What are the different types of knee injections for bone on bone knees

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

If you are reading this article, there is a very strong chance that one of three things is happening to you.

“What is the best injection for knee pain?”

Many times someone will reach out to us and ask the simple question: “What is the best injection for knee pain?” The answer is, “the one that works for you.”

In this article we will explore:

Everyone of these injections treatments have success stories behind them. Every one of these treatments have less than successful stories behind them. For some people these injections could not prevent knee replacement.

Cortisone Knee Injections: In the past, your doctor may have recommended against the use of cortisone because it was clear to him or her that there was knee surgery in your future.

The caption of this image reads” “articular cartilage deterioration as evidenced by fibrillation (fraying, splitting and erosion of cartilage), fissures (cracks) and flaking. Cortisone is known to cause this condition.

articular cartilage deterioration as evidenced by fibrillation (fraying, splitting and erosion of cartilage), fissures (cracks) and flaking. Cortisone is known to cause this condition.

In the past, your doctor may have recommended against the use of cortisone because it was clear to him or her that there was a knee surgery in your future.

In the past, your doctor may have recommended against the use of cortisone because it was clear to him or her that there was a knee surgery in your future. The concern is if you get cortisone injections into your knee prior to surgery, you will have a greater risk of complications after the surgery. There is a lot of debate around this subject. Some doctors say avoid the cortisone, other doctors are saying it is okay to get one shot to hold you over until you can get surgery or maybe the cortisone will reduce your inflammation enough after the first shot that you will have some degree of pain relief and comfort for a few months, a year, maybe longer.

We are going to start with cortisone because cortisone was the injection of choice. Much has changed.

In a January 2021 paper from doctors at Northwestern University McGaw Medical Center, Rutgers School of Medicine, and Boston College, a current guideline was given for the use of cortisone: The paper appeared in the journal Pain Physician (1) and included the following observations.

Cortisone is no longer considered the miracle cure for knee pain and should be used sparingly if at all.

The one thing that has become the general consensus is: Cortisone is no longer considered the miracle cure for knee pain and should be used sparingly if at all.

You are sitting in the orthopedist’s office: The discussion turns to cortisone

If you have been to your orthopedist recently and are planning treatment options or surgical options you may have been given a paper handout or webpage to visit or verbal advice on what to expect if you are getting a cortisone injection into your knee.

You may have been told:

The cortisone injection is to help you now, it is not a permanent solution.

Physical therapy may be an option instead of the cortisone injection

You need to lose weight so the cortisone will work better

Corticosteroid knee injections provided no significant pain relief after two years. Researchers say: Do not give cortisone for knee osteoarthritis.

In 2017, doctors from Tufts Medical Center in Boston asked, “What are the effects of intra-articular injection of 40 mg of triamcinolone acetonide (a synthetic corticosteroid medication) every 3 months on the progression of cartilage loss and knee pain in patients with osteoarthritis?” Writing in the Journal of the American Medical Association, (JAMA) (3) they published their answer:

“Among patients with symptomatic knee osteoarthritis, 2 years of intra-articular triamcinolone, compared with intra-articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain. These findings do not support this treatment for patients with symptomatic knee osteoarthritis.

Although surgery and cortisone are common, randomized trials have failed to produce evidence for their effectiveness or how much they do work.

Moving forward on that research, a February 2020 review study with the title “Medical Reversals in Family Practice: A Review,” (4) published in the journal Current Therapeutic Research, Clinical and Experimental offered these points:

Cortisone can make bone on bone worse by thinning out the meniscus. But one injection appears okay

One of the reasons that you are considering a knee replacement or are thinking about getting a cortisone injection is because you have been told you have a bone on bone knee. So the idea that cortisone may make this worse by thinning out your meniscus is concerning doctors.

In August of 2020 in the journal Scientific Reports (5) doctors expressed concerns about damaging the meniscus tissue with cortisone injections. It should be noted that this research’s main findings were that it was okay to get one cortisone injection. For many people, one injection would be considered safe. Here are the learning points of that research:

The cortisone debate goes on

A December 2020 (6) study published in the medical journal Rheumatology gives this overview assessment of the debate surrounding the use of cortisone for a bone on bone knee. Here are the summary learning points:

Returning to the research study:

Returning to the research study: In some people swelling comes and goes, it is hard to suggest who cortisone would be successful for among these people.

Returning to the research study: The more suitable cortisone patient is:

We do not offer cortisone injections at our center. In approaching three decades of helping people with knee pain this is a treatment that we did not find beneficial. In 2009, our research team wrote in the Journal of Prolotherapy: “It is (our) opinion that there is no doubt that the rise of osteoarthritis, as well as the number of hip and knee replacements, is a direct result of the injection of corticosteroids into these joints.”(7)

The evidence then was a summary of the effects of cortisone on articular cartilage which included:

Cortisone injections before knee surgery lead to greater post-surgical infection risk.

In August 2021, research lead by the Department of Orthopaedics, University of Colorado School of Medicine and published in the Orthopaedic journal of sports medicine (8) suggested that “patients undergoing knee arthroscopy who receive an intra-articular corticosteroid injection during the perioperative period can be expected to experience significantly higher postoperative infection rates when compared with patients not receiving an injection. Furthermore, patients receiving a corticosteroid injection pre- or intraoperatively may experience significantly higher rates of postoperative infection when compared with patients receiving an injection postoperatively.”

For a more detailed discussion on cortisone please see our article: Alternatives to cortisone shots.

Hyaluronic acid injections or Viscosupplementation for Knee Osteoarthritis: What to expect when getting gel injections in knee

Much like cortisone, it is very likely that this knee injection treatment has been explained to you already by your orthopedist. It is a conservative care plan to help you try to manage along until you can get a knee surgery scheduled or you are trying to do everything you can to avoid the knee surgery.

Also like cortisone, you may have already had viscosupplementation and the effects and benefits have now worn off and you need to treat your knee differently. For some people, they may not even be reading this sentence because they have moved down the article to other treatments because this one is no longer an option for them.

What is Hyaluronic acid injections or Viscosupplementation?

The explanation that you may have been given is that hyaluronic acid injections will provide a gel-like cushion in your knee, getting between the shin and thigh bones to alleviate your bone-on-bone situation. The injections increase the volume of the protective synovial fluid in the knee.

Over the years we have seen many patients who have been on the “gel shots.”

Over the years we have seen many patients who have been on the “gel shots.” Many people do get very good results with the treatment. They are, however, designed as short-term treatments to help put off or delay knee replacement surgery.

The debate over Hyaluronic Acid Injections knee injections. One study suggests that Hyaluronic Acid is a waste of time, money, and resources another study says it works okay

We do see many patients who have tried hyaluronic acid injections. For some, they did have a degree of success and the injections provided short-term pain relief.  Many of these people are now in our office because the short-term has not transpired to the long-term and now they are on the path to knee replacement.

The idea behind hyaluronic acid injections is to protect the knee by reintroducing lost or diminished hyaluronic acid in the knee’s synovial fluid or “providing a cushion.” The synovial fluid is a thick gel-like liquid that helps cushion the knee and acts to absorb the daily impact of walking and running and stair climbing our knees are subjected to.

The treatment of Hyaluronic Acid Injections is also called Viscosupplementation – supplementing the “viscosity” or the thick, sticky, gel-like properties of the synovial fluid. People will also recognize these injection treatments as Viscosupplementation “rooster comb injections,” “rooster shots,” “chicken shots,” as well as by trade names Euflexxa ®, Supartz ® Supartz FX ®, Synvisc-One ®, Synvisc ®, Hyalgan ®, Orthovisc ®, et al. All these products offer subtle differences in their treatment goals including the number of injections – however, none of them offer a permanent solution. This is what the American Academy of Orthopaedic Surgeons posted on their website:

“Although some patients report relief of arthritis symptoms with viscosupplementation, the procedure has never been shown to reverse the arthritic process or re-grow cartilage. The effectiveness of viscosupplementation in treating arthritis is not clear. It has been proposed that viscosupplementation is most effective if the arthritis is in its early stages (mild to moderate), but more research is needed to support this. Research in viscosupplementation and its long-term effects continues.”

We have two studies here: The first says Hyaluronic Acid Injections are okay. The second says Hyaluronic Acid Injections are a waste.

Do Hyaluronic Acid Injections Work for Knee Osteoarthritis?

“Repeated courses of treatment with Hyaluronic Acid are safe and are associated with the delay of total knee replacement for up to 3 years.”

A July 2018 study in the American Journal of Orthopedics (11) recognized that for some people: “Total knee replacement is a significant procedure with potential risk for serious complications and high costs. Alternative lower risk therapies that can delay or (prevent) total knee replacement are valuable to those who are poor candidates for surgery or wish to avoid total knee replacement as long as possible.”

Are Hyaluronic Acid Injections the answer? Here is what the study concluded: “Repeated courses of treatment with Hyaluronic Acid are safe and are associated with the delay of total knee replacement for up to 3 years.” So again, we have a three-year delay after repeated courses of Hyaluronic Acid injections supported in the research. But what about the study that says “Hyaluronic Acid Injections that delay inevitable knee replacement are a waste of time, money, and resources?”

Research: Multiple intra-articular hyaluronic acid injections can delay the need for total knee replacement for one and a half years.

A 2021 paper published in the Journal of long-term effects of medical implants (12) explored the effect of single versus multiple rounds of intra-articular hyaluronic acid in delaying the need for total knee arthroplasty in patients with knee osteoarthritis, and if additional benefits were seen when used in conjunction with other multimodal treatment options. The other treatments were knee braces and cortisone injections. The researchers found that “treatment of knee osteoarthritis should consider the use of multimodal therapy instead of focusing on individual treatment options. Additionally, the use of repeated courses of intra-articular hyaluronic acid should be considered for prolonged benefit for patients with symptomatic knee osteoarthritis.”

Are Hyaluronic injections low-value health care? Using Medicare Data to Understand Low-Value Health Care: The Case of Intra-articular Hyaluronic Acid Injections.

A research letter in the Journal of the American Medical Association Internal Medicine, (13) with the title: Are Hyaluronic injections low-value health care? Using Medicare Data to Understand Low-Value Health Care: The Case of Intra-articular Hyaluronic Acid Injections, backed that up with “based on high-quality evidence that hyaluronic acid injections were not associated with clinically meaningful improvement in symptoms compared with placebo injections.”

This statement paper is from 2014, let’s see if we can advance the research forward towards 2021.

The first stop is February 2016 and the journal Clinical Orthopaedics and Related Research. (14) It is an editorial from Seth S. Leopold, MD. Here are the quoted learning points:

Then why is your doctor still recommending this treatment?

Let’s let Dr. Leopold continue:

“One reason might be that surgeons have relatively few effective nonsurgical alternatives that help patients with their joint pain, and—being members of a helping profession—we find this frustrating. However, our lack of effective nonsurgical treatments cannot justify the use of an ineffective one, and it must not be used to justify surgery unless surgery is indicated. Some patients will have pain that persists despite well-tested nonsurgical treatments, but not enough to warrant major joint surgery; others may not fit the biopsychosocial profile that supports a decision to perform elective arthroplasty. The answer to this is not to use a treatment like viscosupplementation that studies suggest is ineffective, nor to take a chance on surgery when it seems ill-considered to do so, but rather to explain to patients that there are some problems for which we have no effective treatments, and to help those patients adjust and adapt.”

One injection just as good as a series of Hyaluronic Acid Injections

The next stop will be a March 2019 study in the journal Current Therapeutic Research. (15)

The question being asked here is maybe more than one injection would make the treatment more effective. In fact, the question is how this paper opens: “Viscosupplementation of the synovial fluid with intra-articular hyaluronic acid is a well-known symptomatic treatment of knee osteoarthritis. The question arises whether a mono-injection (ie, single injection) could be as efficient as multi-injection (ie, 3–5 injections) regimens.”

Here is how this paper concluded: In the symptomatic treatment of knee osteoarthritis with intra-articular hyaluronic acid, the results of mono-injections (one injection) demonstrate (similar effectiveness) to the multi-injections and also when compared to a placebo injection.

Conclusion: Results of this meta-analysis suggest that the effects of a single injection of hyaluronic acid produce results similar to multi-injections of intra-articular hyaluronic acid in terms of pain relief in the treatment of knee osteoarthritis.

You can delay knee replacement realistically for about 11 months with hyaluronic acid injections

In September 2020, a study in the journal American Health and Drug Benefits,(16) assessed the value of intra-articular hyaluronic acid injections monetarily. This is a way to determine the effectiveness of the treatment. This is what the study said:

Although limiting hyaluronic acid use may reduce knee osteoarthritis-related costs, in this study hyaluronic acid injection only comprised a small fraction of the overall costs related to knee osteoarthritis. Among patients who had a knee replacement, those who received treatment with hyaluronic acid had surgery delayed by an average of 10.7 months.

Platelet-Rich Plasma (PRP)

This is one of the injections that you may have been researching because it is somewhat off the traditional conservative care options path and you stumbled upon PRP online. You may have even asked your orthopedist about “PRP” injections and you were told: “They do not work, they are not covered by insurance.”

That is probably enough to chase anyone away. Except for one thing. There is a lot of research that when administered correctly by a doctor experienced in the treatment, PRP works pretty well. So just like the debate about cortisone and the debate about Hyaluronic Acid Injections, there is a debate about PRP injections.

Growth and healing factors in PRP. This is what makes PRP work

A paper in the journal Clinical Cases in Mineral and Bone Metabolism (17) describes the growth, healing, and repair factors found in platelet-rich plasma. These are the healing factors and what they do:

So the concept is here. These healing growth factors in your blood are taken and “spun,” to separate out a platelet-rich plasma solution filled with these healing and growth factors, and then the solution is injected into your knee.

PRP is not a single shot miracle cure. Effectiveness of PRP is in how many times the treatment is given

PRP is not a single shot miracle cure. While for the rare patient a single shot may work for them, we have seen in our clinical experience, PRP not to be as effective as a stand-alone, single-shot treatment. When someone contacts our center with a question about PRP, they understand the concept and that it should have helped them. But it did not. Why?

PRP does not work for every patient. The two main reasons are that some knees are indeed “too far gone.” What is typically too far gone? A knee that does not bend anymore or there is significant structural changes like bone spurs that have fused the knee.

The second reason is that they did not allow the treatment a chance to work. Many people think they are supposed to get immediate relief. That is not how PRP works.

Cortisone is a one-shot treatment, PRP should not be given the same way. This is when PRP does not work

People get confused with PRP treatment because they think it is “just like cortisone, only safer.” PRP is NOT just like cortisone. Cortisone has an immediate pain-reducing effect for many people, not all, because it is reducing pain brought on by chronic inflammation. Nothing is being healed. PRP brings healing through inflammation. When tissue is repaired, the inflammation goes away. Please read below for a direct comparison of cortisone injection and PRP and the PRP time frame of healing. You will see cortisone is short-term, PRP is long-term. Cortisone will eventually suppress the body’s natural healing mechanism and send you to knee replacement. PRP will rebuild and repair tissue in the knee and help you avoid a knee replacement or arthroscopic surgery.

Researchers at Queens University in Belfast published a June 2021 paper in the journal BioMed Central Musculoskeletal Disorders (18) in which they compared PRP to cortisone. Here are the observations of care and the findings:

Results: “Intra-articular platelet-rich plasma (PRP) injections produce superior outcomes when compared with Intra-articular corticosteroid injections for symptomatic management of knee osteoarthritis, including improved pain management, less joint stiffness, and better participation in exercise/sporting activity at 12 months follow-up. Giving Intra-articular platelet-rich plasma (PRP) injections, with injections separated by a week, appears more effective than one Intra-articular platelet-rich plasma (PRP) injection.”

In this video, Ross Hauser, MD explains how one injection of PRP will likely not work

A transcript summary is below the video

We will often get emails from people who had previous PRP therapy without the desired healing effects. We explain to these people that their treatment probably did not work because the single PRP injection did not resolve knee instability. The PRP may have tried to create a patch in the meniscus or cartilage to help with a bone-on-bone situation but the instability and the wear and tear grinding down the meniscus and cartilage remains.

When a person has a ligament injury or instability, the knee becomes hypermobile causing degenerative wear and tear on the meniscus and knee cartilage. In other words, the cells of the meniscus and cartilage are being crushed to death. When you inject PRP cells into the knee, without addressing the knee instability, (treating the ligaments,) the injected PRP cells will also be subjected to the crushing hypermobile action of the knee. The single injection PRP treatment will not work for many people. The knee instability needs to be addressed with comprehensive Prolotherapy around the joint. Prolotherapy is the companion injection of simple dextrose. This is explained in detail below.

Is PRP controversial? Yes. Is it effective? Also yes.

When it works. Below are many citations and references showing the effectiveness of PRP. 

Let’s start with the most recent research of the effectiveness of PRP for knee osteoarthritis.

“the efficacy of intra-articularinjections as a nonoperative modality for treating symptomatic knee osteoarthritis-related pain while maintaining function has become a subject of increasing interest.”

An August 2021 paper from Department of Orthopaedic Surgery, Rush University Medical Center published in  The American journal of sports medicine (22) compared the effectiveness of PRP against other knee injections in “younger patients and those without severe degenerative changes.” The reason? “the efficacy of intra-articular injections as a nonoperative modality for treating symptomatic knee osteoarthritis-related pain while maintaining function has become a subject of increasing interest.”

In this study the following treatments were compared:

A brief understanding of the differences between PRP and PRGF

Studies have shown a favor towards the use of plasma rich in growth factors (PRGF) in surgical healing. The difference in the injections is that in plasma rich in growth factors (PRGF) red and white blood cells are removed leaving only the growth factors. The benefit of this is that in wound healing, removing the red and white blood cells will help reduce inflammation. This is why this treatments is more favored in surgical repair. As regenerative medicine outside of surgery relies on controlled inflammation, PRP is seen as better choice in many situations where there is knee pain.

Here are the highlights of this study:

Conclusion: “PRP yielded improved outcomes when compared with plasma rich in growth factors (PRGF), Hyaluronic acid, Corticosteroids, and placebo for the treatment of symptomatic knee osteoarthritis at a minimum six-month follow-up.”

When PRP doesn’t work, it is usually not the solution used during treatment, but how the treatment itself is given.

In the Journal of Knee Surgery, (23) doctors at the Division of Sports Medicine, Department of Orthopedics, at Rush University Medical Center in Chicago wrote:

Simply put, PRP methods vary by practitioner. Research consistently points to PRP ineffectiveness as being caused by the way the treatment is given and poor patient selection.

In a December 2018 paper titled: “Clinical Update: Why PRP Should Be Your First Choice for Injection Therapy in Treating Osteoarthritis of the Knee,” researchers wrote in the journal Current Reviews in Musculoskeletal Medicine:(24)

“Moving forward, it is imperative that future clinical research be conducted in a more standardized manner, ensuring that reproducible methodology is available and minimizing study-to-study variability. This includes PRP preparation methods (centrifugation times and speeds, harvest methodology, systems being used); PRP composition (platelet concentrations, activation agents, white blood cell concentrations, growth factor, and cytokine concentrations); PRP injection protocols (single versus multiple injections); sufficient clinical follow-up (a minimum of 6 months); and strict inclusion/exclusion criteria.”

Two groups of patients, one group gets PRP the other group gets cortisone. How did this comparison work out?

In this study from The Journal of Sports Medicine and Physical Fitness, (25) a comparison is made between the effects of a one-time injection of PRP and corticosteroid (a cortisone shot) for the patients suffering from osteoarthritis.

Compared to the group treated with corticosteroid, PRP showed significant results for:

This study demonstrated that one shot of PRP injection, decreased joint pain more and longer-term, alleviated the symptoms, and enhanced the activity of daily living and quality of life in short-term duration in comparison with the corticosteroid.

Study 2: Two groups of patients, one group gets PRP the other group gets cortisone. How did this comparison work out?

In an October 2020 study (26) also comparing PRP and corticosteroid, similar findings were recorded. PRP results were better over time and the lack of side-effects should be considered if debating between one treatment or the other.

“Patients undergoing treatment for knee osteoarthritis with PRP can be expected to experience improved clinical outcomes when compared with hyaluronic acid.”

There is a lot of research comparing PRP to hyaluronic acid. Here are some of the papers:

An April 2020 study lead by the Department of Orthopedics, University of Colorado School of Medicine, published in The American Journal of Sports Medicine (27) suggested: “Patients undergoing treatment for knee osteoarthritis with PRP can be expected to experience improved clinical outcomes when compared with hyaluronic acid.”

Doctors writing in the September 2019 issue of the World Journal of Orthopedics (28) offered these findings in assessing PRP versus hyaluronic acid injections over four, eight, and twelve-week follow-ups after treatments.

In February 2020, a multi-national team of researchers published findings in the European Journal of Orthopaedic Surgery & Traumatology (29) comparing intra-articular knee injection of PRP and hyaluronic acid and investigate clinical outcomes and pain at both 6 and 12 months.

Research comparing PRP injections, cortisone injections, and hyaluronic acid injections 

Doctors wrote in a January 2019 study (30) that while PRP injections, cortisone injections, and hyaluronic acid injections are considered equally effective at relieving patient symptoms at three months, at 6, 9, and 12 months the PRP injections delivered significantly better results.

A July 2020 study (31) published in the Journal of Pain Research also suggested that PRP injections provided better results for patients than hyaluronic acid injections. The study’s conclusions were: Besides significantly higher satisfaction belonging to the (PRP) group, there was a statistically significant improvement in pain and function scores at 12 months compared to hyaluronic acid injections

In research published in the Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, PRP was shown to provide significant healing of the meniscus (32as well as out out-perform hyaluronic acid in patients with knee joint cartilage degeneration. Similar results were documented in the journal Archives of physical medicine and rehabilitation. (33)

An August 2021 paper in the Orthopaedic journal of sports medicine (34) suggests however that corticosteroid and hyaluronic acid injections are favored for different knee problems, while PRP currently has insufficient evidence to make a conclusive recommendation for or against its use.

In our article Platelet Rich Plasma for Knee Osteoarthritis: When it works, when it does not, we point to more research on when the treatment can be successful and when the treatment may not help you.

Stem Cell Therapy

This is one of the treatments that is considered very promising and equally very controversial. This is also a treatment that may suffer from an over-expectation of what this treatment can do and a misunderstanding of what this treatment cannot do.

If you have a bone on bone knee, stem cell therapy will not grow a new meniscus out of thin air.

As we say to many patients, if you have a bone on bone knee, stem cell therapy will not grow a new meniscus out of thin air. Stem cell therapy can grow new cartilage as a method to patch cartilage and meniscus defects but is not a “miracle” one-shot cure that will rebuild your knee to “good as new.” Some people may get benefit from the one-time shot, others will not. As we will point out in this article and links to our other articles, there is too much being made of young versus old stem cells. We may be getting ahead of ourselves here so let’s start with a basic understanding.

There are different types of stem cell therapy. You have:

At our center we use stem cell therapy, but not all of these listed above. We also use stem cell therapy on a few patients, not every patient.

We estimate that 1 in 10 patients who we see in our clinic have already received some type of stem cell therapy in another office. They are in our clinic because the treatment they have received has failed to meet the patient’s expectations. Simply, One injection stem cell “treatments” are not sustainable pain relief

People with knee osteoarthritis pain, probably like yourself, go to the orthopedist and hear over and over about their eventual need for a knee replacement. You may have been given a much more critical, “we should schedule this knee replacement now,” recommendation because it took you a long time to walk from the reception area to the examination room, and all along the way you may have been reaching and lunging for chairs, walls, and counters to use as support and your doctor saw you do it.

You would like to avoid the knee replacement for various reasons, all equally important to you. In your research, you have come upon stem cell therapy. You read through some websites that suggest this simple, possibly one-time injection, will make all your pain go away. This is unrealistic thinking as this is almost never the case. The reason it is almost never the case is that stem cell therapy, even when most effective, requires a comprehensive approach to treatment that includes multiple treatments or the use of Prolotherapy injections into the knee’s supportive ligaments.

In the video below, Ross Hauser, MD explains the 5 myths we see concerning Stem Cell Therapy. The biggest one is that people believe that one stem cell injection will make all their pains go away. For most this is not true. It is not true for the same reasons outlined above, a single injection will not be comprehensive enough to reverse years and possibly decades’ worth of damage affecting the entire knee structure. This one-shot thinking leads to an unrealistic expectation of pain relief and joint regeneration.

Bone Marrow Aspirate Concentrate or bone marrow concentrate type stem cell therapy

Using stem cells taken from a patient’s bone marrow is becoming a therapy of interest due to the potential of these mesenchymal stem cells to differentiate into other types of cells such as bone and cartilage. This is not a new revolutionary treatment, this treatment has been studied and applied for many years. It is a difficult treatment for some doctors to give. You do need experience in all aspects of the treatment to give the patient the best chance at achieving their healing goals.

Bone Marrow is the liquid spongy-type tissue found in the hallow (interior) of bones. It is primarily a fatty tissue that houses stem cells that are responsible for the formation of other cells. These mesenchymal stem cells (MSC), also called marrow stromal cells, can differentiate (change) into a variety of cell types including osteoblasts (bone cells)chondrocytes (cartilage cells), myocytes (muscle cells), adipocytes (fat), fibroblasts (ligament and tendon) and others when reintroduced into the body by injection. Bone marrow also contains hematopoietic stem cells that give rise to the white and red blood cells and platelets.

Where do the bone marrow stem cells come from?

The bone marrow aspirate is taken from the iliac crest of the pelvic bone. It is a simple, easily tolerated procedure and is demonstrated in this video below:

In clinical observations at Caring Medical, benefit is seen in injecting bone marrow directly after extracting it.

The theory is that the number of stem cells is not as important as how long they live in their natural environment. In other words, when the bone marrow is directly injected, the source of stem cells is fresh and has great potential for healing. We also believe that the body knows best – it can use these immature cells to regenerate all injured tissues in the joint.

Mayo Clinic and Yale University studies on your own bone marrow stem cells

Doctors at the Mayo Clinic and Yale University published their research on the benefits of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis in the American Journal of Sports Medicine. Here is the summary of that research:(35)

“The current literature demonstrates the potential benefits of utilizing concentrated bone marrow aspirate for the repair of cartilaginous lesions, bony defects, and tendon injuries”

Doctors in New Jersey at the Department of Orthopedic Surgery, Jersey City Medical Center published their findings in support of this research, in the World Journal of Orthopedics, here is what the paper said:

A June 2018 study in the journal Arthritis and Musculoskeletal Disorders (37) presents the short-term progress of 15 patients (20 knees) with knee osteoarthritis through four bone marrow concentrate treatments.

Patients experienced statistically significant improvements in active pain and functionality scores after the first treatment.

Successful, safe, and encouraging results

A January 2020 (38) study published in the journal Knee Surgery, Sports Traumatology, Arthroscopy found:

“Pre-clinical studies have demonstrated (intra-articular injections of bone marrow-derived mesenchymal stem cells is) successful, safe and (with) encouraging results for articular cartilage repair and regeneration. This is concluded to be due to the multilineage differential potential, immunosuppressive and self-renewal capabilities of bone marrow derived mesenchymal stem cells, which have shown to augment pain and improve functional outcomes.”

Caring Medical Research – Case studies

Our research team has published research on patient outcomes and case studies using bone marrow aspirate. Here is a sample of those outcomes. Again, we must remind you that this treatment does not work for everyone. Unfortunately, if you are reading this article you are probably very attuned to medical treatments that do not work.

In the medical journal Clinical Medicine Insights Arthritis and Musculoskeletal Disorders, (39) our Caring Medical research team published our findings in seven patients. The patients who were treated for knee pain are featured below:

Patient case  – Knee pain: A 69-year-old man

A 69-year-old male came into our office with pain in both knees, with his right knee significantly more painful. Pain resulted in frequent sleep interruption and limitation of exercise.

The patient had received prolotherapy (another injection treatment explained below) at another office in the previous two years but felt that the treatment has reached its maximum ability to heal.

The patient was diagnosed with osteoarthritis and received five bone marrow/dextrose treatments (a combination of bone marrow and Prolotherapy injections) in each knee at two-month intervals.

Patient case  – Knee pain – A 56-year-old woman

A 56-year-old female came into our office with pain in both knees and her right hip. She reported the knee pain started 3 years prior. The pain was severe in the right knee, with frequent crepitus and instability, and had forced the patient to discontinue running. MRI with a previous physician had shown cartilage degeneration. Right hip pain had been intermittent for 16 years, but instability and continuous pain began six months before her first office visit.

The patient received bone marrow/dextrose treatments for six visits with 8–10 week intervals.

Patient case  – Knee pain – A 56-year-old man

A 56-year-old male came into our office with pain in both knees. The patient is a former competitive weightlifter who continues to do strength training exercises. He complained of instability in both knees during exercise, as well as sleep interruption.

The patient received 29 bilateral dextrose prolotherapy treatments over five years.

At the final prolotherapy visit, sleep interruption was still present, pain intensity was 4/10, and pain frequency was 100%.

Four months later, the patient was treated with platelet-rich plasma. Three months after plasma treatment, the patient began a series of three bone marrow stem cell injection treatments (without dextrose prolotherapy) at 2–3 month intervals.

At the time of the second bone marrow stem cell injection treatment, stability was improved. At the time of the third treatment, pain intensity was 2/10, and pain frequency was 30%. Sleep was no longer affected. These gains were maintained for nine months.

Patient case  – Knee pain – A 69-year-old woman

A 69-year-old female came into our office with pain in both knees. She had been previously diagnosed with osteoarthritis, had arthroscopic surgery to both knees eight years earlier, and medial meniscus repair in both knees 15 years earlier.

The patient reported pain occurred climbing or descending stairs and with standing or walking for two hours. Pain interrupted sleep and limited participation in racquet sports and golf.

The patient received six treatments in both knees with dextrose prolotherapy over a ten-month period.

One year after the final prolotherapy, pain intensity had returned to 4/10 with a frequency of 20%, and sleep interruption had resumed. At this time, the patient received the first of two bone marrow stem cell injection/dextrose treatments, five months apart.

Lipoaspiration, Adipose-derived stem cells, Microfragmented Fat, or Lipogems type stem cell therapy

Lipoaspirate or Adipose-derived stem cell therapy is a regenerative injection treatment that stimulates repair of osteoarthritic cartilage and bone through the use of liposuction aspirates (fat stem cells).

Liopgems is better understood as an FDA-approved device that may make it easier for your doctor to inject adipose stem cells.

There is a lot of controversy surrounding the use of adipose-derived stem cells. This is a treatment that we rarely employ we will use it in selected cases where we would have a good expectation that this is the best option for the patient. The reason we don’t go first to this treatment is that we believe we can achieve similar results with much less invasive treatments.

While bone marrow has historically been used as a source of stem cells, adipose (fat)-derived stem cells have been shown to have:

Researchers have suggested the benefits of Adipose stem cells, here are the take-home points of that research published in the journal Stem Cell Reviews (40):

Direct injection of fat stem cells 

In reviewing the cumulative research of both animal and human studies, doctors at the Rizzoli Orthopaedic Institute in Italy, publishing in the journal Stem Cell International, (41) found the injection of adipose-derived mesenchymal stem cell was first, safe and effective, and that secondly, several aspects favor the use of freshly harvested adipose-derived mesenchymal stem cell instead of expanded or cultured adipose-derived mesenchymal stem cell.

Let’s explore this research a little further. The researchers looked at 11 clinical studies. In these studies, the application of fat stem cells into the knee was performed in many different ways including during arthroscopic knee procedures. This is what they found:

All clinical studies showed that adipose-derived stem cells improve pain and functional scores at a follow-up of between 3 and 36 months.

In three studies MRI analysis was performed, which revealed improved features, including increased cartilage thickness.

Research comparing PRP, Bone Marrow, and Adipose-Derived Stem Cells. Results: They all worked well.

A July 2020 study published in the journal Clinical Medicine Insights Arthritis and Musculoskeletal Disorders, (42) compared platelet-rich plasma (PRP), bone marrow aspirate concentrate, and adipose-derived mesenchymal stem cell (MSC) injections in the treatment of osteoarthritis of the knee using functional scores.

Results: They all worked well.

This is also a validation of our policy of not going straight to stem cell therapy in some of our patients. PRP or Prolotherapy, which is discussed below can provide equally good results without the added expense.

Amniotic, Cord Blood and Placenta Tissue

There is a great amount of misinformation surrounding “amniotic stem cell therapy,” and “umbilical cord blood stem cell therapy.” We have never offered these treatments.

The primary reason we do not offer these products is that we did not find them to be more effective or economically viable to the patient than the utilization of the patient’s own stem cells (which we rarely offer) and because we find simple dextrose Prolotherapy and Platelet Rich Plasma (PRP) to be effective treatments which, in our observations, yield similar if not better results.

Amniotic “stem cells” marketed in many chiropractic offices are, in reality, micronized amniotic fluid. The micronization process takes amniotic fluid, freeze-dries it, and then processes it. The process kills the stem cells. NO live stem cells are present. However, growth factor remnants remain.

Many people attend webinars and seminars on the benefits of amniotic/placenta, umbilical cord stem cell therapy. These seminars are often conducted by a chiropractor whose presentation includes a segment on how the attendees of the seminar have joint pain because their own stem cells are too few, too weak, too feeble, and too old to repair the damage.

The great irony of this argument is if you have been told that your own stem cells are too few, too weak, too feeble, and too old, how does the amniotic tissue then work if it has no new stem cells in it?

For amniotic tissue treatment to work, it must work at the expense of debunking its own marketing claim that your stem cells are too few, too weak, too feeble, and too old to work.

Initial comparison:

How does Prolotherapy work in your knees?

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

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. (43) In this review, we examined the research in the use of dextrose Prolotherapy for the treatment of tendinopathies, knee and finger joint osteoarthritis, and spinal/pelvic pain due to ligament dysfunction. In our section on knee pain, we referred to a study by Dr. Fariba Eslamian and Dr. Bahman Amouzandeh of Tabriz University of Medical Sciences. This is what they published in the journal Therapeutic Advances in Musculoskeletal Disease. (44)

“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.”

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

Recent research:

We have extensive research at our explained article: Prolotherapy knee osteoarthritis research: An option to knee surgery. This article presents the summarized learning points.

A May 2020 study in the Annals of Family Medicine (45) made this simple statement at the conclusion of the research findings:

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

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

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

Another study from May 2020 published in The Journal of Alternative and Complementary Medicine (46) made these observations:

In January 2019, David Rabago, MD, of the University of Wisconsin School of Medicine and Public Health, published research on Dextrose Prolotherapy for Symptomatic Knee Osteoarthritis in the Journal of Alternative and Complementary Medicine. (47)

Here are the learning points of that research:

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

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

In this image of a patient being prepped for and 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: Prolotherapy treatments for patients with knee osteoarthritis showed significant improvement in scores for pain, function, and range of motion

In February 2020, Lisa May Billesberger, MD  a private practice physician in Canada teamed with Duke Anesthesiology, Duke University School of Medicine to offer a current assessment of injectable treatments for Knee Osteoarthritis. (48) Here are the summary points on Prolotherapy.

Caring Medical Research – Prolotherapy for Knee Pain

In published research in the Journal of Prolotherapy, (49) Ross Hauser MD investigated the outcomes of patients receiving Prolotherapy treatment for unresolved, difficult to treat knee pain at a charity clinic in Illinois.

Prolotherapy for knee osteoarthritis

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.

Comparison research

We are going to cite some research that compares Prolotherapy to other treatments. We will start with this study. Then further below we will cite other studies.

In an August 2019 study, researchers published data comparing Prolotherapy to other injection techniques. The data was published in the journal Advances in Rheumatology. (50)

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

This is what the researchers noted:

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

To finish our comparisons first an explanation of Botox injections, then Ozone injections.

Botox for knee pain

Botox® is better known as a muscle paralyzer or relaxer and can help with muscle pain or spasms, in knee pain, it also works primarily as a “nerve blocker.” Therefore Botox® does not offer a repair of a damaged knee but rather it is a suppressor of symptoms.

Some people do find pain relief. While there is not, however, a lot of research to support the use of Botox® for knee pain, some studies suggest benefits, and other comparative studies pitting Botox® against other treatments seem so-so.

In July 2019 researchers published data to suggest the benefits of Botox® in the journal Toxicon. (51) This journal studies the use of toxins in medicine.

Here are the learning points:

What the researchers wanted to measure was:

Comparing Botox® to other treatments

A June 2019 study in the journal Clinical Rehabilitation (52) compared the effectiveness of intra-articular injection of Botulinum toxin type A (Botox), triamcinolone hexacetonide (cortisone), and saline in primary knee osteoarthritis. The study found the cortisone injections had higher effectiveness than Botox or the saline (placebo) in the short-term assessment (four weeks) for pain in movement.

Study: A comparison between Prolotherapy, Botox, Physical Therapy and Hyaluronic Acid Injections

Here we have a September 2020 study published in the International Journal of Rehabilitation Research. (53) In it, researchers compared the effectiveness of four treatments in the management of knee osteoarthritis.


Comparison of Ozone Therapy, Cortisone, Hyaluronic Acid Injections, and Dextrose Prolotherapy injections

There is a significant amount of research surrounding the use of ozone (o3) in treating various diseases. In this section, we will limit this research to comparative research.

An October 2018 study in the Journal of Pain Research (54) compared ozone treatments with Hyaluronic Acid Injections or Dextrose Prolotherapy injection as the control group.

Please note that this is not a comparison of Prolozone® to the other treatments, this is a comparison of ozone alone.

The researchers wrote that “the existing body of evidence had well demonstrated that ozone injection was evidently effective for short-term management (1–3 months) of mild-to-moderate knee osteoarthritis patients (grade I–III KLS). But the main challenge was on longer periods of time in which different studies had declared heterogeneous (or mixed) results.”

The researchers gathered dates from a series of randomized control trials and made these observations:

A 2015 study in the journal Anesthesiology and Pain Medicine (55) showed that:

Prolozone® is a Prolotherapy technique developed by Frank Shallenberger, MD, that utilizes ozone gas, along with other therapeutic substances to stimulate healing and reduce pain in injured soft tissues and joints. Dr. Shallenberger describes Proloze in a 2011 article in the Journal of Prolotherapy as: “a technique that marries concepts from neural therapy, Prolotherapy, and ozone therapy. It involves injecting various combinations of procaine, anti-inflammatory medications/homeopathics, vitamins, minerals, proliferative, and a mixture of ozone/oxygen gas into degenerated or injured joints, and into areas of pain. The result of this combination is nothing short of remarkable in that damaged tissues can be regenerated, and otherwise, untreatable pain can be permanently cured.”(56)

The ozone gas is produced when oxygen is exposed to an electric spark via a corona discharge ozone generator. The concentration of ozone in the final gas mixture is between 1­3%. Therapeutic injections of ozone into soft tissue structures, such as muscles, tendons, and ligaments as well as arthritic joints for the relief of pain have been utilized for decades in medical clinics around the world.

Various case series have been published documenting the analgesic effect of ozone in osteoarthritis. Double ­blind randomized ­controlled studies have also documented the therapeutic effects of Prolozone® in the treatment of low back pain with and without sciatica. As a powerful oxidizing agent, ozone has been found to have a pro-­inflammatory as well as an anti-­inflammatory effect, depending on the concentration utilized. Its proposed mechanisms for tissue repair and regeneration include the stimulating of growth factor production and release.

Another comparison of Ozone, PRP, and Hyaluronic Acid

A February 2021 study (57) compared the short and long-term efficacy of the intraarticular injections of hyaluronic acid, platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), and ozone in patients with knee osteoarthritis.

Results: In 2 months of follow-up, significant improvement of pain, stiffness, and function were seen in all groups compared to the baseline, but the ozone group had the best results. In 6 month follow up hyaluronic acid, PRP, and PRGF groups demonstrated better therapeutic effects in all scores in comparison with ozone. At the end of the 12th month, only PRGF and PRP groups had better results versus hyaluronic acid and ozone groups in all scores. Despite the fact that ozone showed better early results, its effects begin to wear off earlier than other products and ultimately disappear in 12 months.

Conclusions: Ozone injection had rapid effects and better short-term results after 2 months, but its therapeutic effects did not persist after 6 months and at the 6-month follow-up, PRP, PRGF, and hyaluronic acid were superior to ozone.


We hope you found this article informative and it helped answer many of the questions you may have surrounding these various injection treatments. If you have questions you can Get help and information from our Caring Medical staff


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This article was updated September 20, 2021

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