Gout may be associated with greater risk of severe knee osteoarthritis, which in turn requires total knee replacement surgery. That’s according to a new study in Osteoarthritis & Cartilage.

“This implies that treating gout or hyperuricemia may reduce the progression of knee osteoarthritis,” says Gim Gee Teng, lead study author and director of the senior rheumatology residency program at Singapore’s National University Healthy System. Hyperuricemia, which had long been thought to be the same as gout, involves an excess of uric acid in the blood.

But further studies are needed to replicate her and her colleagues’ research, Teng says. “Lifestyle modifications and weight loss remain as the mainstay of treatment for knee osteoarthritis.”

She and colleagues analyzed data from a cohort of 63,257 Chinese adults, aged 45 to 74, in the Singapore Chinese Health Study. Of that larger group, 51,858 people — about 7,500 more women than men — were selected, and that group had 1,435 cases of total knee replacement surgery after about 10 years. Gout, the researchers found, was associated with a 39 percent higher rate of total knee replacement surgery in women, but that wasn’t the case for the men.

That association of gout and total knee replacement in women persisted even after subjects were excluded who self-reported arthritic histories, and it was a stronger association for women who were leaner than for those who were heavier.

“It is well recognised that other than age and female gender, higher body mass index is the single most important risk factor for knee osteoarthritis,” Teng says. “Therefore, obesity constitutes the highest attributable risk factor for total knee replacement in severe knee osteoarthritis.”

[Learn which foods and supplements lower uric acid levels in the blood.]

The cohort that Teng and colleagues studied allowed them to evaluate how gout influences total knee replacement surgery for severe knee osteoarthritis in non-overweight women.

“The explanation for why the association between gout and total knee replacement was not observed in the overweight group is possibly due to the fact that high body mass index has a much stronger impact on knee osteoarthritis, thus obscuring the impact of gout on the disease,” Teng says.

The findings aren’t surprising, Teng says, as research has long recognized that joints affected by gout are likelier to have knee osteoarthritis. And a prior study showed correlations between levels of serum urate, a prerequisite for gout’s occurrence, and bone spurs (called osteophytosis) in knee osteoarthritis. But there are several difficulties studying the association between gout and knee osteoarthritis, Teng says.

  1. Osteoarthritis is a disease that evolves and is difficult to define, so Teng and colleagues used total knee replacement surgery as a “surrogate” for severe knee osteoarthritis — meaning it became so severe that it necessitated surgery.
  2. Cross-sectional studies, which had explored the association of gout and osteoarthritis, including knee osteoarthritis, by design cannot differentiate between a “temporal” relationship (meaning gout predisposes patients to developing osteoarthritis) and the opposite, meaning osteoarthritic joints facilitate localized deposits of urate crystals and hyperuricemia.
  3. And finally, age and obesity are common risks factors for both gout and knee osteoarthritis. “It is important to adjust for these and other potential confounders, which may not have been done in some previous studies,” Teng says.

[Read about the 2017 state of gout survey.]

Future epidemiological research needs to validate the findings in other populations or ethnicities, which may have different total knee replacement rates for severe knee osteoarthritis, Teng says. It will also be necessary for future studies to validate the impact of gender and body mass index. “We also hope to see more experimental studies to evaluate possible molecular pathways mediated by uric acid crystals in the pathogenesis of osteoarthritis,” she says.

In an interview with MedPage, the director of Drexel University College of Medicine’s rheumatology fellowship Arundathi Jayatilleke was skeptical of the findings. “I think the most likely explanation is that this is a fluke due to the low number of knee replacement cases,” she said in the interview.