What to ask when a joint treatment sounds promising

What to ask before believing a claim

Ask what happened to people who did not get the new treatment. Joint soreness rises and falls, so feeling better later doesn't prove why it changed. A study is more helpful when it compares both groups in the same way. Also ask whether relief lasted days, weeks or longer.

Shown means people felt a clear difference after a careful comparison. Suggested means a few people improved, but the study was too small to be sure. Unknown means the study never checked the question or ended too soon. These answers are not equal.

What to write down before you choose

Choose one activity and note how it goes over several days. Record how far you walk, how well you sleep or how easily you rise. Check the same activity at about the same time each day. That makes any change easier to notice.

Ask about cost, side effects and how long relief lasted for other people. Find out what care continues if the treatment helps only a little. Brief relief can still help you rebuild strength. It isn't the same as healing worn parts of the joint.

Sources

1. The RESTORE randomized clinical trial (n=288) compared three weekly intra-articular injections of leukocyte-poor PRP with saline placebo in symptomatic mild-to-moderate medial knee OA. At 12 months the mean change in knee pain was -2.1 versus -1.8 points (difference -0.4, 95% CI -0.9 to 0.2, P=.17) and the mean change in medial tibial cartilage volume was -1.4% versus -1.2% (P=.81). Twenty-nine of 31 prespecified secondary outcomes showed no significant between-group difference.

   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.

2. A BMJ systematic review and meta-analysis of 169 trials (21,163 participants) found that in the pre-specified main analysis of 24 large placebo-controlled trials (8,997 participants), viscosupplementation reduced pain by only SMD -0.08 (95% CI -0.15 to -0.02) - about 2.0 mm on a 100 mm scale - with the confidence interval excluding the minimal clinically important difference of -0.37. Trial sequential analysis indicated conclusive evidence of clinical equivalence to placebo since 2009.

   Pereira TV, et al. — Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis.. BMJ, 2022. DOI: 10.1136/bmj-2022-069722.

3. A systematic review and meta-analysis of 25 randomized trials (1,048 participants) found mesenchymal stromal cell therapy for knee OA lowered 12-month pain VAS by 1.91 points versus viscosupplementation and by only 0.99 points versus placebo - and rated the certainty of evidence VERY UNCERTAIN by GRADE for both comparisons. Excluding high-risk-of-bias studies left a similar effect at moderate certainty versus viscosupplementation.

   Tabet CG, et al. — Advanced therapy with mesenchymal stromal cells for knee osteoarthritis: Systematic review and meta-analysis of randomized controlled trials.. J Orthop Translat, 2024. DOI: 10.1016/j.jot.2024.07.012.

4. A separate 2024 meta-analysis of 18 articles concluded mesenchymal stem cells were superior to placebo for pain relief and function at 12 months in knee osteoarthritis, with no significant difference in treatment-related adverse events - while explicitly listing high heterogeneity and short follow-up as limitations that prevent conclusions about long-term efficacy or safety.

   Tian X, et al. — Relative efficacy and safety of mesenchymal stem cells for osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.. Front Endocrinol (Lausanne), 2024. DOI: 10.3389/fendo.2024.1366297.

5. A triple-blind randomized within-patient trial injected placental mesenchymal stromal cell-derived extracellular vesicles into one knee and saline into the other in 29 patients with bilateral grade 2-3 knee OA. NO statistically significant difference was detected between the treated and control knees on VAS, WOMAC or Lequesne scores at 2 or 6 months.

   Bolandnazar NS, et al. — Safety and efficacy of placental mesenchymal stromal cells-derived extracellular vesicles in knee osteoarthritis: a randomized, triple-blind, placebo-controlled clinical trial.. BMC Musculoskelet Disord, 2024. DOI: 10.1186/s12891-024-07979-w.

6. A meta-analysis of six randomized trials (860 patients, 334 receiving bone marrow aspirate concentrate) found overall complication rates of 41.91% for BMAC versus 41.25% for comparison injectables (P=0.85), with knee effusion the most common BMAC complication at 18.26% and a number-needed-to-harm of 152.

   Fucaloro S, et al. — Complication rates of bone marrow aspirate concentrate injections versus other injectable therapies for knee osteoarthritis: A systematic review and meta-analysis.. J Orthop, 2025. DOI: 10.1016/j.jor.2024.10.005.

7. FDA states verbatim that stem cell products, stromal vascular fraction (adipose-derived), umbilical cord blood, Wharton's jelly, amniotic fluid and exosome products have NOT 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.