Serological evidence linking viral infections to incident risk of hip and knee osteoarthritis

Aims: Infections, including viral and bacterial agents, can trigger acute arthritis, with some potentially playing a role in the development of chronic arthritis such as osteoarthritis (OA). However, the role of pathogens in OA development remains unexplored. Therefore, this study aimed to investigate the associations between infectious agents and the risk of incident hip and knee OA. Methods: Data were analyzed from 7,352 UK Biobank participants (mean age 56.1 years (SD 8.2); 54.1% female), who were free of hip or knee OA at baseline. A multiplex serology panel measured serum immunoglobulin G antibody levels for 20 infectious agents, including herpesviruses, polyomaviruses, papillomaviruses, retroviruses, hepatitis viruses, bacteria, and protozoa. Incident hip and knee OA were identified through hospital and death registry records. Cox regression was used for the analyses, and the Hochberg method was used for multiple testing correction. Results: Over a median follow-up of 12.7 years (IQR 12.4 to 14.0), 262 participants developed hip and 311 developed knee OA. Seroprevalence rates for the infectious agents ranged from 0.2% to 95.5%. In fully adjusted model, seropositive agents (BK Virus (BKV) (HR 2.88; 95% CI 1.19 to 6.98), Human Papillomavirus type 18 (HPV-18) (HR 1.93; 95% CI 1.03 to 3.65), Kaposi's Sarcoma-Associated Herpesvirus (KSHV) (HR 1.50; 95% CI 1.03 to 2.20), and Merkel Cell Polyomavirus (MCV) (HR 1.40; 95% CI 1.07 to 1.85)) were associated with an increased risk of incident hip OA. Cytomegalovirus (CMV) seropositivity (HR 1.39; 95% CI 1.08 to 1.78) was associated with a higher risk of incident knee OA. BKV, MCV, and CMV remained significant after multiple testing adjustments. Conclusion: This study identified specific viral pathogens associated with an increased risk of incident hip and knee OA, with differences at the knee and hip, suggesting a potential role of preceding infections in OA pathogenesis.