Effect of Atorvastatin on Knee Cartilage Volume in Patients With Symptomatic Knee Osteoarthritis: Results From a Randomized Placebo‐Controlled Trial

Abstract

Objective To determine whether atorvastatin slows tibial cartilage volume loss in patients with symptomatic knee osteoarthritis (OA) in a multicenter, randomized, double‐blind, placebo‐controlled trial. Methods Participants ages 40–70 years were randomized to receive oral atorvastatin (40 mg once daily) (n = 151) or matching placebo (n = 153). The primary end point was annual percentage change in tibial cartilage volume over 2 years, assessed using magnetic resonance imaging (MRI). The prespecified secondary end points were progression of cartilage defects and bone marrow lesions over 2 years, which were assessed using MRI and change in Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index pain, stiffness, and function scores. Results A total of 248 of 304 participants (81.6%) completed the trial (mean age 55.7 years; 55.6% women). The annual change in tibial cartilage volume differed minimally between the atorvastatin and placebo groups (mean change –1.66% versus –2.17%, between‐group difference 0.50% [95% confidence interval (95% CI) –0.17%, 1.17%]). There were no significant differences in the progression of cartilage defects (odds ratio [OR] 0.86 [95% CI 0.52, 1.41]) or progression of bone marrow lesions (OR 1.00 [95% CI 0.62, 1.63]). Moreover, there were no significant differences in change in WOMAC pain, stiffness, or function scores over 2 years between the atorvastatin and placebo groups (mean change in pain score –36.0 versus –29.5, adjusted difference –2.7 [95% CI –27.1, 21.7]; mean change in stiffness score –14.2 versus –11.8, adjusted difference –0.2 [95% CI –12.2, 11.8]; mean change in function score –89.4 versus –87.5, adjusted difference 0.3 [95% CI –83.1, 83.6]). The incidence of adverse events (AEs) was similar between the atorvastatin and placebo groups (57 [37.7%] versus 52 [34.0%] experiencing AEs). Conclusion Treatment with oral atorvastatin (40 mg once daily), compared to placebo, did not significantly reduce cartilage volume loss over 2 years in patients with symptomatic knee OA. These findings do not support the use of atorvastatin for the treatment of knee OA.

Standardized study of atorvastatin possible osteoarthritis disease‐modifying effect in a rat model of osteoarthritis

“…Our results contradicted the results of the work by Wang et al [50] as oral atorvastatin did not significantly reduce knee cartilage volume loss in patients diagnosed with OA when compared with placebo. In our study, we used atorvastatin as a prophylactic therapy, not a therapeutic one, and this could be supported by subgroup analysis showing that widespread use of statins in the management of cardiovascular disease could reduce the progression of knee OA.…”

Effect of atorvastatin on skeletal muscles of patients with knee osteoarthritis: Post-hoc analysis of a randomised controlled trial

“…The Osteoarthritis of the Knee Statin (OAKS) study was a 2-year multicentre randomised, double-blind, placebo-controlled trial evaluating whether atorvastatin had a disease-modifying effect in patients with symptomatic knee OA ( 15 , 16 ). In brief, eligible participants aged 40–70 years with symptomatic knee OA for ≥6 months with a pain score of >20 mm on a 100 mm visual analog scale, and who met the American College of Rheumatology clinical criteria for knee OA ( 17 ) were enrolled.…”

“…Participants were randomly assigned in 1:1 ratio to receive either 40 mg atorvastatin once daily or inactive matching placebo once daily. Details concerning randomisation and masking have been reported previously ( 15 , 16 ). All participants were provided usual care by their treating health practitioners.…”

“…Details of the adverse event and its relationship with the intervention were recorded and reported to the Ethics Committees. The primary outcome of the OAKS study was the annual percentage change in tibial cartilage volume, measured by magnetic resonance imaging (MRI) ( 15 ).…”

“…As those with symptomatic OA are excluded from clinical trial of statins, the effect of statin on skeletal muscles in populations with symptomatic OA is unknown. Thus, the aim of this study was to examine the effect of atorvastatin on skeletal muscle properties (biochemistry, strength, size, and myalgia) in a post-hoc analysis of a randomised controlled trial examining the effect of atorvastatin on progression of knee OA ( 15 ).…”