Serum uric acid levels influence osteoarthritis knee in non-gout population: does reference range need a revisit?

Abstract

Purpose: The strong association between hyperuricemia and gout is well known. At levels more than normal, needle like crystals of serum urate are formed and get deposited into joints producing a reversible inflammatory response. The effect of uric acid within its normal range when it remains in soluble form has also been studied; and in osteoarthritis knee a correlation was found with radiological severity, which remains irreversible. This led us to investigate the true nature of normal uric acid levels in osteoarthritis knee. Methods: In this cross-sectional study, 650 subjects of primary osteoarthritis knee having normal serum uric acid levels (Male: 3.4–7 mg/dl, Female: 2.4–5.7 mg/dl) were recruited from outpatient clinic of Dept of Orthopaedic Surgery, King George's Medical University (KGMU). The normal uric acid range was divided into three tertiles: <3.5, 3.5–5.5 and >5.5 mg/dl as lower normal, middle and upper normal respectively. The correlation among the three tertiles was evaluated with the clinical and radiological severity of the disease. The clinical severity was studied by Western Ontario Mac Master University (WOMAC) scores and the radiological severity by Kellgren & Lawrence (KL) grading of the disease. The study was approved by Institutional Ethics Committee, KGMU. Informed consent was obtained from all the participants. Data was analyzed using statistical softwares SPSS 16.0 and Graphpad. Student t test was used to analyze continuous data and one way ANOVA was used for comparing the three tertiles. Results: Mean uric acid levels in KL grade 2, 3 and 4 were 4.74 + 1.02, 4.77 + 0.97 and 5.30 + 1.67 mg/dl respectively. There was a significant increase in uric acid levels with radiological severity (P = 0.000). The association of the upper normal, middle and lower normal tertiles of serum uric acid levels with KL grade was significant (P = 0.00). The association of these three tertiles was also assessed with self reported WOMAC – pain, stiffness and physical function and were significantly different in all the three tertiles of uric acid levels (P = 0.005, 0.016 and 0.035) respectively. Conclusions: A significant association exists between the rising levels of serum uric acid and the severity of knee osteoarthritis. Despite being in the normal range and in the soluble form, uric acid seems to be producing irreparable damage to the joint by mechanisms yet to be defined. The risks associated with serum uric acid in its supposedly innocuous soluble form needs to be validated and if proven, the cut-off values of normal uric acid levels would need a revisit.