The current study shows that prolotherapy with hypertonic dextrose or prolozone (intraarticular ozone injection) can be effectively used in the nonoperative management of patients with KOA. Prolotherapy is an injection therapy for the management of chronic musculoskeletal disorders such as KOA (10). Although prolotherapy is being increasingly used worldwide, its mechanism of action in pain relief is not yet clearly understood. Several mechanisms have been proposed, such as accelerating the healing process of damaged tissue (10, 11), releasing growth factors (14-16), having a positive effect on the nociceptive system (33), and the effect of needle insertion and volume enhancement (34). Reeves and Hassanein found that prolotherapy with 10% dextrose resulted in significant pain relief, decrease in knee swelling, decrease in bulking episodes, and improvement in the knee range of motion. They also found, on the basis of radiographic images, that prolotherapy was associated with improvement in OA severity. In recent years, the treatment of several musculoskeletal disorders with ozone has increasingly attracted attention. Ozone is a toxic and soluble gas with high oxidative activity (35). Ozone has an antinociceptive effect with several mechanisms (35, 36). Paoloni et al. treated patients with lumbar disc herniation by using intramuscular oxygen-ozone injection. They observed that 61% of the patients became pain free compared with 33% of the control group (30). Li et al. and Mishra et al. reported improved function and decreased pain intensity after intraarticular injection of ozone in patients with KOA (24, 25). To our knowledge, there is no study comparing the effects of prolotherapy with hypertonic dextrose and injection of ozone. Therefore, it is possible to compare the outcomes of the current study with those of others. However, our findings confirmed the outcome of previous studies indicating the pain killing and therapeutic effects of prolotherapy with ozone or dextrose. In our study, the pain intensity was significantly reduced after the treatment. However, there was no statistically significant difference between the two groups. We believe that our study is limited by the small sample size; if more patients were investigated, it is possible that we could have found some differences between the two groups. In addition, we only investigated the short-term results; mid-term and long-term follow-up are required.
Hashemi M, et al. (2015). The effects of prolotherapy aith hypertonic dextrose versus prolozone (intraarticular ozone) in patients with knee osteoarthritis. Anesth Pain Med. 5(5). Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4644302/.
1. Hawamdeh ZM, Al-Ajlouni JM. The clinical pattern of knee osteoarthritis in Jordan: a hospital based study. Int J Med Sci. 2013;10(6):790–5.
2. Gupta S, Hawker GA, Laporte A, Croxford R, Coyte PC. The economic burden of disabling hip and knee osteoarthritis (OA) from the perspective of individuals living with this condition. Rheumatology (Oxford). 2005;44(12):1531–7.
3. Li Y, Wei X, Zhou J, Wei L. The age-related changes in cartilage and osteoarthritis. Biomed Res Int. 2013;2013:916530.
4. Samson DJ, Grant MD, Ratko TA, Bonnell CJ, Ziegler KM, Aronson N. Treatment of primary and secondary osteoarthritis of the knee. Evid Rep Technol Assess (Full Rep). 2007;(157):1–157.
5. Peat G, McCarney R, Croft P. Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care. Ann Rheum Dis. 2001;60(2):91–7. Hashemi M et al. 4 Anesth Pain Med. 2015;5(5):e27585
6. Felson DT. The sources of pain in knee osteoarthritis. Curr Opin Rheumatol. 2005;17(5):624–8.
7. Shengelia R, Parker SJ, Ballin M, George T, Reid MC. Complementary therapies for osteoarthritis: are they effective? Pain Manag Nurs. 2013;14(4):e274–88.
8. Buckwalter JA, Stanish WD, Rosier RN, Schenck RJ, Dennis DA, Coutts RD. The increasing need for nonoperative treatment of patients with osteoarthritis. Clin Orthop Relat Res. 2001;(385):36–45.
9. Hackett GMG. Ligament and tendon relaxation treated by prolotherapy. 5 ed 1993.
10. Linetsky F, Botwin K, Gorfine L, Jay GW, McComb B, Miguel R, et al. Regenerative injection therapy (RIT): effectiveness and appropriate usage. Florida Academy of Pain Medicine (FAPM); 2001.
11. Banks AR. A rationale for prolotherapy. J Orthopa Med. 1991;13(3)
12. Jensen KT, Rabago DP, Best TM, Patterson JJ, Vanderby RJ. Early inflammatory response of knee ligaments to prolotherapy in a rat model. J Orthop Res. 2008;26(6):816–23.
13. Rabago D, Slattengren A, Zgierska A. Prolotherapy in primary care practice. Prim Care. 2010;37(1):65–80.
14. Scarpone M, Rabago DP, Zgierska A, Arbogast G, Snell E. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sport Med. 2008;18(3):248–54.
15. Di Paolo S, Gesualdo L, Ranieri E, Grandaliano G, Schena FP. High glucose concentration induces the overexpression of transforming growth factor-beta through the activation of a platelet-derived growth factor loop in human mesangial cells. Am J Pathol. 1996;149(6):2095–106.
16. Murphy M, Godson C, Cannon S, Kato S, Mackenzie HS, Martin F, et al. Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells. J Biol Chem. 1999;274(9):5830–4.
17. Krump E, Nikitas K, Grinstein S. Induction of tyrosine phosphorylation and Na+/H+ exchanger activation during shrinkage of human neutrophils. J Biol Chem. 1997;272(28):17303–11.
18. 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.
19. 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.
20. 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.
21. Rabago D, Patterson JJ, Mundt M, Zgierska A, Fortney L, Grettie J, et al. Dextrose and morrhuate sodium injections (prolotherapy) for knee osteoarthritis: a prospective open-label trial. J Altern Complement Med. 2014;20(5):383–91.
22. Rahimzadeh P, Imani F, Faiz SH, 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;19(8):696–702.
23. Al-Jaziri AA, Mahmoodi SM. Painkilling effect of ozone-oxygen injection on spine and joint osteoarthritis. Saudi Med J. 2008;29(4):553–7.
24. Li JH, Zhou LX, Li GY, Cheng B. [Treatment of middle-aged and aged patients with knee osteoarthritis of yang-deficiency induced cold-damp syndrome by ozone combined Chinese materia medica: a clinical research]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2013;33(4):471–5.
25. Mishra SK, Pramanik R, Das P, Das PP, Palit AK, Roy J, et al. Role of intra-articular ozone in osteo-arthritis of knee for functional and symptomatic improvement. Ind J Phys Med Rehabil. 2011;22(2):65–9.
26. Andreula CF, Simonetti L, De Santis F, Agati R, Ricci R, Leonardi M. Minimally invasive oxygen-ozone therapy for lumbar disk herniation. AJNR Am J Neuroradiol. 2003;24(5):996–1000.
27. Bonetti M, Fontana A, Martinelli F, Andreula C. Oxygen-ozone therapy for degenerative spine disease in the elderly: a prospective study. Acta Neurochir Suppl. 2011;108:137–42.
28. Gallucci M, Limbucci N, Zugaro L, Barile A, Stavroulis E, Ricci A, et al. Sciatica: treatment with intradiscal and intraforaminal injections of steroid and oxygen-ozone versus steroid only. Radiology. 2007;242(3):907–13.
29. Oder B, Loewe M, Reisegger M, Lang W, Ilias W, Thurnher SA. CTguided ozone/steroid therapy for the treatment of degenerative spinal disease–effect of age, gender, disc pathology and multisegmental changes. Neuroradiology. 2008;50(9):777–85.
30. Paoloni M, Di Sante L, Cacchio A, Apuzzo D, Marotta S, Razzano M, et al. Intramuscular oxygen-ozone therapy in the treatment of acute back pain with lumbar disc herniation: a multicenter, randomized, double-blind, clinical trial of active and simulated lumbar paravertebral injection. Spine (Phila Pa 1976). 2009;34(13):1337–44.
31. Apuzzo D, Giotti C, Pasqualetti P, Ferrazza P, Soldati P, Zucco GM. An observational retrospective/horizontal study to compare oxygen-ozone therapy and/or global postural re-education in complicated chronic low back pain. Funct Neurol. 2014;29(1):31–9.
32. Benvenuti P. Oxygen-ozone treatment of the knee, shoulder and hip. A personal experience. Rivista italiana di ossigeno-ozonoterapia. 2006;5:135–44.
33. Yelland MJ, Sweeting KR, Lyftogt JA, Ng SK, Scuffham PA, Evans KA. Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: a randomised trial. Br J Sports Med. 2011;45(5):421–8.
34. 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.
35. Bocci V. Ozone as Janus: this controversial gas can be either toxic or medically useful. Mediators Inflamm. 2004;13(1):3–11.
36. Shallenberger F. Prolozone™–Regenerating Joints and Eliminating Pain. J Prolother. 2011;3(2):630–8.