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Cited by 181Periodontal Regeneration and TreatmentsOsteoarthritis Treatment and MechanismsMedical and Biological Ozone Research

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The comparison effects of intra-articular injection of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factor (PRGF), Hyaluronic Acid (HA), and ozone in knee osteoarthritis; a one year randomized clinical trial

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Raeissadat, Seyed Ahmad, Ghazi Hosseini, Parsa, Bahrami, Mohammad Hasan, Salman Roghani, Reza, Fathi, Mohammad, Gharooee Ahangar, Azadeh, Darvish, Mahtab·2021·BMC Musculoskeletal Disorders
DOI 10.1186/s12891-021-04017-xPMC PMC7860007
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Abstract

BACKGROUND: Our study compare the short and long-term efficacy of the intra articular injections (IAIs) of hyaluronic acid (HA), platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), and ozone in patients with knee osteoarthritis (OA). METHODS: In this randomized clinical trial, 238 patients with mild to moderate knee OA were randomized into 4 groups of IAIs: HA (3 doses weekly), PRP (2 doses with 3 weeks interval), PRGF (2 doses with 3 weeks interval), and Ozone (3 doses weekly). Our outcome measures were the mean changes from baseline (immediately from the first injections) until 2,6, and 12 months post intervention in scores of visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. RESULTS: A total of 200 patients enrolled in the final analysis. The mean age of patients was 56.9 ± 6.3 years, and 69.5% were women. In 2 months follow up, significant improvement of pain, stiffness, and function were seen in all groups compared to the baseline, but the ozone group had the best results (P < 0.05). In 6 month follow up HA, PRP, and PRGF groups demonstrated better therapeutic effects in all scores in comparison with ozone (P < 0.05). At the end of the 12th month, only PRGF and PRP groups had better results versus HA and ozone groups in all scores (P < 0.05). Despite the fact that ozone showed better early results, its effects begin to wear off earlier than other products and ultimately disappear in 12 months. CONCLUSIONS: Ozone injection had rapid effects and better short-term results after 2 months, but its therapeutic effects did not persist after 6 months and at the 6-month follow up, PRP,PRGF and HA were superior to ozone. Only patients in PRP and PRGF groups improved symptoms persisted for 12 months. Therefore, these products could be the preferable choices for long-term management. TRIAL REGISTRATION: Registered in the Iranian Center of Clinical Trials ( www.irct.ir ) in 11/11/2017 with the following code: IRCT2017082013442N17.

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  • In patients with knee osteoarthritis (KL grade 2-3), PRP resulted in a WOMAC change of Δ-36.2% in cross comparisons.

    “WOMAC: PRGF Δ-37.1%; PRP Δ-36.2%; Ozone Δ-14.9%.”

    From Management of platelet-rich plasma and stem cells versus conventional treatments in musculoskeletal injury repair: A systematic review (2025) · cites this paper as [26]

    Table 2 in the Results reports a 36.50% reduction in total WOMAC score for PRP from baseline to 12 months, not 36.2%. This is a within-group change; the between-group comparisons in Table 3 report mean differences rather than the claimed percentage. (LLM, conf=0.87)

    Checked by a reasoning model — may be wrong.

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  • In patients with knee osteoarthritis (KL grade 2-3), PRGF resulted in a WOMAC change of Δ-37.1% in cross comparisons.

    “WOMAC: PRGF Δ-37.1%; PRP Δ-36.2%; Ozone Δ-14.9%.”

    From Management of platelet-rich plasma and stem cells versus conventional treatments in musculoskeletal injury repair: A systematic review (2025) · cites this paper as [26]

    The Results (Table 1; page unavailable) include patients with osteoarthritis grades 2 and 3, and Table 2 reports a reduction in WOMAC scores after PRGF. But Table 2 gives a 38.5% reduction in total WOMAC at 12 months, not 37.1%; its 37.41% figure is for the function subscore. The reported percentage is a within-group change from baseline, not a cross-group comparison. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • In patients with knee osteoarthritis (KL grade 2-3), ozone resulted in a WOMAC change of Δ-14.9% in cross comparisons.

    “WOMAC: PRGF Δ-37.1%; PRP Δ-36.2%; Ozone Δ-14.9%.”

    From Management of platelet-rich plasma and stem cells versus conventional treatments in musculoskeletal injury repair: A systematic review (2025) · cites this paper as [26]

    Results, Table 1 shows that participants had grade 2 or 3 knee osteoarthritis. Results, Table 2 reports a 14.99% reduction for the ozone group's WOMAC function subscore at 12 months, close to the claimed 14.9%, but its WOMAC total-score reduction was 15.5%. The table reports within-group changes, not the claimed percentage from cross-group comparisons; it also gives different percentages for PRGF and PRP than those in the citing sentence. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Metadata

Authors
Raeissadat, S. A., Ghazi Hosseini, P., Bahrami, M. H., Salman Roghani, R., Fathi, M., Gharooee Ahangar, A., & Darvish, M.
Affiliations
Shahid Beheshti University (IR)
ORCID
Venue
BMC Musculoskeletal Disorders
Publisher
Springer Science and Business Media LLC
Published
2021-02-03
Volume
22
Issue
1
Pages
134-134
ISSN
1471-2474 (ISSN-L)
DOI
10.1186/s12891-021-04017-x
PMC
PMC7860007
OpenAlex
W3128022084
Cited by
181
References
1
Citations by year
2026: 30 · 2025: 51 · 2024: 44 · 2023: 37 · 2022: 14 · 2021: 5
FWCI
27.94
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Musculoskeletal Disorders (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Vice chancellor for research, Shahid Beheshti University of Medical Sciences. (IR.SBMU.MSP.REC.1396.230)
Topics
  • Health Sciences › Dentistry › Periodontics › Periodontal Regeneration and Treatments
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Pharmacology (medical) › Medical and Biological Ozone Research
Keywords
knee osteoarthritis, intra-articular injection, platelet-rich plasma, plasma rich in growth factors, hyaluronic acid, ozone therapy, long-term efficacy, pain and stiffness, WOMAC, Lequesne index, treatment persistence, knee function outcomes, visual analogue scale, one-year follow-up, Iranian patients, elderly patients
MeSH terms
Female, Humans, Hyaluronic Acid, Injections, Intra-Articular, Iran, Male, Middle Aged, Ozone, Treatment Outcome, Osteoarthritis, Knee, Intercellular Signaling Peptides and Proteins, Platelet-Rich Plasma

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