Comparative effectiveness of intra-articular prolotherapy versus peri-articular prolotherapy on pain reduction and improving function in patients with knee osteoarthritis

A randomized clinical trial

Authors

  • Hamid Reza Farpour M.D. Physiatrist, Assistant Professor, Bone and Joint Diseases Research Center, Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Shiraz University of Medical Science, Shiraz, Iran

Keywords:

Intra-articular Injection, Knee, Osteoarthritis, Prolotherapy

Abstract

Background: Osteoarthritis is a common degenerative disease. Prolotherapy is an alternative therapy used in multiple musculoskeletal disorders.

Objective: To compare the effectiveness of intra-articular dextrose injection versus peri-articular prolotherapy in patients with knee osteoarthritis (KOA). 

Methods: Fifty-two adults with painful primary knee osteoarthritis for at least three months were randomized to intra- and peri-articular injection groups. Prolotherapy was done twice with two week intervals. The outcome measures included the Oxford Knee Scale (OKS), Western Ontario McMaster University Osteoarthritis Index (WOMAC), and Visual Analogue Scale (VAS), which were obtained from patients before the first injection at the base line and after the second injection at the fourth and eighth weeks.

Results: There were no statistically significant differences between demographic characteristics; before the injection, pain intensity, OKS, and WOMAC scores were approximately equal between the two groups. After dextrose prolotherapy, VAS, OKS, and WOMAC scores improved from baseline through the fourth and eighth weeks in both groups without any superiority between the two methods of injections (p<0.001).

Conclusion: Dextrose prolotherapy either intra- or peri-articular injection resulted in significant improvement, so it could be an inexpensive and effective management of knee osteoarthritis.

Trial registration: The study protocol was registered as a clinical trial under registration ID of IRCT2016091229795N1 at the Iranian Registry of Clinical Trials (http://www.irct.ir).

Funding: The authors received no financial support for the research, authorship, or publication of this article.

References

Rabago D, Kijowski R, Woods M, Patterson JJ, Mundt M, Zgierska A, et al. Association between disease- specific quality of life and magnetic resonance imaging outcomes in a clinical trial of prolotherapy for knee

osteoarthritis. Arch Phys Med Rehabil. 2013; 94(11): 2075-82. doi: 10.1016/j.apmr.2013.06.025. PMID:

, PMCID: PMC3812343.

Rabago D, Zgierska A, Fortney L, Kijowski R, Mundt M, Ryan M, et al. Hypertonic dextrose injections

(prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. J

Altern Complement Med. 2012; 18(4): 408-14. doi: 10.1089/acm.2011.0030. PMID: 22515800, PMCID:

PMC3326267.

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; 9: 139-59. doi:

4137/CMAMD.S39160. PMID: 27429562, PMCID: PMC4938120.

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 radiofrequency on pain

level reduction and range of motion improvement in primary osteoarthritis of knee. J Res Med Sci. 2014;

(8): 696. PMID: 25422652, PMCID: PMC4235087.

Ekinci S, Tatar O, Akpancar S, Turgut H, Seven MM. A New Treatment Option in Osteoarthritis:

Prolotherapy Injections. J Orthop Res. 2016; 26: 816-23. doi: 10.4172/2167-7921.1000197.

Shoara R, Hashempur MH, Ashraf A, Salehi A, Dehshahri S, Habibagahi Z. Efficacy and safety of topical

Matricaria chamomilla L. (chamomile) oil for knee osteoarthritis: a randomized controlled clinical trial.

Complement Ther Clin Pract. 2015; 21(3): 181-7. doi: 10.1016/j.ctcp.2015.06.003. PMID: 26256137.

Hashemi M, Jalili P, Mennati S, Koosha A, Rohanifar R, Madadi F, et al. The effects of prolotherapy with

hypertonic dextrose versus prolozone (intraarticular ozone) in patients with knee osteoarthritis. Anesth Pain

Med. 2015; 5(5): e27585. doi: 10.5812/aapm.27585. PMID: 26587401, PMCID: PMC4644302.

Slattengren AH, Christensen T, Prasad S, Jones K. PURLs: Prolotherapy: A nontraditional approach to knee

osteoarthritis. J Fam Pract. 2014; 63(4): 206-8. PMID: 24905123, PMCID: PMC4042896.

Rabago D, Mundt M, Zgierska A, Grettie J. Hypertonic dextrose injection (prolotherapy) for knee

osteoarthritis: Long term outcomes. Complement Ther Med. 2015; 23(3): 388-95. doi:

1016/j.ctim.2015.04.003. PMID: 26051574.

Hauser RA, Sprague IS. Outcomes of prolotherapy in chondromalacia patella patients: improvements in pain

level and function. Clin Med Insights Arthritis Musculoskelet Disord. 2014; 7: 13-20. doi:

4137/CMAMD.S13098, PMID: 24596471, PMCID: PMC3937178.

Reeves KD, Hassanein K. Randomized prospective double-blind placebo-controlled study of dextrose

prolotherapy for knee osteoarthritis with or without ACL laxity. Altern Ther Health Med. 2000; 6(2): 68-74.

PMID: 10710805.

Dagenais S, Ogunseitan O, Haldeman S, Wooley JR, Newcomb RL. Side effects and adverse events related

to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain: a survey of

practitioners. Arch Phys Med Rehabil. 2006; 87(7): 909-13. doi: 10.1016/j.apmr.2006.03.017. PMID:

Hung CY, Hsiao MY, Chang KV, Han DS, Wang TG. Comparative effectiveness of dextrose prolotherapy

versus control injections and exercise in the management of osteoarthritis pain: a systematic review and meta- analysis. J Pain Res. 2016; 9: 847-57. doi: 10.2147/JPR.S118669. PMID: 27799816, PMCID: PMC5079700.

Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet.

; 377(9783): 2115-26. doi: 10.1016/S0140-6736(11)60243-2. PMID: 21684382.

Kellgren J, Lawrence J. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957; 16(4): 494-502.

doi: 10.1136/ard.16.4.494. PMID: 13498604, PMCID: PMC1006995.

Price DD, McGrath PA, Rafii A, Buckingham B. The validation of visual analogue scales as ratio scale

measures for chronic and experimental pain. Pain. 1983; 17(1): 45-56. doi: 10.1016/0304-3959(83)90126-4.

PMID: 6226917.

Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health

status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy

in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988; 15(12): 1833-40. PMID: 3068365.

Ebrahimzadeh MH, Makhmalbaf H, Birjandinejad A, Soltani-Moghaddas SH. Cross-cultural adaptation and

validation of the Persian version of the Oxford Knee Score in patients with knee osteoarthritis. Iran J Med

Sci. 2014; 39(6): 529-35. PMID: 25429175, PMCID: PMC4242987.

Soliman D, 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 Rehabil.

; 43(2): 47. doi: 10.4103/1110-161X.181858.

Nourani B, Rabago D. Prolotherapy for Knee Osteoarthritis: A Descriptive Review. Curr Phys Med Rehabil

Rep. 2016; 4(1): 42-9. doi: 10.1007/s40141-016-0111-z.

Jacks A, Edgeworth A. A retrospective audit of patients with osteo-arthritic knees treated with prolotherapy

in a general practice. Int Musculoskelet Med. 2008; 30(2): 61-6. doi: 10.1179/175361408X293371.

Fullerton BD. High-resolution ultrasound and magnetic resonance imaging to document tissue repair after

prolotherapy: a report of 3 cases. Arch Phys Med Rehabil. 2008; 89(2): 377-85. doi:

1016/j.apmr.2007.09.017. PMID: 18226666.

Rabago D, Patterson JJ, Mundt M, Kijowski R, Grettie J, Segal NA, et al. Dextrose prolotherapy for knee

osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013; 11(3): 229-37. doi: 10.1370/afm.1504.

PMID: 23690322, PMCID: PMC3659139.

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; 7(2): 35-44. doi: 10.1177/1759720X14566618. PMID: 25829954, PMCID:

PMC4357593.

Sit RW, Chung VC, Reeves KD, Rabago D, Chan KK, Chan DC, et al. Hypertonic dextrose injections

(prolotherapy) in the treatment of symptomatic knee osteoarthritis: a systematic review and meta-analysis.

Sci Rep. 2016; 6: 25247. doi: 10.1038/srep25247. PMID: 27146849, PMCID: PMC4857084.

Uthman I, Raynauld J, Haraoui B. Intra-articular therapy in osteoarthritis. Postgrad Med J. 2003; 79(934):

-53. doi: 10.1136/pmj.79.934.449. PMID: 12954956, PMCID: PMC1742771.

Published

2022-02-12