Steroid, Hyaluronic Acid or PRP for Knee Arthritis
A knee injection can buy an arthritic patient a few weeks of relief, but the wrong choice can cost money with no benefit, thin the cartilage with repeat use, or raise the risk of infection if its given within months of a knee replacement.
Key terminology
- Articular cartilage
- This smooth layer caps the ends of the femur, tibia and patella. OA is its progressive loss, which shows on x-ray as a narrowed joint space.
- Intra-articular
- This injection places a drug directly into the joint space. In the knee it is usually given from the side, just under the patella. (inferolateral injection)
- Standardized mean difference (SMD)
- This statistic puts results from different pain scales on one common scale. By convention, 0.2 is small, 0.5 is moderate and 0.8 is large.
- Hyaluronic acid (HA)
- This gel injection aims to restore the lubricating fluid of an arthritic joint. It is also called viscosupplementation.
- Platelet-rich plasma (PRP)
- This injection is made by spinning the patient's own blood to concentrate platelets. Products vary widely in platelet and white cell content.
- Kellgren-Lawrence (KL) grade
- This 0 to 4 scale grades knee OA on plain x-ray by joint space narrowing and osteophytes. Grade 2 is mild and grade 4 is severe.
- WOMAC
- This questionnaire scores OA pain, stiffness and function. Higher scores mean worse symptoms, so a drop is an improvement.
- Periprosthetic joint infection (PJI)
- This is an infection around a joint replacement. It usually needs repeat surgery and may mean removing the implant.
Takeaways
- An intra-articular steroid injection eases knee OA pain for weeks, yet the benefit is gone by 6 months. A Cochrane review of 27 trials (1,767 patients) found a moderate effect at 1-2 weeks (standardized mean difference, SMD -0.48), a small to moderate effect at 4-6 weeks (SMD -0.41) and a small effect at 13 weeks. At 26 weeks there was no effect (SMD -0.07). The authors graded all of this evidence as low quality (Jüni et al, Cochrane Database Syst Rev 2015;10:CD005328, PMID 26490760).
- The 3 major guidelines agree on steroid injections and are split on HA and PRP. ACR 2019 strongly backs steroids for knee OA, is conditionally against HA and strongly against PRP. AAOS 2021 backs steroid for short-term relief, does not recommend HA for routine use and says PRP may help (limited strength). OARSI 2019 rates steroid and HA as Level 1B/2 for the knee (Kolasinski et al, Arthritis Rheumatol 2020;72:220-233, PMID 31908163; Bannuru et al, Osteoarthritis Cartilage 2019;27:1578-1589, PMID 31278997; AAOS CPG, Knee OA Non-Arthroplasty, 3rd ed, 2021).
- A steroid injection every 3 months accelerates cartilage loss and knee joint degradation without providing long-term pain benefit over placebo. In a 2-year trial of 140 patients receiving triamcinolone 40 mg or saline every 12 weeks, quantitative MRI demonstrated significantly greater cartilage thinning with steroids (0.21 vs 0.10 mm) and no difference in pain reduction. An earlier 68-patient trial using the same protocol detected no extra joint space loss, likely because plain X-rays are less sensitive to subtle cartilage changes than MRI. Further supporting structural toxicity, observational data tied steroid injection use to a 3-fold higher risk of worsening Kellgren-Lawrence (KL) grade progression (HR 3.02) (McAlindon et al, JAMA 2017;317:1967-1975, PMID 28510679; Raynauld et al, Arthritis Rheum 2003;48:370-377, PMID 12571845; Zeng et al, Osteoarthritis Cartilage 2019;27:855-862, PMID 30703543).
- Physical therapy beat a steroid injection at 1 year. In 156 patients randomized to PT or glucocorticoid injection, WOMAC scores at 1 year were 37.0 with PT vs 55.8 with injection (a gap of 18.8 points, lower is better). Both groups started near 108. A 2025 trial of 273 patients found the same direction (Deyle et al, N Engl J Med 2020;382:1420-1429, PMID 32268027; Lee et al, BMC Med 2025;23:277, PMID 40346599).
- Hyaluronic acid shrinks to a clinically irrelevant effect in the best trials. Across 89 trials (12,667 adults), HA reduced pain with an effect size of -0.37. Restricted to 18 large blinded trials, the effect fell to -0.11. Serious adverse events were more common with HA (RR 1.41). The review called the benefit small and clinically irrelevant (Rutjes et al, Ann Intern Med 2012;157:180-191, PMID 22868835).
- PRP beats hyaluronic acid in pooled trials and ties saline in the best placebo trial. A meta-analysis of 18 level 1 trials found WOMAC improved 44.7% with PRP vs 12.6% with HA. The RESTORE trial randomized 288 patients to 3 platelet-rich plasma or saline injections and found no difference in pain at 12 months (-2.1 vs -1.8 points) or cartilage volume. HA itself barely beats placebo in blinded trials (Belk et al, Am J Sports Med 2021;49:249-260, PMID 32302218; Bennell et al, JAMA 2021;326:2021-2030, PMID 34812863).
- A saline shot in the knee relieves pain better than a sugar pill. A network meta-analysis of 149 knee OA trials found intra-articular placebo had a larger effect than oral placebo (effect size 0.29). Any injection trial without a saline arm will overstate what the drug adds (Bannuru et al, Ann Intern Med 2015;163:365-372, PMID 26215539).
- Most database studies associate an injection within 3 months of TKA to more periprosthetic joint infection. Injection within 3 months doubled the odds (OR 2.0), with no rise beyond that. One cohort saw higher odds out to 6 months, and HA within 3 months was also linked to PJI (OR 1.55). A 2023 meta-analysis found the link after THA and none after TKA (Cancienne et al, J Arthroplasty 2015;30:1879-1882, PMID 26071248; Bedard et al, Clin Orthop Relat Res 2017;475:45-52, PMID 26970991; Richardson et al, J Bone Joint Surg Am 2019;101:112-118, PMID 30653040; Albanese et al, J Arthroplasty 2023;38:1184-1193, PMID 36592824).