Caring Medical - Where the world comes for ProlotherapyThe evidence for Prolotherapy Injections for knee osteoarthritis

Ross Hauser, MD  | Caring Medical Regenerative Medicine Clinics, Fort Myers, Florida
Danielle R. Steilen-Matias, MMS, PA-C
 | Caring Medical Regenerative Medicine Clinics, Oak Park, Illinois
Katherine L. Worsnick, MPAS, PA-C  | Caring Medical Regenerative Medicine Clinics, Fort Myers, Florida
David Woznica, MD | Caring Medical Regenerative Medicine Clinics, Oak Park, Illinois

The evidence for Prolotherapy Injections for knee osteoarthritis

In this article, we will update new information 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.

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

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

Knee Osteoarthritis is:

  • a slow, progressive, degenerative disease that destroys articular cartilage,
  • causes destructive changes to the knee’s lubricating and protective synovial membrane,
  • damages and causes the death of subchondral bone,
  • causes weakness, damage, and laxity in the knee’s supporting ligaments and tendons,
  • destroys and causes the death of the meniscus,
  • and in general causes destructive hypertrophy (enlargement or swelling) of the knee joint capsule.

Comprehensive Prolotherapy can address all these issues simultaneously and spontaneously (it starts working immediately). Let’s get to the research.

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 is presented here and intermingled with out own 26+ years of empirical observation of patient benefit.

How does Prolotherapy work in your knees?

In 2016, our Caring Medical research team published our “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 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)

  • “Prolotherapy has been reported as a useful method in the treatment of chronic musculoskeletal and joint diseases. It is proposed that prolotherapy causes mild inflammation and cell stress in the weakened ligament or tendon area, releases cytokines and growth factors, and induces a new healing cascade in that area, which leads to activation of fibroblasts, generation of collagen precursors, and strengthening of the connective tissue.”
    • In more simpler terms Prolotherapy injections cause a controlled inflammation to occur bymimicking an injury response. It tricks the cells into thinking a new wound has occurred. This stresses the cells to cause and call for the release of growth and repair factors to initiate healing. These factors are found in the initial inflammatory response and include:
      • fibroblasts – a collagen and cartilage builder
      • chondrocytes – A chondrocyte is a cell that makes cartilage. In the human body, the chondrocyte is the only cell type in cartilage. Your entire cartilage is a wall of chondrocystes.
      • osteocytes – bone makers
  • “These cells then excrete extracellular matrix, which enhances the stability of the joints by tightening and strengthening the ligaments, tendons, and joint stabilizing structures.”

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

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.”

  • Then we ask the patient, “Then what is it that brought you in for a consultation?
  • The patient will respond, “A friend had Prolotherapy, they said it helped them a lot. They told me I should look into it.”
  • There is a lot of research on Prolotherapy injections for knee osteoarthritis, almost 70 years worth of research.

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

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.(3)

Here are the learning points of that research:

  • Patients received up to six prolotherapy sessions.
  • Primary question the researchers wanted to answer: Patient satisfaction with three or more prolotherapy sessions.
  • Secondary: Scoring assessment for improvement in function ability to get out of a chair, increase in walking ability, increase in ability to climb stairs.
  • Of the patients who participated in the study: “Satisfaction was high.

The study conclusion “(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.

knee osteoarthritis

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 (4) 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 purpose of this study was to investigate the effect of dextrose injection on pain control associated with knee osteoarthritis.
  • The findings showed that injection of 15% and 25% of dextrose Prolotherapy had a significant effect on the visual (scoring scales) of pain and function of patients so that during treatment, (scoring scales) scales showed improvement in treatment in these patients.
  • Also, other findings showed that injection of 25% dextrose Prolotherapy compared to 15% had a significant effect on visual scale of pain and function of patients.

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

  • 80 knee osteoarthritis patients referred to Taleghani Hospital in Iran.
  • Randomly divided into two groups: 15% dextrose injection and injection of hypertonic dextrose 25%.
  • the group of 25% Dextrose injection experienced more pain relief than the 15% group.
  • However, even a 10% solution, significant results could be achieved.

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 research from June 2017, doctors publishing in the British Medical Bulletin (5) reviewed and evaluated Prolotherapy findings and determined Prolotherapy treatments for patients with knee osteoarthritis showed significant improvement in scores for pain, function, and range of motion, both in the short term and long term. Patient satisfaction was also high in these patients (82%).
  • Citing the previous research from Dr. Fariba Eslamian and Dr. Bahman Amouzandeh, they found that  Prolotherapy treatments in female patients with knee osteoarthritis resulted in significant improvement in pain, function, and range-of-motion scores.(2)
    • In this study they took 24 female patients with an average age of 58 (the youngest being 46 the oldest 70) and gave them three monthly Prolotherapy injections.
    • At the end of week 24 of the study, knee range of motion increased, pain severity in rest and activity decreased. Improvements of all parameters were considerable until week 8, and were maintained throughout the study period.
  • In June 2017 research, doctors from the University of Wisconsin School of Medicine and Public Health write: Systematic review, including meta-analysis, and randomized controlled trials suggest that Prolotherapy may be associated with symptom improvement in mild to moderate symptomatic knee osteoarthritis and Prolotherapy was effective in overuse tendinopathy.(6)
  • Doctors from the University of Wisconsin continued on their research into Prolotherapy. They found Prolotherapy resulted in safe, significant, progressive improvement of knee pain, function and stiffness scores among most participants and continued as such at follow up an average of 2.5 years after initial treatment, this study from 2015.(7)
    • This followed up on a 2013 study which appeared in the Archives of physical medicine and rehabilitation and suggested “Prolotherapy resulted in safe, substantial improvement in knee osteoarthritis-specific Quality of Life compared with control over 52 weeks. Among prolotherapy participants, but not controls, magnetic resonance imaging-assessed intra-articular cartilage volume change (intra-articular cartilage volume stability) predicted pain severity score change, suggesting that prolotherapy may have a pain-specific disease-modifying effect.”(8)
  • In Caring Medical research appearing in the Journal of Prolotherapy,  Dr. Hauser was able to document articular cartilage regeneration.(9)
  • In April 2016, A multinational team representing university researchers in Argentina and Dr. Dean Reeves from the University of Kansas Medical Center, Dr. J Johnson Michigan State University and Dr Rabago from the University of Wisconsin, School of Medicine and Public Health researchers confirmed that Prolotherapy could regrow articular cartilage in the knee in a study of patients with an average age of 71 seventy-one.(10More on this study appears below.
  • A study, published in the journal Scientific reports doctors in Hong Kong found that three to five sessions of Prolotherapy knee injections have a statistically significant and clinically relevant effect in the improvement of WOMAC composite score, (a scoring system of pain, function, and stiffness) at 12 to 16 weeks compared to formal at-home exercise. The benefits of the treatment were sustained up to 1 year.(11)
  • In another study led by University of Wisconsin School of Medicine and Public Health researchers, patients reported substantially improved knee-specific effects, resulting in improved quality of life and activities of daily living.(12)

New Research comparing Prolotherapy to other treatments

In an August 2019 study, researchers published data comparing Prolotherapy to other injection techniques. The data was published in the journal Advances in rheumatology. (13)

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 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 in grade IV knee osteoarthritis

In 2016 the Universities of Wisconsin, Kansas, and Michigan team with doctors from Argentina is publishing combined research on the positive clinical and chondrogenic (cartilage growing) effects of Prolotherapy in participants with symptomatic grade IV knee osteoarthritis.(10)

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 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.

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

Results

  • Six participants (1 female and 5 male) with median age of 71 years, and average pain duration of 9-years.
  • 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 the 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.

  • This suggested a disease-modifying effect or a “reversal” of the disease progression.

Caring Medical Research – Prolotherapy for Knee Pain

In published research in the Journal of Prolotherapy, (14) 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.

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:

  • 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.

Patients reported:

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

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:

  • Ignoring the patient’s other pain sources including joint-surrounding tendons and ligaments could be another potential cause of treatment failure; (in the study) we did not treat enthesopathies or the ligament fibro-osseous junctions with extra-articular dextrose injections around these elements in our study.
  • So, it appears that ligaments or other structures need to be treated to get the full benefit from prolotherapy.

Knee Regeneration

Doctors writing in the Journal of Pain Research (15) 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.

  • Both peri- and intra-articular prolotherapy patients showed reduced pain and disability of their knee osteoarthritis after 5 months of follow-up.
  • Interestingly, periarticular prolotherapy had better effects on pain scores and disability scores in some respects.
    • Periarticular Prolotherapy injections showed superior effects on healing of knee disability and pain score compared with intra-articular injections.
    • Pain score was significantly lower at 1-, 2-, 3-, 4-, and 5-month visits in the periarticular group compared with the intra-articular group.
    • Periarticular injections have been suggested in some recent reports for analgesic effect after total knee replacement
    • Periarticular injections can significantly reduce the requirements for patient-controlled analgesia and can improve patient satisfaction following total knee replacement.
  • Periarticular injection showed adjuvant effects to intra-articular prolotherapy.

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.

If you have questions and would like to discuss your knee pain issues with our staff you get get help and information from our Caring Medical staff.

Prolotherapy Specialists

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]
2. 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. [Google Scholar]
3 Rabago D, Kansariwala I, Marshall D, Nourani B, Stiffler-Joachim M, Heiderscheit B. Dextrose Prolotherapy for Symptomatic Knee Osteoarthritis: Feasibility, Acceptability, and Patient-Oriented Outcomes in a Pilot-Level Quality Improvement Project. The Journal of Alternative and Complementary Medicine. 2019 Jan 28. [Google Scholar]
4 Ghasemi M, Behnaz F, Sajjadi MM, Zandi R, Hashemi M. The effect of Hypertonic Dextrose injection on the control of pain associated with knee osteoarthritis. Middle East Journal of Family Medicine. 7(10):193. [Google Scholar]
5 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. [Google Scholar]
Rabago D, Nourani B. Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review. 2017 Jun;19(6):34. doi: 10.1007/s11926-017-0659-3.  [Google Scholar]
7 Rabago D, Mundt M, Zgierska A, Grettie J. Hypertonic dextrose injection (prolotherapy) for knee osteoarthritis: Long term outcomes. Complementary therapies in medicine. 2015 Jun 1;23(3):388-95. [Google Scholar]
8 Rabago D, Kijowski R, Woods M, Patterson JJ, Mundt M, Zgierska A, Grettie J, Lyftogt J, Fortney L. Association between disease-specific quality of life and magnetic resonance imaging outcomes in a clinical trial of prolotherapy for knee osteoarthritis. Archives of physical medicine and rehabilitation. 2013 Nov 30;94(11):2075-82.  [Google Scholar]
9 Hauser R. The regeneration of articular cartilage with prolotherapy. Journal of Prolotherapy. 2009;1(1):39-44.  [Google Scholar]
10 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 Apr 4. pii:S1934-1482(16)30054-5.  [Google Scholar]
11 Sit RW, Chung VCh, 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. Sci Rep. 2016 May 5;6:25247  [Google Scholar]
12 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. Journal of alternative and complementary medicine (New York, NY). 2016 Dec;22(12):983.  [Google Scholar]
13 Arias-Vázquez PI, Tovilla-Zárate CA, Legorreta-Ramírez BG, Fonz WB, Magaña-Ricardez D, González-Castro TB, Juárez-Rojop IE, López-Narváez ML. Prolotherapy for knee osteoarthritis using hypertonic dextrose vs other interventional treatments: systematic review of clinical trials. Advances in Rheumatology. 2019 Dec;59(1):1-9. [Google Scholar]
14 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]
15 Rezasoltani Z, Taheri M, Mofrad MK, Mohajerani SA. Periarticular dextrose prolotherapy instead of intra-articular injection for pain and functional improvement in knee osteoarthritis. Journal of Pain Research. 2017;10:1179-1187.  [Google Scholar]

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