SAN DIEGO – Male gender, obesity, pain level, and baseline radiographic severity independently predict the progression of knee osteoarthritis, while race and baseline multiple joint involvement, knee misalignment, and physical inactivity do not, according to the results of a large cohort study.
The findings could help drug developers figure out whom to include in trials of drugs aimed at slowing progression. Also, the blood, DNA, and other samples collected in the study, upon further analysis, may suggest new drug targets in people at risk for progression, said lead investigator Dr. Charles Eaton, professor of family medicine at Brown University, Providence, R.I.
"It may be some of the metabolic factors related to obesity," such as inflammation, "make you progress," and could be targeted in drug development, he said.
Meanwhile, it’s a good idea to encourage obese patients who have knee osteoarthritis (OA) to lose weight. Also, "if you have a male coming in complaining of a lot of knee pain, they might be at high risk for progression. Get an x-ray and see if they actually have arthritis, and see how severe it is," Dr. Eaton said at the World Congress on Osteoarthritis.
He and his colleagues used publicly available data from the Osteoarthritis Initiative, a multicenter longitudinal cohort study looking for biomarkers of incidence and progression, to track 1,842 knees in 1,247 knee OA patients. For each knee, the investigators analyzed x-rays taken at baseline and at 4 years of follow-up to see who had medial joint-space narrowing of 0.5 mm or more. The researchers then looked to see what baseline characteristics predicted progression. Subjects were 45-79 years old. Almost 60% of the knees in the study belonged to women.
Compared with women, the adjusted odds ratio for progression among men was 1.27 (95% confidence interval 1.02-1.59).
Patients who entered the study with Kellgren-Lawrence grade 3 disease, instead of grade 2 disease, had twice the risk of progression (OR 2.09, 95% CI 1.72-2.54). Those who enrolled with a body mass index of 30 kg/m2 or higher were about 1.5 times more likely to progress than those who entered with a BMI below 25 kg/m2 (OR 1.41, 95% CI 1.02-1.96).
Patients with the worst pain at baseline – WOMAC (Western Ontario and McMaster Universities index) pain scores in the fourth quartile – were twice as likely to progress as those who entered with first quartile pain (OR 2.18, 95% CI 1.69-2.82).
Time itself was a factor, too; 4 years into the trial, patients were nine times as likely as in the first year to have progressed (OR 9.14, 95% CI 7.45-11.22).
"Previously, it was thought that females were more likely to progress. Initial studies suggested that African Americans were more likely to progress. But when we adjusted for everything, that was no longer true," Dr. Eaton said. Baseline income, smoking, depression, and Knee Injury and Osteoarthritis Outcome Score (KOOS) functionality were among the other potential risk-factors that did not pan out on multivariate analysis.
"We are trying to understand" the increased risk for men. Men may have entered the trial with a greater burden of meniscal damage than women, and a greater likelihood of past knee surgery; there was a trend in the data toward increased progression risk for previous knee operations, but it dropped out on multivariate analysis.
The meeting was sponsored by the Osteoarthritis Research Society International.
The Osteoarthritis Initiative is funded by the National Institutes of Health, Merck, GlaxoSmithKline, Novartis Pharmaceuticals, and Pfizer. Dr. Eaton said he had no disclosures.