Prolotherapy: Can it help your patient?

,; ,; ,; ,

Applied Evidence

Prolotherapy: Can it help your patient?

J Fam Pract. 2015 December;64(12):763-768

Carlton J. Covey, MD, FAAFP

Marvin H. Sineath Jr., MD, CAQSM

Joseph F. Penta, MD, CAQSM

Jeffrey C. Leggit, MD, CAQSM

Prolotherapy appears to be effective for Achilles tendinopathy and knee osteoarthritis, but has limited efficacy for low back pain. Find out when—and whether—to consider this option.

PDF Download

References

1. Khan KM, Cook J, Bonar F, et al. Histopathology of common tendinopathies: update and implications for clinical management. Sports Med. 1999;27:393-408.

2. Streit JJ, Shishani Y, Rodgers M, et al. Tendinopathy of the long head of the biceps tendon: histopathologic analysis of the extraarticular biceps tendon and tenosynovium. Open Access J Sports Med. 2015;10:63-70.

3. Maganaris CN, Narici MV, Almekinders LC, et al. Biomechanics and pathophysiology of overuse tendon injuries. Sports Med. 2004;34:1005-1017.

4. Jensen KT, Rabago DP, Zgierska A, et al. Response of knee ligaments to prolotherapy in a rat injury model. Am J Sports Med. 2008;36:1347-1357.

5. Kim SR, Stitik TP, Foye PM, et al. Critical review of prolotherapy for osteoarthritis, low back pain, and other musculoskeletal conditions: A physiatric perspective. Am J Phys Med Rehabil. 2004;83:379–389.

6. Rabago D, Slattengren A, Zgierska A. Prolotherapy in primary care practice. Prim Care. 2010;37:65-80.

7. Joseph MF, Denegar CR. Treating tendinopathy: perspective on anti-inflammatory intervention and therapeutic exercise. Clin Sports Med. 2015;34:363-374.

8. Eslamian F, Amouzandeh B. Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with osteoarthritis: a single-arm study with 6 months follow up. Ther Adv Musculoskelet Dis. 2015;7:35-44.

9. Rabago D, Patterson JJ, Mundt M, et al. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013;11:229-237.

10. Yelland MJ, Sweeting KR, Lyftogt JA, et al. Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: a randomised trial. Br J Sports Med. 2011;45:421-428.

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. 2000;6:68–74.

12. Yelland MJ, Glasziou PP, Bogduk N, et al. Prolotherapy injections, saline injections, and exercises for chronic low back pain: a randomized control trial. Spine. 2004;29:9-16.

13. Dagenais S, Yelland MJ, Del Mar C, et al. Prolotherapy injections for chronic low back pain. Cochrane Database Syst Rev. 2007;18(2):CD004059.

14. Staal JB, de Bie R, de Vet HCW, et al. Injection therapy for subacute and chronic low-back pain. Cochrane Database Syst Rev. 2011;(3):CD001824.

15. Scarpone M, Rabago DP, Zgierska A, et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sport Med. 2008;18:248.

16. Topol GA, Podesta LA, Reeves KD, et al. Hyperosmolar dextrose injection for recalcitrant Osgood-Schlatter disease. Pediatrics. 2011;128:e1121-e1128.

17. Ryan MB, Wong AD, Gillies JH, et al. Sonographically guided intratendinous injections of hyperosmolar dextrose/lidocaine: a pilot study for the treatment of chronic plantar fasciitis. Br J Sports Med. 2009;43:3003-3006.

18. Kim E, Lee JH. Autologous platelet-rich plasma versus dextrose prolotherapy for the treatment of chronic recalcitrant plantar fasciitis. PMR. 2014;6:152-158.

19. Hauser RA, Sprague IS. Outcomes of prolotherapy in chondromalacia patella patients: improvements in pain level and function. Clin Med Insights Arthritis Musculoskelet Disord. 2014;17:13-20.

20. United Healthcare medical policy. Prolotherapy for musculoskeletal indications. Available at: https://www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en-US/Assets/ProviderStaticFiles/ProviderStaticFilesPdf/Tools%20and%20Resources/Policies%20and%20Protocols/Medical%20Policies/Medical%20Policies/Prolotherapy_for_Musculoskeletal_Indications.pdf. Accessed October 26, 2015.

21. Davidson J, Javaraman S. Guided interventions in musculoskeletal ultrasound: where’s the evidence? Clin Radiol. 2011;66:140-152.

22. Maxwell NJ, Ryan MB, Taunton JE, et al. Sonographically guided intratendinous injection of hyperosmolar dextrose to treat chronic tendinosis of the Achilles tendon: a pilot study. Am J Roentgenol. 2007;189:W215.

23. Reeves KD, Hassanein K. Randomized, perspective, placebo-controlled double-blind study of dextrose prolotherapy for osteoarthritic thumb and finger (DTaP, PIP and Traneziometacarpal) joints: Evidence of clinical efficacy. J Altern Complem Med. 2000;6:311-320.

24. Cusi M, Saunders J, Hungerford B, et al. The use of prolotherapy in the sacroiliac joint. Br J Sports Med. 2010;44:100-104.

25. Kim WM, Lee HG, Jeong CW, et al. A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. J Altern Complement Med. 2010;16:1285-1290.

26. Khan SA, Kumar A, Varshney MK, et al. Dextrose prolotherapy for recalcitrant coccygodynia. J Orthop Surg. (Hong Kong) 2008;16:27–29.

27. Miller MR, Mathews RS, Reeves KD. Treatment of painful advanced internal lumbar disc derangement with intradiscal injection of hypertonic dextrose. Pain Physician. 2006;9:115–121.

PRACTICE RECOMMENDATIONS

› Advise patients with Achilles tendinopathy that a combination of prolotherapy and eccentric exercise is likely to provide more rapid and sustained pain relief than either option alone. A
› Offer a third round of prolotherapy to a patient whose pain and/or function has not improved or has returned after 2 treatments. C
› Consider prolotherapy administered by a physician with expertise in the technique for adolescents with recalcitrant Osgood-Schlatter disease. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

Over the past several years, prolotherapy has been gaining support as an option for patients with tendinopathies and painful osteoarthritic conditions. Yet the technique lacks both a consistent definition and an abundance of evidence.

Because the prefix “prolo” is thought to refer to proliferation or regeneration, some physicians prefer the term “sclerotherapy” when injecting sclerosing agents. Others point out that “prolotherapy” refers to the proliferation of tissue that the injections provoke, which has never been proven. We believe that the material injected should dictate the term used to describe it—dextrose prolotherapy (DPT) or platelet-rich plasma therapy (PRP), for example.

In this update, we focus on DPT—the injection of a solution containing hypertonic dextrose into ligaments, tendons, and joints to promote healing. You’ll find an overview of the proposed mechanism of action and a description of the technique (see “How DPT works”^1-9), as well as a look at the evidence of its effectiveness for a variety of musculoskeletal conditions in the text and TABLE^9-19 that follow. Our review is limited by the dearth of large, definitive studies, and consists mainly of anecdotal evidence, case reports, and other low-quality studies.

Considering DPT—for which patients?

Even for conditions for which the evidence of its efficacy is unequivocal, DPT is only one part of a comprehensive treatment plan. Functional assessment and correction of any weaknesses, inflexibilities, and/or training errors are also essential.

Dextrose prolotherapy is rarely covered by health insurance and is often considered only after conservative treatment has failed.

There are a number of other considerations, as well. For one thing, DPT is rarely covered by health insurance²⁰ and is often considered only after conservative treatment has failed. What’s more, it is not suited to every patient.

Absolute contraindications include acute infections at the injection site, such as cellulitis, abscess, or septic arthritis. Relative contraindications include acute gout flare and acute fracture near the site.⁶

When DPT is a viable alternative, keep in mind that the procedure should only be done by a physician experienced in the technique—and that ultrasound guidance should be used to ensure precise anatomical delivery (FIGURE 1).²¹ Consent must be obtained and documented, and universal precautions observed.

Read on to find out whether to consider DPT for particular patients.

Achilles tendinopathy: DPT decreases pain, improves function (SOR A)

Non-insertional Achilles tendinopathy can be treated with prolotherapy to decrease pain and tendon thickness (FIGURE 2). A small, single blind randomized trial compared the effectiveness of eccentric exercise (ie, contractions performed to lengthen the muscle), DPT alone, and a combination of DPT and exercise for patients with chronic Achilles tendinopathy.¹⁰

The investigators found greater improvement in the Victorian Institute of Sport Assessment-Achilles (VISA-A) score at 12 months with the combined therapy (41.1 on a 0-100 scale) vs either eccentric exercise (23.7) or DPT (27.5) alone. The increase from baseline was greater for those who received combination therapy at 6 weeks (+11.7) compared with the eccentric-only group.¹⁰ Adding DPT (injected into the tender points of the subcutaneous tissues adjacent to the Achilles tendon) to eccentric exercise resulted in a more rapid and sustained improvement in pain, function, and stiffness.

In an earlier observational study, researchers achieved improvement in pain scores using a different DPT technique.²² Here, patients with chronic Achilles tendinosis received ultrasound-guided intratendinous dextrose injections every 6 weeks until symptoms resolved. Pain scores, calculated using a visual analogue scale (VAS), showed a mean reduction at rest (88%), during normal daily activities (84%), and during physical activity (78%). The mean number of treatment sessions was 4, and the mean time to achieve results was 30 weeks.²²

How DPT works: Variations complicate the picture

Studies have shown that inflammatory changes are infrequently associated with chronic painful tendon conditions.^1,2 Instead, the changes are degenerative in nature, and can occur in the main body of the tendon, in its bony insertion site, and in the structures surrounding the tendon.³ While the exact mechanism of action for DPT is unknown, studies have shown that cells exposed to hypertonic dextrose undergo osmotic lysis, creating a proinflammatory environment. This leads to recruitment of several growth factors that promote the healing of tendons, ligaments, and cartilage.^4-6

Neovascularity and neuronal ingrowth, also present in tendinopathies, are believed to be a source of pain, as well. The injection of hypertonic dextrose may destroy the neovasculature, thus removing a nidus, or focal point, for pain.⁷

Concentrations of dextrose used may range from 10% to 50% and be combined with an injectable anesthetic alone or with other proliferants/sclerosing agents.⁶ We prefer a 50/50 mixture of 50% dextrose and 2% xylocaine without epinephrine, resulting in a final injection concentration of 25% dextrose and 1% xylocaine.

Techniques for tendinopathies vary from bathing the tendon without tenotomy to performing multiple tenotomies (with or without injection material into the tenotomy). For knee osteoarthritis, for example, both extra- and intra-articular approaches can be used alone or in combination.^8,9 The extra-articular injections are done either at tender locations around the knee joint or at ligamentous attachment sites. The number of injection sessions can vary, as well. Variations in both the concentrations and techniques contribute to the difficulty in interpreting existing evidence.