Effect of Dextrose Prolotherapy, Platelet Rich Plasma and Autologous Conditioned Serum on Knee Osteoarthritis: A Randomized Clinical Trial
Knee osteoarthritis (OA) is one of the common degenerative articular disorders that are related to decreased quality of life. Currently, novel biologic therapeutic approaches are introduced in the literature for OA management. In this study, the clinical efficiency of Dextrose prolotherapy, platelet-rich plasma (PRP) and autologous conditioned serum (ACS) injection on the level of pain and function in Knee OA were compared.
A randomized clinical trial was directed on 92 knee OA patients. Patients were randomly divided into three groups: 30 were received dextrose prolotherapy once in a week for three weeks, 30 received autologous PRP for two times with seven days interval, and in the remaining 32 patients 2ml of ACS were injected two times every seven days. Study participants were measured through the Western Ontario and McMaster Universities (WOMAC) score, the visual analogue scale (VAS), at baseline, 1 and 6 months post-intervention.
Both ACS and PRP treated patients showed improvement in pain intensity and knee function during 1 and 6 months pursue; however, this progress was more significant in the ACS group. Dextrose prolotherapy showed no substantial changes in pain and function of the affected knee in treated patients.
Treatment of Knee OA with ACS and PRP injections are associated with pain reduction and knee function improvement. Not only, ACS therapy is more effective than that of PRP, but also due to its less variability in processing and less reported side effects, it could be considered as a safe and effective non-surgical alternative for OA management.
2. Karami KS, Gheitasi M, Miri H. The effects of six weeks of Core stabilization exercise on pain, Functional disability and Isometric strength of the trunk and lower extremities Muscle in women with patellofemoral pain syndrome. Adv nurs midwifery.2018;112-120.
3. Wollheim FA. Osteoarthritis. In: Mallia C, Uitto J, editors. Rheumaderm: Current Issues in Rheumatology and Dermatology. Boston: Springer US. 1999:423-8.
4. Sinusas K. Osteoarthritis: diagnosis and treatment. Am Fam Physician. 2012;85(1):49-56.
5. Cho HY, Kim EH, Kim J, Yoon YW. Kinesio taping improves pain, range of motion, and proprioception in older patients with knee osteoarthritis: a randomized controlled trial. Am J Phys Med Rehabil. 2015;94(3):192-200.
6. Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis.2014;73(7):1323-30.
7. Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet. 2011;377(9783):2115-26.
8. Eftekharsadat B, Niknejad-Hosseyni S, Babaei-Ghazani A, Toopchizadeh V, Sadeghi H. Reliability and validity of Persian version of Western Ontario and McMaster Universities Osteoarthritis index in knee osteoarthritis. J Anal Res Clin Med. 2015;3:170-7.
9. Karadağ S, Taşci S, Doğan N, Demir H, and Kiliç Z. Application of heat and a home exercise program for pain and function levels in patients with knee osteoarthritis: A randomized controlled trial. Int J of Nurs Pract. 2019;25.5: e12772.
10. Hunziker EB. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage. 2002;10(6):432-63.
11. Roberts S, Genever P, McCaskie A, De Bari C. Prospects of stem cell therapy in osteoarthritis. Regen Med. 2011;6(3):351-66.
12. Wood AM, Brock TM, Heil K, Holmes R, Weusten A. A Review on the Management of Hip and Knee Osteoarthritis. Int J Chronic Dis.2013;2013:10.
13. Alderman D. The new age of prolotherapy. Pract Pain Manag. 2010;10(4):54-72.
14. Hackett GS. Ligament and tendon relaxation (skeletal disability) treated by prolotherapy (fibro-osseous proliferation): With special reference to occipito-cervical and low back disability, trigger point pain, referred pain, headache and sciatica. Thomas. 1958.
15. Hackett GS. Joint stabilization through induced ligament sclerosis. Ohio State Med J 1953;49(10):877-84.
16. Hackett GS. Prolotherapy in whiplash and low back pain. Postgrad Med.1960;27:214-9.
17. Hackett GS. Shearing injury to the sacroiliac joint. J Int Coll Surg. 1954;22(6 Pt 1):631-42.
18. 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.
19. Murphy M, Godson C, Cannon S, Kato S, Mackenzie HS, 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.
20. Ohgi S, Johnson PW. Glucose modulates growth of gingival fibroblasts and periodontal ligament cells: correlation with expression of basic fibroblast growth factor. J Periodontal Res.1996;31(8):579-88.
21. Pugliese G, Pricci F, Locuratolo N, Romeo G, Romano G, Giannini S, et al. Increased activity of the insulin-like growth factor system in mesangial cells cultured in high glucose conditions. Relation to glucose-enhanced extracellular matrix production. Diabetologia. 1996;39(7):775-84.
22. Reinhold D, Ansorge S, Schleicher ED. Elevated glucose levels stimulate transforming growth factor-beta 1 (TGF-beta 1), suppress interleukin IL-2, IL-6 and IL-10 production and DNA synthesis in peripheral blood mononuclear cells. Horm Metab Res. 1996;28(6):267-70.
23. 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.
24. Okuda Y, Adrogue HJ, Nakajima T, Mizutani M, Asano M, Tachi Y, et al. Increased production of PDGF by angiotensin and high glucose in human vascular endothelium. Life Sci. 1996;59(17):1455-61.
25. 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.
26. Lin CL, Huang CC, Huang SW. Effects of hypertonic dextrose injection in chronic supraspinatus tendinopathy of the shoulder: a randomized placebo-controlled trial. Eur J Phys Rehabil Med. 2019;55(4):480-487.
27. Pietrzak WS, Eppley BL. Platelet rich plasma: biology and new technology. J Craniofac Surg. 2005;16(6):1043-54.
28. Sampson S, Gerhardt M, Mandelbaum B. Platelet rich plasma injection grafts for musculoskeletal injuries: a review. Curr Rev Musculoskelet Med. 2008;1(3-4):165-74.
29. Marx RE. Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent. 2001;10(4):225-8.
30. Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41(2):356-64.
31. Filardo G, Kon E, Di Martino A, Di Matteo B, Merli ML, Cenacchi A, et al. Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC Musculoskelet Disord. 2012;13:229.
32. Meijer H, Reinecke J, Becker C, Tholen G, Wehling P. The production of anti-inflammatory cytokines in whole blood by physico-chemical induction. Inflamm Res. 2003;52(10):404-7.
33. Auw Yang KG, Raijmakers NJ, van Arkel ER, et al. Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial. Osteoarthritis Cartilage. 2008;16(4):498-505.
34. Ahmad HS, Farrag SE, Okasha AE, Kadry AO, Ata TB, Monir AA, et al. Clinical outcomes are associated with changes in ultrasonographic structural appearance after platelet-rich plasma treatment for knee osteoarthritis. Int J Rheum Dis.2018;21(5):960-6.
35. Rutgers M, Saris DB, Dhert WJ, Creemers LB. Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection. Arthritis Res Ther. 2010;12(3):R114.
36. Crichton N. Visual analogue scale (VAS). J Clin Nurs. 2001;10(5):706-6.
37. 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. 2005;44(12):1531-7.
38. Manek NJ, Lane NE. Osteoarthritis: current concepts in diagnosis and management. Am Fam Physician. 2000;61(6):1795-804.
39. Nwe A, Tun M, Aung S, Tun L, Myaing K. Effectiveness of Kinesio Taping in the Management of Knee Osteoarthritis. J Adv Med Med Res. 2019;1-10.
40. Zakaria ZF, Bakar AA, Hasmoni HM, Rani FA, Kadir SA. Health-related quality of life in patients with knee osteoarthritis attending two primary care clinics in Malaysia: a cross-sectional study. Asia Pac Fam Med. 2009;8(1):10.
41. Goldring SR, Goldring MB. The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res. 2004;427:S27-36.
42. Goldring MB, Berenbaum F. Emerging targets in osteoarthritis therapy. Curr Opin Pharmacol.2015;22:51-63.
43. Kivitz A, Eisen G, Zhao WW, Bevirt T, Recker DP. Randomized placebo-controlled trial comparing efficacy and safety of valdecoxib with naproxen in patients with osteoarthritis. J Fam Pract. 2002;51(6):530-7.
44. Simon LS, Lanza FL, Lipsky PE, Hubbard RC, Talwalker S, Schwartz BD, et al. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum. 1998;41(9):1591-602.
45. 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.
46. 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.
47. Jensen KT, Rabago DP, Best TM, Patterson JJ, Vanderby Jr R. Response of knee ligaments to prolotherapy in a rat injury model. Am J Sports Med.2008;36(7):1347-57.
48. Chen CPC, Cheng CH, Hsu CC, Lin HC, Tsai YR, Chen JL. The influence of platelet rich plasma on synovial fluid volumes, protein concentrations, and severity of pain in patients with knee osteoarthritis. Exp Gerontol. 2017;93:68-72.
49. Fotouhi A, Maleki A, Dolati S, Aghebati-Maleki A, Aghebati-Maleki L. Platelet rich plasma, stromal vascular fraction and autologous conditioned serum in treatment of knee osteoarthritis. Biomed Pharmacother. 2018;104:652-60.
50. Chang KV, Hung CY, Aliwarga F, Wang TG, Han DS, Chen WS. Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: a systematic review and meta-analysis. Arch Phys Med Rehabil. 2014;95(3):562-75.
51. 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;13:73-9.
52. Wu YT, Hsu KC, Li TY, Chang CK, Chen LC. Effects of Platelet-Rich Plasma on Pain and Muscle Strength in Patients With Knee Osteoarthritis. Am J Phys Med Rehabil. 2018;97(4):248-54.
53. Fox BA, Stephens MM. Treatment of knee osteoarthritis with Orthokine-derived autologous conditioned serum. Expert Rev Clin Immunol.2010;6(3):335-45.
54. Frisbie DD, Kawcak CE, Werpy NM, Park RD, McIlwraith CW. Clinical, biochemical, and histologic effects of intra-articular administration of autologous conditioned serum in horses with experimentally induced osteoarthritis. Am J Vet Res. 2007;68(3):290-6.
55. Barreto A, Braun TR. A new treatment for knee osteoarthritis: Clinical evidence for the efficacy of Arthrokinex autologous conditioned serum. J Orthop. 2017;14(1):4-9.
56. Tassara M, De Ponti A, Barzizza L, Zambelli M, Parisi C, Milani R, et al. Autologous conditioned serum (ACS) for intra-articular treatment in Osteoarthritis: Retrospective report of 28 cases. Transfus Apher Sci.2018;57(4):573-7.
57. Baselga Garcia-Escudero J, Miguel Hernandez Trillos P. Treatment of Osteoarthritis of the Knee with a Combination of Autologous Conditioned Serum and Physiotherapy: A Two-Year Observational Study. PLoS One. 2015;10(12):e0145551.
58. Zarringam D, Bekkers JEJ, Saris DBF. Long-term Effect of Injection Treatment for Osteoarthritis in the Knee by Orthokin Autologous Conditioned Serum. Cartilage. 2018;9(2):140-5.