Serum Urate Levels Alter the Spatial Distribution of Urate Crystals in Synovium and Correlate With Synovitis and Pain in Non‐Gout Female Patients With Anteromedial Knee Osteoarthritis

Objective This study aimed to investigate alterations in the spatial distribution of urate crystals in the osteoarthritic synovium of patients with different levels of serum uric acid (SUA). Additionally, we examined the association between SUA levels and the severity of synovitis and pain in anteromedial osteoarthritis (AMOA) of the knee. Methods Patients who underwent knee arthroplasty due to AMOA were prospectively enrolled. Blood, synovial fluid, and synovium samples were collected and UA levels were quantified. The degree of synovitis was evaluated histologically, and the levels of inflammatory cytokines in the synovial fluid were measured. The spatial distribution of urate crystals in the synovium was determined using Gomori methenamine silver staining, and the pain subscale of the Western Ontario McMaster Universities Osteoarthritis Index was used to evaluate knee pain. The relationships among SUA, degree of synovitis, and knee pain were assessed using Spearman rank correlation and multivariable analyses. Results The pattern of urate crystal deposition in the osteoarthritic synovium was significantly altered in populations with different SUA levels. The capillary wall, sublining layer, and lining cells were sequentially affected. SUA level was the only risk factor for high‐grade synovitis and severe pain in the multivariate analysis. SUA level was also positively correlated with UA level in the synovial fluid and synovium, Krenn histologic score of the synovium, knee pain, and inflammatory cytokine level in the synovial fluid. Conclusion Spatial urate crystal distribution in the synovium was altered when SUA levels were elevated. Elevated SUA levels were also associated with aggravated synovitis and pain.