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Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review

  • Complementary and Alternative Medicine (S Kolasinski, Section Editor)
  • Published:
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Abstract

Purpose of Review

Osteoarthritis and overuse tendinopathy are common chronic conditions of high societal and patient burden. The precise etiology of pain and disability in both conditions is multifactorial and not well understood. Patients are often refractory to conservative therapy. The development of new therapeutic options in both conditions is a public health priority. Prolotherapy is an injection-based outpatient regenerative therapy for chronic musculoskeletal conditions, including osteoarthritis and tendinopathy. The authors reviewed the basic science and clinical literature associated with prolotherapy for these conditions.

Recent Findings

Systematic review, including meta-analysis, and randomized controlled trials suggest that prolotherapy may be associated with symptom improvement in mild to moderate symptomatic knee osteoarthritis and overuse tendinopathy.

Summary

Although the mechanism of action is not well understood and is likely multifactorial, a growing body of literature suggests that prolotherapy for knee osteoarthritis may be appropriate for the treatment of symptoms associated with knee osteoarthritis in carefully selected patients who are refractory to conservative therapy and deserves further basic and clinical science investigation for the treatment of osteoarthritis and tendinopathy.

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References

Recently published papers of particular interest have been highlighted as: • Of importance •• Of major importance

  1. Reginster JY. The prevalence and burden of arthritis. Rheumatology. 2002;41(suppl 1):3–6. doi:10.1093/rheumatology/1041.suppl_1091.1093.

    Article  PubMed  Google Scholar 

  2. CDC. Prevalence and impact of chronic joint symptoms-seven states, 1996. MMWR. 1998;47(17):345–51.

    Google Scholar 

  3. CDC. Prevalence of disabilities and associated health conditions—United States, 1991-1992. MMWR. 1994;43(40):730–9.

    Google Scholar 

  4. Felson DT, Zhang Y. An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis & Rheumatism. 1998;41(8):1343–55.

    Article  CAS  Google Scholar 

  5. Wilson MG, Michet CJ, Ilstrup DM, Melton LJ. Ideopathic symptomatic osteoarthritis of the hip and knee: a population-based incidence study. Mayo Clic Proc. 1990;65(9):1214–21.

    Article  CAS  Google Scholar 

  6. Oliveria SA, Felson DT, Klein RA, Reed JI, Walker AM. Estrogen replacement therapy and the development of osteoarthritis. Epidemiology. 1996;7(4):415–9.

    Article  CAS  PubMed  Google Scholar 

  7. Levy E, Ferme A, Perocheau D, et al. Socioeconomic costs of osteoarthritis in France. Rev Rhum. 1993;60(6 Pt 2):63S–7S.

    CAS  Google Scholar 

  8. Samson DJ, Grant MD, Ratko TA, Bonnell CJ, Ziegler KM, Aronson N. (2007) Treatment of primary and secondary osteoarthritis of the knee. Agency for Healthcare Research and Quality (Publication No. 07-E012): Evidence Report/Technology Assessment: Prepared by Blue Cross and Blue Shield Association Technology Evaluation Center Evidence-based Practice Center under Contract No. 290–02-0026). Rockville, MD. 157:1–157.

  9. McClindon TE, Bannuru RR, Sullivan MC, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthr Cartil. 2014;22(3):363–88.

    Article  Google Scholar 

  10. Khan KM, Cook JL, Kannus P, Maffuli N, Bonar SF. Time to abandon the ‘tendinitis’ myth. BMJ. 2002;324:626–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bongers PM. The cost of shoulder pain at work. Variation in work tasks and good job opportunities are essential for prevention. BMJ. 2001;322(7278):64–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wilson JJ, Best TM. Common overuse tendon problems: a review and recommendations for treatment. Am Fam Physician. 2005;72(5):811–8.

    PubMed  Google Scholar 

  13. Rabago D, Best T, Beamsly M, Patterson J. A systematic review of prolotherapy for chronic musculoskeletal pain. Clin J Sports Med. 2005;15(5):376–80.

    Article  Google Scholar 

  14. Schultz L. A treatment for subluxation of the temporomandibular joint. JAMA. 1937;109(13):1032–5.

    Article  Google Scholar 

  15. Hackett GS, Hemwall GA, Montgomery GA. (1993) Ligament and tendon relaxation treated by prolotherapy. 5th ed. Oak Park: Gustav A. Hemwall.

  16. DeChellis DM, Cortazzo MH. Regenerative medicine in the field of pain medicine: Prolotherapy, platelet-rich plasma, and stem cell therapy—theory and evidence. Techniques in regional anesthesia and pain management. 2011;15(2):74–80. doi:10.1053/j.trap.2011.1005.1002.

    Article  Google Scholar 

  17. Liu YK, Tipton CM, Matthes RD, Bedford TG, Maynard JA, Walmer HC. An in-situ study of the influence of a sclerosing solution in rabbit medial collateral ligaments and its junction strength. Connect Tissue Res. 1983;11(2–3):95–102.

    Article  CAS  PubMed  Google Scholar 

  18. Maynard JA, Pedrini VA, Pedrini-Mille A, Romanus B, Ohlerking F. Morphological and biochemical effects of sodium morrhuate on tendons. J Orthop Res. 1985;3(2):236–48.

    Article  CAS  PubMed  Google Scholar 

  19. Linetsky FS, FRafael M, Saberski L. (2002) Pain management with regenerative injection therapy (RIT). In: Weiner RS, ed. Pain Management. Boca Raton: CRC Press. 381–402.

  20. Jensen KT, Rabago D, Best TM, Patterson JJ, Vanderby R. Early inflammatory response of knee ligaments to prolotherapy in a rat model. J Orthop Res. 2008;26(6):816–23.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Jensen KT, Rabago D, Best TM, Patterson JJ, Vanderby R. Longer term response of knee ligaments to prolotherapy in a rat injury model. Am J Sports Med. 2008;36:1347–57.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Yoshi T, Zhao C, Schmelzer JD, Low PA, An K, Amadio A. The effects of hypertonic dextrose injection on connective tissue and nerve conduction through the rabbit carpal tunnel. Arch Phys Med Rehabil. 2009;90(2):333–9.

    Article  Google Scholar 

  23. Yelland MJ, Sweeting KR, Lyftogt JA, Ng SK, Scuffham PA. Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: a randomised trial. Br J Sports Med. 2011;45:421–8.

    Article  PubMed  Google Scholar 

  24. Reeves KD, Hassanein K. Randomized, prospective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DIP, PIP, and Trapeziometacarpal) joints: evidence of clinical efficacy. J Altern Complem Med. 2000;6(4):311–20.

    Article  CAS  Google Scholar 

  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 M. 2000;6(2):68.

    CAS  Google Scholar 

  26. Ehrich E, Davies G, Watson D, Bolognese J, Seidenberg B, Bellamy N. Minimal perceptible clinical improvement with the western Ontario and McMaster universities osteoarthritis index questionnaire and global assessments in patients with osteoarthritis. J Rheumatol. 2000;27(11):2635–41.

    CAS  PubMed  Google Scholar 

  27. Tubach F, Wells G, Ravaud P, Dougados M. Minimal clinically important difference, low disease activity state, and patient acceptable symptom state: methodological issues. J Rheumatol. 2005;32(10):2025–9.

    PubMed  Google Scholar 

  28. Rabago D, Zgierska A, Fortney L, 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;18:408–14.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Altman RD. Criteria for classification of clinical osteoarthritis. J Rheumatol Suppl. 1991;27(Suppl 65):10–2.

    CAS  PubMed  Google Scholar 

  30. Dumais R, Benoit C, Dumais A, et al. Effect of regenerative injection thereapy on fuction and pain in patients with knee osteoarthitis: a randomized crossover study. Pain Med. 2012;13:990–9.

    Article  PubMed  Google Scholar 

  31. 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.

    CAS  PubMed  Google Scholar 

  32. •• Rabago D, Patterson JJ, Mundt M, et al. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013;11(3):229–37. This study is the first rigorous RCT to report clinically important and statistically significant results for prolotherapy compared with masked “inert” control injections for any condition. The study suggests that hypertonic dextrose has independent efficacy compared with sham injection

  33. Filardo G, Di Matteo B, Di Martino A, et al. Platelet-rich plasma intra-articular knee injections show no superiority versus viscosupplementation. Am J Sports Med. 2015;43(7):1575–82.

    Article  PubMed  Google Scholar 

  34. •• Sit RWS, Chung VCH, Reeves KD, et al.2016. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: a systematic review and meta-analysis. Scientific Reports. 6. This systematic review with meta-analysis reported positive outcomes for prolotherapy for knee osteoarthritis compared with at-home exercise on composite WOMAC scores, as well as pain and function WOMAC subscale scores. It provides the highest level (meta-analysis) of data supporting prolotherapy

  35. Rabago D, Patterson JJ, Mundt M, et al. Dextrose and Morrhuate sodium injections (prolotherapy) for knee osteoarthritis: the results of a prospective open label trial. J Altern Complement Med. 2014;20(5):383–91.

    Article  PubMed  PubMed Central  Google Scholar 

  36. • Rabago D, Kijowski R, Woods M, 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. This controlled study assessed mechanism of action of prolotherapy and reported that prolotherapy does not produce intra-articular cartilaginous growth on MRI at 1 year among participants with knee osteoarthritis who received prolotherapy, compared with those who did not. However, results suggest that prolotherapy may have a pain-specific mechanism of action

  37. Guermazi A, Hayashi D, Roemer FW, Felson DT. Osteoarthritis: a review of strengths and weaknesses of different imaging options. Rheum Dis Clin N Am. 2013;39:567–91.

    Article  Google Scholar 

  38. • Topol GA, Podesta L, Reeves KD, et al. The chondrogenic effect of intra-articular hypertonic-dextrose (prolotherapy) in severe knee osteoarthritis. PM&R. 2016;8:1072–82. This open label pilot study provides intriguing data based on pre-post arthroscopically derived data among participants with severe knee osteoarthritis. Participants receiving prolotherapy reported clinical improvement consistent with prior studies. Visual examination of post-treatment arthroscopy and biopsy specimens suggested growth of hyaline cartilage

  39. • Rabago D, Mundt M, Zgierska A, Grettie J. Hypertonic dextrose injection (prolotherapy) for knee osteoarthritis: long term outcomes. Complementary Therapies in Medicine. 2015;23(3):388–95. This open label study followed 65 participants who received prolotherapy for knee osteoarthritis recipients to a mean 2.5 years and reported an average of 20.9 ± 2.8 points improvement on the 0–100 point composite WOMAC outcome measure. However, the group was made up of responders (82%), who improved by a total of 28.3 ± 17.5 points, and non-responders (18%) who lost 12.1 ± 7.9 points.

  40. • Rabago D, van Leuven L, Benes L, et al. Qualitative assessment of patients receiving prolotherapy for knee osteoarthritis in a multi-method study. J Alt and Comp Med. 2016;22(12):983–9. This open-label study reported the qualitative outcomes of participants in studies assessing prolotherapy for knee osteoarthritis. Themes included good safety profile, effectiveness, the importance of pre-procedure counseling, and a willingness to recommend prolotherapy to others. A minority of participants noted improved function but minimal improvement in pain, and 18% ( n = 4) noted no improvement in pain

    Article  Google Scholar 

  41. Verhar J. Tennis elbow: anatomical, epidemiological and therapeutic aspects. Int Orthop. 1994;18:263–7.

    Article  Google Scholar 

  42. Hamilton P. The prevalence of humeral epicondylitis: a survey in general practice. J R Coll Gen Pract. 1986;36(291):464–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Kivi P. The etiology and conservative treatment of lateral epicondylitis. Scand J Rehabil Med. 1983;15(1):37–41.

    CAS  PubMed  Google Scholar 

  44. Ono Y, Nakamura R, Shimaoka M, Hattori Y, Ichihara G. Epicondylitis among cooks in nursery schools. Occup Environ Med. 1998;55(3):172–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ritz BR. Humeral epicondylitis among gas and waterworks employees. Scand J Work Environ Health. 1995;21(6):478–86.

    Article  CAS  PubMed  Google Scholar 

  46. Scarpone M, Rabago D, Zgierska A, Arbogest J, Snell ED. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sport Med. 2008;18(3):248–54.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Rabago D, Lee KS, Ryan M, et al. Hypertonic dextrose and morrhuate sodium injections (prolotherapy) for lateral epicondylosis (tennis elbow): results of a single-blind, pilot-level randomized controlled trial. Am J Phys Med Rehab. 2013;92(7):587–96.

    Article  Google Scholar 

  48. Yelland M, Rabago D, Bisset L, Ryan M. (2014) Randomised clinical trial of prolotherapy injections and an exercise program used singly and in combination for refractory tennis elbow. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000993897. Griffith University, Queensland Australia.

  49. Topol GA, Podesta LA, Reeves KD, Raya MF, Fullerton BD, Yeh H. Hyperosmolar dextrose injection for recalcitrant Osgood-Schlatter disease. Pediatrics. 2011;128(5):e1121–8.

    Article  PubMed  Google Scholar 

  50. Bertrand H, Reeves KD, Bennett CJ, Bicknell S, Cheng AL. Dextrose prolotherapy versus control injections in painful rotator cuff tendinopathy. Arch Phys Med Rehabil. 2016;97:17–25. doi:10.1016/j.apmr.2015.1008.1412.

    Article  PubMed  Google Scholar 

  51. Holmich P, Uhrskou P, Ulnits L. Effectiveness of active physical training as treatment of long-standing adductor-related groin pain in athletes: a randomized controlled trial. Lancet. 1999;353(9151):439–43.

    Article  CAS  PubMed  Google Scholar 

  52. Topol GA, Reeves KD, Hassanein KM. Efficacy of dextrose prolotherapy in elite male kicking-sport athletes with groin pain. Arch Phys Rehabil. 2005;86(4):697–702.

    Article  Google Scholar 

  53. Kvist M. Achilles tendon injuries in athletes. Sports Med. 1994;18(3):173–2001.

    Article  CAS  PubMed  Google Scholar 

  54. Maxwell NJ, Ryan MB, Taunton JE, Gillies JH, Wong AD. Sonographically guided intratendinous injection of hyperosmolar dextrose to treat chronic tendinosis of the Achilles tendon: a pilot study. AJR Am J Roentgenol. 2007;189:W215–20.

    Article  PubMed  Google Scholar 

  55. Buchbinder R. Plantar fasciitis. N Engl J Med. 2004;350(21):2159–66.

    Article  CAS  PubMed  Google Scholar 

  56. Taunton J, Ryan M, Clement D, McKenzie D, Lloyd-Smith D, Zumbo B. A retrospective case-control analysis of 2002 running injuries. Br J Sports Med. 2002;36(2):95–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Crawford F, Thomson C. Interventions for treating plantar heel pain. Cochrane Database. 2003;3:CD000416. doi:10.1002/14651858.CD14000416.

    Google Scholar 

  58. Ryan MB, Wong AD, Gillies JH, Wong J, Taunton JE. Sonographically guided intratendinous injections of hyperosmolar dextrose/lidocaine: a pilot study for the treatment of chronic plantar fasciitis. Br J Sports Med. 2009;43(4):303–6.

    Article  CAS  PubMed  Google Scholar 

  59. Rabago D, Nourani B, Weber M. (2017) Prolotherapy for chronic musculoskeletal pain. In: Rakel D, ed. Integrative Medicine. Vol In Press. Philadelphia, PA: Saunders Elsevier.

  60. Baumgartner JJ. 2016 Regenerative injections: the art of healing complete injection manual, Sixth Ed. http://regenerative-md.com/: Rejuvmedical.

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Correspondence to David Rabago.

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Conflict of Interest

Dr. Rabago is president of the Hackett Hemwall Patterson Foundation, a non-profit (501c3) organization that provides prolotherapy teaching and service. Dr. Nourani has nothing to disclose.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Complementary and Alternative Medicine

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Rabago, D., Nourani, B. Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review. Curr Rheumatol Rep 19, 34 (2017). https://doi.org/10.1007/s11926-017-0659-3

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