Hyaluronic Acid for Knee Pain: Does It Really Work?

randomized-controlled-trial PMID: 33536010

Quick Summary: This study looked at different injections for knee osteoarthritis, including hyaluronic acid (HA). It found that HA helped with pain and stiffness for about 6 months, but the benefits weren't as long-lasting as some other treatments like PRP and PRGF.

What The Research Found

Researchers compared several injections for knee pain caused by osteoarthritis. They looked at:

Hyaluronic Acid (HA)

Platelet-Rich Plasma (PRP)

Plasma Rich in Growth Factors (PRGF)

Ozone

The study found that:

HA helped with pain and stiffness for about 6 months.

PRP and PRGF seemed to work better for longer. Their benefits lasted for a full year.

Ozone provided quick relief at first, but the effects didn't last as long as the other treatments.

Study Details

Who was studied: 200 adults with mild to moderate knee osteoarthritis. Most were women, with an average age of about 57.

How long: The study followed patients for a year.

What they took:

HA group: Received 3 injections, one each week.
PRP and PRGF groups: Received 2 injections, spaced 3 weeks apart.
Ozone group: Received 3 injections, one each week.

What This Means For You

If you have knee osteoarthritis, this research suggests:

Hyaluronic acid (HA) can provide some relief from pain and stiffness. It might be a good option if you're looking for a treatment that works for a few months.

PRP and PRGF might be better choices for longer-lasting relief. Talk to your doctor about whether these treatments are right for you.

Ozone injections might offer quick relief, but the effects may not last.

Study Limitations

It's important to keep these things in mind:

Some people dropped out of the study, which could affect the results.

The study only looked at a specific dose and frequency of HA injections. Other approaches might have different results.

The study didn't compare the injections to a "fake" injection (placebo), so it's hard to know how much of the improvement was due to the treatment itself.

Most of the people in the study were women, so the results might not be the same for men.

Key Findings

Intra-articular hyaluronic acid (HA) injections improved pain, stiffness, and function in knee osteoarthritis (OA) patients at 6 months but not at 12 months. While HA outperformed ozone at 6 months, its effects waned by 12 months, unlike platelet-rich plasma (PRP) and plasma-rich in growth factors (PRGF), which maintained benefits long-term. Ozone provided rapid short-term relief (best at 2 months) but lacked durability.

Study Design

This was a 12-month randomized controlled trial (RCT) involving 200 adults (mean age 56.9 ± 6.3 years; 69.5% women) with mild-to-moderate knee OA. Participants were assigned to four groups: HA, PRP, PRGF, or ozone. Outcomes included changes in Visual Analog Scale (VAS), WOMAC, and Lequesne index scores at 2, 6, and 12 months post-treatment.

Dosage & Administration

HA group: Three weekly intra-articular injections.
PRP/PRGF groups: Two injections spaced 3 weeks apart.
Ozone group: Three weekly injections.
All interventions were administered directly into the knee joint.

Results & Efficacy

2 months: Ozone showed superior improvements in VAS, WOMAC, and Lequesne scores (p < 0.05 vs. all other groups).
6 months: HA, PRP, and PRGF demonstrated significantly better outcomes than ozone (p < 0.05 for all scores).
12 months: Only PRP and PRGF maintained significant improvements over baseline (p < 0.05); HA and ozone effects diminished.
Comparisons: HA’s benefits peaked at 6 months but declined by 12 months, indicating inferior long-term efficacy compared to PRP/PRGF.

Limitations

High dropout rate: 38 participants withdrew, potentially introducing selection bias.
Short intervention period: Three weekly injections may not reflect optimal HA protocols (e.g., longer intervals or higher doses).
Lack of placebo control: No sham or saline comparison group to assess baseline placebo effects.
Blinding limitations: Participants and clinicians could not be blinded to injection types, risking performance bias.
Demographic skew: Results may not generalize to men or severe OA cases, as 69.5% of participants were women with mild-to-moderate OA.
Mechanistic gaps: The study did not explore biological mechanisms (e.g., inflammatory markers) underlying differential efficacy.

Clinical Relevance

For knee OA patients, HA injections offer moderate symptom relief lasting up to 6 months but fail to sustain benefits long-term. While HA outperforms ozone in intermediate outcomes (6 months), PRP and PRGF appear more effective for lasting symptom management. Clinicians should consider HA as a short-to-intermediate-term option (e.g., for patients seeking temporary relief) but prioritize PRP/PRGF for sustained benefits. Patients should weigh injection frequency (HA requires three sessions vs. PRP/PRGF’s two) against duration of effect when selecting treatments. These findings align with HA’s known viscosupplementation role but highlight its limitations for long-term OA management.

Note: The study’s population (predominantly women aged ~57) may limit applicability to men or younger patients. Further research is needed to optimize HA protocols (e.g., dosing intervals, combination therapies).