What do people ask about biologic therapy, the body-material joint shots?

Sources

1. The ESSKA-ORBIT European consensus on blood-derived orthobiologics graded 28 question-statement sets; only 9 of 28 had high-level scientific support. Three statements reached grade A: that there is enough preclinical and clinical evidence to support PRP use in knee OA; that clinical evidence shows effectiveness in MILD TO MODERATE knee OA (KL grade 3 or lower); and that PRP provides a longer effect than the short-term effect of corticosteroid with a safer profile. The panel regarded PRP as a valid and possible first-line injectable option for KL grades 1-3.

   Laver L, et al. — The use of injectable orthobiologics for knee osteoarthritis: A European ESSKA-ORBIT consensus. Part 1-Blood-derived products (platelet-rich plasma).. Knee Surgery, Sports Traumatology, Arthroscopy, 2024. DOI: 10.1002/ksa.12077.

2. The companion ESSKA-ORBIT consensus on cell-based therapy (77 experts, 22 countries, 27 statements) found only 5 of 27 statements reached recommendation level A or B; 22 were rated C or D. It concluded that cell-based therapy shows clinical benefit in pain and function up to 12 months for KL grades 1-3 with some benefit in selected KL 4, but that because of limited high-quality studies and NO clear superiority over other injectables it should be considered a SECOND-LINE option, after other non-operative treatment fails.

   de Girolamo L, et al. — The use of injectable orthobiologics for knee osteoarthritis: A formal ESSKA-ORBIT consensus. Part 2-Cell-based therapy.. Knee Surgery, Sports Traumatology, Arthroscopy, 2025. DOI: 10.1002/ksa.70001.

3. The AAOS third-edition clinical practice guideline on non-arthroplasty management of knee osteoarthritis contains 29 recommendations and explicitly highlights intra-articular corticosteroid, hyaluronic acid AND platelet-rich plasma as the areas where better research is still needed - including osteoarthritis characterisation, subgroup and severity stratification, control for bias, and cost-effectiveness analysis.

   Brophy RH, Fillingham YA. — AAOS Clinical Practice Guideline Summary: Management of Osteoarthritis of the Knee (Nonarthroplasty), Third Edition.. Journal of the American Academy of Orthopaedic Surgeons, 2022. DOI: 10.5435/JAAOS-D-21-01233.

4. The 2025 Cochrane review of stem cell injections for knee osteoarthritis pooled 25 randomised trials (1,341 participants) and found that, compared with placebo injection, stem cell injection MAY slightly improve pain (1.2 points better on a 0-10 scale, 7 studies, 445 participants) and function (14.2 points better on a 0-100 scale, 7 studies, 432 participants) up to six months - both rated LOW-certainty evidence, downgraded for indirectness (cell source, preparation and dose varied across studies) and suspected publication bias, since up to three larger RCTs were conducted and withdrawn before reporting results. Radiographic progression was not assessed in any included study.

   Whittle SL, et al. — Stem cell injections for osteoarthritis of the knee.. Cochrane Database of Systematic Reviews, 2025. DOI: 10.1002/14651858.CD013342.pub2.

5. 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.

6. The largest head-to-head trial of cell-based orthobiologics to date randomised 480 patients with KL II-IV knee OA across four arms: autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction, allogeneic umbilical cord tissue-derived MSCs, and a corticosteroid injection control. At 12 months NONE of the three orthobiologic injections was superior to another or to the corticosteroid control on either co-primary endpoint (VAS pain, KOOS pain), and none of the four groups showed a significant change in MRI osteoarthritis score from baseline. No procedure-related serious adverse events were reported.

   Mautner K, et al. — Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial.. Nature Medicine, 2023. DOI: 10.1038/s41591-023-02632-w.

7. 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.