Statin Use and Knee Osteoarthritis Outcomes: A Longitudinal Cohort Study

Veronese, Nicola; Koyanagi, Ai; Stubbs, Brendon; Cooper, Cyrus; Guglielmi, Giuseppe; Rizzoli, René; Schofield, Patricia; Punzi, Leonardo; Al-Daghri, Nasser M.; Smıth, Lee; Maggi, Stefania; Reginster, Jean Yves

doi:10.1002/acr.23735

Cited by 43 publications

(37 citation statements)

References 25 publications

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“…From the previously published works with conflicting results regarding the association between statin use and OA, a recent study by Veronese et al on the OAI dataset showed no association between statin use and radiographic OA incidence. Results of the Veronese et al study may be criticized because of the inclusion of prevalent statin users, which subjects the design to incident-prevalent bias (10). Valdes et al suggested a possible cross-sectional relationship between statin use and less severe hip and knee OA in only HN-positive patients as a marker for generalized OA (8).…”

Section: Longitudinal Analysismentioning

confidence: 99%

“…In comparison with the previous report, the major strength of our study was a consideration of the presence of HNs as a hallmark of generalized OA and a distinct clinical biomarker for the protective effect of statins using a cohort design (6,9,10,(25)(26)(27). We used the OAI dataset and were able to match our cohorts for the confounders and minimize the possibility of confounding by indication and incidence-prevalent bias (6,(8)(9)(10)(25)(26)(27). Details about the variables used for the matching process (ie, associated medical conditions to statin use and knee OA) are discussed in Appendix E1 (online).…”

Section: Longitudinal Analysismentioning

confidence: 99%

“…Details about the variables used for the matching process (ie, associated medical conditions to statin use and knee OA) are discussed in Appendix E1 (online). Moreover, knee-based sampling gave us the advantage of assessing knee-specific outcomes (6,(8)(9)(10)(25)(26)(27). With a mean follow-up of more than 4 years in both HN-positive and HN-negative cohorts, we were able to investigate chronic exposure to statins, considering the unclear role of duration of statin use in previous studies.…”

Section: Longitudinal Analysismentioning

confidence: 99%

“…With a mean follow-up of more than 4 years in both HN-positive and HN-negative cohorts, we were able to investigate chronic exposure to statins, considering the unclear role of duration of statin use in previous studies. Further, we addressed both symptomatic and radiographic outcomes of knee OA (6,(8)(9)(10)(25)(26)(27). We used a per-protocol approach instead of intention-to-treat analysis (6,8,9,(25)(26)(27).…”

Section: Longitudinal Analysismentioning

confidence: 99%

“…This approach may not be as valid as exact pill count and cannot be used to explore the dose-dependent effects of statins, but it may be more reliable than asking patients to self-report their medication use. A similar approach has been implemented in previous OAI studies (5,(7)(8)(9)(10)29). Second, our sample size in longitudinal assessment was restricted to participants included in matching with available data at follow-up, decreasing the 7.02; 95% CI: 0.90, 54.92; P = .19) (homogeneity test, P , .01) ( Table 5).…”

Section: Longitudinal Analysismentioning

confidence: 99%

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Statin Use and Knee Osteoarthritis Outcome Measures according to the Presence of Heberden Nodes: Results from the Osteoarthritis Initiative

et al. 2019

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S tatins are widely prescribed to asymptomatic and symptomatic patients as a prevention therapy for cardiovascular disorders (1). In addition to their lipidlowering capabilities, statins are believed to have pleiotropic effects that may be mediated by antioxidant properties and inhibition of inflammatory processes (2). Despite research focusing on developing diseasemodifying osteoarthritis (OA) drugs, to our knowledge, no disease-modifying OA drugs have been proven to be effective in slowing OA-related structural damage progression (3,4). There has been recent interest in the potential role of statins as a disease-modifying knee OA drug. Some studies suggested a protective role for statin use against knee OA outcomes (5-7). In this regard, to date, one cross-sectional study from the Osteoarthritis Initiative (OAI) has shown an association between statin use and lower prevalence of knee OA in a subgroup of 238 patients with generalized OA (8); however, two other studies found no significant association with the longitudinal risk of radiographic knee OA progression in all OAI participants (9,10). These

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Section: Longitudinal Analysismentioning

confidence: 99%

Section: Longitudinal Analysismentioning

confidence: 99%

Section: Longitudinal Analysismentioning

confidence: 99%

Section: Longitudinal Analysismentioning

confidence: 99%

Section: Longitudinal Analysismentioning

confidence: 99%

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Statin Use and Knee Osteoarthritis Outcome Measures according to the Presence of Heberden Nodes: Results from the Osteoarthritis Initiative

et al. 2019

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Potential Benefits of Statin Therapy in Reducing Osteoarthritis Risk: A Mendelian Randomization Study

Zhang,

Sui,

et al. 2024

Arthritis Care & Research

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ObjectiveThe purpose of this study was to determine the causal effect of statins on osteoarthritis (OA) risk using Mendelian randomization (MR).MethodsSingle‐nucleotide polymorphisms (SNP)‐based genome‐wide association analyses (GWAS) of statins were collected from the UK Biobank and FinnGen dataset, and OA data was collected from the UK Biobank and arcOGEN study. Two‐sample MR analyses were performed utilizing the inverse variance weighted (IVW) technique. MR Egger, weighted median, and weighted mode served as supplementary analyses. Mendelian randomization‐Egger regression, Cochran's Q test, and MR‐PRESSO analysis were performed as sensitivity analyses. HMGCR expression and OA risk were evaluated using summary data‐based Mendelian randomization (SMR).ResultsMR analyses consistently supported a causal connection between statin use and OA risk. A causal effect was observed for atorvastatin (IVW: β=‐2.989, P=0.003) and rosuvastatin (IVW: β=‐14.141, P=0.006) treatment on hip OA. Meta‐analysis showed the association between atorvastatin and knee OA was statistically significant (OR=0.15, p = 0.004). Simvastatin use exhibited a protective effect against knee (IVW: β=‐1.056, P=0.004) and hip OA (IVW: β = ‐1.405, P = 0.001). Statin medication showed a protective effect on hip osteoarthritis (IVW: β =‐0.054, P = 0.013). HMGCR correlated significantly with a reduced risk of knee OA (β= ‐0.193, PSMR=0.017), rather than hip OA (β=0.067, PSMR=0.502), which suggested that statins' protective effect on OA may not be related to its lipid‐lowering effect.ConclusionThis MR study provides compelling evidence that statin treatment may be a protective factor for OA. Further research is required to clarify its underlying mechanism.

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

Wang

Jones

Hill

et al. 2021

Arthritis & Rheumatology

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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.

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Statin Use and Knee Osteoarthritis Outcomes: A Longitudinal Cohort Study

Abstract: The effect of statins use on knee OA outcomes remains unclear, although in our study those using statins for over five years and those using atorvastatin reported a significant lower risk of developing knee pain. This article is protected by copyright. All rights reserved.

Cited by 43 publications

References 25 publications

Statin Use and Knee Osteoarthritis Outcome Measures according to the Presence of Heberden Nodes: Results from the Osteoarthritis Initiative

Statin Use and Knee Osteoarthritis Outcome Measures according to the Presence of Heberden Nodes: Results from the Osteoarthritis Initiative

Potential Benefits of Statin Therapy in Reducing Osteoarthritis Risk: A Mendelian Randomization Study

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

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