What the published evidence shows

Why this study is unusual

Most trials of joint injections recruit straightforward osteoarthritis. This one deliberately did the opposite.1 Every patient had knee osteoarthritis and calcium pyrophosphate deposition, the crystal condition also called chondrocalcinosis or pseudogout.

That combination is known to behave worse than osteoarthritis alone: more sustained inflammation, faster cartilage destruction, and no standard treatment for the periods between acute attacks. The median X-ray grade was 3, the mean age was 70, and a fifth of the group had already failed hyaluronic acid or PRP.

A result in that population is a harder result to obtain than the same result in mild disease.

What was done

Twenty-nine patients, 34 knees, each received a single 2 ml ultrasound-guided intra-articular injection of high molecular weight hyaluronic acid combined with collagen tripeptide. Patients were assessed at baseline, then at one, three and six months, with a telephone call at two weeks to capture early adverse events.

The primary measure was pain on a 0 to 10 numeric rating scale. Secondary measures were the WOMAC index and its subscales, plus ultrasound findings for joint effusion, synovial hypertrophy and power Doppler signal. Improvement was judged against accepted thresholds for a clinically meaningful change rather than statistical significance alone.2

What was found

• Pain fell consistently at every follow-up point, with statistically significant differences against baseline, and the largest improvement at six months.
• Seventy-nine per cent of patients, 19 of 24 assessed, achieved the minimum clinically meaningful improvement in pain.
• Eighty-three per cent, 20 of 24, achieved it on the total WOMAC score, covering pain, stiffness and physical function.
• The authors concluded that the combination of hyaluronic acid and collagen tripeptide can provide a strong anti-inflammatory effect in this population.

Safety

No side effects related to the injections were recorded in the cohort. Specifically, no acute post-injection flare was reported, and no patient complained of acute pain after injection. Two patients who missed scheduled visits did so because they felt well, and neither reported any adverse effect.

What the study does not show

It is worth being direct about the limits, because they matter when you weigh this against other options.

• It is retrospective and has no control group. Patients were not randomised and there was no placebo comparison, so part of the improvement may reflect the natural course, the ultrasound-guided aspiration performed at the same visit, or expectation.
• The cohort is small. Twenty-nine patients, with six-month data available for 24 of them.
• Follow-up stops at six months. The nine month to one year duration cited for the product comes from manufacturer data, not from this study.
• No predictors reached significance. Radiographic grade, prior treatment failure and ultrasound findings trended towards predicting non-response, but the confidence intervals crossed unity in every case.

How to read this against conventional hyaluronic acid

The commonly cited figure for conventional hyaluronic acid products is three to six months of effect.3 The study above shows a meaningful effect still present at six months in a difficult cohort, from one injection rather than a course. That is a fair comparison to make. Claiming a head-to-head superiority trial would not be, because no such trial is cited here.