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Individuals with gout are at significantly increased risk of having a total joint replacement (TJR) both before and after the gout diagnosis, a population-based study conducted in two countries found.

At the time of diagnosis, the prevalence of TJR was increased in patients from Taiwan, with an odds ratio of 1.44 (95% CI 1.29-1.60) and also in those from the U.K., with an odds ratio of 1.50 (95% CI 1.35-1.67), according to Chang-Fu Kuo, MD, PhD, of Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues.

And after the diagnosis of gout, the adjusted hazard ratio for TJR was 1.56 (95% CI 1.45-1.68) in Taiwan and 1.14 (95% CI 1.05-1.22) in the U.K., the researchers reported online in .

"Monosodium urate crystal deposition can cause mechanical and inflammatory damage to tissues within and around joints and clinically results in chronic usage-related pain, functional impairment, and radiographic structural changes of osteoarthritis in people with gout," the authors wrote. "Therefore gout is a potential risk factor for TJR."

In addition, has demonstrated that there is a long preclinical phase in gout, with asymptomatic hyperuricemia that can lead to irreversible joint damage before a gout attack has even occurred.

Therefore, to explore the possible association of gout and total knee or hip replacement, and to determine whether urate-lowering therapy can influence this, the researchers analyzed data from the Taiwan National Health Insurance database, which includes approximately 29 million people, and the U.K. Clinical Practice Research Datalink, which includes about 14 million people.

Urate-lowering therapy was calculated as cumulative defined daily doses and stratified into quartiles.

In the Taiwan and U.K. databases, there were 74,560 and 34,505 patients with gout, respectively. In both groups, each patient was matched to a healthy control.

The mean age at gout diagnosis was notably older in the U.K. group (61.4 versus 48.8). Median follow-up in the two groups was 8.5 and 8.8 years, and in both groups, comorbidities such as diabetes and osteoarthritis were more common among gout patients than controls.

At the time of gout diagnosis, 1.16% of patients and 0.82% of controls in the Taiwan cohort had undergone TJR, and 2.61% of patients versus 1.76% of controls in the U.K. cohort. After adjusting for covariates such as age, sex, comorbidities, and medication use, the odds ratio for prevalent TJR at the time of gout diagnosis remained significant, at 1.21 (95% CI 1.09-1.35) in the Taiwan cohort and 1.21 (95% CI 1.07-1.37) in the U.K. cohort, the researchers reported. This finding supports the concept that joint damage had already occurred when gout first becomes symptomatic, they said.

After the diagnosis of gout, there were 1,898 incident cases of TJR in the Taiwan cohort and 1,906 in the U.K. cohort, with incidence rates of 3.23 versus 1.91 per 1,000 person-years in the Taiwan cohort and 6.87 versus 4.61 per 1,000 person-years in the U.K. cohort.

For hip replacement specifically, the adjusted hazard ratio was 1.37 (95% CI 1.25-1.52, P<0.05) in the Taiwan cohort and 1.19 (95% CI 1.08-1.32, P<0.05) in the U.K. cohort. For knee replacement, the hazard ratios were 1.77 (95% CI 1.59-1.97, P<0.05) and 1.09 (95% CI 0.98-1.20), respectively.

Contrary to the authors' expectations, cumulative daily doses of urate-lowering drugs were not associated with decreased risks of TJR after adjustment for factors such as socioeconomic status, comorbidities, and lifestyle. Compared with patients with the lowest cumulative doses, the adjusted odds ratios for higher doses all were not significantly different, with odds ratios ranging from 1.02 to 1.25 in the Taiwan cohort and 0.93 to 1.08 in the U.K. cohort.

The finding that urate-lowering therapy at commonly used dosages failed to lower the risk for TJR may reflect that patients with gout are often not treated to target with dose titration, but rather are given fixed doses, and hyperuricemia can persist. Alternatively, screening asymptomatic individuals for hyperuricemia may be "a rational approach, although in most countries urate-lowering therapy is not licensed to treat hyperuricemia per se in the absence of gout or urolithiasis," the researchers noted.

A limitation of the study, they said, was the lack of information on lifestyle factors in the Taiwan cohort. In addition, the authors relied on prescription data rather than on actual patient drug adherence information, "and gout patients are recognized to have possibly the worst adherence to long-term medications of all patients with chronic illnesses," the team wrote.

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