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Policy Number: MP-235

Latest Review Date: December 2023

Category:  Surgery                                                                 



Prolotherapy is considered investigational as a treatment of musculoskeletal pain or other conditions. 


Prolotherapy describes a procedure for healing and strengthening ligaments and tendons by injecting an agent that induces inflammation and stimulates endogenous repair mechanisms. Prolotherapy may also be referred to as proliferant injection, Prolo, joint sclerotherapy, regenerative injection therapy, growth factor stimulation injection, or nonsurgical tendon, ligament, and joint reconstruction.

The goal of prolotherapy is to promote tissue repair or growth by prompting release of growth factors, such as cytokines, or increasing the effectiveness of existing circulating growth factors. The mechanism of action is not well understood, but may involve local irritation and/or cell lysis. Agents used with prolotherapy have included zinc sulfate, psyllium seed oil, combinations dextrose, glycerine, and phenol, or dextrose alone, often combined with a local anesthetic. Polidocanol and sodium morrhuate, vascular sclerosants, have also been used to sclerose areas of high intratendinous blood flow associated with tendinopathies. Prolotherapy typically involves multiple injections per session conducted over a series of treatment sessions.

A similar approach involves the injection of autologous platelet-rich plasma (PRP), which contains a high concentration of platelet derived growth factors. Treatment of musculoskeletal pain conditions (e.g., tendinopathies) with PRP is discussed in policy #241 Recombinant and Autologous Platelet-Derived Growth Factors as a Treatment of Wound Healing and Other Conditions.


This policy has been updated periodically with searches of the MEDLINE database. The most recent update was performed through September 20, 2023.

Summary of Evidence

For individuals who have musculoskeletal pain (e.g., chronic neck, back pain), osteoarthritic pain, or tendinopathies of the upper or lower limbs who receive prolotherapy, the evidence includes small randomized trials with inconsistent results. Relevant outcomes are symptoms, functional outcomes, and quality of life. The strongest evidence evaluates the use of prolotherapy for the treatment of osteoarthritis, but the clinical significance of the therapeutic results is uncertain. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements

American College of Foot and Ankle Surgeons

A 2017 guideline from the American College of Foot and Ankle Surgeons on acquired infracalcaneal heel pain states that evidence regarding the efficacy and safety of prolotherapy for treatment of plantar fasciitis is uncertain, which makes its use neither appropriate nor inappropriate. The same statement is made for platelet-rich plasma, amniotic tissue, botulinum toxin, and needling.

American College of Rheumatology/Arthritis Foundation

The 2019 American College of Rheumatology/Arthritis Foundation guideline for osteoarthritis of the hand, hip, and knee conditionally recommends against the use of prolotherapy in patients with knee and/or hip osteoarthritis, given limited number of trials involving small sample sizes showing limited effect. The guideline does not make any recommendation regarding hand osteoarthritis, given lack of trials.

North American Spine Society

A 2020 guideline on low back pain from the North American Spine Society does not provide a recommendation on prolotherapy but states that sacroiliac ligament prolotherapy deserves further study.

U.S. Preventive Services Task Force Recommendations

Not applicable.


Prolotherapy, Psyllium seed oil, sclerosing injections, regenerative injection therapy, growth factor stimulation injection, Prolo


The U.S. Food and Drug Administration has approved sclerosing agents for use in treating spider/varicose veins. These sclerosing agents include: Asclera® (polidocanol), Varithena® (an injectable polidocanol foam), Sotradecol® (sodium tetradecyl sulfate), Ethamolin® (ethanolamine oleate), and Scleromate® (sodium morrhuate). These agents are not currently approved as joint and ligamentous sclerosing agents.


Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Covered if covered by the Participating Home Plan

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan.






**The M0076 is the correct code to use to report prolotherapy.


CPT codes:

Providers should not bill for prolotherapy using the following codes:


Injection(s); tendon sheath, ligament, trigger points, or ganglion cyst


Injection(s); single tendon origin/insertion


Injection(s); Single or multiple trigger point(s), 1 or 2 muscle(s)


Unlisted procedure, musculoskeletal system, general


Injection procedure for sacroiliac joint, anesthetic/steroid, with image guidance (fluoroscopy or CT) including arthrography when performed


Code range for injection(s), diagnostic or therapeutic agent, paravertebral facet (zygapophyseal) joint (or nerves innervating that joint)



  1. Ahadi T, Cham MB, Mirmoghtadaei M, et al. 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. Feb 10 2023; 16(1): 5.
  2. Akcay S, Gurel Kandemir N, Kaya T, et al. Dextrose Prolotherapy Versus Normal Saline Injection for the Treatment of Lateral Epicondylopathy: A Randomized Controlled Trial. J Altern Complement Med. Dec 2020; 26(12): 1159-1168.
  3. Apaydin H, Bazancir Z, Altay Z. Injection Therapy in Patients with Lateral Epicondylalgia: Hyaluronic Acid or Dextrose Prolotherapy? A Single-Blind, Randomized Clinical Trial. J Altern Complement Med. Dec 2020; 26(12): 1169-1175.
  4. Arias-Vazquez PI, Tovilla-Zarate CA, Castillo-Avila RG, et al. Hypertonic Dextrose Prolotherapy, an Alternative to Intra-Articular Injections With Hyaluronic Acid in the Treatment of Knee Osteoarthritis: Systematic Review and Meta-analysis. Am J Phys Med Rehabil. Sep 01 2022; 101(9): 816-825.
  5. Bahgat MM, Abdel-Hamid AM. Is dextrose prolotherapy beneficial in the management of temporomandibular joint internal derangement? A systematic review. Cranio. Apr 25 2023: 1-9.
  6. Bayat M, Hojjati F, Boland Nazar NS, et al. Comparison of Dextrose Prolotherapy and Triamcinolone Intraarticular Injection on Pain and Function in Patients with Knee Osteoarthritis - A Randomized Clinical Trial. Anesth Pain Med. Apr 2023; 13(2): e134415.
  7. Bayat M, Raeissadat SA, Mortazavian Babaki M, et al. Is Dextrose Prolotherapy Superior To Corticosteroid Injection In Patients With Chronic Lateral Epicondylitis?: A Randomized Clinical Trial. Orthop Res Rev. 2019; 11: 167-175.
  8. Bertrand H, Reeves KD, Bennett CJ, et al. Dextrose Prolotherapy Versus Control Injections in Painful Rotator Cuff Tendinopathy. Arch Phys Med Rehabil. Jan 2016; 97(1): 17-25.
  9. Carayannopoulos A, Borg-Stein J, Sokolof J et al. Prolotherapy versus corticosteroid injections for the treatment of lateral epicondylosis: a randomized controlled trial. PMR 2011; 3(8):706-715.
  10. Chou R, Atlas SJ, Stanos SP and Rosenquist RW. Nonsurgical interventional therapies for low back pain: A review of the evidence for an American Pain Society clinical practice guideline. Spine, May 2009; 34(10): 1078-1093.
  11. Chung MW, Hsu CY, Chung WK, et al. Effects of dextrose prolotherapy on tendinopathy, fasciopathy, and ligament injuries, fact or myth?: A systematic review and meta-analysis.Medicine (Baltimore). Nov 13 2020; 99(46): e23201.
  12. Cortez VS, Moraes WA, Taba JV, et al. Comparing dextrose prolotherapy with other substances in knee osteoarthritis pain relief: A systematic review. Clinics (Sao Paulo). 2022; 77: 100037.
  13. Dagenais S, Yelland M, Del Mar C, and Schoene M. Prolotherapy injections for chronic low-back pain. Cochrane Database Syst Review, April 2007; (2): CD004059.
  14. Dagenais S, Mayer J, Haldeman S, et al. Evidence-informed management of chronic low back pain with prolotherapy. Spine J 2008; 8(1):203-212.
  15. Fong HP, Zhu MT, Rabago DP, et al. Effectiveness of hypertonic dextrose injection (prolotherapy) in plantar fasciopathy: A systematic review and meta-analysis of randomized controlled trials. Arch Phys Med Rehabil. Apr 23 2023.
  16. Goh SL, Jaafar Z, Gan YN, et al. Efficacy of prolotherapy in comparison to other therapies for chronic soft tissue injuries: A systematic review and network meta-analysis. PLoSOne. 2021; 16(5): e0252204.
  17. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
  18. Jahangiri A, Moghaddam FR, Najafi S. Hypertonic dextrose versus corticosteroid local injection for the treatment of osteoarthritis in the first carpometacarpal joint: a double-blind randomized clinical trial. J Orthop Sci. Sep 2014; 19(5):737-743.
  19. Kazempour Mofrad M, Rezasoltani Z, Dadarkhah A, et al. Periarticular Neurofascial Dextrose Prolotherapy Versus Physiotherapy for the Treatment of Chronic Rotator Cuff Tendinopathy: Randomized Clinical Trial. J Clin Rheumatol. Jun 01 2021; 27(4): 136-142.
  20. 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(12):1285-1290.
  21. Klein RG, Eek BC, DeLong WB et al. A randomized double-blind trial of dextrose-glycerine-phenol injections for chronic, low back pain. J Spinal Disord 1993; 6(1): 23-33.
  22. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. Feb 2020; 72(2): 220-233.
  23. Lin LC, Lee YH, Chen YW, et al. Comparison Clinical Effects of Hypertonic Dextrose and Steroid Injections on Chronic Subacromial Bursitis: A Double-Blind Randomized Controlled Trial. Am J Phys Med Rehabil. Oct 01 2023; 102(10): 867-872.
  24. North American Spine Society. Diagnosis and Treatment of Low Back Pain. 2020.  
  25. Ongley MJ, Klein RG, Dorman TA et al. A new approach to the treatment of chronic low back pain. Lancet 1987; 2(8551): 143-146.
  26. Rabago D, Best TM, Zgierska AE, et al. A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet-rich plasma. Br J Sports Med. Jul 2009; 43(7):471-481.
  27. Rabago D, Mundt M, Zgierska A, et al. Hypertonic dextrose injection (prolotherapy) for knee osteoarthritis: Long term outcomes. Complement Ther Med. Jun 2015; 23(3):388-395.
  28. Rabago D, Patterson JJ, Mundt M et al. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med 2013; 11(3):229-237.
  29. 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, 77-80.
  30. 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 Complement Med 2000; 6(4): 311-320.
  31. Reeves KD, Hassanein KM. Long-term effects of dextrose prolotherapy for anterior cruciate ligament laxity. Altern Ther Health Med 2003; 9(3): 58-62.
  32. Scarpone M, Rabago DP, Zgierska A, et al. The efficacy of prolotherapy for lateral epicondylosis: A pilot study. Clin J Sport Med 2008; 18(3):248-254.
  33. Schneider HP, Baca JM, Carpenter BB, et al. American College of Foot and Ankle Surgeons Clinical Consensus Statement: Diagnosis and Treatment of Adult Acquired Infracalcaneal Heel Pain. J Foot Ankle Surg. 2018; 57(2): 370-381.
  34. Sert AT, Sen EI, Esmaeilzadeh S, et al. The Effects of Dextrose Prolotherapy in Symptomatic Knee Osteoarthritis: A Randomized Controlled Study. J Altern Complement Med. May 2020; 26(5): 409-417.
  35. Waluyo Y, Artika SR, Insani Nanda Wahyuni AMAK, et al. Efficacy of Prolotherapy for Osteoarthritis: A Systematic Review. J Rehabil Med. Feb 27 2023; 55: jrm00372.
  36. Wee TC, Neo EJR, Tan YL. Dextrose prolotherapy in knee osteoarthritis: A systematic review and meta-analysis. J Clin Orthop Trauma. Aug 2021; 19: 108-117.
  37. Yelland MJ, Glasziou PP, Bogduk N et al. Prolotherapy injections, saline injections, and exercises for chronic low-back pain: A randomized trial. Spine 2004; 29(1): 9-16.
  38. Yelland MJ, Sweeting KR, et al. Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: A randomised trial. Br J Sports Med, Apr 2011; 45(5):421-428.
  39. Zhu M, Rabago D, Chung VC, et al. Effects of Hypertonic Dextrose Injection (Prolotherapy) in Lateral Elbow Tendinosis: A Systematic Review and Meta-analysis. Arch Phys Med Rehabil. Feb 28 2022.


Medical Policy Group, July 2005 (3)

Medical Policy Administration Committee, July 2005

Available for comment July 28-September 10, 2005

Medical Policy Group, June 2006 (1)

Medical Policy Group, June 2007 (1)

Medical Policy Group, February 2009 (4)

Medical Policy Group, February 2010 (1): Updated Description, Key Points and References

Medical Policy Panel, August 2010

Medical Policy Group, September 2010 (2)

Medical Policy Group August 2011 (3): Updated Key Points and References

Medical Policy Group, September 2012 (3): 2012 Update to Key Points and References

Medical Policy Panel, August 2013

Medical Policy Group, September 2013 (2): Updated with literature search through July 2013.  Policy statement unchanged.  Key Points and References updated.

Medical Policy Panel, August 2014

Medical Policy Group, August 2014 (1): Update to Key Points and References, no change to policy statement.

Medical Policy Panel, August 2015

Medical Policy Group, August 2015 (2): Updates to Key Points, Key Words, Approved by Governing Bodies, and References; no change to policy statement.

Medical Policy Panel, November 2017

Medical Policy Group, November 2017 (7): 2017 Updates to Key Points and References. No change in Policy Statement.

Medical Policy Panel, November 2018

Medical Policy Group, December 2018 (7): Updates to Key Points and References. No change in Policy Statement.

Medical Policy Panel, November 2019

Medical Policy Group, November 2019 (7): Minor update to Key Points. No new References added. No change in Policy Statement.

Medical Policy Panel, November 2020

Medical Policy Group, November 2020 (7): Updates to Key Points and References. No change in Policy Statement

Medical Policy Panel, November 2021

Medical Policy Group, November 2021 (7): Updates to Key Points and References. Added Key Word: “Prolo.” Removed “not medically necessary” verbiage from Policy Statement. No change in intent.

Medical Policy Panel, November 2022

Medical Policy Group, November 2022 (7): Updates to Key Points and References. No change in Policy Statement.

Medical Policy Panel, November 2023

Medical Policy Group, December 2023 (7): Updates to Key Points, Benefit Application, and References. No change in Policy Statement.


This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.


This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

  1. The technology must have final approval from the appropriate government regulatory bodies;
  2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;
  3. The technology must improve the net health outcome;
  4. The technology must be as beneficial as any established alternatives;
  5. The improvement must be attainable outside the investigational setting.


Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

  1. In accordance with generally accepted standards of medical practice; and
  2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and
  3. Not primarily for the convenience of the patient, physician or other health care provider; and
  4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.