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Use of statins did not significantly reduce the likelihood of worsening pain among individuals with knee osteoarthritis (OA), except in those who used these medications for extended periods, analysis of data from the Osteoarthritis Initiative showed.

During the study's 4 years of follow-up and after adjustment for potential confounders, adults with any exposure to statins did not report a significant decrease in risk for worsening pain (RR 0.97, 95% CI 0.93-1.02, P=0.23), according to Nicola Veronese, MD, of the National Research Council Neuroscience Institute in Padua, Italy, and colleagues.

However, those who received statins for longer than 5 years did note a decrease in pain (RR 0.91, 95% CI 0.83-0.997, P=0.04), the researchers reported online in .

While statins are most commonly used for lowering cholesterol, "there is growing evidence that statins also have important pleiotropic effects, such as the improvement of endothelial dysfunction, stabilization of atherosclerotic plaques, increased nitric oxide bioavailability, antioxidant properties, and inhibition of inflammatory responses."

Inflammation is recognized as an important contributor to knee OA, and previous work has demonstrated that statins can reduce the level of inflammatory cytokines and interfere with T cell activation -- factors that influence OA.

However, statins also have been associated with musculoskeletal pain, especially after long-term use, and few studies have examined the effects of statins on OA features such as pain and disease progression.

Therefore, to explore the possible influences of statins on risks of radiographic knee OA, symptomatic radiographic knee OA, and worsening of pain in OA, the researchers conducted a study that included 4,448 individuals enrolled in the Osteoarthritis Initiative from 2004 to 2006. Participants all had knee OA with pain for at least 30 days in the past year or were at high risk for developing knee OA because of obesity or family history.

Statin use was determined by questionnaire and interview, and included rosuvastatin, atorvastatin, lovastatin, simvastatin, pravastatin, and fluvastatin. Duration of use was categorized as less than 1 month, from 1 month to 1 year, from 1 to 3 years, from 3 to 5 years, and more than 5 years.

Covariates included race, education, and income, body mass index, depression, smoking, physical activity, medications used, and comorbidities.

A total of 58% of the cohort were women, and mean age was 61. Among the entire cohort, 25.3% used statins at baseline, with the most common being atorvastatin, used by 13.6%. Radiographic knee OA was present in 56.5% at baseline, and 24.3% had symptomatic knee OA.

Individuals using statins more often were male, older, white, and sedentary. They also more often were obese and had comorbidities, had radiographic knee OA at baseline (59.4% versus 55.5%, P=0.02), and had higher levels of pain in both knees.

During 4 years of follow-up, 431 participants developed radiographic OA, 201 reported symptomatic OA, and 3,678 reported worsening of their pain.

Statin use did not increase the risk for incident knee OA during follow-up (RR 1.31, 95% CI 0.83-2.09, P=0.25) or symptomatic OA (RR 0.97, 95% CI 0.87-1.09, P=0.63).

Regarding the individual statins, only atorvastatin showed an association with a lower risk of pain worsening (RR 0.95, 95% CI 0.91-0.996, P=0.03), whereas rosuvastatin was associated with an increased risk (RR 1.18, 95% CI 1.12-1.24, P<0.0001).

A possible explanation for the lower risk seen with atorvastatin is its lipophilic properties that can prevent collagen breakdown in the cartilage, according to the authors.

The findings of this study suggested that despite the potential anti-inflammatory effects of statins on OA, the musculoskeletal adverse effects may negate the potential benefits.

Nonetheless, subchondral bone typically becomes damaged with OA progression, leading to small vessel damage and local vascular ischemia that in turn can further worsen progression. Statins can encourage vasodilation and might therefore help minimize the damage to subchondral bone, but assessing this would have required MRI evaluations, which were not done, the researchers wrote.

Future studies therefore will be needed to further explore the effects of statins on structural damage and progression in knee OA, and to confirm or refute the clinical outcomes seen in this cohort.

A limitation of the study, the team said, was its inclusion of only patients with OA or who were at high risk for the condition, so the results may therefore not be generalizable to the larger population.

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