What to ask about knee soreness

Sources

1. The 2019 ACR/Arthritis Foundation guideline makes STRONG recommendations for exercise, weight loss in people with overweight or obesity, self-efficacy and self-management programs, tai chi, cane use, tibiofemoral bracing, topical NSAIDs, oral NSAIDs and intra-articular glucocorticoid injections in knee OA; radiofrequency ablation for knee OA is only a conditional recommendation.

   Kolasinski SL, et al. — 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee.. Arthritis & Rheumatology, 2020. DOI: 10.1002/art.41142.

2. OARSI 2019 designates arthritis education plus structured land-based exercise (with or without dietary weight management) as CORE treatments for knee OA; topical NSAIDs are strongly recommended (Level 1A); oral and transdermal opioids are strongly NOT recommended (Level 5).

   Bannuru RR, et al. — OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis.. Osteoarthritis and Cartilage, 2019. DOI: 10.1016/j.joca.2019.06.011.

3. High-quality evidence from 44 trials (3,537 participants) shows land-based exercise reduced knee OA pain by an equivalent of 12 points on a 0-100 scale (SMD -0.49) immediately after treatment, with moderate-quality evidence for a ~10-point function gain; the effect attenuated but persisted at 2-6 months (SMD -0.24). No serious adverse events were reported in any included trial.

   Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL. — Exercise for osteoarthritis of the knee.. Cochrane Database of Systematic Reviews, 2015. DOI: 10.1002/14651858.CD004376.pub3.

4. In a 2-year, double-blind RCT of 140 patients with symptomatic knee OA and ultrasound synovitis, intra-articular triamcinolone 40 mg every 12 weeks caused significantly GREATER cartilage volume loss than saline (index-compartment cartilage thickness change -0.21 mm vs -0.10 mm; between-group difference -0.11 mm, 95% CI -0.20 to -0.03) with NO significant difference in pain (-1.2 vs -1.9 on the WOMAC Likert pain subscale).

   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. DOI: 10.1001/jama.2017.5283.

5. The RESTORE trial randomized 288 adults aged 50+ with symptomatic mild-to-moderate medial knee OA to three weekly leukocyte-poor PRP injections or saline placebo. At 12 months, pain change was -2.1 vs -1.8 points (difference -0.4; 95% CI -0.9 to 0.2; P=.17) and medial tibial cartilage volume change was -1.4% vs -1.2% (P=.81). 29 of 31 prespecified secondary outcomes showed no significant between-group difference. The authors concluded the findings 'do not support use of PRP for the management of knee OA.'

   Bennell KL, Paterson KL, Metcalf BR, et al. — Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial.. JAMA, 2021. DOI: 10.1001/jama.2021.19415.

6. An individual-participant-data meta-analysis of 621 placebo participants across 10 intra-articular injection trials found placebo response (>=20% pain reduction) was itself predictable: use of local anaesthetic and ultrasound guidance were associated with REDUCED odds of short-term placebo response, and longer trial duration with increased odds at midterm. Any single-arm 'our patients got better' claim about an injection is therefore uninterpretable.

   Zou K, et al. — Predictors of Placebo Response to Local (Intra-Articular) Therapy In Osteoarthritis: An Individual Participant Data Meta-Analysis.. Arthritis Care & Research, 2024. DOI: 10.1002/acr.25212.

7. A Bayesian network meta-analysis restricted to LARGE randomized trials (>=100 patients per group) of 18 intra-articular interventions in knee and hip OA found treatment effects were larger in the 35 high-risk-of-bias trials than in the 22 low/unclear-risk trials. Excluding high-risk trials, triamcinolone had the highest probability of exceeding the minimal important difference at weeks 2 and 6; hyaluronic acid had NO effect on pain (SMD -0.04, 95% CrI -0.19 to 0.11) but higher odds of dropouts due to adverse events (OR 2.01) and of serious adverse events (OR 1.86) than placebo. Effects of 16 of the 18 interventions were smaller than the MID and most were consistent with placebo.

   da Costa BR, et al. — Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomized trials: A systematic review and network meta-analysis.. Osteoarthritis and Cartilage, 2025. DOI: 10.1016/j.joca.2024.08.014.

8. FDA states verbatim: 'None of these products have been approved for the treatment of any orthopedic condition, such as osteoarthritis, tendonitis, disc disease, tennis elbow, back pain, hip pain, knee pain, neck pain, or shoulder pain.' The only FDA-approved stem cell products in the United States are blood-forming (hematopoietic progenitor) cells derived from umbilical cord blood, approved only for disorders of blood production. There are currently NO FDA-approved exosome products.

   U.S. Food and Drug Administration — Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. FDA (Center for Biologics Evaluation and Research), 2020.

9. A safety review of intra-articular PRP in knee OA found significantly higher rates of mild knee pain and swelling than hyaluronic acid (p<0.001), driven specifically by leukocyte-RICH formulations; leukocyte-poor PRP showed a safety profile similar to HA. No severe adverse events were reported in any group.

   PM&R authors — Assessment of adverse events and safety associated with intra-articular platelet-rich plasma injections compared with hyaluronic acid and saline in knee osteoarthritis.. PM&R, 2026. DOI: 10.1002/pmrj.70141.