What to ask about relief for a sore joint

Sources

1. A Bayesian network meta-analysis of 48 Level I-II randomized trials (9,338 knees) with a minimum 6-month follow-up ranked the four commonest intra-articular injections. HA and PRP both significantly improved pain versus placebo; HA, PRP and BMAC all significantly improved function versus placebo. SUCRA rankings were PRP 91.54, BMAC 76.46, HA 53.12, corticosteroid 15.18 and placebo 13.70 - corticosteroid ranked barely above placebo at six months and beyond.

   Jawanda H, et al. — Platelet-Rich Plasma, Bone Marrow Aspirate Concentrate, and Hyaluronic Acid Injections Outperform Corticosteroids in Pain and Function Scores at a Minimum of 6 Months as Intra-Articular Injections for Knee Osteoarthritis: A Systematic Review and Network Meta-analysis.. Arthroscopy, 2024. DOI: 10.1016/j.arthro.2024.01.037.

2. A network meta-analysis restricted to LARGE randomized trials (at least 100 patients per group; 57 RCTs, 22,795 participants, 18 intra-articular interventions) found treatment effects were consistently larger in the 35 high-risk-of-bias trials than in the 22 low/unclear-risk trials. In the main analysis 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, 11 trials) but higher odds of dropouts due to adverse events (OR 2.01) and of serious adverse events (OR 1.86). The effects of 16 of the 18 interventions were smaller than the MID and most were consistent with placebo effects.

   Pereira TV, 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.

3. RESTORE, the largest and most rigorously blinded placebo-controlled PRP trial in knee OA (n=288, participant-, injector- and assessor-blinded), gave three weekly injections of a commercial leukocyte-poor PRP or saline. At 12 months the change in knee pain was -2.1 vs -1.8 points (difference -0.4; 95% CI -0.9 to 0.2; P=.17) and the change in medial tibial cartilage volume was -1.4% vs -1.2% (difference -0.2%; P=.81). Twenty-nine of 31 prespecified secondary outcomes showed no between-group difference. The authors concluded the findings do not support the use of PRP for knee OA.

   Bennell KL, 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.

4. FDA states verbatim of stem cell products, stromal vascular fraction (adipose-derived cells), umbilical cord blood, Wharton's jelly, amniotic fluid and exosome products: '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, and 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.

5. The 2015 Cochrane review of 27 trials (1,767 participants) found intra-articular corticosteroid better than sham for knee OA pain (SMD -0.40, 95% CI -0.58 to -0.22; NNTB 8), but the benefit decayed with time: moderate at 1-2 weeks, small at 13 weeks, and no evidence of any effect at 26 weeks. All outcomes were graded LOW quality.

   Jüni P, et al. — Intra-articular corticosteroid for knee osteoarthritis.. Cochrane Database Syst Rev, 2015. DOI: 10.1002/14651858.CD005328.pub3.

6. In a 2-year double-blind RCT of 140 patients with symptomatic knee OA and ultrasound synovitis, 40 mg intra-articular triamcinolone every 12 weeks produced 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 knee pain.

   McAlindon TE, 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.

7. A meta-analysis of 8 trials (648 patients, judged at low risk of bias overall) comparing intra-articular PRP with intra-articular corticosteroid found PRP significantly better for pain, stiffness and function at 3, 6 and 9 months (P<0.01), with the largest effects at 6 months (SMD -0.78) and 9 months (SMD -1.63). Three PRP injections a week apart outperformed a single injection over 12 months.

   McLarnon M, Heron N. — Intra-articular platelet-rich plasma injections versus intra-articular corticosteroid injections for symptomatic management of knee osteoarthritis: systematic review and meta-analysis.. BMC Musculoskeletal Disorders, 2021. DOI: 10.1186/s12891-021-04308-3.

8. A meta-analysis of 34 RCTs (1,403 PRP knees vs 1,426 controls) found WOMAC favoured PRP over placebo at 12 months and over hyaluronic acid at 6 and 12 months, and favoured PRP over steroids on VAS pain, KOOS pain, daily function and quality of life at 6 months. Crucially, the authors state that the superiority of PRP DID NOT REACH the minimal clinically important difference for any outcome and the quality of evidence was low.

   Filardo G, et al. — PRP Injections for the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials.. Cartilage, 2021. DOI: 10.1177/1947603520931170.