dextrose prolotherapy for knee osteoarthritis cover

Dextrose Prolotherapy for Knee Osteoarthritis


Timeline of the bodies response to dextrose prolotherapy.[1]
Osteoarthritis is the leading cause of disability worldwide, affecting more than 300 million people, of which the knee is the most commonly affected.[2]James SL, Abate D, Abate KH, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 Diseases and Injuries for 195 countries and territories, 1990-2017: A … Continue reading There are a wide variety of treatment options including oral and topical medications, bracing, intra-articular injections and surgical procedures. Regarding injections, options include corticosteroids, NSAIDS, hyaluronic acid and prolotherapy among others. In this article, we will review the paper published by Zhao et al reviewing dextrose prolotherapy.[3]Zhao, Alex Tang, et al. “A Comprehensive Update of Prolotherapy in the Management of Osteoarthritis of the Knee.” Orthopedic Reviews 14.4 (2022): 33921.

Prolotherapy is a regenerative therapy which uses an injectant to promote regeneration of tissue within the joint. Most commonly, this is dextrose. The exact mechanism of action is not entirely clear. Conceptually, the injectate initiates a local inflammatory response leading to a healing cascade. This subsequently leads to release of growth factors, proliferation of fibroblasts, and deposition of collagen, strengthening the joint and reducing pain.

The biology of prolotherapy.[4]


Prolotherapy is indicated for osteoarthritis, although there is some controversy about which patients are most likely to benefit.[5]Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res. … Continue reading It can also be considered for patients with enthesopathies, tendinopathies and ACL laxity. Prolotherapy should be considered in patients who have failed to improve with other conservative treatments such as physical therapy and NSAIDS. Chronic sprains and strains also may benefit from prolotherapy.
Hypertonic dextrose is the most commonly used injectant with concentrations ranging from 10% to 25% which can be diluted with local anesthetic. Dextrose is largely considered safe and 25% appears to be the favored concentration in some studies. Sodium morrhuate (5%) or DPG (dextrose, phenol, glycerin) can also be considered, especially if patient does not improve with dextrose.[6]Linetsky FS, Miguel R, Saberski L. Pain management with regenerative injection therapy (RIT). Pain Manag A Pract Guid Clin Sixth Ed. Published online 2001:381-402.

Contraindications & Adverse Reactions

Contraindications to prolotherapy primarily relate allergies to the ingredients. Prolotherapy should be avoided in acute inflammatory conditions such as acute arthritis flare, bursitis, tendinitis, gout, tendon or ligament rupture and rheumatoid arthritis. In patients with immunocompromised system conditions, prolotherapy should probably be avoided. Corticosteroids and NSAIDS can suppress the immune response from prolotherapy and patients on these medications should seek alternative treatment. Prolotherapy has few side effects. The most common side effects are swelling and soreness at the site of the injection which resolve after 24-48 hours. Less commonly, patients may have bruising, headaches, allergic reaction, transient numbness and rarely infection.[7]Alderman D. Prolotherapy For Musculoskeletal Pain. Pract Pain Manag. 2007;(February):10-15.

Literature Review

Sits et al compared injecting 25% dextrose prolotherapy with normal saline.[8]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. … Continue reading Both groups had improved pain scores at 52 weeks compared to baseline, however the prolotherapy had significantly greater improvement compared to the normal saline group. The prolotherapy group also had improved visual analogue scale (VAS) scores for knee pain at 52 weeks. Other studies have had similar results. Rabago et al found dextrose prolotherapy had significantly better WOMAC and knee pain scores compared to normal saline and home exercise programs.[9]Rabago D, Patterson JJ, Mundt M, et al. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013;11(3):229-237. doi:10.1370/afm.1504 Another study compared prolotherapy to anesthetic and found prolotherapy to be superior.[10]Reeves KD, Hassanein K. Study of Dextrose Prolotherapy for Knee Osteoarthritis Randomized Prospective Double-Blind Placebo-Controlled Study of Dextrose Prolotherapy for Knee Osteoarthritis with or … Continue reading
Several studies have compared intra-articular and periarticular injections of dextrose prolotherapy. Farpour et al found that both intra-and periarticular dextrose prolotherapy resulted in significant improvement from baseline in VAS, Oxford knee scale (OKS), and WOMAC scores at eight weeks. [11]Farpour HR, Fereydooni F. Comparative effectiveness of intra-articular prolotherapy versus peri-articular prolotherapy on pain reduction and improving function in patients with knee osteoarthritis: A … Continue reading This suggests that either may be useful in the treatment of knee osteoarthritis. Curiously, a 2017 found greater improvement in VAS scores treated with periarticular therapy when compared with intra-articular injections.[12]Rezasoltani Z, Taheri M, Mofrad MK, Mohajerani SA. Periarticular dextrose prolotherapy instead of intra-articular injection for pain and functional improvement in knee osteoarthritis. J Pain Res. … Continue reading Another study compared intra-articular prolotherapy alone to intra-articular plus peri-articular.[13]Soliman DMI, Sherif N, Omar O, El Zohiery A. Healing effects of prolotherapy in treatment of knee osteoarthritis healing effects of prolotherapy in treatment of knee osteoarthritis. Egypt Rheumatol … Continue reading The combined group achieved both faster and more significant improvement in WOMAC and VAS scores.
Platelet rich plasma (PRP) has also been compared to dextrose prolotherapy. A 2018 study by Rahimzedah et al compared IA PRP to 25% dextrose prolotherapy.[14]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 … Continue reading They found similar improvements at 8 weeks and 6 months however the improvements were greater in the PRP group. A 2016 randomized, placebo controlled study compared PRP to dextrose prolotherapy which resulted in non-significant improvement in pain and function.[15]Eroglu A, Sari A, Durmis B. Platelet-Rich Plasma vs Prolotherapy in the Management Of Knee Osteoarthritis: Randomized Placebo-Controlled Trial. Turkish J Sport Med. 2017;51(2):34-43. … Continue reading A 2020 study compared 50% dextrose prolotherapy to PRP and although patients improved, they also found no significant difference in VAS scores.[16]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 … Continue reading Both the 2018 and 2020 studies demonstrated greater improvement in the PRP group compared to the prolotherapy group at both 1 and 6 months.
Other studies have compared less commonly used injectants. One study compared IA autologous conditioned serum (ACS), PRP, and 50% dextrose prolotherapy and found ACS improved VAS and WOMAC pain scores at one month and 6 months compared to dextrose prolotherapy.[17]Pishgahi, Alireza, et al. “Effect of dextrose prolotherapy, platelet rich plasma and autologous conditioned serum on knee osteoarthritis: a randomized clinical trial.” Iranian Journal of … Continue reading Rezasoltani et al compared 20% dextrose prolotherapy with IA botulinum neurotoxin injections, IA hyaluronic acid injections, and physical therapy.[18]Rezasoltani Z, Azizi S, Najafi S, Sanati E, Dadarkhah A, Abdorrazaghi F. Physical therapy, intra-articular dextrose prolotherapy, botulinum neurotoxin, and hyaluronic acid for knee osteoarthritis: … Continue reading The authors found the prolotherapy and botulinum toxin groups had the greatest benefit in stiffness, pain, daily function, sports function and quality of life. Hashemi and colleagues compared dextrose prolotherapy to IA ozone therapy.[19]Hashemi M, Jalili P, Mennati S, et al. The effects of prolotherapy with hypertonic dextrose versus prolozone (intraarticular ozone) in patients with knee osteoarthritis. Anesthesiol Pain Med. … Continue reading They found both groups had significant improvement in WOMAC scores at 3 months with no significant difference between groups. Finally, Rahimzadeh et al compared prolotherapy to IA erythropoietin and IA radiofrequency ablation and found similar benefit between the three groups with no difference in outcomes at 3 months.[20]Rahimzadeh P, Imani F, Faiz SHR, Entezary SR, Nasiri AA, Ziaeefard M. Investigation the efficacy of intra-articular prolotherapy with erythropoietin and dextrose and intra-articular pulsed … Continue reading


Prolotherapy suffers from significant methodological heterogeneity among studies leading to criticism and difficulty in interpreting outcomes. These studies fluctuate among many variables including outcome measurements, dosages and quality of data. Study designs are not consistent. For this reason, prolotherapy has been classified as a complementary rather than primary therapeutic intervention. There is a need for larger studies with a standardized treatment regimen and long term follow up data.


The current data supports the use of dextrose prolotherapy as part of a larger treatment algorithm for people with knee osteoarthritis. Most studies show benefit from performing 3-4 injections 4 weeks apart with symptoms improving as early as 8 weeks. In some studies, those benefits persist up to 1 year. No major adverse events or side effects are regularly reported. What is less clear is which patients will benefit from prolotherapy? In order for prolotherapy to gain a more mainstream role in managing knee arthritis, more robust studies with standardized methods need to be performed. Further clarification is needed to determine the role of prolotherapy among other injectates and treatment options for knee OA.
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