For knee osteoarthritis, does injecting hyaluronic acid combined with PRP relieve pain better than hyaluronic acid alone?

In this study, HA+PRP and HA alone both reduced pain and improved knee function over 12 months, with no statistically significant clinical difference between the groups. In the early phase (months 1 and 6) HA even showed somewhat more pain relief, but the difference did not reach clinical significance. These are trial results and do not predict any individual's outcome.

Why does the effect of PRP sometimes take longer to appear?

The study notes that PRP works through a gradual release of growth factors and a process of tissue regeneration, so its effect may take longer to reach its peak. As a result, its short-term pain relief may be less noticeable than that of hyaluronic acid, which has better viscoelastic properties.

What difference did this study see on MRI?

The two groups showed no significant difference in the overall knee lesion score (WORMS), but after 12 months of treatment the HA+PRP group showed a marked reduction in bone marrow edema, while the HA group showed no improvement. Bone marrow edema is an important imaging finding in osteoarthritis, so this may suggest that HA+PRP has some potential for structural improvement, though longer-term studies are still needed to confirm it.

Knee Osteoarthritis Therapy: Is Platelet-Rich Plasma Combined With Hyaluronic Acid More Effective?

Knee osteoarthritis (OA) is a common chronic degenerative condition, most often seen in middle-aged and older adults, though younger people can also develop symptoms earlier because of sports injuries or obesity. The pathological features of osteoarthritis include cartilage wear, bony overgrowth (bone spur formation), and fluid within the joint cavity, and it may be accompanied by inflammation. Common symptoms include joint pain, stiffness, and abnormal sounds on movement (for example a crackling noise); in severe cases it affects daily mobility and quality of life.

Treatment options include conservative care and surgery. Conservative care usually involves weight management, physical therapy, oral medications such as non-steroidal anti-inflammatory drugs (NSAIDs), and intra-articular injection therapies. Hyaluronic acid (HA) has been used as an intra-articular injection for many years, because it provides viscoelasticity and lubrication within the joint, improving joint mobility and easing pain.

In recent years, platelet-rich plasma (PRP) has drawn increasing attention because it is rich in growth factors and cytokines that may promote cartilage repair and regeneration. Beyond using it alone, some recent studies have looked at whether combining hyaluronic acid with platelet-rich plasma works better than hyaluronic acid alone. A study conducted by a team in Singapore used MRI analysis to examine this question.

Study methods

This was a double-blind randomized controlled trial that enrolled 58 patients with knee osteoarthritis (Kellgren-Lawrence grade 2 to 3), divided into two groups: one received combined treatment with hyaluronic acid and platelet-rich plasma (HA+PRP), and the other received hyaluronic acid alone (HA).

The primary outcome measure was pain level (using the visual analog scale, VAS), and secondary measures included the WOMAC knee function scale, health-related quality of life (EQ-5D-5L), and structural changes in the knee assessed by MRI (the WORMS scoring system). Follow-up lasted 12 months.

Study results

Based on the results, both therapies effectively reduced pain and improved knee function over 12 months. Notably, HA alone showed more marked pain relief in the early phase (months 1 and 6), although these differences did not reach clinical significance.

It is worth noting that on MRI the two groups showed no significant difference in the overall knee lesion score (WORMS), but after 12 months of treatment the HA+PRP group showed a marked reduction in bone marrow edema, while the group receiving HA alone showed no improvement. Bone marrow edema is considered an important imaging finding in osteoarthritis, so this may suggest that HA+PRP has some potential for structural improvement.

Possible mechanism behind the effect

The benefit of platelet-rich plasma comes from the various growth factors and anti-inflammatory substances released by platelets, which promote tissue repair and reduce inflammation within the joint. In this study, however, the HA group had better pain relief in the early phase, which may be related to its superior viscoelasticity and ability to cushion impact.

The study notes that the effect of PRP may take longer to reach its peak, because its mechanism involves a gradual release of growth factors and a process of tissue regeneration. As a result, its short-term effect may be less noticeable than HA used alone.

Conclusion

Although this study did not show that HA+PRP is superior to HA alone for clinical pain relief, its effect on bone marrow edema is worth exploring further. Future studies should consider longer follow-up and different doses or frequencies of PRP injection to assess its more complete clinical and structural benefits.

Current evidence suggests that both HA alone and HA combined with PRP can improve pain and function in patients with knee osteoarthritis. HA+PRP, however, showed some structural improvement on imaging, which is worth studying in more depth in the hope of providing more effective clinical treatment options. The actual treatment approach still depends on your condition and a physician’s assessment.

References

Zhang, M., et al. (2025). Clinical Efficacy of Platelet-Rich Plasma and Hyaluronic Acid Versus Hyaluronic Acid for Knee Osteoarthritis with MRI Analysis: A Randomized Controlled Trial. Journal of Clinical Medicine, 14(3553).