Prolotherapy knee osteoarthritis research: An option to knee surgery

Ross Hauser, MD., Danielle R. Steilen-Matias, MMS, PA-C.

The evidence for Prolotherapy Injections for knee osteoarthritis

In this article, we will update new research and discuss Prolotherapy knee osteoarthritis injections. The knee is the most common joint treated with Prolotherapy at Caring Medical. We use a comprehensive Prolotherapy approach that stimulates the natural repair of connective tissue. Prolotherapy research shows significant improvement in selected patients with knee osteoarthritis. Treating the whole knee joint as opposed to selective parts of the knee is more effective in alleviating knee pain and healing the damage.

In a study from July 2016, our team published findings (1) that summarized the benefits of Prolotherapy.

Prolotherapy’s popularity as a treatment for chronic pain has intensified over the past two decades among both physicians and patients as clinical and anecdotal observations have proved in many cases its reliance as a non-surgical option for joint and back pain.

Irritant solutions most often contain dextrose (d-glucose), a natural form of glucose normally found in the body.

Research on the benefits of Prolotherapy for knee osteoarthritis

Prolotherapy is a remarkable treatment in its simplicity. The treatment can help many patients avoid joint replacement. But it is not a miracle cure. The research and evidence for how Prolotherapy may help you are presented here and intermingled with our own 27+ years of empirical observation of patient benefit.

The path to knee replacement is inevitable unless you address the knee as a whole and not a problem of bone on bone. Prolotherapy addresses whole knee instability.

The benefits of a holistic approach to treating the knee can be clearly seen in the definition of knee osteoarthritis:

Knee Osteoarthritis is:

Comprehensive Prolotherapy can address all these issues simultaneously and spontaneously (it starts working immediately). 

How does Prolotherapy work in your knees?

In 2016, our Caring Medical research team published our study, “A Systematic Review of Dextrose Prolotherapy for Chronic Musculoskeletal Pain” in the journal Clinical Medicine Insights. Arthritis and Musculoskeletal Disorders. (1) In this review, we examined the research in the use of dextrose Prolotherapy for the treatment of tendinopathies, knee and finger joint osteoarthritis, and spinal/pelvic pain due to ligament dysfunction. In our section on knee pain, we referred to a study by Dr. Fariba Eslamian and Dr. Bahman Amouzandeh of Tabriz University of Medical Sciences. This is what they published in the journal Therapeutic Advances in Musculoskeletal Disease. (2)

Simply put, that is how Prolotherapy works. It rebuilds damaged soft tissue.

How do you know if Prolotherapy will work for me? Assessment: Fair candidate for Prolotherapy

In this image, the patient has lost nearly all of her cartilage from outside to the middle of the knee. This is displayed by the arrow. Because of this loss of cartilage and because of her limited range of motion in that knee the patient was told that she was realistically, a fair candidate. Meaning we could anticipate fair (as opposed to good or excellent) results at the outcome. In this case, the outcome exceeded expectation (this is not always the case). The patient responded very well to treatment and had improved function and quality of life. She also had a significant reduction in knee pain.

What are we seeing in this image?

This is not the best candidate for Prolotherapy but a fair candidate. The arrow to the left demonstrates that this patient has lost nearly all of her cartilage at the medial side of her knee. Because of this cartilage loss and her limited range of motion revealed during her physical examination, this patient was rated a fair candidate for treatment success. Treatment outcomes were discussed with the patient, the patient decided to proceed. In this situation (which may not be typical of all situations) this patient responded very well to treatment and had significant improvement in her knee pain and quality of life.

Fair candidate for Prolotherapy knee treatments: In this image, the patient has lost nearly all of her cartilage from outside to middle of the knee. This is displayed by the arrow. Because of this loss of cartilage and because of her limited range of motion in that knee the patient was told that she was realistically, a fair candidate. Meaning we could anticipate fair (as opposed to good or excellent) results at outcome. In this case the outcome exceeded expectation (this is not always the case). The patient responded very well to treatment and had improved function and quality of life. She also had significant reduction in knee pain.

What are we seeing in this image? A very good candidate for Prolotherapy.

In this x-ray image, we can see that this patient is suffering from a mild loss of joint space. Her range of motion on physical examination was mildly limited patient’s range of motion but we still considered this patient a very good candidate for Prolotherapy injections.

In this x-ray image we can see that this patient is suffering from a mild loss of joint space. This limited the patients range of motion but we still considered a patient a very good candidate for Prolotherapy injections. 

The research:

So many times, a patient will come into our office and the first thing they will say is, “my doctor never heard of Prolotherapy“, then “he/she recommended against it.”

When we ask, “How could your doctor recommend against it if they never heard of it?,” the patient will often respond,  “My doctor says there is no research or they would have heard about it.”

We will now present the research that answers many questions about treatment success and realistic outcomes.

A May 2020 study in the Annals of Family Medicine (3) made this simple statement at the conclusion of the research findings:

“Intra-articular dextrose Prolotherapy injections reduced pain, improved function and quality of life in patients with knee osteoarthritis compared with blinded saline injections. The procedure is straightforward and safe; the adherence and satisfaction were high.”

In this study, the research team assessed their findings in 76 patients with knee osteoarthritis:

Three treatments in a 12 week period and positive outcomes at 1 year. Prolotherapy reduced pain and improved function and quality of life. Further, the researchers noted: “Our findings are also consistent with other studies that have tested an intra-articular dextrose Prolotherapy protocol for knee osteoarthritis.” Let’s look at these other studies.

Another study from May 2020 published in The Journal of Alternative and Complementary Medicine (4) made these observations:

In January 2019, David Rabago, MD, of the University of Wisconsin School of Medicine and Public Health, published research on Dextrose Prolotherapy for Symptomatic Knee Osteoarthritis in the Journal of Alternative and Complementary Medicine. (5)

Here are the learning points of that research:

The study concluded “(suggested) that Prolotherapy in this primary care clinic is feasible and acceptable.” In other words, it is beneficial to patients.

More of Dr. Rabago’s research is cited in this article as well as our own Caring Medical published findings.

Evidence that Prolotherapy injections may regrow cartilage in the knee

Led by researchers at the University of California at Los Angeles (UCLA) and the Department of Biological Sciences, at the University of Southern California (USC) a June 2021 paper in the medical journal Cartilage (6) offered these observations:

“Hypertonic dextrose injections (Prolotherapy) for osteoarthritis are reported to (be able to) reduce pain. Cartilage regeneration is hypothesized as a mechanism. This in vitro study identifies a Prolotherapy concentration that stimulates chondrogenic cells to increase metabolic activity and assesses whether this concentration affects collagen deposition and proliferation.”

What the researchers are doing is taking hypertonic dextrose (a concentrate simple sugar, the main ingredient in the Prolotherapy solution) to see if, in a lab setting, they can grow cartilage cells with it. This was their observation.

(Prolotherapy)  “solution appears to be associated with the increased metabolic activity of chondrocytes (reproduction of the cells that make cartilage), increased collagen deposition, and increased chondrocyte proliferation. These results support clinical Prolotherapy research suggesting that intra-articular Hypertonic dextrose joint injections reduce knee pain. Further study of Hypertonic dextrose injections and cellular processes is warranted.”

What are we seeing in this image?

In this image of a patient being prepped for receiving Prolotherapy injections into their knee, the dots on the skin represent those areas of the knee that should receive an injection. In this particular patient, there are 50 dots on their knee. Each dot would represent where each injection would be given. This is one comprehensive Prolotherapy treatment for the knee. This is the type of treatment recommended for knee osteoarthritis.

In this image of a patient being prepped for an receiving Prolotherapy injections into their knee, the dots on the skin represent those areas of the knee that should receive an injection. In this particular patient, there are 50 dots on their knee. Each dot would represent where each injection would be given. This is one comprehensive Prolotherapy treatment to the knee. 

Research: significant pain relief after Prolotherapy injections in patients suffering from knee osteoarthritis

In October 2017, a team of researchers from Shahid Beheshti University of Medical Sciences, Tehran, Iran published their findings in the Middle East Journal of Family Medicine (7) in which they found significant pain relief after Prolotherapy injections in patients suffering from knee osteoarthritis.

Here are the bullet points of the research:

Prolotherapy had a significant effect

The study was a single-blind clinical trial. (The patients did not know they were getting Prolotherapy).

According to the results, it can be concluded that the mechanism of the effect of Dextrose Prolotherapy is direct effects, osmotic (growth in the number of cells), and inflammatory growth. Dextrose injection with a concentration of less than 10% still directly promotes cell and tissue proliferation without inflammatory reaction and a high concentration of 10% results in an extracellular osmotic gradient at the injection site resulting in loss of intracellular and lyse cellular cells (a breakdown of damaged cells) and the beneficial invasion of growth factors and inflammatory cells that start the wound healing cascade in that particular area.

Research: Prolotherapy treatments for patients with knee osteoarthritis showed significant improvement in scores for pain, function, and range of motion

In February 2020, Lisa May Billesberger, MD a private practice physician in Canada teamed with Duke Anesthesiology, Duke University School of Medicine to offer a current assessment of injectable treatments for Knee Osteoarthritis. (16) Here are the summary points on Prolotherapy.

New Research comparing Prolotherapy to other treatments

A September 2020 study published in the International Journal of Rehabilitation Research (17) compared the effectiveness of four treatments in the management of knee osteoarthritis.


In an August 2019 study, researchers published data comparing Prolotherapy to other injection techniques. The data was published in the journal Advances in Rheumatology. (18)

This study examined previous research and compared the effect of intra-articular (inside the joint) and/or extra-articular (outside and around the joint) injections of hyper dextrose Prolotherapy vs :

This is what the researchers noted:

“In terms of pain reduction and function improvement, Prolotherapy with hypertonic dextrose was more effective than infiltrations with local anesthetics, as effective as infiltrations with hyaluronic acid, ozone or radiofrequency and less effective than PRP and erythropoietin, with a beneficial effect in the short, medium and long term. In addition, no side effects or serious adverse reactions were reported in patients treated with hypertonic dextrose.”

Prolotherapy and Platelet Rich Plasma

A May 2021 study in the Journal of Clinical Orthopaedics and Trauma (19) sought to explore the benefits of Prolotheray for knee osteoarthritis and offer a comparison to Platelet-Rich Plasma

In this paper, the researchers examined previously reported research on the effectiveness of Prolotherapy on knee osteoarthritis.

In total, the researchers found eleven articles (with 837 patients examined) that met their criteria for a fair evaluation. Of these 11 articles, two were found to be a low risk for bias. What does this mean? It generally means that when there is a high risk of bias, the “biased” researchers noted that a specific treatment was working and that when they published research on the “working treatment” they had a preconceived notion that their study would demonstrate statistically what they (the administering doctors) were observed clinically. In other words, the research would conclude that the treatment was working because clinically, it was. This is considered “bias.”

So what these researchers did was take two studies that were not biased or at low risk for bias and examine that. This was their suggested findings:

Conclusion: Prolotherapy in knee osteoarthritis confers potential benefits for pain but the studies are at high risk of bias. Based on two well-designed studies, dextrose Prolotherapy may be considered in knee osteoarthritis (strength of recommendation B – based on limited by good evidence)). This treatment is safe and may be considered in patients with limited alternative options (strength of recommendation C – based more on clinical observation than double-blinded or placebo drive study).

Prolotherapy in grade IV knee osteoarthritis

In research cited above, a 2016 study from a team of doctors at the Universities of Wisconsin, Kansas, Michigan, and Argentine researchers published combined research on the positive clinical and chondrogenic (cartilage growing) effects of Prolotherapy in participants with symptomatic grade IV knee osteoarthritis. (13)

Dextrose injection 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. This study assessed the biological and clinical effects of intra-articular hypertonic dextrose injections (Prolotherapy) 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.


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 the collection of robust intra-articular data.

In this video, Danielle R. Steilen-Matias, MMS, PA-C., of Caring Medical demonstrates how we treat a patient with a primary complaint of knee osteoarthritis.

Caring Medical Research – Prolotherapy for Knee Pain

In published research in the Journal of Prolotherapy, (20) Ross Hauser MD investigated the outcomes of patients receiving Prolotherapy treatment for unresolved, difficult to treat knee pain at a charity clinic in  Illinois.

Caring Medical documents Quality of Life changes after Prolotherapy treatment for knee osteoarthritis

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

Long-term results

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

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.

Patients reported:

Therefore, Prolotherapy appears to be a viable treatment option for people suffering from unresolved knee pain.

In this video Ross Hauser, MD demonstrates an ultrasound examination of a patient’s knee with complete loss of articular cartilage

Comprehensive and aggressive treatment can help prevent knee replacement

In the previously cited study above about female patients in the journal Therapeutic Advances in Musculoskeletal Disease, researchers also noted:

Knee osteoarthritis is a degenerative process that occurs over a long period of time. Patients do not wake up one day with significant knee damage. They have usually had a long medical history of knee pain treatments that have ultimately lead to a recommendation for a knee replacement.

Knee osteoarthritis is a degenerative process that occurs over a long period of time. Patients do not wake up one day with significant knee damage. They have usually had a long medical history of knee pain treatments that have ultimately led to a recommendation for a knee replacement.

Doctors writing in the Journal of Pain Research (21) have published research supporting what we have known here for decades. To most effectively treat knee osteoarthritis with Prolotherapy, Platelet Rich Plasma, or Stem Cells, you must treat the whole knee and not simply the cartilage degeneration.

In this study, doctors from the University of Tehran compared results in patients who received Prolotherapy with dextrose periarticular injections around the knee joint with patients who received Prolotherapy intra-articular injections. In other words, one group received injections around the knee joint, another group received injections directly into the knee joint.

Research case study – Prolotherapy as an alternative to knee surgery

A case report that was published in the medical journal Anesthesiology and Pain Medicine (22) discusses the clinical and radiological outcomes of Prolotherapy in a patient whose total knee prosthesis had been planned but surgery couldn’t be performed due to other existing medical conditions.

Six sessions of knee Prolotherapy protocol were applied to the patient, one session monthly.

Significant improvement was noted at WOMAC scale:

Knee function and mobility improvements

The researchers found periarticular Prolotherapy showed healing effects in many aspects of knee function that were better than with intra-articular Prolotherapy. This healing effect was observed particularly in active movements, including walking on flat surfaces and ascending and descending stairs.

Simply, Prolotherapy for knee osteoarthritis is not a single or few injections, it is many injections.

In more difficult cases we may introduce Platelet Rich Plasma and for cases where warranted Stem Cells and/or a combination of therapy. If we get to a situation where we decide to use stem cell therapy, we augment this treatment with Prolotherapy, PRP, and sometimes a combination treatment using bone marrow stem cells.


In our research and the independent research noted in this article, we have shown that Prolotherapy can help resolve chronic knee pain. In many people, the effects of Prolotherapy are often permanent, future treatments are rarely needed.

The goal of the treatment is to produce articular cartilage, ligament, meniscus, and joint capsular tissue that is able to withstand the forces a person puts on them and then to replenish the joint fluid sufficiently to cushion the joint effectively.

Can we help you?

We hope you found this article informative and it helped answer many of the questions you may have surrounding your knee issues.  If you would like to get more information specific to your challenges please email us: Get help and information from our Caring Medical staff

This is a picture of Ross Hauser, MD, Danielle Steilen-Matias, PA-C, Brian Hutcheson, DC. They treat people with non-surgical regenerative medicine injections.

Brian Hutcheson, DC | Ross Hauser, MD | Danielle Steilen-Matias, PA-C

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1 Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A systematic review of dextrose prolotherapy for chronic musculoskeletal pain. Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. 2016 Jan;9:CMAMD-S39160. [Google Scholar]
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This article was updated July 30, 2021


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