Atorvastatin fails to reduce knee cartilage loss in osteoarthritis compared with placebo
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Once-daily atorvastatin 40 mg fails to significantly reduce cartilage loss over 2 years in patients with symptomatic knee osteoarthritis, compared with placebo, according to data published in Arthritis & Rheumatology.
“Current [osteoarthritis (OA)] therapies have short-term, small to moderate effects on joint pain; there is no approved disease-modifying therapy slowing structural progression,” Yuanyuan Wang, PhD, of Monash University, in Melbourne, Australia, and colleagues wrote. “Increased levels of serum cholesterol are associated with incident bone marrow lesions, which play a role in the pathogenesis of knee OA. Statins, the most commonly prescribed and effective treatment for hypercholesterolemia, also target inflammatory and metabolic mechanisms, suggesting their potential for slowing the progression of knee OA.
“A recent meta-analysis of observational studies showed no significant association between any statin use and incidence or progression of knee OA, but use of atorvastatin was associated with reduced risk of OA in subgroup analysis,” they added. “There was significant heterogeneity among the studies in terms of study populations, definitions of statin use, OA outcomes, and length of follow-up and observational studies are subject to bias and confounding. Thus, a randomized controlled trial is needed to determine whether statins improve structural and symptomatic outcomes in knee OA.”
To examine whether atorvastatin reduces the loss of tibial cartilage volume, compared with placebo, among patients with symptomatic knee OA, Wang and colleagues conducted the Osteoarthritis of the Knee Statin (OAKS) study, a multicenter, randomized, double‐blind, placebo‐controlled trial. The researchers enrolled 304 adults aged 40 to 70 years, all with symptomatic knee OA for at least 6 months and a pain score of more than 20 mm on a 100 mm visual scale, from the OA Clinical Trial Network in Melbourne, Hobart and Adelaide, Australia. The study stretched from August 2013 to May 2018.
Among the participants, 151 were randomly assigned to a regimen of 40 mg of oral atorvastatin once daily, while the remaining 153 patients received a matching placebo. The primary endpoint was the annual percent change in tibial cartilage volume, as measured by MRI over 2 years. Secondary endpoints included the progression of cartilage defects and bone marrow lesions, also assessed using MRI, as well as change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness and function over two years. A total of 248 participants completed the study.
According to the researchers, annual changes in tibial cartilage volume did not significantly differ between the two treatment cohorts, with –1.66% for the atorvastatin group, compared with –2.17% for placebo (difference = 0.5%; 95%CI –0.17% to 1.17%). In addition, there were no significant differences in the progression of cartilage defects (OR = 0.86; 95% CI, 0.52-1.41) or bone marrow lesions (OR = 1; 95% CI, 0.62‐1.63).
Nor were there any significant differences regarding changes in pain, with –36 for atorvastatin compared with –29.5 for placebo (adjusted difference = –2.7; 95% CI, –27.1 to 21.7); stiffness, at –14.2 compared with –11.8 (–0.2; 95% CI, –12.2 to 11.8); or function, with –89.4 versus –87.5 (0.3; 95% CI, –83.1 to 83.6).
The incidence of adverse events was also similar between the groups, at 37.7% among patients treated with atorvastatin, compared with 34% for placebo.
“In this study we showed that among participants with symptomatic knee OA, oral atorvastatin 40 mg once daily, compared with placebo, did not significantly reduce knee cartilage volume loss over 2 years,” Wang and colleagues wrote. “These findings do not support the use of atorvastatin in the treatment of knee OA. However, based on the findings from the subgroup analysis, it may be that widespread use of statins in the management of cardiovascular disease has some benefit on reducing the progression of knee OA, and this is worthy of further targeted study.”
Perspective
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Carlos M. Alonso, MD, FACR, RhMSUS
As rheumatologists, we understand the many frustrations we face treating osteoarthritis. There are no disease-modifying drugs to control disease progression and there is a lack of effective long-term treatments for symptom control.
The basis of studying statins in knee osteoarthritis (OA) is the association of increased serum cholesterol with incident bone marrow lesions which contribute to the pathogenesis of osteoarthritis. We also know that osteoarthritis is more than just a mechanical process with metabolic and inflammatory mechanisms at play. Besides lipid-lowering, statins have other effects on inflammation and metabolic processes that could have a positive effect on the progression of knee OA.
We have conflicting data from previous cohort studies and meta-analyses on the effects of statins on disease progression and overall function in these patients. The present study looked not only at symptomatic improvement but also at structural changes with the use of MRI after 2 years of atorvastatin use. Patients with severe joint space narrowing or severe pain were excluded.
Results showed no statical significant change at two years in cartilage volume between atorvastatin and placebo groups. In addition, knee pain, stiffness and function improved in both groups but failed to achieve statistical significance.
It should be emphasized that patients with a medical indication for statin therapy were excluded from the study. These patients with metabolic disease and low-grade inflammation might be the ones to benefit the most from statin use in knee OA. There is a possibility that the widespread use of these drugs in patients with metabolic syndrome is having a positive effect on disease progression in patients with concomitant knee OA. However, this is unknown and, based on the prevalence of knee OA, probably unlikely.
We remain hopeful that in the near future there will be new treatment options in OA that will change the disease course, reverse cartilage damage and consequently improve symptoms and function.
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