Knee osteoarthritis (gonarthrosis) is a leading cause of chronic pain and mobility impairment worldwide, affecting over 35% of adults aged 65 and older. It is a complex degenerative condition characterized by the progressive deterioration of cartilage and alterations to the synovial fluid that protects the joint.
When oral medications and physical therapy fail to control symptoms, intra-articular injections serve as the preferred conservative treatment to alleviate pain and delay the need for joint replacement surgery.
Patients are often divided on the choice of injectable substance: is the immediate effect of cortisone preferable, or the structural action of hyaluronic acid? To clarify this issue, orthopedic medicine currently relies on two key pillars of scientific literature: a comprehensive meta-analysis (Wang & He, PMID: 25574222, 2015) and a very recent comparative clinical study focusing on intermediate stages of the disease (Sarkar et al., 2025 – PMCID: PMC12183399).
Comparing Mechanisms of Action: How Do They Work?
To understand the clinical outcomes, it is essential to distinguish between the biological actions of the two treatments within an osteoarthritic knee:
- Corticosteroids (Cortisone): These work by inhibiting the production of inflammatory cytokines. They exert a potent local anti-inflammatory effect, making them ideal for “calming” the joint during an acute pain flare-up.
- Hyaluronic Acid (viscosupplementation and visco-induction): As osteoarthritis progresses, the hyaluronic acid naturally present in the knee degrades, losing molecular weight and protective properties. Hyaluronic acid injections restore synovial fluid viscosity—acting as a true lubricant and mechanical shock absorber—while also stimulating the synthesis of new endogenous hyaluronic acid.
The Efficacy Timeline: What Happens After the Injection?
By cross-referencing historical data from the Wang & He meta-analysis with precise findings from the clinical trial by Sarkar et al. (conducted on patients with Kellgren-Lawrence grade II and III osteoarthritis), a clear evolution of benefits emerges based on the time elapsed since treatment.
1.Short Term (2 to 4 Weeks)
In the weeks immediately following the injection, both treatments demonstrate excellent efficacy. The 2025 study highlights that, at the two-week mark, both the cortisone and hyaluronic acid groups show a marked reduction in pain on the NRS (Numerical Rating Scale). During this initial phase, cortisone provides slightly faster relief due to its immediate biochemical action on inflammation.
2.The Turning Point (At 6 Weeks)
A clear divergence becomes apparent starting at the sixth week. As demonstrated by the trial conducted by Sarkar et al., while the effect of cortisone begins to wane progressively due to drug metabolism, hyaluronic acid consolidates its therapeutic action, outperforming the cortisone in medium-term pain control.
3. Long-Term Outcomes (At 3 and 6 Months)
At the 3-month mark, the difference becomes statistically and clinically highly significant:
- Pain Data: In the 2025 study, the median pain score (NRS) at 3 months was significantly lower in the hyaluronic acid group compared to the cortisone group. The meta-analysis by Wang & He confirms this trend, extending the observation period to 6 months and validating the clear superiority of hyaluronic acid in ensuring sustained relief over time.
- Functionality Data (WOMAC): The WOMAC index rigorously assesses the level of joint stiffness and difficulty with daily activities (such as climbing stairs or rising from a chair). At 3 months, patients treated with hyaluronic acid show a markedly better functional score compared to those who received cortisone.
Comparison Table: Cortisone vs. Hyaluronic Acid Based on Scientific Evidence
The following table provides a structured summary of the comparative efficacy of the two treatments according to international clinical standards:
| Clinical parameter | Corticosteroid (CS) injection | Hyaluronic Acid (HA) injection | Source of Scientific evidence |
| Speed of action | Immediate (a few hours7days) | Gradual (1/2 weeks) | Sarkar et al. (2025) |
| Pain at 1 month | Significant reduction | Significant reduction (Comparable) | Wang & He (2015) |
| Pain at 3 months | Effect wearing off
(higher NRS score) | Peak effect maintained (lower NRS score) | Sarkar et Al (2025) |
| Pain at 6 months | Benefit exhausted | Benefit still active and superior | Wang & He (2015) |
Functional improvement
(WOMAC)
| Short-lived | Superior and sustained at 3 months | Sarkar et Al (2025) |
| Ideal indication | Acute inflammatory | Mild-to-moderate osteoarthritis (Grade II–III) | International Clinical Consensus |
Personalized Osteoarthritis Management in Pavia and Milan
The latest scientific data indicate that there is no single “best” injection; rather, there is a correct treatment for the patient’s specific clinical stage. If a knee presents with severe inflammation and fluid effusion, a specialist might initially opt for an aggressive corticosteroid treatment, followed by a second phase involving protective viscosupplementation with high-molecular-weight hyaluronic acid to preserve cartilage in the long term.
At the Pavia Medical Center and theMilan Medical Center (including the Motta Visconti specialist facility), the approach to treating knee osteoarthritis strictly adheres to rigorous scientific protocols:
- Multidisciplinary Team Approach: Infiltration therapy is not an isolated procedure. Physiatrists work in close synergy with orthopedists and physiotherapists. Hyaluronic acid injections are integrated into a treatment plan that includes targeted rehabilitation for muscle strengthening, thereby maximizing the duration of joint relief.
- No Waiting Lists: We understand that joint pain limits mobility and diminishes quality of life. At our centers, you can book a specialist orthopedic consultation and undergo any necessary injection procedure within less than a week..
- International Clinical Environment: To meet the needs of a global clientele and the international community in the Milan and Pavia areas, our medical and support staff offer consultations and reports in both English and Spanish.
