Which Knee Arthritis Injection Is Right for You? Cortisone vs. Hyaluronic Acid vs. PRP vs. Stem Cells
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By Dr. Jeffrey Peng, MD · Published March 4, 2026 · 10 min read
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Living with knee osteoarthritis often means navigating a confusing landscape of treatment options, especially when it comes to injections. If cortisone shots have given you little to no lasting improvement, you are far from alone. The good news is that there are several alternatives worth considering, and the clinical evidence behind them continues to grow.
In this guide, we will compare the four most common injection therapies for knee osteoarthritis: corticosteroid (cortisone) injections, hyaluronic acid (also known as gel shots or viscosupplementation), stem cell therapies, and platelet-rich plasma (PRP) injections. We will examine what the clinical trial data actually shows about each option so you can make an informed decision about your care.
Do Cortisone Shots Actually Work for Knee Arthritis?
For years, cortisone shots have been the go-to recommendation for arthritis pain. Corticosteroids are potent anti-inflammatory agents that can reduce swelling and alleviate symptoms quickly. However, recent evidence has raised serious questions about their long-term value and safety.
A systematic review and meta-analysis published in 2024 concluded that intra-articular corticosteroid injections offer clinically meaningful pain relief only at short-term follow-up, with benefits losing relevance after approximately six weeks. Beyond that window, cortisone performed no better than placebo.
Even more concerning is evidence that cortisone may accelerate cartilage damage. Corticosteroids have been shown to be chondrotoxic, meaning they can weaken and break down healthy cartilage. Since osteoarthritis is defined by the gradual loss of articular cartilage, a treatment that worsens that loss is counterproductive.
A landmark randomized clinical trial published in JAMA found that patients receiving cortisone injections every three months for two years experienced significantly greater cartilage volume loss compared to those receiving saline placebo, with no meaningful difference in knee pain between the two groups.
Additional research has linked repeated cortisone injections to rapidly destructive joint disease, a condition characterized by progressive joint space narrowing, bone loss, and collapse of joint architecture. One study in the Journal of Bone and Joint Surgery found a dose-response relationship: higher doses and multiple injections significantly increased the risk.
Further data from the Osteoarthritis Initiative, a large multicenter cohort, showed that each cortisone injection increased the absolute risk of knee replacement surgery by 9.4% compared to patients who did not receive injections.
It is important to note that these associations do not definitively establish causation. Patients with more severe arthritis are more likely to receive cortisone and may have been destined for worse outcomes regardless. However, the contrast with alternative treatments is striking: studies suggest that both PRP and hyaluronic acid injections may actually decrease the risk of requiring knee replacement surgery.
In my practice, I am not saying cortisone has no role whatsoever. One or possibly two injections in a specific joint is likely safe and can be a practical choice in certain situations — for example, if a patient is experiencing an acute arthritis flare before a planned vacation and needs rapid relief. However, I strongly recommend transitioning to alternative injection therapies for ongoing management.
Are Hyaluronic Acid Injections Effective for Knee Arthritis?
Hyaluronic acid (HA) is a naturally occurring substance found in the synovial fluid of our joints. It plays a key role in lubrication and cushioning. When injected, HA has both anti-inflammatory and analgesic properties. The goal of viscosupplementation is to restore the normal viscosity and elasticity of the synovial fluid, improving joint mobility and reducing pain.
There is substantial controversy surrounding HA injections. In 2013, the American Academy of Orthopaedic Surgeons recommended against them for knee osteoarthritis. In 2019, the American College of Rheumatology issued a conditional recommendation against their use. However, the 2015 American Medical Society for Sports Medicine consensus statement recommended viscosupplementation for patients over age 60, citing high-quality evidence of benefit.
How can leading medical organizations reach such different conclusions? In my opinion, one of the biggest reasons for the variability in reported effectiveness lies in the method of administration. Most orthopedists and rheumatologists perform injections using a landmark-based technique, palpating for anatomical landmarks and estimating needle placement. Sports medicine physicians are trained in ultrasound-guided injections, which have been shown to significantly improve accuracy and outcomes.
A comprehensive review in the Orthopaedic Journal of Sports Medicine compared injection accuracy between ultrasound-guided and landmark-based techniques across multiple joints. Landmark-based accuracy for knee injections ranged from 55% to 100%, while ultrasound guidance achieved 96% to 100% accuracy. The differences were even more dramatic at other joints, with landmark-based accuracy sometimes falling as low as 17%.
This matters clinically. A study published in the Journal of Ultrasound in Medicine compared outcomes of ultrasound-guided versus landmark-based HA injections in over 1,100 patients. Significantly fewer patients in the ultrasound-guided group went on to require knee replacement surgery (33.2% versus 45.8%). The difference was even more pronounced among obese patients, for whom landmark-based injections are particularly unreliable.
From a practical standpoint, hyaluronic acid injections are covered by most private insurance plans and Medicare for knee arthritis (though often not for other joints). If your insurance covers HA, it makes sense to consider this option — just make sure your physician administers it under ultrasound guidance.
Do Stem Cell Injections Work for Knee Arthritis?
Stem cell therapy is one of the most heavily marketed treatments in orthopedics. While the theoretical promise is compelling — using mesenchymal stem cells and growth factors to repair damaged cartilage and reduce inflammation — the clinical evidence has not yet caught up to the marketing.
There are three main types of stem cell treatments used for osteoarthritis. Bone marrow aspirate concentrate (BMAC) is harvested from the pelvic bone. Adipose stromal vascular fraction (SVF) is derived from fat tissue through liposuction. Umbilical cord-derived mesenchymal stromal cells are ethically sourced from donated tissue.
The results of a large phase 3 randomized controlled trial published in Nature Medicine were particularly significant. This multicenter study enrolled nearly 480 patients with knee osteoarthritis and compared all three stem cell types against cortisone injections. At one year, none of the stem cell therapies outperformed cortisone on pain or function scores. Additionally, no treatment group showed meaningful improvement on MRI, suggesting none of the stem cell treatments successfully repaired or regenerated cartilage.
This was a well-designed study with a large sample size — far larger than the 20 to 30 patients in most earlier stem cell trials, lending considerably more reliability to its findings. The key question it raises is whether it is worth paying thousands of dollars out of pocket for a treatment that does not outperform less expensive alternatives.
For these reasons, I currently do not recommend stem cell treatments for knee osteoarthritis. The combination of mixed results from clinical trials, high cost, and the availability of better-studied alternatives makes it difficult to justify.
Why PRP May Be the Best Injection for Knee Arthritis
Platelet-rich plasma (PRP) injections utilize the healing properties of your own blood. The procedure involves a simple blood draw, centrifugation to concentrate the platelets and growth factors, and then injection of this concentrate into the affected joint under ultrasound guidance. Learn more about PRP injections.
Knee osteoarthritis is one of the best-studied indications for PRP, and the evidence base continues to grow. A network meta-analysis of 35 randomized controlled trials involving over 3,100 patients compared the effectiveness of corticosteroids, PRP, hyaluronic acid, and placebo. PRP was the most successful treatment in improving function and reducing pain at 3, 6, and 12 months of follow-up. Importantly, there were no differences in treatment-related adverse events compared to placebo.
Why are platelets so effective? Our platelets are responsible for tissue healing, remodeling, proliferation, and — critically — controlling pain and inflammation. A PRP injection concentrates your body's own capacity to manage inflammation and injects it directly into the damaged joint under ultrasound guidance. The cellular mechanisms activated by PRP appear to be more effective than any other injectable medication currently available for knee osteoarthritis.
Can PRP Slow the Progression of Knee Arthritis?
Beyond symptom relief, one of the most compelling reasons to consider PRP is its potential to slow the structural progression of arthritis. A randomized controlled trial involving 610 patients compared PRP to saline placebo injections over five years. MRI scans at baseline and at five years showed that PRP led to an approximately 50% reduction in cartilage volume loss compared to placebo.
Previously, the only interventions shown to slow arthritis progression were weight loss, diet, and exercise. How could PRP achieve a similar effect? Osteoarthritis is fundamentally a chronic inflammatory disease. Low-grade inflammation damages healthy cartilage and drives disease progression. PRP introduces a concentrated dose of platelets and growth factors that can shift the inflammatory environment inside the joint.
The researchers in this study analyzed the synovial fluid of both groups. The placebo group showed no change in inflammatory markers, while the PRP group had a significant decrease in inflammatory markers at six months post-injection. This reduction in inflammation helps preserve healthy cartilage and slow the degenerative process.
Leading medical organizations have taken notice. Both the American Academy of Orthopaedic Surgeons and the American Medical Society for Sports Medicine have acknowledged PRP's effectiveness, releasing summaries and consensus statements highlighting its significant benefits in reducing pain and enhancing joint function for knee osteoarthritis. The European ESSKA-ORBIT consensus also endorsed PRP as a valid first-line injectable treatment option for nonoperative management.
It is worth noting that PRP is not the same as stem cell therapy, and the assumption that stem cells must be superior is not supported by current evidence. While stem cell therapies have not outperformed even cortisone in head-to-head trials, PRP consistently demonstrates meaningful benefits across high-quality studies.
What to Consider When Choosing a Knee Arthritis Injection
Choosing the right injection therapy depends on several factors including severity of arthritis, insurance coverage, budget, and your treatment goals. Here is a brief summary to guide your conversation with your physician:
Cortisone can provide rapid short-term relief and may be appropriate for acute flare-ups, but repeated use carries real risks including accelerated cartilage loss. Hyaluronic acid is a reasonable insurance-covered option that can reduce pain and improve function, especially when administered under ultrasound guidance. Stem cell therapies remain expensive and lack sufficient evidence to justify their cost over alternatives. PRP offers the strongest evidence for pain reduction, functional improvement, and potential disease modification, though it is typically not covered by insurance.
If you are interested in exploring PRP or other injection therapies for knee arthritis, I encourage you to schedule a consultation to discuss which approach is right for your specific situation.
References
1. Bensa A, Albanese J, Boffa A, Previtali D, Filardo G. Intra-articular corticosteroid injections provide a clinically relevant benefit compared to placebo only at short-term follow-up in patients with knee osteoarthritis: A systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2024;32(2):311-322. doi:10.1002/ksa.12057
2. McAlindon TE, LaValley MP, Harvey WF, et al. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA. 2017;317(19):1967-1975. doi:10.1001/jama.2017.5283
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4. Wijn SRW, Rovers MM, van Tienen TG, Hannink G. Intra-articular corticosteroid injections increase the risk of requiring knee arthroplasty. Bone Joint J. 2020;102-B(5):586-592. doi:10.1302/0301-620X.102B5.BJJ-2019-1376.R1
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6. Lundstrom ZT, Sytsma TT, Greenlund LS. Rethinking Viscosupplementation: Ultrasound- Versus Landmark-Guided Injection for Knee Osteoarthritis. J Ultrasound Med. 2019;39(1):113-117. doi:10.1002/jum.15081
7. Mautner K, Gottschalk M, Boden SD, et al. Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial. Nat Med. 2023;29(12):3120-3126. doi:10.1038/s41591-023-02632-w
8. Qiao X, Yan L, Feng Y, et al. Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis. BMC Musculoskelet Disord. 2023;24(1):926. doi:10.1186/s12891-023-06925-6
9. Chu J, Duan W, Yu Z, et al. Intra-articular injections of platelet-rich plasma decrease pain and improve functional outcomes than sham saline in patients with knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2022;30(12):4063-4071. doi:10.1007/s00167-022-06887-7
10. Laver L, Filardo G, Sanchez M, et al. The use of injectable orthobiologics for knee osteoarthritis: A European ESSKA-ORBIT consensus. Part 1-Blood-derived products (platelet-rich plasma). Knee Surg Sports Traumatol Arthrosc. 2024;32(4):783-797. doi:10.1002/ksa.12077
Medical Disclaimer: This content is for educational purposes only and does not substitute for the medical advice of a physician. Always consult your healthcare provider before beginning any new treatment program. The information presented reflects the opinion of Dr. Jeffrey Peng and does not represent the views of his employers or affiliated hospital systems.
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