BlueCross BlueShield of Tennessee Medical Policy Manual

Prolotherapy for Musculoskeletal Disorders


Prolotherapy describes a procedure intended 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 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. Agents used with prolotherapy include zinc sulfate, psyllium seed oil, combinations of dextrose, glycerine, and phenol, or dextrose alone. Prolotherapy may involve a single injection or a series of injections, often diluted with a local anesthetic.


See also:  Platelet Rich Plasma as a Treatment for Wound Healing or Other Conditions



Prolotherapy has been investigated as a treatment option of various types of pain. Although there is extensive literature regarding prolotherapy, clinical efficacy has not been proven.


American Association of Orthopaedic Medicine. (2013). Prolotherapy for back pain. Retrieved February 25, 2014 from

BlueCross BlueShield Association. Medical Policy Reference Manual. (8:2015). Prolotherapy (2.01.26). Retrieved August 31, 2015 from BlueWeb. (23 articles and/or guidelines reviewed)

Centers for Medicare & Medicaid Services. NCD for prolotherapy, joint sclerotherapy, and ligamentous injections with sclerosing agents (150.7). Retrieved July 13, 2016 from

Hassan, F., Trebinjac, S., Murrell, W., & Maffulli, N. (2017). The effectiveness of prolotherapy in treating knee osteoarthritis in adults: a systematic review. British Medical Bulletin, 2017 Mar 4:1-18. Doi:10.1093/bmb/ldx006. [Epub ahead of print]. Abstract retrieved May 24, 2017 from PubMed database.

Hauser, R., Lackner, J., Steilen-Matias, D., & Harris, D. (2016). A systematic review of dextrose prolotherapy for chronic musculoskeletal pain. Clinical Medicine insights: Arthritis and Musculoskeletal Disorders, 2016:9, 139-159. (Level 2 evidence)

Hung, C., Hsiao, M., Chang, K., Han, D., & Wang, T. (2016). Comparative effectiveness of dextrose prolotherapy versus control injections and exercise in the management of osteoarthritis pain: a systematic review and meta-analysis. Journal of Pain Research, 2016: 9, 847-858. (Level 2 evidence)

Krstičević, M., Jerić, M., Došenović, S., Jeličić, K., & Puljak, L. (2017). Proliferative injection therapy for osteoarthritis: a systematic review. International Orthopaedics, 41 (4), 671-679. Abstract retrieved May 24, 2017 from PubMed database.

Morath, O., Kubosch, E., Taeymans, J., Zwingmann, J., Konstantinidis, L., Südkamp, N., & Hirschmüller, A. (2017). The effect of sclerotherapy and prolotherapy on chronic painful Achilles tendinopathy – a systematic review including meta-analysis. Scandinavian Journal of Medical & Science in Sports, 2017 Apr 27. Doi.10.1111/sms.12898. [Epub ahead of print]. Abstract retrieved May 24, 2017 from PubMed database.

Rabago, D., Lee, K., Ryan, M., Chourasia, O., Sesto, M., Zgierska, A., et al. (2013). Hypertonic dextrose and morrhuate sodium injections (prolotherapy) for lateral epicondylosis (tennis elbow): results of a single-blind, pilot-level randomized controlled trial. American Journal of Physical Medicine and Rehabilitation. 92 (7), 587-596. (Level 2 evidence)

Rabago, D., Mundt, M., Zgierska, A., & Grettie, J. (2015). Hypertonic dextrose injection (prolotherapy) for knee osteoarthritis: long term outcomes. Complementary Therapies in Medicine, 23 (3), 388-395. Abstract retrieved May 24, 2017 from PubMed database.

Rabago, D., Patterson, J., Mundt, M., Kijowski, R., Grettie, J., Segal, N., et al. (2013). Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Annals of Family Medicine, 11 (3), 229-237. (Level 2 evidence)

Rabago, D., Patterson, J., Mundt, M., Zgierska, A., Fortney, L., Grettie, J., et al. (November, 2014). Dextrose and Morrhuate Sodium Injections (Prolotherapy) for Knee Osteoarthritis: A Prospective Open-Label Trial. The Journal of Alternative and Complementary Medicine. Volume 20, pp. 383-391. (Level 3 evidence)

Sanderson, L., & Bryant, A. (2015). Effectiveness and safety of prolotherapy injections for management of lower limb tendinopathy and fasciopathy: a systematic review. Journal of Foot and Ankle Research, 2015, 8:57. (Level 2 evidence)

Sit, R., Chung, V., Reeves, K., Rabago, D., Chan, K., Chan, D., et al. (2016). Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: a systematic review and meta-analysis. Scientific Reports, 6:25247. DOI:10.1038/srep25247. (Level 2 evidence)




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