Prolotherapy for Knee Pain
Thinking Outside of the Box:
Managing Knee Pain with Prolotherapy and Regenerative Treatment
I have been practicing pain management for longer than I care to admit. In my years of practice, I have seen patients with post-op pain, severe pain–both before and after procedures–patients with knee pain who do not want surgery, others who want to delay surgery as wells as those who are not surgery candidates for medical reasons. I have also seen many patients who have severe chronic pain.
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If you haven’t benefited from physical therapy, pain medicine, or steroid injections– genicular nerve blocks are often the treatment offered. Until I discovered prolotherapy, this is what I recommended. But I encourage you to think outside of the box and try a different treatment path. One that may help you to prevent (or delay) surgery, manage your pain until you have surgery or cope with persistent post-operative pain.
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Don’t get me wrong, surgery is often effective and necessary. Knee replacement surgery is in the vast majority of cases very effective and patients often say that they wish they had done it sooner. Severe injuries and instability need to be treated with surgery. Certain types of meniscal injuries benefit from early surgical intervention.
Prolotherapy and regenerative treatment such as PRP are another option for treatment, they are not a replacement for surgery if surgery is needed. In my opinion, if regenerative treatment was used earlier in joint degeneration and dysfunction as a form of joint maintenance it might be possible to both maintain better function and quality of life as well as even avoid surgery altogether.
First, Understand Knee Anatomy
The knee is a relatively simple but important joint. The knee is a hinge joint and its primary action is flexion (bending) and extension (straightening). There is a small amount of rotation around the knee. Flexion and extension is the main function of the knee. It can be the source of a great deal of pain as well as a loss of function and mobility.
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Bones: The knee is made up of the femur, tibia and patella. The patella is a floating bone that provides a lever to the joint to improve the strength of movement.
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Cartilage: Smooth tissue surrounding the femur and the top of the tibia allowing for smooth movement of the joint.
Meniscus: Two menisci or C-shaped cartilages provide shock absorption and cradle the femur in the depression that is created by these structures to stabilize the joint.
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Cruciate Ligaments: The anterior and posterior cruciate ligaments prevent anterior and posterior movement of the joint and provide flexibility to the joint.
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Coronary Ligaments: Provide structural support to the bottom of the knee joint near the tibia and fibula.
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Medial and Lateral Collateral Ligaments: Provide structural integrity to the inside and outside of the knee preventing excessive lateral movement.
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Knee Joint: Fluid filled space.
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Knee Capsule: Fibrous structure providing support to the knee joint.
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Nerve Supply: Nerves from the femoral and sciatic nerve and the tibial nerve supply innervate this joint. Superficial nerves from the saphenous nerve and fibular nerve and genicular nerves innervate the knee.
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Muscular and Tendon Support: The muscle and tendons of the rectus femoris, vastus lateralis and medialis, popliteus, gastrocnemius and hamstrings provide muscular support.
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Retinaculum: A band of tissue around the knee that acts to stabilize and control movement of the kneecap.
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Arteries and Veins: The knee receives arterial and venous supply from the popliteal artery and veins, genicular artery, femoral vein and tibial artery.
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Bursae: Fluid filled sacks that provide a cushion to the moving parts of the knee. There are several bursae in the knee.
How Joints Function
Joints are preserved and maintained with the proper functioning of all of the anatomical elements of the knee including the bones, muscles, tendons, ligaments, nerves, arteries and veins. Function is maintained and preserved with good nutrition, exercise and weight bearing .
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The act of walking and weight-bearing increases pressure and weight on the joint. This provides feedback to the knee bones, In response they increase their production of bone to adapt to forces in the environment. Nutrition to the meniscus occurs from blood vessels but also occurs from synovial fluid (fluid in the knee joint) through intermittent loading and unloading.
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Muscles, tendons and ligaments provide support to the joint and allow for movement. Arteries and veins bring nutrients and carry away waste products to and from the knee. Nerves provide sensation, sense pain and provide feedback to the body, while bursa and fat provide cushioning for the tendons of the joint.
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Injuries to the tendons and ligaments that occur over time alter joint anatomy and function as do suboptimal nerve function and vasculature.
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By the time surgery is usually considered these elements have undergone significant degeneration, causing pain, dysfunction, sometimes deformity of the joint causing a bow-legged or knock-kneed appearance to the joint and “bone on bone” arthritis. There may be crunching, creaking, loss of cartilage and pain with movement.
Understanding Knee Pain and Joint Dysfunction
Its Not Just Bones
All structures in the joint have the ability to cause pain and disability. Muscles, nerves, bone, tendon, ligaments and even vascular abnormalities can cause pain. Tendons and ligaments are prone to injury and stress in the knee and often undergo degeneration before any significant bony changes develop. It is often mistakenly thought that only bones cause pain. In fact, many of the structures in the knee can cause pain.
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Ligaments (which connect bony structures) have a significant amount of nerve innervation and respond well to treatment with prolotherapy. Most conventional injections do not adequately address tendinous dysfunction and pain. Steroids are not injected into tendons due to the destructive nature of the drug to ligaments.
Tendons (the attachment of muscle to bone) have nerve innervation provided by the tissue that surrounds the tendon itself.
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Menisci are two C-shaped pieces of cartilage that are located on the tibia. They provide shock absorption and stability to the joint as well as provide lubrication to the joint. Tears to the meniscus can be painful and cause a sensation of clicking or locking in the joint.
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Nerve supply to the knee is complex. The saphenous, anterior division of obturator, and common fibular nerves provide supply to the knee. Genicular nerves provide sensory innervation. Nerve dysfunction can also be addressed with neuro-prolotherapy or perineural injection therapy. Many interventional pain specialists treat nerve pain with genicular nerve blocks or radio frequency ablation with varying success.
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Prolotherapy addresses tendinous and ligamentous dysfunction and can provide stability to the joint and alleviate pain. In my opinion, this treatment addresses this important factor in joint injury and dysfunction. It is considered a regenerative treatment that provides pain relief.
Prolotherapy is suitable for chronic back pain resulting from degenerative disc disease, or vertebral instability, promoting healing and enhancing spinal function. Nonspecific low back pain with evidence rating B. Prolotherapy may be helpful in reducing pain and instability in SI joint dysfuction. Evidence rating B.
Common Knee Injuries
Osteoarthritis
Joint function is not only made of bones. “Bone on bone” arthritis is ultimately caused by failure of the structures surrounding the joint including tendons and ligaments
Meniscal Tears
The knee meniscus can be injured with rapid turns and movement in active people. In addition, progressive degeneration and other stressors can cause injuries and tears to the meniscus. This results in pain with quick movements and turning and a clicking sensation in the knee. Certain types of meniscal tears are best repaired surgically. Younger patients with acute injuries should be evaluated by a surgeon to see if surgical repair is indicated. Menisci can also degenerate over time though “wear and tear.”
Anterior and Posterior Cruciate Ligament Injuries
Forces from the front and back of the knees can cause injuries to the anterior and posterior cruciate ligaments.
Patellofemoral Syndrome
Patellofemoral Syndrome results in pain in the front of the knee. It is also known as “runner’s knee” and is most common in people who run or play sports. It can be caused by muscle imbalances, weakness or trauma. This usually affects women and young adults.
Chondromalacia Patella
Chondromalacia Patella occurs when there is repeated stress to the knee joint. Imbalances in the musculature of the knee can cause weakening and destruction of the cartilage of the knee joints resulting in pain and discomfort. There may be grinding in the knee cap.
Iliotibial Band syndrome
The Iliotibial Band is located between the hip and the knee. Injury may result in pain outside of the knee that may spread up to the hip or thigh. This is most common in athletes.
Pes Anserine Bursitis
The Pes Anserine Bursa is located on the inner part of the knee. The Bursa, a fluid filled sac, can become irritated causing knee pain and tenderness.
Conventional Treatments for Knee Pain
The Pes Anserine Bursa is located on the inner part of the knee. The Bursa, a fluid filled sac, can become irritated causing knee pain and tenderness.
Physical Therapy
Knee pain is often initially treated with physical therapy. Physical therapy has been shown to improve knee pain and function. It helps to strengthen muscles and tendons and improves joint function.
Steroid Injections
Steroids Injections are often used in knee osteoarthritis to improve pain and function. Steroids can rapidly decrease inflammation particularly if it is severe and disabling. Most studies show that steroids do a good job of providing short term benefit for pain, but they have minimal long term benefit for pain.
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A 2017 randomized control trial of 140 patients published in JAMA on the effects of intra-articular triamcinolone every 3 months for two years vs saline on knee cartilage volume showed increased cartilage volume loss in the group receiving steroid injections.
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Hyaluronic Acid Injections
If physical therapy injections and steroids are not effective, other possible treatments may be Synvisc or Hhyaluronic Acid Treatments for mild to moderate osteoarthritis. In cases of severe arthritis, these injections may not be helpful. Visco supplementation may decrease inflammatory factors in the joint. I think these are worth trying, but insurance may be reluctant to authorize treatment.
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Genicular Nerve Blocks
Genicular Nerve Bblocks are interventional procedures that are targeted at blocking the genicular nerve that provides sensory innervation to the joint. These procedures can be effective but may not always treat pain effectively and need to be repeated. A study involving 124 patients reported that 81% of patients had pain relief after diagnostic block, but only 35% reported more than 50% pain reduction after radiofrequency ablation. Insurance may sometimes deny coverage of these injections.
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Disadvantages of Conventional Treatments for Knee Pain
Steroids help inflammation but cause destruction of the joint.
Steroid injections are often very effective at reducing pain and inflammation for a short period of time but pain often will reoccur. If done repeatedly, steroid injections can have negative consequences to joint health including loss of cartilage.
These kinds of injections do not address ligamentous dysfunction and laxity and do not improve the integrity of the joint itself. Many studies show that the use of steroid injections for knee osteoarthritis provide only short-term benefit. They often need to be repeated and may stop working after a period of time. In practice, some people do benefit from steroids and one or two injections may resolve pain for a long period of time.
Hyaluronic Acid Injections: a good option, but may stop working.
Hyaluronic Acid Injections such as Synvisc, Euflexxa, Hyalgan and Supartz are joint injections that are designed to improve pain and osteoarthritis through injecting high molecular weight molecules into the joint space to improve synovial fluid function. They are thought to act as a lubricant and shock absorber. Hyaluronic acid is similar to the naturally occurring synvovial fluid. These injections are often not approved by insurance. They need to be repeated every 6 months. They are indicated for mild to moderate osteoarthritis. I have seen some success with these injections, but they do need to be repeated.
Genicular Nerve Blocks: treatment targeted at denervation.
Genicular Nerve Blocks are interventional procedures that are directed at blocking the genicular nerve or performing radiofrequency ablation of the nerve to decrease the painful signal. Genicular nerve blocks do not improve the integrity of the structures of the joint.
Peripheral Nerve Stimulators
There are also several companies that make peripheral nerve stimulators for knee pain. These act by sending a signal to block painful signals. All implanted devices carry some risk of infection, and do not address laxity or ligamentous pain.
Conventional treatments do not address the causes of joint dysfunction.
Consider the conventional treatments offered to treat knee pain: steroids decrease inflammation but may worsen joint anatomy. Hyaluronic acid treatments may improve synovial function but may not always work or be approved by insurance. Genicular nerve blocks decrease pain by destroying the nerve providing sensation to the joint, which eventually grows back.
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All therapies have a role in therapy, but in my opinion, the least invasive treatment that addresses the cause of the dysfunction should be the first line of treatment.
Restoring Joint Function
Getting knee function to return back to normal is the goal of regenerative treatment: improvement of cartilage, bones, nerves, tendons and ligaments. Regenerative treatments such as PRP (Platelet Enriched Plasma) and prolotherapy seek to return knee function.
Platelet Enriched Plasma
Platelet enriched plasma works by providing a concentrated form for platelets and other growth factors to return joint function. PRP requires a blood draw. Your blood is then placed in a centrifuge and a layer of platelets and growth factors are drawn off. They are then injected into the injured area. PRP provides the joint additional growth factors to restore the function of the joint including tendons and ligaments. PRP is a very effective treatment but is expensive and is not covered by insurance.
Prolotherapy
Prolotherapy helps to strengthen the tendinous and ligamentous attachments to bone through the use of dextrose (sugar). A concentrated solution of dextrose is injected into the joint and tendon attachments to strengthen the joint, tendon and ligaments. We still do not understand how dextrose works. It is thought to alter the inflammatory cascade and anti-neuroinflammatory cytokines. From personal experience, having treated others and having had treatment myself, I can tell you that dextrose has pain relieving properties in addition to restoring ligamentous laxity and improving strength in joints.
Work by Dr. John Lyftogt suggests that dextrose also has a role in restoring nerve function which can help in the restoration of joint function. He postulates that dextrose provides the energy that cells need to regenerate.
When I started doing these injections, I saw the beneficial effect of dextrose on pain and tendon dysfunction. I also saw how quickly these injections can work.
When to Consider Prolotherapy and Regenerative Treatments:
Sports Injuries, Tendon and Ligamentous Injury
Sports injuries to the tendons, ligaments and meniscus surrounding the knee may improve with prolotherapy treatment. Injuries and strains to the medial and lateral collateral ligaments, anterior and posterior cruciate ligaments and surrounding knee capsule may benefit from prolotherapy. Severe injury and some meniscal tears require surgery, and it is necessary to see an orthopedic surgeon for evaluation. Prolotherapy treatment is still an option even if surgery is still required. Treatment can help with injuries and pain in the surrounding area.
Osteoarthritis
Osteoarthritis and progressive degeneration of the knee may benefit from treatment with prolotherapy. If you are a candidate for knee replacement prolotherapy can also help with pain and degeneration in the following situations:
You are too young for knee replacement
You are having pain but were told that you were too young to have a knee replacement. You may have tried steroid injections or hyaluronic acid injections in the past.
You are not ready for knee replacement
Life circumstances, medical conditions and other factors may make it inconvenient to have knee replacement.
You are not sure if you want a knee replacement
Prolotherapy and regenerative treatment is worth trying if you are fearful of surgery or if you simply want to try another alternative.
Medical conditions prevent knee replacement.
You are not a candidate for knee replacement due to underlying medical conditions.
Joint Maintenance
You are beginning to experience more regular pain and discomfort due to degenerative changes of the knee, treatment with prolotherapy may be beneficial.
Laxity of the knee— feeling like your knee will give way
If you feel like your knee is giving out or loose, prolotherapy might help to strengthen your joint and prevent further deterioration of your knee.
Studies have shown that prolotherapy can strengthen tendons and ligaments. As we age we lose muscle tone and our ability to regenerate decreases. If you have the sensation that your knee will give way or feels loose, prolotherapy may help to strengthen tendons and ligaments that have weakened over time.
What Prolotherapy Will Not Treat
Complete Tears or Severe Injury
Complete tears of the medial and lateral collateral ligaments or ACL or PCL or some combination of those injuries will likely not improve with prolotherapy. These injuries are usually very painful and require surgery.
Deformity of the Knee
Prolotherapy will not regenerate or treat significant deformity of the knee. It can help with pain but only surgery will correct knee deformity.
Prior Total Knee Replacement
Prolotherapy injections cannot be done over a total knee replacement. If you have pain after a total knee replacement, perineural injection therapy also known as PIT or neuro-prolotherapy may be able to address pain after total knee replacement.
Contraindications to Prolotherapy
Allergy to Dextrose or Corn
Prolotherapy cannot be done if you have an allergy to dextrose or corn.
Cancer
If you are being treated for cancer, you should not have prolotherapy.
Active Infection
Prolotherapy is contraindicated with active infection.
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Relative contraindications include people taking chronic immunosuppressants. Cautions must be exercised in patients who have auto-immune disorders.
Simple and Unsexy
We have a tendency to think that invasive and or highly technical treatments are the most effective: surgery or nerve blocks, radiofrequency ablation and stimulators might seem to be the most technically advanced way to manage pain. It often seems like a very heroic–or technical–measure is necessary to address our very severe pain.
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I have seen many people receive more conventional treatments in pain management often with some relief of symptoms but all too often it is less effective than expected. Hyaluronic acid injections need to be repeated every 6 months. Stimulators can work for periods of time but their effects wear off. There is a risk of infection with implantable devices. Genicular nerve blocks or ablation (destruction of the nerve) may not provide relief for long periods of time and need to be repeated to be effective with a smaller percentage of people achieving 50% relief of symptoms.
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People often do not believe that a simple treatment could be effective. Would the injection of sugar be effective in treating pain? The answer is yes. I have seen it and felt it work myself.
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In my opinion this is because the target of prolotherapy is the treatment of tendinous and ligamentous dysfunction which is not addressed with other treatments. There is also evidence that dextrose therapy can help to restore nerve function. Both can be helpful in the treatment of joint pain and dysfunction.
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This kind of therapy can restore function and strength to tendons and ligaments that provide stability to the joint and also improve pain and may also improve nerve function.
Regenerative Treatment Gives Your Body What It Needs to Repair Itself
There are some important things to understand about regenerative treatment: It helps your body repair itself by giving it the necessary components and fuel to repair itself. We do not know how dextrose works. We know that it can relieve painc and recruit healing factors resulting—first in inflammation— then to regeneration and strengthening of the structures of the tendons and ligaments.
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This seemingly simple treatment allows your body to do its job: to heal. Practitioners of prolotherapy often explain that dextrose gives the body energy it needs support regeneration.
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Early studies in prolotherapy show that treatment can strengthen ligaments by approximately 30%. Ligamentous and tendinous dysfunction is an important and unrecognized source of pain. This source of pain is not treated with steroids or stimulators or nerve ablation.
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Neuro-prolotherapy, also known as peri-neural injection therapy, may also help to restore nerve function and improve pain. Restoration of nerve function may allow your body to repair the surrounding tissue.
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In my opinion, the use of regenerative treatments to improve function before the development of significant disability leads to better outcomes. Prolotherapy can still be used after there is pain and deformity of the knees or joints, but it is less effective if there is severe injury and surgery may still be required.
Studies on Prolotherapy
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Prolotherapy is Not Placebo
The idea of injecting a simple solution of dextrose may seem like it is placebo, studies show that it is not. More studies are needed, but there are now numerous studies showing benefit. A review of prolotherapy for management of Osteoarthritis of the knee by Zhao et al can be found here: 10.52965/ 001c.33921​
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A study by Robago in 2013 conducted a 3 arm blinded randomized controlled trial comparing dextrose and saline and at home exercise. WOMAC scores (a measure of knee pain and function) showed more improvement in the prolotherapy group at 52 weeks.
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A randomized trial for 76 patients by Sit et al in 2020 showed improvement in WOMAC pain score, function score and composite score and VAS (Visual Analog pain scale) score at 52 weeks compared with saline injections.
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A meta-analysis in 2021 by Wee et al included 11 articles and 837 patients. This study showed that prolotherapy was no different from PRP at 6 months, but was inferior to PRP on the stiffness subscale. Based on two studies, prolotherapy can be considered for knee OA.
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Prolotherapy vs PRP
In 2018 a randomized trial of 42 adults by Rahimzadeh et al comparing dextrose to PRP for stage 1 or 2 knee arthritis showed improvement in the WOMAC score for both groups at 6 months. Results for PRP showed slightly more improvement.
Studies show that prolotherapy has a good side effect profile including patient satisfaction and quality of life.
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Things I Have Seen in Prolotherapy
Since I began practicing prolotherapy, I have been impressed with how quickly it works and how effective it can be. It is an important alternative to consider in treatment. There are a few things worth mentioning:
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Significant Improvements in Knee Range of Motion
Many people who have severe knee pain have significant improvements in knee range of motion.
Spasms
Occasionally people develop spasms after treatment. Magnesium or muscle relaxants can help this. This should resolve over time.
Temporary Increase In Pain
Prolotherapy causes an increase in inflammation. The inflammatory response allows your body to heal. This increase in pain is temporary and should resolve. For most people, inflammation lasts one to two days, up to a week.
Prior Steroid Injections May Make It More Difficult for Treatment to Work
People who have had steroid injections in the past, especially if they have had a number of steroid injections, may need more treatments for prolotherapy to be effective.
Expectations and Considerations
People are often suspicious of alternative treatments and initially pursue a more standard approach to treatment. It is only after the failure of more conventional treatment approaches do people seek alternative therapy. People often ask their doctor, friends or another medical professional about this kind of treatment. Not all doctors are aware of the benefits of alternative therapies, they may not be able to give good advice about the risks and benefits of these kinds of therapies. They may also view them as experimental or without merit. Would you ask your plumber about an electrical problem? They both work on houses, but they have expertise in different things.
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Ask yourself what you want to get out of therapy
If you are considering a regenerative treatment, ask yourself what you would like to get out of therapy. Regenerative treatments such as prolotherapy and PRP are not covered by insurance. Many people who seek this option have decided that they want to avoid surgery and want another option. Other people don’t mind having knee replacement surgery and are fearful of trying something different. Cost also limits what people are able to try.
What are the risks, benefits and alternatives?
Physical therapy is effective and recommended for knee osteoarthritis. If that is not working or progress is slow, injection therapy is the next option. All injections carry a risk of infection, bleeding, bruising and nerve injury. Steroids can provide short term benefit, have the potential to weaken cartilage and may not last. Hyaluronic acid injections can be effective but may or may not be covered by insurance. Prolotherapy is less costly and may require more injections. PRP is likely more effective and more costly.
Consider trying prolotherapy before steroid injections
The process of regeneration with prolotherapy may be more difficult if you have already had steroid injections.
Consider trying prolotherapy before PRP
Prolotherapy and PRP both act by stimulating the process of regeneration. Prolotherapy is less expensive than PRP and can yield similar results. If you have benefited from prolotherapy, it is likely that you will also benefit from PRP.
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Prolotherapy is less expensive than PRP and relatively simple to perform.
Prolotherapy is less expensive than PRP and does not require a blood draw. Prolotherapy can cost between $175-$600 depending on the injection, practitioner and location of injections and use of ultrasound guidance. PRP is usually more expensive ranging from $ 750 to $1500. The number of treatments needed depends on the condition being treated and the health of the patient.
Consider Surgical Risk
Surgery is effective for most people who need a knee replacement, nearly 1 million people undergo knee replacement each year. A literature review published in 2023 from 35 articles published between 2010-2022 in suggests that about 10% of people who undergo total knee replacement are dissatisfied. (J arthroplasty 2023 March DeFrance)
​Some percentage of people, from 4-10% may require revision knee surgery due to infection or instability, loss of range of motion or pain. Any surgery carries a risk of complication such as infection or blood clot
How many Treatments will I need?
Prolotherapy often requires between 2 and 8 treatments to be effective. Most people have some benefit from the first injection, but most often at least two treatments are needed. The goal is to achieve 80% relief. Even prolotherapy is not 100% effective, it can help to address some of the structural elements that are needed for joint stability and preservation of joint function. Because prolotherapy is regenerative, it is better to have a series of injections close together to build up the strength of the tendons and ligaments in the joints. After adequate pain relief is achieved, injections can be done as needed.
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Conclusions
Regenerative treatment can have an important role in preserving joint integrity and relieving pain. Prolotherapy and regenerative treatment has been practiced since the 1950’s and is considered safe. Use of dextrose or PRP is better for the tissues of the joint and also may help to strengthen tendons and ligaments. Current treatment options include physical therapy and steroid injections. There is now evidence to suggest that steroid injections may decrease cartilage strength over time.
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Surgery also has risks. Up to 10% of people are not satisfied with the results of knee replacement and some percentage of people will require reoperation. Undergoing surgery itself has some risk depending on your overall state of health and medical condition.
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Using regenerative treatment including PRP and prolotherapy to preserve joint health, maintain function and decrease pain is a safe alternative to address pain and dysfunction and to promote healing and function.
1. McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M, Ward RJ. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA. 2017 May 16;317(19):1967-1975. doi: 10.1001/jama.2017.5283. PMID: 28510679; PMCID: PMC5815012.
2. Peck J, Slovek A, Miro P, Vij N, Traube B, Lee C, Berger AA, Kassem H, Kaye AD, Sherman WF, Abd-Elsayed A. A Comprehensive Review of Viscosupplementation in Osteoarthritis of the Knee. Orthop Rev (Pavia). 2021 Jul 10;13(2):25549. doi: 10.52965/001c.25549. PMID: 34745480; PMCID: PMC8567800.
3 Philip A, Williams M, Davis J, Beeram A, Feng C, Poli J, Vangellow A, Gewandter J. Evaluating predictors of pain reduction after genicular nerve radiofrequency ablation for chronic knee pain. Pain Manag. 2021 Nov;11(6):669-677. doi: 10.2217/pmt-2021-0014. Epub 2021 Jun 9. PMID: 34102879.
4 Zhao AT, Caballero CJ, Nguyen LT, Vienne HC, Lee C, Kaye AD. A Comprehensive Update of Prolotherapy in the Management of Osteoarthritis of the Knee. Orthop Rev (Pavia). 2022 May 31;14(4):33921. doi: 10.52965/001c.33921. PMID: 35769650; PMCID: PMC9235417.
5 Rabago D, Patterson JJ, Mundt M, Kijowski R, Grettie J, Segal NA, Zgierska A. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013 May-Jun;11(3):229-37. doi: 10.1370/afm.1504. Erratum in: Ann Fam Med. 2013 Sep-Oct;11(5):480. PMID: 23690322; PMCID: PMC3659139.
6 Sit RWS, Wu RWK, Reeves KD, Rabago D, Chan DCC, Yip BHK, Chung VCH, Wong SYS. Efficacy of intra-articular hypertonic dextrose prolotherapy versus normal saline for knee osteoarthritis: a protocol for a triple-blinded randomized controlled trial. BMC Complement Altern Med. 2018 May 15;18(1):157. doi: 10.1186/s12906-018-2226-5. PMID: 29764447; PMCID: PMC5952445.
7 Wee TC, Neo EJR, Tan YL. Dextrose prolotherapy in knee osteoarthritis: A systematic review and meta-analysis. J Clin Orthop Trauma. 2021 May 20;19:108-117. doi: 10.1016/j.jcot.2021.05.015. PMID: 34046305; PMCID: PMC8144680.
8 Rahimzadeh P, Imani F, Faiz SHR, Entezary SR, Zamanabadi MN, Alebouyeh MR. The effects of injecting intra-articular platelet-rich plasma or prolotherapy on pain score and function in knee osteoarthritis. Clin Interv Aging. 2018 Jan 4;13:73-79. doi: 10.2147/CIA.S147757. PMID: 29379278; PMCID: PMC5757490.
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9 DeFrance MJ, Scuderi GR. Are 20% of Patients Actually Dissatisfied Following Total Knee Arthroplasty? A Systematic Review of the Literature. J Arthroplasty. 2023 Mar;38(3):594-599. doi: 10.1016/j.arth.2022.10.011. Epub 2022 Oct 14. PMID: 36252743.