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Prolotherapy and the Use of Sugars in Orthopedics

Updated: Jul 14, 2020

Prolotherapy has been a part of modern orthopedic practices since the 1940s. It is growing in popularity not just in the U.S., but globally as well. Also known as “regenerative injection therapy” (RIT), prolotherapy is a procedure used to treat musculoskeletal conditions including tendinopathies, osteoarthritis, and chronic pain of the cervical spine, lumbar spine, and pelvis (Sit et al. 2017). The procedure involves the administration of a therapeutic solution injected into the tendons, ligaments, and joint space (Houser et al. 2016). There are typically several injection sessions, which take place every 2 to 6 weeks. It is currently one of the leading nonsurgical interventions used for treating musculoskeletal conditions that result in chronic pain.

Some of the most common solutions used in prolotherapy are saline (saltwater), hypertonic dextrose (sugar water), and P2G (phenol-glycerine-glucose) — with dextrose being the principal solution used (Rabago 2010). These solutions cause low-grade inflammation at the affected site, which encourages internal repair without causing long-term damage to the tissue. Dextrose in particular is considered an ideal constituent of prolotherapy because it is water soluble, a normal component of blood, and can be administered safely in large quantities. Concentrations of hypertonic dextrose prolotherapy typically range from 12.5% to 25% (Houser et al. 2016). In laboratory studies of human fibroblasts and chondrocytes, dextrose exposure in concentrations as low as 0.5% resulted in cellular proliferation and growth factor production, which are essential for tissue regeneration (Reeves 2006).

The primary goal of prolotherapy is to stimulate the natural regenerative process in tissue and facilitate the restoration of tissue and joint stability. When the immune system fails to recognize injury, as in the case of chronic musculoskeletal disorders, the tissue regeneration process is impaired. Dextrose prolotherapy functions by stimulating the immune system to initiate tissue repair and regeneration. The treatment first causes inflammation at the site of administration resulting in an immune response known as the inflammatory cascade. Fibroblasts and endothelial cells migrate to the affected site to form new blood vessels, encourage cellular proliferation, and deposit collagen (Houser et al. 2016; Reeves et al. 2016). Dextrose stimulates the production of growth factors, such as platelet-derived growth factor, transforming growth factor β, epidermal growth factor, and connective tissue growth factor, that are essential for tissue repair and the expression of multiple collagen cell types (Houser et al. 2016). The tissue remodeling process continues in tendon, ligament, and cartilage tissue over the course of several weeks to a few months. For most patients, pain resolves when the structural and functional integrity of the tissue approaches that of the normal parent tissue or has been completely restored.

Dextrose prolotherapy has been shown to reduce pain for athletes suffering from adductor tendinopathy. In one clinical study, dextrose prolotherapy treatment brought 20 out of 24 subjects from a full prevention of sports participation to feeling no pain at the affected areas, with 22 of the subjects being able to participate unrestricted by the end of the study (Topol et al. 2005). Dextrose prolotherapy has been used to treat nonspecific lower back pain, and has shown positive results in feedback from patients. In another clinical trial, 35 of 40 patients receiving dextrose prolotherapy reported a 50% decrease in pain at 6 months, while only 16 of 41 patients in the control group reported the same reduction in pain (Ongley et al. 1987).

As with many clinical interventions, prolotherapy can result in side effects. Patients sometimes experience pain or numbness at the site of injection. Other side effects include lightheadedness, allergic reactions, and minor nerve damage. Although these seem concerning, the number of reported adverse events is minimal (Sit et al. 2017) and the existing cases are likely a result of the injection process as opposed to the therapeutic solution being administered. In general, prolotherapy is exceedingly safer than surgical interventions. Furthermore, the hypertonic dextrose treatment utilizes a sugar compound that is endogenous, or naturally occurring in the body, making it biocompatible and unlikely to cause adverse effects.

Prolotherapy is still being researched today, but it is well on its way to becoming a more common procedure in clinical orthopedics. There is a growing body of research that supports the safety and efficacy of sugar-based therapies, such as dextrose prolotherapy, for orthopedic use (Houser et al. 2016). An increasing understanding of the biological microenvironment and the role of sugars during tissue regeneration can inform future therapeutic development and promote treatments that harness the body’s innate regenerative capacity.


Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A Systematic Review of Dextrose Prolotherapy for Chronic Musculoskeletal Pain. Clin Med Insights Arthritis Musculoskelet Disord. 2016;9:139-159.

Ongley MJ, Klein RG, Dorman TA, Eek BC, Hubert LJ. A new approach to the treatment of chronic low back pain. Lancet. 1987;2(8551):143-146.

Rabago D, Slattengren A, Zgierska A. Prolotherapy in primary care practice. Prim Care. 2010;37(1):65-80.

Reeves KD. Prolotherapy: injection of growth factors or growth factor production stimulants to growth normal cells or tissue. Pain Management. Philadelphia: Elsevier; 2006. pp. 1106–27.

Reeves KD, Sit RW, Rabago DP. Dextrose Prolotherapy: A Narrative Review of Basic Science, Clinical Research, and Best Treatment Recommendations. Phys Med Rehabil Clin N Am. 2016;27(4):783-823.

Sit RW, Chung VCh, Reeves KD, et al. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis Sci Rep. 2016;6:25247.

Topol GA, Reeves KD, Hassanein KM. Efficacy of Dextrose Prolotherapy in Elite Male Kicking-Sport Athletes with Chronic Groin Pain. Archives of Physical Medicine and Rehabilitation, vol. 86, no. 4, Apr. 2005, pp. 697–702.

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