Prolotherapy knee osteoarthritis research: An option to knee surgery
Ross Hauser, MD., Danielle R. Steilen-Matias, MMS, PA-C.
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.
Discussion points of this article:
- The evidence for Prolotherapy Injections for knee osteoarthritis.
- Research on the benefits of Prolotherapy for knee osteoarthritis.
- Prolotherapy addresses whole knee instability.
- How does Prolotherapy work in your knees?
- How do you know if Prolotherapy will work for me? Assessment: Fair candidate for Prolotherapy.
- Who is a candidate for Prolotherapy?
- Evidence that Prolotherapy injections may regrow cartilage in the knee.
- Research: significant pain relief after Prolotherapy injections in patients suffering from knee osteoarthritis.
- Research: Prolotherapy treatments for patients with knee osteoarthritis showed significant improvement in scores for pain, function, and range of motion.
- New Research comparing Prolotherapy to other treatments.
- Prolotherapy and Platelet Rich Plasma.
- Prolotherapy in grade IV knee osteoarthritis.
- Quality of Life changes after Prolotherapy treatment for knee osteoarthritis.
- Treatment may help prevent knee replacement.
- Prolotherapy as an alternative to knee surgery.
- Knee function and mobility improvements after Prolotherapy.
The evidence for Prolotherapy Injections for knee osteoarthritis
A May 2022 study in the journal Orthopedic reviews (27) lead by doctors at Georgetown University School of Medicine, Louisiana State University School of Medicine, and Creighton University School of Medicine, “covers the background, efficacy, and advantages of prolotherapy in the management of osteoarthritis symptoms and then covers the existing evidence of the use of prolotherapy for this purpose.” In their investigation, the researchers found this: “Numerous clinical trials show significant improvement of osteoarthritic pain of the knee without any significant side effects reported following the use of prolotherapy. Although there is heterogeneity between studies with regard to study variables, the results consistently show significant improvement in radiographic outcomes, pain scores, and quality of life with prolotherapy treatment. Prolotherapy appears to be a safe and effective alternative to physical therapy, surgery, NSAIDs, steroids, and opiates when they fail to provide clinical relief.
A June 2022 study in the journal Clinical Rehabilitation (26) assessed the effectiveness, compliance, and safety of dextrose Prolotherapy for patients with knee osteoarthritis. A total of 14 previously published studies with outcomes of 978 patients were included in this meta-analysis.
- Compared with placebo injection and noninvasive control therapy, dextrose Prolotherapy had favorable effects on pain, global function, and quality of life during the overall follow-up.
- Dextrose Prolotherapy yielded greater reductions in pain score over each follow-up duration than did the placebo.
- Compared with other invasive therapies, dextrose Prolotherapy generally achieved comparable effects on pain and functional outcomes for each follow-up duration.
- Subgroup results indicated that combined intra-articular and extra-articular injection techniques may have stronger effects on pain than a single intra-articular technique. (This would be the technique, as we use, for injections into and around the knee joint).
Six years earlier: in a study from July 2016, our Caring Medical team published findings (1) that summarized the benefits of Prolotherapy.
- Prolotherapy is a “new” old treatment that has been utilized in clinical practices for over 80 years. Standardized and reviewed in clinical application by Dr. George Hackett in the 1950s, Prolotherapy has been shown to be an effective treatment in patients who suffer from joint instability due to ligament damage and overuse and related musculoskeletal and osteoarthritis.
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.
- Prolotherapy is a nonsurgical regenerative injection technique that introduces small amounts of an irritant solution to the site of painful and degenerated tendon insertions (entheses), joints, ligaments, and adjacent joint spaces during several treatment sessions to promote the growth of normal cells and tissues.
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 28+ 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:
- 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).
How does Prolotherapy work on 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 on 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)
- “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 simpler terms, Prolotherapy injections cause a controlled inflammation to occur by mimicking an injury response. It tricks the cells into thinking a new wound has occurred. This stresses the cells to cause and calls 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 chondrocytes.
- osteocytes – bone makers
- In simpler terms, Prolotherapy injections cause a controlled inflammation to occur by mimicking an injury response. It tricks the cells into thinking a new wound has occurred. This stresses the cells to cause and calls for the release of growth and repair factors to initiate healing. These factors are found in the initial inflammatory response and include:
- “These cells then excrete extracellular matrix, which enhances the stability of the joints by tightening and strengthening the ligaments, tendons, and joint stabilizing structures.”
- We have a fascinating article The Extracellular matrix (ECM) | How comprehensive Prolotherapy repairs cartilage on this website if you would like to research that more.
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 the 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 realistic, 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.
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.
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.
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:
- Patients were tested for pain and function at baseline.
- The patients were then treated with Prolotherapy or saline at 4, 8, and then 16 weeks.
- All outcomes were evaluated at baseline and at 16, 26, and 52 weeks.
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:
- The study included 66 patients aged 40-70 years with chronic knee pain that was not responding to conservative therapy and diagnosed with grade II or III knee osteoarthritis.
- The patients were assigned to the dextrose Prolotherapy group (22 patients), saline group (22 patients), or control group (22 patients).
- The intra- and extra-articular dextrose Prolotherapy and saline injections were administered at 0, 3, and 6 weeks. The patients were blinded to their injection group status.
- A home-based exercise program was prescribed for all patients in all three groups.
- Following pain and functional scoring outcomes, the researchers put their findings together and concluded: “These findings suggest that dextrose Prolotherapy is effective at reducing pain and improving the functional status and quality of life in patients with knee osteoarthritis.
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:
- Patients received up to six Prolotherapy sessions.
- The primary data desired for analysis: 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 the ability to climb stairs.
- Of the patients who participated in the study: “Satisfaction was high.
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 concentrated 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.”
A January 2022 paper (7) from leading university researchers in Taiwan investigated the inflammation-related protein-expression profile characterizing the efficacy of the hypertonic dextrose Prolotherapy in knee osteoarthritis as prognostic markers. More simply, was the Prolotherapy treatment causing healing inflammation to occur, and what was the proof it was.
The researchers recruited patients over the age of 65 who had clearly defined and diagnosed knee osteoarthritis. To test the effectiveness of Prolotherapy in this group the patients were assessed using the Western Ontario McMaster University Osteoarthritis (WOMAC) disability, function and pain index, knee X-ray evaluation, and knee joint synovial fluid analysis before and after hypertonic dextrose Prolotherapy. The expressions of inflammation-related factors were also measured.
Results: The WOMAC Index and minimum joint space width prior to receiving the intra-articular injection and at 2-week intervals were compared.
- 12 patients received clinical evaluation of 12 knee joints (one knee per patient) and knee synovial fluid samples were analyzed. In this study, after receiving hypertonic dextrose Prolotherapy, the osteoarthritis patients clearly demonstrated a significant improvement in WOMAC index and an increasing tendency in the medial minimum joint space width after the intervention. Additionally, the researchers observed a significantly associated tendency between the high-glucose treatment of knee osteoarthritis and the upregulation of signaling enzymes and proteins that facilitate cartilage repair and regrowth.
Conclusion: “These findings provide knee osteoarthritis patients receiving hypertonic dextrose Prolotherapy, which accompanies the improvement of knee pain, stiffness, and function and increasing tendency in the medial minimum joint space width (more joint space).
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.
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 (8) 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 the visual analog 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 were referred to Taleghani Hospital in Iran.
- Randomly divided into two groups: 15% dextrose injection and injection of hypertonic dextrose 25%.
- the group with 25% Dextrose injections experienced more pain relief than the 15% group.
- However, even with 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
A paper from June 2022 in the journal Clinical Rehabilitation (24) “assessed the effectiveness, compliance, and safety of dextrose Prolotherapy for patients with knee osteoarthritis.” To make this assessment, the researchers gathered data from 14 previously published studies with a combined 978 patients examined. The researchers found: “Compared with placebo injection and noninvasive control therapy, dextrose Prolotherapy had favorable effects on pain, global function, and quality of life during the overall follow-up. Dextrose Prolotherapy yielded greater reductions in pain score over each follow-up duration than did the placebo. Compared with other invasive therapies, dextrose Prolotherapy generally achieved comparable effects on pain and functional outcomes for each follow-up duration.”
In research from June 2017, doctors publishing in the British Medical Bulletin (9) 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 and the oldest 70) and gave them three monthly Prolotherapy injections.
- At the end of week 24 of the study, the knee range of motion increased, and pain severity in rest and activity decreased. Improvements in 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. (10)
Doctors from the University of Wisconsin continued their research into Prolotherapy. They found Prolotherapy resulted in the 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. (11)
- This followed up on a 2013 study that appeared in the Archives of Physical Medicine and Rehabilitation (12) and suggested that “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.”
In Caring Medical research appearing in the Journal of Prolotherapy, Dr. Hauser was able to document articular cartilage regeneration. (13)
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 from 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. (14) More on this study appears below.
In 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 on 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 for up to 1 year. (15)
In another study led by the 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. (16)
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. (17) Here are the summary points on Prolotherapy.
- Prolotherapy is a relatively simple and inexpensive treatment with a high safety profile, is something that could easily be performed in the primary care setting, and is thus worth consideration.
- The exact mechanism of Prolotherapy is not well understood, but it is thought to induce a pro-inflammatory response that results in the release of growth factors and cytokines, ultimately resulting in a regenerative process within the affected joint.
- Injection of the hyperosmolar dextrose solution might also hyperpolarize nociceptive pain fibers by forcing open potassium channels, resulting in reduced pain perception.
- In sum, Prolotherapy likely provides at least some benefit, although the quality of available data makes this statement hard to prove and it certainly does not cause harm.
Recent research comparing Prolotherapy to other treatments
A September 2020 study published in the International Journal of Rehabilitation Research (18) compared the effectiveness of four treatments in the management of knee osteoarthritis.
- In total, 120 patients with knee osteoarthritis, all over the age of 50 years of age were randomly allocated to four groups.
- The test results were based on pain and functional scoring systems.
- Exercise recommendations were prescribed daily for all participants throughout the study.
- For physical therapy (group 1), participants received superficial heat, transcutaneous electrical nerve stimulation, and pulsed ultrasound.
- Botox: Researchers administered a single intra-articular injection of botulinum neurotoxin type A (group 2)
- Hyaluronic acid: Researchers administered three injections of hyaluronic acid (group 3)
- Prolotherapy: Researchers administered 20% dextrose (group 4) to patients in the corresponding groups.
- There was a statistically significant difference (effectiveness) between the groups in pain and function.
- Pairwise between- and within-group comparisons showed that botulinum neurotoxin and dextrose Prolotherapy were the most effective, and hyaluronic acid was the least efficient treatment for controlling pain and recovering function in patients.
- Intra-articular injection of botulinum toxin type A or dextrose Prolotherapy is an effective first-line treatment. In the next place stands physical therapy particularly if the patient is not willing to continue regular exercise programs. Our study was not very supportive of intra-articular injection of hyaluronic acid as an effective treatment 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. (19)
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 :
- hyaluronic acid,
- PRP or Platelet Rich Plasma
- Erythropoietin. (A hormone said to activate bone marrow cells)
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.”
In September 2022, a paper in the American journal of physical medicine & rehabilitation (29) compared Prolotherapy to hyaluronic acid injections in knee osteoarthritis patients. Here are the summary findings of this research:
“Intra-articular injections with hyaluronic acid are recommended in the treatment of knee osteoarthritis; however, hypertonic dextrose prolotherapy has been reported as effective and safe. The aim (of this study) was to evaluate the effectiveness of hypertonic dextrose prolotherapy for pain reduction and improvement of function in individuals with knee osteoarthritis in comparison with hyaluronic acid by meta-analysis (comparing data from previous research).”
The researchers used six previously published studies with the data of 395 patients.
The researchers reported: “Initially there was no statistically significant differences found between Prolotherapy and hyaluronic acid treatments in pain control in the short-term; however, in the subanalysis that included only the studies that used intra-articular injections, an effect was found in favor of the Prolotherapy groups. Also, an effect was found in favor of the prolotherapy group in the improvement in function. No major adverse reactions or side effects were reported in any of the studies. Hypertonic dextrose prolotherapy seems to be an effective intervention to decrease pain and improve function in knee osteoarthritis, with efficacy similar to intra-articular injections with hyaluronic acid in the short-term follow-up. Nonetheless, better-quality clinical trials are necessary.”
Prolotherapy and Platelet-Rich Plasma
A May 2021 study in the Journal of Clinical Orthopaedics and Trauma (20) sought to explore the benefits of Prolotherapy 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. These were their suggested findings:
- Prolotherapy was no different from Platelet-Rich Plasma on the pain subscale at the 6-month time point. (Both Prolotherapy and PRP were effective treatments).
- Prolotherapy was inferior to Platelet-Rich Plasma at 6 months on the stiffness subscale.
- Prolotherapy was found to be safe with no major adverse effects.
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 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).
A September 2022 paper (28) compared the effectiveness of PRP, Prolotherapy and exercise therapy in knee osteoarthritis patients. In this study:
- A total of 108 patients with a diagnosis of knee osteoarthritis were divided into three groups of treatment:
- Prolotherapy group – 35 patients.
- PRP group – 35 patients.
- Exercise group – 38 patients.
- Visual Analogue Scale (Pain scale from 0 – 10) and The Western Ontario McMaster University Osteoarthritis Index (to assess pain, stiffness and function) were used as outcome measures at baseline, 1 month, and 3 months.
- All three groups showed similarities in demographics and baseline assessments of pain intensity, disability and function.
- At the first and third months, all groups showed a substantial improvement in the Visual Analogue Scale reduced pain with activity and reduced pain with resting and the pain, stiffness and function scores after treatments.
- When the three treatments were compared the PRP and Prolotherapy groups improved significantly in the first and third months compared to the exercise group.
Conclusion: Pain and disability were significantly improved with Prolotherapy and PRP compared with exercise therapy. Although PRP is more effective than Prolotherapy in the first month after treatment, Prolotherapy may be preferred due to its low cost, long-term efficacy, and low complication rates due to the periarticular application.
Prolotherapy in grade IV knee osteoarthritis
In the 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. (14)
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.
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 a median age of 71 years, and an 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 by 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 the collection of robust intra-articular data.
- This suggested a disease-modifying effect or a “reversal” of the disease progression.
Generally speaking however, patients will no range of motion, locked up or frozen knees will not benefit from Prolotherapy injections
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.
- The person in this video is being treated for knee osteoarthritis as the primary complaint. The treatment takes a few minutes. The person in this video is not sedated and tolerates the treatment very well. For some patients, we do provide IV or oral medications to lessen treatment anxiety and pain.
- The first injection is given to the knee joint. The Prolotherapy solution is given here to stimulate repair of the knee cartilage, meniscal tissue, and the ACL as well.
- The injections continue over the medial joint line making sure that all the tendons and ligaments such as the medial collateral ligament are treated.
- This patient-reported the greatest amount of pain along the medial joint line. This is why a greater concentration of injections is given here.
- The injections continue on the lateral side of the knee, treating the lateral joint line and all the tendon and ligament attachments there such as the LCL or lateral collateral ligament.
Caring Medical Research – Prolotherapy for Knee Pain
In published research in the Journal of Prolotherapy, (21) 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, 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 who were 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%.
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.
- less pain,
- depressed and anxious thoughts,
- medication and other pain therapy usage,
- improved walking ability,
- improved range of motion,
- improved ability to work and activities of daily living.
Therefore, Prolotherapy appears to be a viable treatment option for people suffering from unresolved knee pain.
Prolotherapy injections upregulate healing growth factors
An April 2022 study (25) published by Taiwanese researchers in the Journal of the Chinese Medical Association investigated the use of hypertonic dextrose prolotherapy injections to not only reduce knee pain and increase knee function but to also measure if any drop in inflammatory markers occurred and to see if any joint space increase occurred. To do this patients over the age of 65 were recruited and tested for knee function, disability and pain. The patients also had knee x-rays and knee joint synovial fluid analysis before and after dextrose prolotherapy treatment.
Results: Pain and function scores and minimum joint space width before receiving the intra-articular injection and at 2-week intervals were compared. Twelve patients who received osteoarthritis intervention were enrolled and finally a clinical evaluation of 12 knee joints and knee synovial fluid samples were analyzed. In this study, after receiving hypertonic dextrose prolotherapy, the osteoarthritis patients clearly demonstrated a significant improvement in pain and function scores and an increasing tendency in the medial minimum joint space width after the intervention. Meanwhile, we observed a significantly associated tendency between hypertonic dextrose treatment of knee OA and the upregulation of healing inflammatory factors.
In this video Ross Hauser, MD demonstrates an ultrasound examination of a patient’s knee with complete loss of articular cartilage
- At 1:14 the patient’s knee instability caused a COMPLETE LOSS OF ARTICULAR CARTILAGE
- In this patient, we would recommend Prolotherapy to the ligaments and stem cell treatment into the joint. Prolotherapy to address the knee instability and stem cell treatments to address the cartilage issue.
- We rarely offer stem cell treatments. In this case, the complete loss of cartilage in the knee calls for it.
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 enthesopathy 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.
Doctors writing in the Journal of Pain Research (22) 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.
Research case study – Prolotherapy as an alternative to knee surgery
A case report that was published in the medical journal Anesthesiology and Pain Medicine (23) 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.
- The patient was a 72-year-old woman with severe pain in 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 the radiological evaluation, the patient was diagnosed with grade IV osteoarthritis due to significant osteophyte presence and complete joint space narrowing.
Six sessions of knee Prolotherapy protocol were 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).
- The 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 levels.
Knee function and mobility improvements after Prolotherapy
The researchers found periarticular Prolotherapy showed healing effects in many aspects of knee function that were better than 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.
- For more information on stem cells, please read: Stem Cell Injections for Knee Osteoarthritis and Stem Cell Therapy for Cartilage Regeneration
- For more information on PRP, please read: Platelet Rich Plasma Therapy for Knee Osteoarthritis
- For more information on the different types of injections for knee pain. Please see our article: What are the different types of knee injections for bone on bone knees
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 replenish the joint fluid sufficiently to cushion the joint effectively.
The primary cause of knee pain is knee joint instability. This can be due to a number of ligaments and tendons attachments becoming torn or degenerated, as well as damaged or removed cartilage and meniscal tissue. Prolotherapy causes a stabilization of the knee after these ligaments are treated.
Can we help you?
Arthritis in the knee is one of the most common complaints that patients present to us at Caring Medical. More often than not, they have experienced years of traditional care for knee pain, from regularly taking NSAIDs to cortisone injections, and even surgery to “clean out” the joint as they tell us. By the time they arrive in our office, the possibility of a future knee replacement has already been discussed with their local orthopedic surgeon as the progression of arthritis appears unstoppable. No doubt, continuing with most of the traditional pain management methods, a person will end up with a knee replacement. Preferring to not take that route, Prolotherapy, and often Stem Cell Prolotherapy, can be an excellent alternative to surgery because it addresses the root cause of what started the arthritic progression in addition to the ongoing damage. The underlying cause of the arthritis is actually structural damage that leads to degenerative changes in the knee. Meniscus tears or injuries to the supporting knee ligamentous system will eventually lead to degenerative arthritis. Determine the underlying cause of the weakness and instability; stop the degenerative process with regenerative injection treatments such as Prolotherapy and/or Cellular Prolotherapy; halt the progression of arthritis.
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
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This article was updated July 14, 2022