Medical Policy: 02.01.18 

Original Effective Date: November 1996 

Reviewed: October 2020 

Revised: October 2019 



This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.


Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.


This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.



Prolotherapy, also referred to as regenerative injection therapy, joint sclerotherapy, and proliferation therapy, as well as a therapy called prolozone, refers to a procedure performed to strengthen the lax or injured ligaments by injecting proliferating agents/sclerosing solutions directly into torn or stretched ligaments. The mild inflammatory response that is created by the injection promotes growth of new ligament or tendon fibers, resulting in a tightening of the weakened area. The goal of prolotherapy is to promote tissue repair or growth by prompting the release of growth factors, such as cytokines, or by 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. It is proposed that additional treatments of prolotherapy, over a period of a few weeks, allow a gradual buildup of tissue to restore the original strength to the area and may relieve pain.


Prolotherapy may involve a single or a series of injections of the proliferating agent, which are often diluted with a local anesthetic. Agents used for prolotherapy include zinc sulfate, psyllium seed oil, combinations of dextrose; glycerin; and phenol or dextrose alone. Polidocanol and sodium morrhuate, vascular sclerosants, have also been used to sclerose areas of high intratendinous blood flow associated with tendinopathies.



The relevant populations of interest are individuals who suffer from musculoskeletal pain, osteoarthritic pain, or upper- or lower-limb tendinopathies.



The therapy being considered is prolotherapy.


Injections are administered in an outpatient setting.



The following therapies and practices are currently being used to treat musculoskeletal pain, osteoarthritic pain, and upper- or lower-limb tendinopathies: observation and other conservative therapies.



The general outcomes of interest are reductions in pain and medication use, improvements in function, and treatment-related adverse events (mostly mild but in rare instances serious).


Varying by condition, injections are administered over a series of sessions, which can last from several weeks to months. 


Practice Guidelines and Position Statements

American College of Occupational and Environmental Medicine (2007, updated in 2011)

Guidelines on low back pain have concluded that the use of prolotherapy for acute, subacute, chronic or radicular pain syndromes is not recommended.


American College of Occupational and Environmental Medicine (2011)

Guidelines on hand, wrist, and forearm disorders were unable to make a recommendation about the use of prolotherapy because of insufficient evidence.


American Pain Society

A practice guideline from the American Pain Society on low LBP (Chou et al, 2009) stated that prolotherapy is not recommended for persistent non-radicular LBP.


American Association of Orthopedic Medicine

The American Association of Orthopedic Medicine currently has a recommendation posted online for the use of prolotherapy for back pain. The Association has indicated that "....prolotherapy should be considered a valid treatment option in a selected group of chronic low back pain patients."


Regulatory Status

Prolotherapy is a procedure and, therefore, not subject to FDA regulation. Sclerosing agents have been approved by the U.S. Food and Drug Administration for use in treating spider and varicose veins. These sclerosing agents include Asclera® (polidocanol), Varithena® (an injectable polidocanol foam), Sotradecol® (sodium tetradecyl sulfate), Ethamolin® (ethanolamine oleate), and Scleromate® (sodium morrhuate). The agents used in the historic studies, (dextrose, lidocaine, and approved sclerotherapy agents for varicose veins) are approved for injection by the FDA but are not specifically approved for prolotherapy as joint and ligament injections and these agents are not currently approved as joint and ligamenous sclerosing agents. The use for prolotherapy is considered off-label.


Prior Approval:

Not applicable



Prolotherapy is considered investigational for all applications, including but not limited to:

  • Achilles tendinosis
  • Back pain
  • Epicondylitis
  • Iliotibial band syndrome
  • Knee ligament instability
  • Knee osteoarthritis
  • Myofascial pain
  • Neuropathic pain
  • Osteomyelitis pubis
  • Sacroiliac joint pain
  • Temporomandibular joint syndrome/Temporomandibular joint hypermobility
  • Tendinopathies
  • Groin pain
  • Shoulder pain
  • All lower limb tendinopathies
  • All musculoskeletal pain
  • Stimulation of tendon/ligament tissue


Prolotherapy as a part of another procedure is considered investigational.


The literature consists of small randomized trials on a variety of pain syndromes with inconsistent results. The body of scientific evidence does not permit conclusions concerning the effect of prolotherapy on health outcomes for chronic neck or back pain, tendinopathies of the upper or lower limbs, osteoarthritic pain, or other musculoskeletal pain conditions. For individuals who have musculoskeletal pain (eg, 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.


Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.

  • M0076 Prolotherapy


Selected References:

  • Reeves, K.D., 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. The Journal of Alternative and Complementary Medicine 2000; vol 6, No 4: 311-320.
  • Reeves, K.D., Hassanein, K. Randomized prospective double-blind placebo-controlled study of dextrose prolotherapy for knee osteoarthritis with or without ACL laxity. The Journal of Alternative and Complementary Medicine 2000; vol 6, No.2: 68-7. 
  • Hauser, R.A. Punishing the pain - Treating chronic pain with prolotherapy. Rehab Management Feb/March 1999;26-30.
  • Dechow E, Davies RK, Carr AJ, Thompson PW. A randomized, double-blind, placebo-controlled trial of sclerosing injections in patients with chronic low back pain. Rheumatology (Oxford) 1999 Dec;38(12):1255-9. 
  • Tsatsos G, Mandal R. Prolotherapy in the treatment of foot problems. J Am Podiatr Med Assoc 2002 Jun;92(6):366-8.
  • ECRI. Prolotherapy for ligament or tendon pain. Plymouth meeting (PA): ECRI Health technology Information Service 2004 May 14. 8 p. (ECRI Hotline Response).
  • Linetsky, F. S., Miguel, R., and Torres, F. Treatment of cervicothoracic pain and cervicogenic headaches with regenerative injection therapy. Curr Pain Headache Rep. 2004;8(1):41-8.
  • 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):1285-90.
  • Scarpone M, Rabago DP, ZZgierska A et al. The efficacy of prolotherapy for lateral epicondylosis: a pilot study. Clin J Sport Med 2008; 18(3):248-54.
  • Rabago D, Best TM, Zgierska A et al. A systematic review of four injection therapies for lateral epicondylosis: prolotherapy, polidocanol, whole blood and platelet rich plasma. Br J Sports Med 2009; 43(7):471-81.
  • Robago 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 Apr;18(4):408-14.
  • Carayannopoulos A, Borg-Stein J, Sokolof J, et al. Prolotherapy versus corticosteroid injections for the treatment of lateral epicondylosis: a randomized controlled trial. PM R. 2011 Aug; 3(8): 706-15.
  • Refai H, Altahhan O, Elsharkawy R. The efficacy of dextrose prolotherapy for temporomandibular joint hypermobility: a preliminary prospective, randomized, double-blind, placebo-controlled clinical trial. J Oral Maxillofac Surg. 2011 Dec; 69(12): 2962-70.
  • CMS. National Coverage Determniation (NCD) for Prolotherapy, Joint Sclerotherapy and Ligamentous Injections with Scelorosing Agents (150.7).
  • UpToDate. Epicondylitis (Tennis and Golf Elbow). Neeru Jayanthi M.D.. Topic last updated January 13, 2014.
  • UpToDate. Subacute and Chronic Low Back Pain: Nonsurgical Interventional Treatment. Roger Chou M.D.. Topic last updated December 5, 2013.
  • UpToDate. Treatment of Acute Low Back Pain. Christopher L. Knight M.D., Richard A. Deyo, M.D., MPH, Thomas O. Staiger, M.D., Joyce E. Wipf, M.D,, Topic last updated September 26, 2013.
  • UpToDate. Overview of the Management of Overuse (Chronic) Tendinopathy. Karim Kahn, M.D., Alex Scott, PhD, RPT.
  • American Association of Orthopaedic Medicine (AAOM). Position Statement. Prolotherapy for the Treatment of Back Pain.
  • American Association of Orthopedic Medicine, Klein RG, Patterson J, et al. Prolotherapy for Back Pain Treatment. n.d.;
  • American College of Occupational and Environmental Medicine (ACOEM). NGC: 9327. Low back disorders. Occupational medicine practice guidelines: evaluation and management of common health problems and functional recovery in workers. 2nd ed. 2007.
  • European Commission Research Directorate General (ECRDG) [website]. European Guidelines for Management of Non-specific Low Back Pain. 2004. Updated June 14, 2005.
  • 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. PMID 26051574
  • 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. PMID 25158896
  • Sanderson, L. Bryant, A. Effectiveness and safety of prolotherapy injections for management of lower limb tendinopathy and fasciopathy: a systematic review. J Foot Ankle Res 2015 Oct (20);8:57. doi: 10.1186/s13047-015-0114-5
  • U.S. National Institutes of Health (NIH). Clinical trials: prolotherapy
  • Bertrand H, Reeves KD, Bennett CJ, et al. Dextrose prolotherapy versus control injections in painful rotator cuff tendinopathy. Arch Phys Med Rehabil. 2016; 97(1):17-25.
  • UpToDate. Chou, R., Atlas, S., Subacute and chronic back pain. Topic last updated October 18, 2017.
  • Chou R, Loeser JD, Owens DK, et al. Interventional therapies, surgery, and interdisciplinary rehabilitation for low back pain: an evidence-based clinical practice guideline from the American Pain Society. Spine (Phila Pa 1976) 2009; 34:1066.
  • Hung, C., Hsaio, M., et al. Comparitive effectiveness of dextrose prolotherapy versus control injections and exercise in the management of osteoart
  • Seenauth C, Inouye V, Langland JO. Dextrose prolotherapy for chronic shoulder pain: A case report. Altern Ther Health Med. 2018;24(1):56-60.
  • American Association of Orthopedic Medicine, Klein RG, Patterson J, et al. Prolotherapy for Back Pain Treatment. n.d.;  ï‚§ 
  • Hassan F, Murrell WD, Refalo A, Maffulli N. Alternatives to Biologics in Management of Knee Osteoarthritis: A Systematic Review. Sports Med Arthrosc Rev. 2018 Jun;26(2):79-85.


Policy History:

  • October 2020 - Annual Review, Policy Renewed
  • October 2019 - Annual Review, Policy Revised
  • October 2018 - Annual Review, Policy Revised
  • October 2017 - Annual Review, Policy Renewed
  • October 2016 - Annual Review, Policy Revised
  • November 2015 - Annual Review, Policy Revised
  • December 2014 - Annual Review, Policy Revised
  • February 2014 - Annual Review, Policy Renewed
  • May 2013 - Annual Review, Policy Renewed
  • June 2012 - Annual Review, Policy Renewed
  • August 2011 - Annual Review, Policy Renewed

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.


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