Nodal knee osteoarthritis and gout incidence, a longitudinal study on the osteoarthritis initiative (OAI) data

Purpose: Gout is the most common inflammatory arthritis and globally affecting 2-5% of the adult population. In addition to well-characterized risk factors for gout incidences, the relationship between gout and osteoarthritis (OA) has been suggested by a few cross-sectional studies. However, the causal relationship between these two medical conditions is yet to be understood, and it is not clear which disease precedes the other. A mounting body of evidence showed that OA, especially its nodal subtype (defined as presence of Heberden’s nodes (HN) in addition to peripheral joint OA), is associated with the metabolic dysregulations, i.e. increased systemic inflammatory biomarkers and hyperuricemia which may lead to generalized MSU crystallization and gout incidence in any joints. As such, we aimed to assess whether knee osteoarthritis (OA) predicts the development of gout. Methods: Annual clinical and radiographic data from 4,746 participants (9492 knees) in the Osteoarthritis Initiative (OAI) were examined during 9-years of follow-up. Subjects with physician-confirmed gout before enrollment (n = 50) were excluded. Next, by combining the status of knee OA with the presence of Heberden’s nodes at baseline physical-examinations, subjects were categorized into nodal and non-nodal knee OA groups. At each annual visit, the outcome of incident gout was based on self-reported physician-confirmed gout as well as reported use of anti-gout therapy (including Colchicine, Probenecid, Sulfinpyrazone, and Allopurinol). Adjusted Cox proportional-hazards models were used to assess the association between knee OA phenotypes (exposures) and longitudinal risk of gout incidence (outcome). At each annual visit, presence of knee OA was defined as radiographic knee OA (Kellgren and Lawrence grade ≥2), symptomatic knee OA (presence of radiographic knee OA and self-reported knee pain), and the American College of Rheumatology (ACR) criteria-based knee OA. Results: After adjustment for potential confounders (age, gender, body mass index, and racial background), nodal symptomatic (HR: 2.78 [95% CI: 1.08 - 7.19]) and ACR criteria-based (HR: 3.25 [95% CI: 1.40 - 7.53]) knee OA demonstrated an increase in risk of longitudinal gout incidence. Despite these associations, nodal radiographic knee OA failed to show statistically significant associations with gout incidence (HR: 1.82 [95% CI: 0.72 - 4.58]). Conclusions: Nodal knee OA phenotype, as a hallmark of “generalized OA,” could be considered as a potential risk factor in the development of gout.