A. S. Al-Arfaj ( Rheumatology Division, Department of Medicine (38), King )
Osteoarthritis (OA) is the most common arthritis worldwide.1 The association with age, obesity, sex and metabolic factors has been studied.2-7 All of these studies showed an association of osteoarthritis with obesity. Some of these studies accounted for serum uric acid and found no association between it and osteoarthritis.3-5,7 Davis et al found a positive association between knee osteoarthritis and uric acid albeit a small one not reaching significant level.2 Sun Ye et al specifically investigated serum uric acid relationship with osteoarthritis and concluded that although uric acid was associated with generalized osteoarthritis in patients undergoing hip replacement, there were no association with knee OA or bilateral hip or knee OA.8 Others reported an association with OA of multiple joints.9 Both osteoarthritis and hyperuricemia are common in Saudi Arabia.10,11 We sought to investigate the relationship between serum uric acid and knee and generalized osteoarthritis in this community.
Patients and Methods
As part of a study of the prevalence of rheumatic diseases in the northern part of Riyadh, Saudi Arabia, and over a period of seven months extending from September 1998 to March 1999, covering 14 primary care clinics, we interviewed the first two adult patients over the age of 20 years each day.A total of 471 patients attending these clinics for a variety of medical complaints were interviewed, consented and their uric acid level was assayed. Radiograph of hands and knees [anteroposterior (AP), lateral (L)] were available for 241 patients (135 males, 106 females). Their age, sex, BMI (weight in kg divided by the square of height in meters), serum uric acid, serum cholesterol and triglycerides were recorded. The presence of osteoarthritis was defined as having grade 2 or more of the Kellgren-Lawrence grading system.12 This system has the following scheme: grade 0 normal, grade 1 minute osteophytes of doubtful significance, grade 2 definite osteophytes, grade 3 moderate narrowing of joint space, grade 4 greatly reduced joint space and subchondral bone sclerosis. Generalized OA was defined as the simultaneous presence of radiographic changes of knee and hand OA.
The serum uric acid values were classified into tertiles, and patients in the higher second and third tertile were compared to first tertile (lowest) for presence of osteoarthritis of knee and generalized osteoarthritis. The crude odd ratio was calculated for higher two tertiles in reference to the first (lowest). This was then adjusted for age, sex, BMI, serum cholesterol, and serum triglycerides using the Mantel-Haenszel stratified analysis method.
Two hundred and forty one cases (135 males and 106 females) were available for analysis. The mean age was 48.9 ± 15.3 (female mean age 46.1 ± 13.9, male mean age 51.3 ± 16.1) years. Knee osteoarthritis was present in 120 (49.8%) patients, 57 (23.7%) females and 63 (26.1%) males. Generalized OA was seen in 54 (22.4%) patients, 20 (8.2%) females and 34 (14.1%) males. Their distribution among the different serum uric acid tertiles is outlined in Table 1. Table 2 shows this relationship expressed as odd ratio. The crude OR was above unity in the relationship between generalized OA, knee OA and the second uric acid tertile [1.05 (95% CI, 0.54-2.06), 1.92 (95% CI, 0.98-3.74)] respectively. After adjusting for age only, the most significant association with knee and generalized OA were seen in the third tertile group [2.21 (95% CI, 1.42-3.68), 3.29 (95% CI, 1.93-6.85)] respectively. In the 2nd tertile group, after controlling for age, the association was with generalized OA only, OR 2.50 (95% CI, 1.30-4.88). When we adjusted for all parameters (age, sex, BMI, serum cholesterol and triglycerides), OR was most significant for the association between the third tertile of uric acid values and both knee and generalized OA [OR 2.03 (95% CI, 1.58-2.71), OR 1.81 (95% CI, 1.33-2.57)] respectively. The odds ratio adjusted for age only, showed clear upward change from its crude value suggesting confounding by age in all groups. Some of this known effect of age on OA was dampened after adjusting for other paramaters, resulting in OR of 2.03 and 1.81 between the third uric acid tertile and knee and generalized OA respectively. However, the higher OR for knee OA compared to generalized OA for the third triglyceride tertile (data not shown) which was not seen when the age only was controlled, would suggest confounding by BMI.
This report found an association between hyperuricemia and generalized OA as has been reported previously.8,9 We also found an association between hyperuricemia and knee OA. A possible association between hyperuricemia and knee OA was previously reported by Hart et al.7 Others reported no association between OA and hyperuricemia.3,13,14 Confounding by age and BMI may have contributed to our positive results in relation to knee OA, which is usually age and weight dependent. This phenomenon was also noted by Sun et al.8 Another reason for the observed association between uric acid level and OA in our study may be that we did not control for glucose level, hypertension and medications including diuretics which have been shown to be associated with OA.7
This is a cross-sectional study and no conclusions are drawn about the direction of the association between hyperuricemia and OA. Possible explanatory mechanism for the association between hyperuricemia and OA includes genetic predisposition, insulin resistance and endogenous hormonal environment.15-17 Relatives of OA patients with increased uric acid levels were also found to have hyperuricemia.16 The increase in both hyperuricemia and OA in women after menopause may point to hormonal mechanisms.15
In conclusion, our data points to a possible association between hyperuricemia and knee and generalized OA.
1. Cooper C. Osteoarthritis and related disorders. In: Klippel J, Dieppe P (eds). Radiology 2nd ed. London: Mosby, 1998, pp. 2, 1-8.
2. Davis MA, Ettinger WH, Neuhaus JM. The role of metabolic factors and blood pressure in the association of obesity with osteoarthritis of the knee. J Rheumatol 1988;15:1827-32.
3. Felson DT, Anderson JJ, Naimark A, et al. Obesity and knee osteoarthritis: The Framingham Study. Ann Int Med 1988;109:18-24.
4. Bagge E, Bjelle A, Eden S, et al. Factors associated with radio-graphic osteoarthritis: Results from the population study: 70-year old people in Götenborg. J Rheumatol 1991;18:1218-22.
5. Schouten JSA, Vanden Ouweland FA, Valkenburg HA. A 12-year follow-up study in the general population on prognostic factors of cartilage loss in osteoarthritis of the knee. Ann Rheum Dis 1992;51:932-37.
6. Hart DJ, Spector TD. The relationship of obesity, fat distribution and osteoarthritis in women in the general population: the Chingford Study. J Rheumatol 1993;20:331-5.
7. Hart DJ, Doyle DV, Spector TD. Association between metabolic factors and knee osteoarthritis in Women: the Chingford Study. J Rheumatol 1995; 22:1118-23.
8. Sun Y, Brenner H, Sauerland S, et al. Serum uric acid and pattern of radiographic osteoarthritis: the U/M osteoarthritis study. Scand J Rheumatol 2000;29:380-6.
9. Acheson R, Collart AB. New Haven survey of joint diseases XVII: Relationship between some systemic characteristics and osteoarthritis in a general population. Ann Rheum Dis 1975;34:379-87.
10. Al-Arfaj A, Al-Boukai A. Prevalence of radiographic knee osteoarthritis in Saudi Arabia. Clin Rheumatol 2002;21:102-5.
11. Al-Arfaj A. Hyperuricemia in Saudi Arabia. Rheumatol Int 2001;20:61-4.
12. Kellgren JK, Lawrence JS. Radiological assessment of osteoarthritis. Ann Rheum Dis 1957;15:494-501.
13. Anderson JJ, Felson DT. Factors associated with osteoarthritis of the knee in the First National Health and Nutrition Examination Survey (NHANES I: Evidence for an association with overweight, race and physical demands of work. Am J Epidemiol 1988;127:1019-30.
14. Schouten JSAG, Van den Ouweland FA, Valkenburg HA. A 12-year follow-up study in the general population on prognostic factors of cartilage loss in osteoarthritis of the knee. Ann Rheum Dis 1992;51:932-7.
15. Spector TD, Campion GD. Generalized osteoarthritis: a hormonally mediated disease. Ann Rheum Dis 1989;48:523-7.
16. Lawrence JS. Rheumatism in populations. London: Heinemann, 1977
17. Reaven GM. Barting Lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-1607.