Do injections of hyaluronic acid help knee osteoarthritis?

Those of us hoping that hyaluronic acid injections for knee osteoarthritis would be validated by new studies are being educated by research just published in Annals of Internal Medicine. The authors set out to...

"...assess the benefits and risks of viscosupplementation for adults with symptomatic knee osteoarthritis."

The authors examined all randomized trials that compared viscosupplementation with sham or nonintervention control in adults with knee osteoarthritis that were reported in MEDLINE from 1966 to January 2012, EMBASE from 1980 to January 2012, the Cochrane Central Register of Controlled Trials from 1970 to January 2012, and other sources. Their primary outcomes were pain intensity and flare-ups. What did the data show for benefit versus risk for knee osteoarthritis?

"Eighty-nine trials involving 12 667 adults met inclusion criteria. Sixty-eight had a sham control, 40 had a follow-up duration greater than 3 months, and 22 used cross-linked forms of hyaluronic acid. Overall, 71 trials (9617 patients) showed that viscosupplementation moderately reduced pain (effect size, −0.37 [95% CI, −0.46 to −0.28])...Five unpublished trials (1149 patients) showed an effect size of −0.03 (CI, −0.14 to 0.09). Eighteen large trials with blinded outcome assessment (5094 patients) showed a clinically irrelevant effect size of −0.11 (CI, −0.18 to −0.04). Six trials (811 patients) showed that viscosupplementation increased, although not statistically significantly, the risk for flare-ups (relative risk, 1.51 [CI, 0.84 to 2.72]). Fourteen trials (3667 patients) showed that viscosupplementation increased the risk for serious adverse events (relative risk, 1.41 [CI, 1.02 to 1.97])."

While methods of ameliorating biomechanical stress factors, treating dysregulated inflammatory responses and enhancing the biomechanical environment are important principles in case management of knee osteoarthritis, taken as a whole these studies are not encouraging for viscosupplementation by injection. The authors conclude:

"In patients with knee osteoarthritis, viscosupplementation is associated with a small and clinically irrelevant benefit and an increased risk for serious adverse events."