Effectiveness of ProlotherapyInjection in Elderly Patients with Knee Osteoarthritis: A Double-Blind Randomized Controlled Trial
DOI:
https://doi.org/10.36408/mhjcm.v12i1.1201Keywords:
dextrose, knee, pain, prolotherapy, osteoarthritisAbstract
BACKGROUND : Knee osteoarthritis (OA) is a painful chronic disease in elderly population. Research has shown that prolotherapy is an effective pain-relieving treatment, particularly when used in combination with other therapies.
AIMS : To evaluate the effectiveness of prolotherapy for knee OA based on The Western Ontario McMaster University OA Index (WOMAC) composite score (100 points), Knee Pain Scale, and self-reported satisfaction. We performed a randomized-controlled trial (RCT) with a double-blinded approach.
METHOD: An injection saline, 10% dextrose (D10) prolotherapy, or at-home knee exercise was administered to twenty-seven elderly patients (≥60 years old) experiencing painful knee OA for at least three months. Extra- and intra-articular injections were administered at weeks 1, 4, and 7, with follow-up at weeks 11 and 15. Exercise group received in-person training and an exercise guidebook. WOMAC composite score (100 points), Knee Pain Scale, and self-reported satisfaction evaluated the outcomes. The results were considered statistically significant if p < 0.05.
RESULT: There are no significant difference in baseline among groups. At 21 weeks, all groups exhibited improved composite WOMAC scores (p <0.02) compared to baseline. After adjusting for age, sex, and body mass index, D10 prolotherapy showed a significant WOMAC score improvement at 21 weeks (p <0.04) compared to saline and exercise (score change: 16.2 ± 4.4 vs. 8.5 ± 4.3, and 9.1 ± 3.2, respectively), surpassing the minimal clinically significant difference based on WOMAC. Self-reported satisfaction with D10 prolotherapy was high without reported adverse effects.
CONCLUSION: When compared to saline injections and at-home exercises, D10 prolotherapy resulted in a clinically significant sustained improvement in pain, function, and stiffness scores for knee OA in elderly.
Downloads
References
1. Berteau J-P. Knee Pain from Osteoarthritis: Pathogenesis, Risk Factors, and Recent Evidence on Physical Therapy Interventions. J Clin Med [Internet]. 2022 Jun 7;11(12):3252. Available from: https://www.mdpi.com/2077-0383/11/12/3252 doi: 10.3390/jcm11123252
2. Palo N, Chandel SS, Dash SK, Arora G, Kumar M, Biswal MR. Effects of Osteoarthritis on Quality of life in Elderly Population of Bhubaneswar, India. Geriatr Orthop Surg Rehabil [Internet]. 2015 Dec 24;6(4):269–75. Available from: http://journals.sagepub.com/doi/10.1177/2151458515604357 doi: 10.1177/2151458515604357
3. Bharde S, Caxaria S, Dell’Accio F, Sikandar S. Update on pain in arthritis. Curr Opin Support Palliat Care [Internet]. 2021 Jun;15(2):99–107. Available from: https://journals.lww.com/10.1097/SPC.0000000000000551 doi: 10.1097/SPC.0000000000000551
4. Dantas LO, Salvini T de F, McAlindon TE. Knee osteoarthritis: key treatments and implications for physical therapy. Brazilian J Phys Ther [Internet]. 2021 Mar;25(2):135–46. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1413355520302434 doi: 10.1016/j.bjpt.2020.08.004
5. Askari A, Ariya M, Davoodi SH, Shahraki HR, Ehrampoosh E, Homayounfar R. Vitamin K and D Status in Patients with Knee Osteoarthritis: An Analytical Cross-sectional Study. Mediterr J Rheumatol [Internet]. 2021;32(4):350. Available from: http://www.mjrheum.org/assets/files/792/file339_1394.pdf doi: 10.31138/mjr.32.4.350
6. 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 [Internet]. 2016 Jan 7;9:CMAMD.S39160. Available from: http://journals.sagepub.com/doi/10.4137/CMAMD.S39160 doi: 10.4137/CMAMD.S39160
7. Ahadi T, Cham MB, Mirmoghtadaei M, Raissi GR, Janbazi L, Zoghi G. The effect of dextrose prolotherapy versus placebo/other non‐surgical treatments on pain in chronic plantar fasciitis: a systematic review and meta‐analysis of clinical trials. J Foot Ankle Res [Internet]. 2023 Jan 10;16(1). Available from: https://onlinelibrary.wiley.com/doi/10.1186/s13047-023-00605-3 doi: 10.1186/s13047-023-00605-3
8. Bayat M, Hojjati F, Boland Nazar NS, Modabberi M, Rahimi M sadat. Comparison of Dextrose Prolotherapy and Triamcinolone Intraarticular Injection on Pain and Function in Patients with Knee Osteoarthritis - A Randomized Clinical Trial. Anesthesiol Pain Med [Internet]. 2023 Apr 8;13(2). Available from: https://brieflands.com/articles/aapm-134415.html doi: 10.5812/aapm-134415
9. Reeves KD, Sit RWS, Rabago DP. Dextrose Prolotherapy. Phys Med Rehabil Clin N Am [Internet]. 2016 Nov;27(4):783–823. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1047965116300420 doi: 10.1016/j.pmr.2016.06.001
10. 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 [Internet]. 2012 Apr;18(4):408–14. Available from: http://www.liebertpub.com/doi/10.1089/acm.2011.0030 doi: 10.1089/acm.2011.0030
11. 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 [Internet]. 2000 Mar;6(2):68–74, 77–80. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10710805
12. Bujang MA. A Step-by-Step Process on Sample Size Determination for Medical Research. Malaysian J Med Sci [Internet]. 2021 Apr 21;28(2):15–27. Available from: http://www.mjms.usm.my/MJMS28022021/MJMS28022021_02.pdf doi: 10.21315/mjms2021.28.2.2
13. Allen KD, Arbeeva L, Callahan LF, Golightly YM, Goode AP, Heiderscheit BC, et al. Physical therapy vs internet-based exercise training for patients with knee osteoarthritis: results of a randomized controlled trial. Osteoarthr Cartil [Internet]. 2018 Mar;26(3):383–96. Available from: https://linkinghub.elsevier.com/retrieve/pii/S106345841731381X doi: 10.1016/j.joca.2017.12.008
14. Ackerman I. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Aust J Physiother [Internet]. 2009;55(3):213. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0004951409700881 doi: 10.1016/S0004-9514(09)70088-1
15. Ittenbach RF, Huang G, Barber Foss KD, Hewett TE, Myer GD. Reliability and Validity of the Anterior Knee Pain Scale: Applications for Use as an Epidemiologic Screener. Rudan J, editor. PLoS One [Internet]. 2016 Jul 21;11(7):e0159204. Available from: https://dx.plos.org/10.1371/journal.pone.0159204 doi: 10.1371/journal.pone.0159204
16. Dudaric L, Dumic-Cule I, Divjak E, Cengic T, Brkljacic B, Ivanac G. Bone Remodeling in Osteoarthritis—Biological and Radiological Aspects. Medicina (B Aires) [Internet]. 2023 Sep 7;59(9):1613. Available from: https://www.mdpi.com/1648-9144/59/9/1613 doi: 10.3390/medicina59091613
17. Soliman AM, Barreda DR. Acute Inflammation in Tissue Healing. Int J Mol Sci [Internet]. 2022 Dec 30;24(1):641. Available from: https://www.mdpi.com/1422-0067/24/1/641 doi: 10.3390/ijms24010641
18. Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol [Internet]. 2014 Dec 21;15(12):786–801. Available from: https://www.nature.com/articles/nrm3904 doi: 10.1038/nrm3904
19. Bolamperti S, Villa I, Rubinacci A. Bone remodeling: an operational process ensuring survival and bone mechanical competence. Bone Res [Internet]. 2022 Jul 18;10(1):48. Available from: https://www.nature.com/articles/s41413-022-00219-8 doi: 10.1038/s41413-022-00219-8
20. Wee TC, Neo EJR, Tan YL. Dextrose prolotherapy in knee osteoarthritis: A systematic review and meta-analysis. J Clin Orthop Trauma [Internet]. 2021 Aug;19:108–17. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0976566221002873 doi: 10.1016/j.jcot.2021.05.015
21. Kim, Soo A , Kim, Eui Han , Kim, Sang Yun , Lee, Sung Yong , Yoon, Jae Nam , Lee YK. The Effects of Hyperosmolar Dextrose and Autologous Serum Injection in the Experimental Articular Defect of Rabbit. J Korean Acad Rehabil Med [Internet]. 2006;30(2):173–8. Available from: https://www.e-arm.org/journal/view.php?number=1604
22. Topol GA, Podesta LA, Reeves KD, Giraldo MM, Johnson LL, Grasso R, et al. Chondrogenic Effect of Intra‐articular Hypertonic‐Dextrose (Prolotherapy) in Severe Knee Osteoarthritis. PM&R [Internet]. 2016 Nov 4;8(11):1072–82. Available from: https://onlinelibrary.wiley.com/doi/10.1016/j.pmrj.2016.03.008 doi: 10.1016/j.pmrj.2016.03.008
23. Maniquis-Smigel L, Reeves KD, Rosen HJ, Lyftogt J, Graham-Coleman C, Cheng A-L, et al. Analgesic Effect and Potential Cumulative Benefit from Caudal Epidural D5W in Consecutive Participants with Chronic Low-Back and Buttock/Leg Pain. J Altern Complement Med [Internet]. 2018 Dec;24(12):1189–96. Available from: https://www.liebertpub.com/doi/10.1089/acm.2018.0085 doi: 10.1089/acm.2018.0085
Additional Files
Published
How to Cite
Issue
Section
Citation Check
License
Copyright (c) 2025 Faizal Muhammad, Afifah Syifaul Ummah, Farida Aisyah, Isa Ridwan, Yulie Erida Nur Rahmawati (Author)

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Copyrights Notice
Copyrights:
Researchers publishing manuscrips at Medica Hospitalis: Journal of Clinical Medicine agree with regulations as follow:
Copyrights of each article belong to researchers, and it is likewise the patent rights
Researchers admit that Medica Hospitalia: Journal of Clinical Medicine has the right of first publication
Researchers may submit manuscripts separately, manage non exclusive distribution of published manuscripts into other versions (such as: being sent to researchers’ institutional repository, publication in the books, etc), admitting that manuscripts have been firstly published at Medica Hospitalia: Journal of Clinical Medicine
License:
Medica Hospitalia: Journal of Clinical Medicine is disseminated based on provisions of Creative Common Attribution-Share Alike 4.0 Internasional It allows individuals to duplicate and disseminate manuscripts in any formats, to alter, compose and make derivatives of manuscripts for any purpose. You are not allowed to use manuscripts for commercial purposes. You should properly acknowledge, reference links, and state that alterations have been made. You can do so in proper ways, but it does not hint that the licensors support you or your usage.