Prolotherapy research | Knee osteoarthritis

This page will offer brief reviews and links to Prolotherapy research surrounding knee osteoarthritis.

The effectiveness of prolotherapy in treating knee osteoarthritis in adults: a systematic review.

June 2017: A team of multi-national researchers publishing in the British Medical Bulletin evaluated ten studies which showed significant improvement in patient scores related to knee osteoarthritis pain, function and range of motion, both in the short term and long term. Patient satisfaction was also high in these patients (82%) for Prolotherapy knee osteoarthritis treatment.

Hassan F, Trebinjac S, Murrell WD, Maffulli N. The effectiveness of prolotherapy in treating knee osteoarthritis in adults: a systematic review. Br Med Bull. 2017 Mar 4:1-18.

Chondrogenic Effect of Intra-articular Hypertonic-Dextrose (Prolotherapy) in Severe Knee Osteoarthritis

Dextrose injection (Prolotherapy) is reported to improve knee osteoarthritis −related clinical outcomes, but its effect on articular cartilage is unknown. A chondrogenic effect of dextrose injection has been proposed (Prolotherapy would regrow cartilage).  This study which was published in PM & R : the journal of injury, function, and rehabilitation, assessed biological and clinical effects of intra-articular hypertonic dextrose Prolotherapy injections in painful knee osteoarthritis.

The study design was case series with blinded arthroscopic evaluation before and after treatment.

Study Participants
Symptomatic knee osteoarthritis for at least 6 months, arthroscopy-confirmed medial compartment exposed subchondral bone (a bone on bone situation), and temporary pain relief with intra-articular lidocaine injection.

Four to 6 monthly 10-mL intra-articular injections with 12.5% dextrose.


  • Six participants (1 female and 5 male) with median age of 71 years, and average 9-year pain duration
  • WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) a pain measurement scoring system) composite score of 57.5 points, signifying problems with pain, stiffness, and function.
  • Patients received an average of 6 dextrose injections and follow-up arthroscopy at 7.75 months (range 4.5-9.5 months) – to measure effectiveness of treatment.
  • Posttreatment showed cartilage growth compared with the pretreatment.
  • Biopsy specimens showed metabolically active cartilage with variable cellular organization, fiber parallelism, and cartilage typing patterns consistent with fibro- and hyaline-like cartilage.
  • Compared with baseline status, the median WOMAC score improved 13 points.

Positive clinical and chondrogenic (cartilage growth) effects were seen after prolotherapy with hypertonic dextrose injection in participants with symptomatic grade IV Knee Osteoarthritis, suggesting disease-modifying effects and the need for confirmation in controlled studies. Minimally invasive arthroscopy (single-compartment, single-portal) enabled collection of robust intra-articular data.

Topol GA, Podesta LA, Reeves KD, Giraldo MM, Johnson LL, Grasso R, Jamín A, Clark T, Rabago D. Chondrogenic Effect of Intra-articular Hypertonic-Dextrose (Prolotherapy) in Severe Knee Osteoarthritis. PM R. 2016 Nov;8(11):1072-1082.
doi: 10.1016/j.pmrj.2016.03.008

Qualitative Assessment of Patients Receiving Prolotherapy for Knee Osteoarthritis in a Multimethod Study

September 2016: From the University of Wisconsin School of Medicine and Public Health, a late 2016 study followed twenty-two participants treated with prolotherapy for symptomatic knee osteoarthritis who were previously enrolled in three randomized and open-label studies. At 52 weeks following enrollment, the patients were interviewed about the overall experience with Prolotherapy.


  • improvement in knee-specific quality of life was found in 18 of 22 patients. Four patients reported limited response.
  • pretreatment counseling enhanced treatment adherence and optimism of the success of the Prolotherapy treatments.
  • patients reported overall positive experience with Prolotherapy.


Most participants reported substantially improved knee-specific effects, resulting in improved quality of life and activities of daily living; four participants reported minimal or no effect. Clear, complete description of procedural rationale may enhance optimism about and adherence to treatment appointments.

Rabago D, van Leuven L, Benes L, Fortney L, Slattengren A, Grettie J, Mundt M. Qualitative Assessment of Patients Receiving Prolotherapy for Knee Osteoarthritis in a Multimethod Study. J Altern Complement Med. 2016 Dec;22(12):983-989.

May 2016: Published in the science journal Nature: Scientific Reports, research come from doctors at The Chinese University of Hong Kong, The Jockey Club School of Public Health and Primary Care, Hong Kong, The University of Wisconsin School of Medicine and Public Health, Department of Family Medicine and Community Medicine, Madison, Wisconsin.

Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis

Explanation of Prolotherapy

Hypertonic dextrose injection, “prolotherapy”, is an injection-based treatment used for a variety of painful chronic musculoskeletal pain conditions, including knee osteoarthritis.

The core practice principle of prolotherapy is injection of relatively small volumes (0.5–6 ml) of an irritant solution, usually hypertonic dextrose, at painful ligament and tendon attachments, as well as in adjacent joint spaces.

The hypothesized mechanisms for pain relief include:

  1. stimulation of local healing among chronically injured extra- and intra-articular tissue;
  2. reduction of joint instability through the strengthening of stretched or torn ligaments, and
  3. stimulation of cellular proliferation.

Prolotherapy is practiced throughout the world; the strongest interest appears to be among physicians and patients in primary care


Pooling data from two Randomized Control Trials, researchers reported:

  • peri- and intra-articular hypertonic dextrose knee injections (inside the knee and to surrounding tissue) in three to five sessions have a statistically significant and clinically relevant effect in the improvement of WOMAC composite score, functional and pain subscale at 12 to 16 weeks compared to formal at-home exercise.
  • Self-reported outcomes favoring prolotherapy are also observed in unpooled data when dextrose prolotherapy groups are compared with other control groups. The majority of the effect sizes are higher than the MCID, and the benefits were sustained up to 1 year. (MCID is a measurement for minimal clinically important difference. It is score given to something that makes at least a minimal difference in the patient’s outcome. The results showed Prolotherapy’s positive effcet was above levels considered minimal levels of improvement)
  • Overall, prolotherapy injections appear to be safe, but no study was powered to detect rare adverse events.

Some warnings about research

While the overall direction of the effect is positive, some uncertainty of the effect size (number of patients reporting) still exists due to the low to moderate heterogeneity (diversity of patient) and wide confidence intervals (the probability of positive or negative results).

Due to a lack of uniform longer-term follow up data across both studies, pooling of results could only be done with data collected between 12 to 16 week follow-up. Given that prolotherapy is hypothesized to work by healing and regeneration over several months , the effects reported here may underestimate longer term benefits.

The results of this systematic review indicate that hypertonic dextrose prolotherapy conferred a positive, significant beneficial effect meeting criteria for clinical relevance in the treatment of knee OA, compared with saline injection and exercise. Larger, long-term trials with uniform outcomes and high methodological standards are needed for more a more comprehensive assessment of the overall treatment effect of prolotherapy.

Sit RW, Chung VC, Reeves KD, Rabago D, Chan KK, Chan DC, Wu X, Ho RS, Wong SY. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: a systematic review and meta-analysis. Scientific reports. 2016;6.

April 2015

Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up

Doctors at the Physical Medicine and Rehabilitation Research Center, Tabriz University of Medical Sciences in Iran published their findings in the medical journal Therapeutic advances in musculoskeletal disease.

  • In this single-arm prospective study, participants with symptomatic moderate knee osteoarthritis underwent prolotherapy with intra-articular injection of 20% dextrose water at baseline, and at 4 weeks and 8 weeks later.
  • Patients were followed for 24 weeks.
  • Pain severity at rest and activity, according to the visual analog scale (VAS), articular range of motion (ROM), and Western Ontario and McMaster Universities arthritis index (WOMAC) scores were measured at baseline, 4, 8, and 24 weeks later.


A total of 24 female patients (average age: 58.37 years) received 3-monthly injection therapies.

Prolotherapy with three intra-articular injections of hypertonic dextrose given 4 weeks apart for selected patients with knee osteoarthritis, resulted in significant improvement of validated pain, ROM, and WOMAC-based function scores, when baseline levels were compared at 24 weeks.

Eslamian F, Amouzandeh B. Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up. Ther Adv Musculoskelet Dis. 2015 Apr;7(2):35-44. doi: 10.1177/1759720X14566618. [Pubmed] [Google Scholar]

Research case study | Prolotherapy as alternative to knee surgery

July 2012: A case report that was published in the medical journal Anesthesiology and Pain Medicine discusses the clinical and radiological outcomes of prolotherapy in a patient whom total knee prosthesis had been planned but surgery couldn’t be performed due to other existing medical conditions.

The patient was a 72 year old woman with severe pain at her knees for over 5 years. Treatment methods include weight loss, decreasing the weight bearing on the joint, stretching exercises, nonsteroid anti-inflammatory and steroid drugs, and physiotherapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale was applied to measure the osteoarthritis level of the patient: Pain level; 25 points, stiffness level; 10 points, Physical function loss; 80 points, and total WOMAC 115 points. At radiological evaluation, the patient was diagnosed as grade IV osteoarthritis due to significant osteophyte presence and complete joint space narrowing.

Six sessions of knee prolotherapy protocol was applied to the patient, one session monthly.

Significant improvement was noted at WOMAC scale (Pain level; 5 points, stiffness level; 2 points, Physical function loss; 15 points, and total WOMAC 22 points). Osteoarthritis level of the patient was improved to grade I at radiological evaluation after a year. Our case is the report that presents radiological evidence in addition to clinical findings of improvement of osteoarthritis level.

We are in the opinion that prolotherapy may be preferred more commonly as an efficient method once the importance of ligamentous structures at pathogenesis of osteoarthritis is established.5

Dumais R, Benoit C, Dumais A, et al. Effect of Regenerative Injection Therapy on Function and Pain in Patients with Knee Osteoarthritis: A Randomized Crossover Study.Pain Med. 2012 Aug;13(8):990-999. doi: 10.1111/j.1526-4637.2012.01422.x. Epub 2012 Jul 3. [Pubmed] [Google Scholar]

Hypertonic dextrose injections (Prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up

Recently researchers from the University of Wisconsin, studied patients who received Prolotherapy for knee osteoarthritis to determine effectiveness or non-effectiveness of treatment. They judged effectiveness as improvement in pain, stiffness, and improved knee function.

The patients received Prolotherapy injections of 15% dextrose 25% dextrose at one, five and nine weeks, with as-needed treatments at weeks 13 and 17 and monitored for 52 weeks.

The researchers found that the patients were reporting progressive improvement during the 52-week study. They concluded that: “In adults with moderate to severe knee osteoarthritis, dextrose Prolotherapy may result in safe, significant, sustained improvement of knee pain, function, and stiffness scores.”

Interesting this study found that of the patients selected: Thirty-six (36) participants with an average age of 60, 21 female and 15 male, was that women, age 46-65 years old, with a healthy body weight were associated with greater improvement.

Rabago D, Zgierska A, Fortney L. 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. [Pubmed] [Google Scholar]

Prolotherapy for Knee Pain

In published research in the Journal of Prolotherapy, Ross Hauser MD investigated the outcomes of patients receiving Prolotherapy treatment for unresolved, difficult to treat knee pain at a charity clinic in  Illinois.

  • 80 patients, representing a total of 119 knees, that were treated quarterly with Prolotherapy.
  • The results of this study showed that patients had a statistically significant decline in their level of pain, stiffness, crunching sensation, and improvement in their range of motion with Prolotherapy.
  • More than 82% showed improvements in walking ability, medication usage, athletic ability, anxiety, depression, and overall disability with Prolotherapy. Ninety-six percent of patients felt Prolotherapy improved their life overall.11

Quality of Life changes after Prolotherapy treatment for knee osteoarthritis

In the same study, we asked the patients a simple yes or no question:

  • Has Prolotherapy changed your life for the better?
    • 96% of patients treated answered yes.
  • In quantifying the response,
    • 43% felt their life was at least radically better with Prolotherapy.
    • 88% rated Prolotherapy at least very successful in treating their condition (50% or greater improvement) with 50% noting the Prolotherapy to be extremely successful (75% or greater improvement).
  • The percentage of patients able to decrease their additional pain-related treatments including chiropractic, physical therapy, acupuncture, and massage after Prolotherapy was 86%.
  • The percentage of patients able to decrease their medication usage by 50% or more was 90%.

Long-term results

The patients in this study were treated four to six years prior to the publishing of this paper.

  • Eighty-seven percent noted that the results of Prolotherapy have mostly continued (at least 50% retained), and 52% of patients noted that their overall results have very much continued to the present (75% to 99%).
  • Seventy-eight percent noted there were reasons besides the Prolotherapy effect wearing off that were causing their continued pain and/or disability.
    • Of the 78%, 42% of these believe they stopped Prolotherapy too soon (before the pain was totally gone),
    • 20% re-injured the area that had received Prolotherapy,
    • 13% had a new area of pain,
    • 10% had increased life stressors, and
    • 15% had other explanations for the pain.
  • Of the patients whose pain recurred after Prolotherapy was stopped, 81% are planning on receiving more Prolotherapy.

Prolotherapy used on patients who had a duration of five years of unresolved knee pain was shown in this observational study to improve their quality of life. They reported less pain, stiffness, disability, depressed and anxious thoughts, medication and other pain therapy usage, as well as improved walking ability, range of motion, ability to work and activities of daily living. Therefore, Prolotherapy appears to be a viable treatment option for people suffering with unresolved knee pain.

Hauser RA, Hauser MA.  A Retrospective Study on Dextrose Prolotherapy for Unresolved Knee Pain at an Outpatient Charity Clinic in Rural Illinois. Journal of Prolotherapy. 2009;1:11-21. [Google Scholar]