1.19% (95% CI -2.09% to -0.30%)] where significant cartilage volume loss was observed in the placebo group but not in the atorvastatin group with a between-group difference of -1.69% (95% CI -3.36% to -0.02%, p=0.047) (Table 1). There were no significant differences in adverse events between groups. Conclusions: Among participants with symptomatic knee osteoarthritis, oral atorvastatin 40 mg once daily did not reduce knee cartilage loss or knee pain over two years. However, atorvastatin reduced cartilage loss in those without BMLs, suggesting atorvastatin may have a disease-modifying effect in those with knee osteoarthritis and without BMLs.Table 1Change in cartilage volume, cartilage defects, bone marrow lesions, knee pain and functionWithin-group change, mean (95% CI)Between-group difference Atorvastatin - PlaceboP for interaction between BMLs and treatmentAtorvastatin (n=151)Placebo (n=153)Mean difference (95% CI)PAnnual % change in tibial cartilage volume-0.26 (-0.92 to 0.41)-0.91 (-1.52 to -0.30)0.66 (-0.24 to 1.55)0.15Without BMLs0.50 (-0.88, 1.87)-1.19 (-2.09, -0.30)-1.69 (-3.36, -0.02)0.0470.11With BMLs-0.61 (-1.37, 0.16)-0.75 (-1.54, 0.04)-0.14 (-1.19, 0.91)0.79Change in WOMAC pain (0-500)-35.9 (-60.1 to -11.7)-31.6 (-49.2 to -14.0)-4.3 (-34.9 to 26.4)0.78Without BMLs-36.0 (-84.1, 12.2)-26.9 (-59.0, 5.1)-9.0 (-69.4, 51.4)0.760.83With BMLs-35.9 (-62.6, -9.1)-34.4 (-56.2, -12.6)-1.4 (-36.4, 33.5)0.94Change in WOMAC function (0-1700)-90.7 (-169.5 to -11.9)-92.8 (-152.3 to -33.4)2.1 (-99.7 to 103.9)0.97Without BMLs-80.3 (-234.5, 73.8)-58.8 (-168.7, 51.1)-21.5 (-226.1, 183.0)0.830.74With BMLs-95.6 (-182.9, -8.2)-113.0 (-185.4, -40.7)17.4 (-97.5, 132.4)0.77No (%)No (%)Odds ratio (95% CI)Atorvastatin vs. PlaceboPP for interaction between BMLs and treatmentWorsening of cartilage defects90 (59.6)97 (63.4)0.86 (0.51, 1.44)0.56Without BMLs25 (52.1)34 (59.6)0.72 (0.30, 1.69)0.440.64With BMLs65 (63.1)63 (65.6)0.92 (0.49, 1.72)0.79Worsening of BMLs87 (57.6)88 (57.5)1.00 (0.62, 1.63)0.99Without BMLs18 (37.5)30 (52.6)0.50 (0.20, 1.29)0.150.09With BMLs70 (68.0)58 (60.4)1.38 (0.74, 2.55)0.31 Open table in a new tab