Abstract
BACKGROUND: Opioids are frequently prescribed for pain control in knee osteoarthritis patients, despite recommendations by current guidelines. Previous studies have investigated the chondrotoxicity of different opioid subtypes. However, the impact opioids may have on progression of osteoarthritis in vivo remains unknown. The aim of this study was thus to describe the associations between opioid use and knee structural changes and clinical outcomes, over 4 years. METHODS: Participants with baseline opioid use (n=181) and who continued use for ≥1 year between baseline and 4-year follow-up (n=79) were included from the Osteoarthritis Initiative cohort and frequency matched with non-users (controls) (1:2). Whole-Organ Magnetic Resonance Imaging Scores (WORMS) were obtained, including a total summation score (WORMS total, range 0-96) and subscores for cartilage (0-36), menisci (0-24), and bone marrow abnormalities and subchondral cyst-like lesions (0-18, respectively). Knee Injury Osteoarthritis Outcomes score (KOOS) symptoms, quality of life (QOL), and pain were also obtained at baseline and follow-up (range 0-100; lower scores indicate worse outcomes). Using linear regression models, associations between baseline and longitudinal findings were investigated. As pain may modify observations, a sensitivity analysis was performed for longitudinal findings. All analyses were adjusted for sex, BMI, age, race, and Kellgren-Lawrence grade. RESULTS: Opioid users had greater structural degeneration at baseline (WORMS total: Coef. [95% CI], P; 7.1 [5.5, 8.8], <0.001) and a greater increase over 4 years (4.7 [2.9, 6.5], <0.001), compared to controls. Cartilage and meniscus scores increased greater in opioid users, compared to controls (P≤0.001), and findings withstood the adjustment for baseline pain (P≤0.002). All baseline KOOS scores were lower in opioid users compared to controls (P<0.001). QOL loss was greater, when adjusted for baseline KOOS pain (QOL -6.9 [-11.6, -2.1], 0.005). CONCLUSIONS: Opioid users had worse baseline knee structural degeneration and faster progression. Opioid use was also associated with worse symptoms, pain, and QOL. Furthermore, QOL loss was greater in opioid users compared to controls, when adjusted for baseline KOOS pain, indicating that opioids may not be suited to prevent subjective disease progression in KOA patients.