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Sep 05, 2022

How does prolotherapy compare to PRP for knee osteoarthritis: What does the literature say?

Recently we have seen more patients with questions about whether prolotherapy or platelet-rich plasma (PRP) is a better option for their knee osteoarthritis. Luckily for us there is data comparing these to treatments. Let’s dive in.

What is knee osteoarthritis?

Osteoarthritis or OA is a chronic joint disease that is progressive and can lead to pain, stiffness, swelling and decreased knee motion. Almost 80% of Americans over the age of 65 suffer from osteoarthritis.

Traditional treatments range from medication management (i.e. anti-inflammatory medications, topical creams, Tylenol), physical therapy, bracing and surgery.

What is prolotherapy?

Prolotherapy for knee OA involves injecting an irritant solution into the damaged joint. In most cases, this is hypertonic dextrose or sugar water. The exact mechanism of prolotherapy in the joint is not well understood [Hauser et al, 2016].

What is platelet rich plasma or PRP?

PRP stands for platelet rich plasma and is an injection that is created by concentrated a patient’s own platelets. The molecular mechanism of PRP and its efficiency in knee OA have been the point of focus in clinical studies.

In knee arthritis, cartilage damage is though to lead to inflammation, and inflammatory plays a role in the progression of OA. PRP is thought to influence the progression of arthritis though the growth factors and the anti-inflammatory of platelets, although the precise mechanisms remains unclear [Belk et al, 2020; Andia & Maffulli, 2013; Andia & Maffulli, 2018; Andia et al, 2018].

What is the evidence for prolotherapy for knee OA?

A number of studies have evaluated prolotherapy for knee OA, but in general the evidence is of low quality. Various guidelines have emerged recommending against dextrose prolotherapy. In the 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee, the use of prolotherapy was conditionally recommended against in patients with knee OA [Kolasinski et al, 2019]. Likewise, the Osteoarthritis Research Society International (OARSI) guidelines strongly recommended against dextrose prolotherapy due to extremely-low quality evidence [Bannuru et al, 2019].

Despite these guidelines against dextrose prolotherapy, clinical trials of prolotherapy have suggested positive benefits of using prolotherapy for knee OA [Sit et al, 2016; Rabago & Nourani, 2017; Sert et al, 2020; Eslamian & Amouzandeh, 2015; Rabago et al, 2019; Sit et al, 2020].

What is better for knee osteoarthritis – prolotherapy or PRP?

There are three studies that have compared dextrose prolotherapy against PRP.

Rahimzadeh et al. (2018)

In this study by Rahimzadeh et al. in 2018 a total of 42 patients with mild knee OA were enrolled in a randomized, double-blind clinical trial. A double-blind, randomized controlled study attempts to eliminate any bias by preventing either the patients and the physician from knowing what was injected into the knee and then measuring the effects of the injection on pain and function. In this study, 21 patients received a PRP injection and or 21 patients received a prolotherapy injection.

Patients received 2 injections of either PRP or a 25% dextrose prolotherapy injection. The protocol for the PRP procedure likely produced a low dose PRP product, but despite this limitation the PRP therapy was more effective than prolotherapy in reducing pain and function.

Eroğlu et al (2016)

In this study, 60 consecutive patients with mild to moderate knee arthritis were randomized to in a placebo-controlled study into 3 groups: a prolotherapy group, PRP group and saline injection group. The prolotherapy group received 3 dextrose prolotherapy injections in 3-week intervals using landmark guidance (i.e. no ultrasound was used to confirm the injection location). The injections targeted the knee joint with 6 mL of solution and surrounding ligaments. The concentration of prolotherapy was not reported. The PRP group also received 3 injections spaced 3 weeks apart. This trial found that while both platelet-rich plasma and dextrose prolotherapy resulted in improvement pain and function, the improvement was not significant in either group.

One significant limitation of this study is that the PRP dose was also not reported.

Pishgahi et al (2020)

The randomized clinical trial by Pishgahi et al enrolled 92 patients and found no significant improvement in pain and functional scores in those treated with 50 % dextrose prolotherapy. Patients treated with platelet-rich plasma, however, demonstrated a significantly improvement in pain and function scores at the 6-month follow-up compared to baseline.


Both the 2018 study by Rahimzadeh et al and the 2020 studies determined that the pain and functional improvements seen in the platelet-rich plasma groups were significantly better compared to the dextrose prolotherapy groups.


  1. Andia I., Maffulli N. A contemporary view of platelet-rich plasma therapies: Moving toward refined clinical protocols and precise indications. Regen. Med. 2018;13:717–728.
  2. Andia I., Maffulli N. Platelet-rich plasma for managing pain and inflammation in osteoarthritis. Nat. Rev. Rheumatol. 2013;9:721–730.
  3. Andia I., Martin J.I., Maffulli N. Platelet-rich Plasma and Mesenchymal Stem Cells: Exciting, But... are we there Yet? Sports Med. Arthrosc. Rev. 2018;26:59–63.
  4. Bannuru R.R., Osani M.C., Vaysbrot E.E. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019;27(11):1578–1589.
  5. Belk J.W., Kraeutler M.J., Houck D.A., Goodrich J.A., Dragoo J.L., McCarty E.C. Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Am. J. Sports Med. 2020;49:249–260.
  6. Eroğlu A., Sari A., Durmuş B. Platelet-rich plasma vs prolotherapy in the management of knee osteoarthritis: randomized placebo-controlled trial. Spor Hekimliği Dergisi. 2016;51(2):34–43.
  7. Eslamian F, Amouzandeh B. Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up. Ther Adv Musculoskelet Dis. 2015 Apr;7(2):35-44.
  8. Kolasinski S.L., Neogi T., Hochberg M.C. American College of rheumatology/arthritis foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis Rheum. 2019;72(2):220–233.
  9. Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A Systematic Review of Dextrose Prolotherapy for Chronic Musculoskeletal Pain. Clin Med Insights Arthritis Musculoskelet Disord. 2016 Jul 7;9:139-59.
  10. Pishgahi A, Abolhasan R, Shakouri SK, et al. Effect of dextrose prolotherapy, platelet rich plasma and autologous conditioned serum on knee osteoarthritis: A randomized clinical trial. Iran J Allergy, Asthma Immunol. 2020;19(3):243-252.
  11. Rabago D, Kansariwala I, Marshall D, Nourani B, Stiffler-Joachim M, Heiderscheit B. Dextrose Prolotherapy for Symptomatic Knee Osteoarthritis: Feasibility, Acceptability, and Patient-Oriented Outcomes in a Pilot-Level Quality Improvement Project. J Altern Complement Med. 2019 Apr;25(4):406-412.
  12. Rabago D., Nourani B. Prolotherapy for osteoarthritis and tendinopathy: a descriptive review. Curr Rheumatol Rep. 2017;19(6):34.
  13. Rahimzadeh P, Imani F, Faiz SHR, Entezary SR, Zamanabadi MN, Alebouyeh MR. The effects of injecting intra-articular platelet-rich plasma or prolotherapy on pain score and function in knee osteoarthritis. Clin Interv Aging. 2018 Jan 4;13:73-79.
  14. Sert AT, Sen EI, Esmaeilzadeh S, Ozcan E. The Effects of Dextrose Prolotherapy in Symptomatic Knee Osteoarthritis: A Randomized Controlled Study. J Altern Complement Med. 2020 May;26(5):409-417.
  15. Sit R.W., Chung V.C.H., Reeves K.D. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: a systematic review and meta-analysis. Sci Rep. 2016;6:25247.
  16. Sit RWS, Wu RWK, Rabago D, et al. Efficacy of Intra-Articular Hypertonic Dextrose (Prolotherapy) for Knee Osteoarthritis: A Randomized Controlled Trial. Ann Fam Med. 2020;18(3):235-242.

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