Asymptomatic Hyperuricemia Predictive of Radiographic Knee Osteoarthritis

Arthritis of the knee. Coloured X-ray of the knee of an obese 48 year old patient showing degenerative arthritis caused by the extreme stress on the knee from being overweight. At top is the femur (thigh bone), at bottom is the tibia (shinbone), with the smaller fibula to its right. In a healthy individual there is usually a clear space between the femur and the tibia. Osteoarthritis results in the loss of cartilage between the joint. The healing process leads to the growth of bone in place of the cartilage, causing pain, stiffness and loss of mobility.
Asymptomatic hyperuricemia is associated with an increased risk for knee osteoarthritis (OA), particularly among adults without obesity.

Asymptomatic hyperuricemia is associated with an increased risk for knee osteoarthritis (OA), particularly among adults without obesity, according to research published in Osteoarthritis and Cartilage.

Using a cross-sectional study, nationally representative dataset collected from the National Health and Nutrition Examination Survey (NHANES), researchers examined the associations between hyperuricemia and knee OA. Researchers also investigated whether obesity confounded or modified any associations. Data were pulled specifically from NHANES III, conducted between 1988 and 1994; this was the most recent NHANES survey to assess knee OA via radiographs. Data included serum urate measurements, self-reported gout diagnoses, and self-reported knee pain. The Kellgren-Lawrence scoring system was used to establish baseline radiographic knee OA (Kellgren Lawrence grade ≥2); symptomatic radiographic knee OA was defined as radiographic knee OA plus knee pain most days for 6 weeks in the same knee. The final patient sample included 2213 participants over the age of 60. Overall mean serum urate level was 5.61±0.04 mg/dL; mean serum urate levels in the asymptomatic hyperuricemia and normouricemic groups were 7.80±0.07 mg/dL and 5.14±0.04 mg/dL, respectively.

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Overall, the presence of asymptomatic hyperuricemia was 17.9% (95% CI, 15.3-20.5%), with a significantly greater prevalence among men vs women (24.5% vs 13.3%, P <.01). Those adults with obesity, compared with those without obesity, were more likely to have asymptomatic hyperuricemia (27.4% vs 14.8%; P <.01). Prevalence of radiographic knee OA was 37.7% (95% CI, 35.0-40.3%); the prevalence was significantly greater in women vs in men (42.1% vs 31.3%; P <.01). In the total study cohort, prevalence of symptomatic radiographic knee OA was 12.1%, and was higher among adults with obesity vs those without obesity (22.9% vs 8.5%; P <.01). Multivariate analyses found that in adults with obesity, the prevalence of unadjusted radiographic and symptomatic radiographic knee OA was 58.4% vs 54.3% and 26.4% vs 21.6%, respectively (P =.53 and P =.55), in those with and without asymptomatic hyperuricemia.

Associations of asymptomatic hyperuricemia with radiographic and symptomatic radiographic knee OA in adults without obesity were borderline significant or significant (prevalence ratio [PR] 1.31; 95% CI, 0.98-1.77 and PR 1.66; 95% CI, 1.02-2.71, respectively). Analyses examining the effect of asymptomatic hyperuricemia on knee OA, based on subcategories of body mass index, found no difference in the effect of asymptomatic hyperuricemia on radiographic knee OA. Prevalence ratios were similar when comparing those who were normal or underweight with those who were overweight (PR 1.24 vs 1.29) and between obesity classes I and II (PR 0.97 vs 0.97). A possible protective effect was noted in obesity class III (PR 0.46).

Limitations of the study included the limits of the cross-sectional methodology, the self-report of several confounders, an older study population, and the use of body mass index to determine obesity, which may obscure more subtle distinctions in terms of the physiologic processes of obesity.

The researchers of the study concluded that “[asymptomatic hyperuricemia] is associated with an increased prevalence of [symptomatic radiographic knee OA] in adults without obesity and a borderline association in all adults aged 60 years or older, suggesting that urate may play a role in OA pathogenesis and/or serve as a biomarker of more severe and painful disease.”

Disclosures: Dr Pillinger reports relationships with AstraZeneca, Crealta, Horizon, Ironwood, and SOBI, as well as the Takeda-sponsored CARES study. Dr Krasnokutsky reports relationships with Crealta, Horizon, and Ironwood. For a complete list of disclosures, please see the full text of the study online.


Wang S, Pillinger MH, Krasnokutsky S, Barbour KE. The association between asymptomatic hyperuricemia and knee osteoarthritis: data from the third National Health and Nutrition Examination Survey [published online May 31, 2019]. Osteoarthritis Cartilage. doi: 10.1016/j.joca.2019.05.013