- Platelet-rich plasma (PRP)
- Stem cells
These injections are used to treat a variety of musculoskeletal injuries and are considered if conservative treatment fails. Controversy still exists around regenerative and non-regenerative injections. Conflicting research shows either favourable or unfavourable results depending on the type of injection. Whether medical injections will become standard in musculoskeletal medicine remains to be seen.
Katie Yamamoto (KY): This is Episode 18 of Functional F1rst Podcast, where we speak with leading experts in the field of functional health. I’m Katie Yamamoto from FXNL Media, and today I’m speaking with Dr. Douglas Stoddard, Medical Director of RegenerVate, about therapeutic medical injections.
KY: Thank you for letting us interview you today.
Dr. Douglas Stoddard: My pleasure
KY: Can we start by having you introduce yourself?
Sure my name is Douglas Stoddard, I’m a sports medicine physician in Toronto. I’ve been practicing sports medicine since the mid-90s and specific interest in regenerative injection therapy for about 7-8 years now.
KY: So what are the different types of injections used in sports medicine?
Well there’s five of them that are used commonly, the first is cortisone. It’s been around for a long time, it’s the go to injection with a lot of physicians who are injecting joints for arthritis, for instance to try and calm down some pain. Prolotherapy is another one, that’s been around for about 70 years or so. Those are usually dextrose or sugar-based solutions with other additives to try and help stimulate healing in damaged tissue. Viscosupplementation has been around for about 20 years or so. Those are lubricating gels that are injected into arthritic joints. The fourth one is platelet rich plasma. That’s been big for about a decade and has a regenerative effect on tissue, tendons, joints, and so has really come of age as far as being commonly used for stubborn injuries. And the fifth one is a stem cell procedure that really has taken off in probably the past 5 to 7 years and adds a source of stem cells usually mixed with platelet rich plasma again in the tendons or joints, wherever the damage is.
KY: What are the differences between the injections? How do you determine which one to use?
Well really you can broadly divide them into regenerative injections and non-regenerative injections. So the non-regenerative injections would be cortisone, and personally I don’t use a lot of cortisone I feel there’s better options for patients nowadays, but cortisone still is used in a lot of circles. In an acutely inflamed joint or area of the body cortisone can still be useful it is a good anti-inflammatory, however there are questions about its safety and especially with repetitive use over time and possibly a degenerative quality to the drug. Prolotherapy and dextrose or sugar-based solutions form one of the regenerative injections, and they’re regenerative so they actually have a healing effect on the tissue and can be very useful from that perspective. Viscosupplementation is non-regenerative, we think it lubricates arthritic joints and probably has some metabolic effect on the joint but the truth is we’re really not certain how these injections work, but they can get some relief in arthritic joints. Platelet rich plasma, again in the regenerative side of things, and for me I’m using more and more regenerative injection so that becomes a common one that I would recommend patients, and the same with stem cells. So again it really comes down to regenerative or non-regenerative and whether you think the drug is ultimately helpful and healthy for the tissue being injected.
KY: What are the physiological mechanisms of how these injections work?
Well cortisone is an anti-inflammatory, very strong anti-inflammatory, so it does do a good job with inflammation as I said, but probably isn’t very healthy for the tissue being injected. The regenerative injections all have a role in terms of stimulating tissue repair, they do it differently but the final outcome is a stimulus to help repair damaged tissue. So whether we’re talking about prolotherapy and dextrose type solutions, or platelet rich plasma, or stem cell transplantation, the goal of all of these injections is to actually stimulate repair in damaged tissue. There are variety of other mechanisms thought to be related too, and we still are trying to understand and discover the extent of these mechanisms, but the bottom line is there’s a positive effect on damaged tissue.
KY: Can you explain the procedure of these types of injections?
The cortisone and viscosupplements are straight injections from a premade vial of the drug, very simple. Prolotherapy involves mixing up a solution of dextrose mixed with some other ingredients, sometimes it’s just normal saline, sometimes it’s anesthetics, sometimes it’s things like cod liver oil, again all designed to stimulate an inflammatory reaction in whatever you’re injecting, with a view to try to help the tissue repair itself. Platelet rich plasma we get a little more interesting, we had to draw some blood out from the patient, small quantity, usually anywhere from 30 to 60 cc’s of blood, which is about 2 to 4 tablespoons, so it’s not a whole lot. And we place it in a container and then place that container into a centrifuge. The centrifuge spins very quickly and separates different components of the blood, and one of the components we’re interested in is called the platelet rich plasma or PRP. This is a component that’s got a higher concentration of platelets, which are cells found in the blood, and these platelets make growth factors, which are compounds, proteins, that are used to help tissue heal itself. So we take that concentrate and then we inject it into the target tissue using ultrasound guidance to help us know exactly where we’re replacing the platelet rich plasma. Stem cells are one step further, where we harvest the source of stem cells. That can either be bone marrow, it can be fat, there are some external sources say from stem cell banks where we can buy stem cells, and whatever the source is we combine that with platelet rich plasma and we inject that into the target, again usually under ultrasound guidance so we know exactly where we’re placing the injection.
KY: Are all the injections done using ultrasound guidance or just the PRP and stem cell?
Prolotherapy uses a slightly different technique, it’s a multiple injection technique that isn’t necessarily ultrasound dependent, whereas platelet rich plasma and stem cells we definitely want to use ultrasound guidance so we know exactly where we’re placing things, because those are typically one-shot approaches, we want to target the area in the body that’s damaged and we want to be very specific with where we’re placing those injections.
KY: With stem cells, are there different types of stem cell procedures?
It’s more based on where you harvest the stem cells from, but the final common pathway is a source of stem cells usually mixed with platelet rich plasma and then injected. So again, we can harvest them from bone marrow, we can take them from fat, or purchase them through third parties who supply them, but at the end of the day, it is believed that all of these sources of stem cells still contribute stem cells that are useful in the repair of the musculoskeletal system.
KY: What are the criteria for someone to be eligible for these treatments?
Usually they’ve not done as well as we would have liked with what I call level 1 interventions, and those are the conservative interventions: therapies of various types, orthotics, bracing, some medications that can be helpful for pain and inflammation, and of course modification of activities allowing the person some time to let their bodies heal. And those interventions work great for the majority of people, I say about 90% of patients who have an injury will respond to the level 1 interventions. The injection level is what I call level 2, so we’re getting more invasive, we’re penetrating the skin, therefore we have some risks when we do that, whereas level 1 interventions really have no risks that are concerning. So level 2, now we’re in the injection level, we are incurring some risks, not many and not high probability of risks, but nonetheless we have some risks. Level 3 is the surgery level, and that’s the level that is most invasive and of course has most risk associated with it. So I divide the treatment of the musculoskeletal system into those three levels and we try and start at the bottom and work up to the top if we have to, only going to a level we have to go to.
KY: So for healthcare practitioners who treat that level 1, at what point would you say that they should refer a patient on to discuss injections?
I think it comes down to when the patient feels frustrated that things aren’t responding the way they want them to respond, and as long as they’ve given it a reasonable try. I really think we have to be encouraging patients, in most cases, at least a six week to eight week period of time of working on level 1, in some cases could be even up to six months working on level 1 interventions before we move them into the level 2 area, and we certainly don’t want to go to level 3, the surgery level, until we’ve exhausted you know both level 1 and level 2. But for most injuries that are acute injuries six to eight weeks, for more chronic related injuries, could be up to six months of working on level 1 interventions, but at that point if patients are frustrated that they’re not progressing and as long as they put in their homework and done what they needed to do to really try with level 1, then we usually start thinking about level 2.
KY: How long do the injections normally last for, the results?
That’s a good question and the answer is that there’s a range and really does depend on the individual. We are seeing results last as long as two to five years with patients and some even longer but some shorter and it really is variable. Our data is showing that we’re seeing 80% of our patients who get these injections have some positive response, and that ranges from one end of the continuum with feeling slightly better, all the way to the other end of the continuum, where they literally feel a miracle has taken place and they feel fantastic. And the length of those results is highly variable, but our aim and what I say to patients is our aim, and we hope for, two to five years of relief and improvements, and we are seeing that, and of course there are outliers on both ends of the spectrum as well.
KY: For someone who does get an injection, do they need to then continue with those level 1 interventions, like physiotherapy, after the injection?
Well right after the injection we want patients to be getting therapy, and I’m talking about the regenerative injections. Target tissue, whether it’s tendons or joints, do get more painful after these injections and that’s very normal, sometimes that’s surprising to patients. They seem to understand that they’re going to be worse after surgery for a while, but sometimes in the excitement of getting a regenerative injection and avoiding surgery they’re not expecting a flare-up. So we always want them in therapy after regenerative injection, usually it’s a six to eight week period that we encourage, and then they’re on their own doing exercises at home. The goal would be to continue with those exercises as part of their lifestyle and incorporating that as part of their workout routine, really for the rest of their life, to maintain the integrity of that structure that we’ve just hopefully improved with these injections.
KY: Are there are specific protocols that therapists should be following for patients post injection?
There are, and we have protocols that we’ve designed for every injection that we do, based on body part. So there are guidelines that we feel are important. You know, a therapist who’s comfortable and familiar with post-operative patients should not have problems doing these types of post-injection rehabilitation projects with patients, but we do have guidelines and protocols in place.
KY: What are the risks of the injections?
Well the risk of any injection, they really come down to a few of the same risks, no matter what your injecting, whether you’re injecting cortisone, prolotherapy, viscosupplements, stem cells, PRP. What you’re injecting actually has very little to do with risk most of the time. It’s the fact that you are injecting, meaning you’re penetrating the skin and opening the body up to the air or the environment. So the number one risk we quote patients is infection, and again whether you’re getting a flu shot or getting an injection into a tendon or joint, regardless of what you’re injecting, there is always a risk of infection. But thankfully the risk with injections is very low terms of infection rate we quote a risk of one and 20,000, which is very, very low and far lower than any surgical infection risk for instance, but the risk isn’t zero so patients have to know about it. Other risks include hitting a nerve or hitting a blood vessel that you may not want to hit. The good news is that even if you were to hit a nerve or blood vessel most of the time, and I’d say 999 times out of a thousand, there is no long-term problem. You know, if a blood vessel is hit it might bleed and we press on it and typically it stops bleeding just like we’d expect. If we hit a nerve, the nerve might be irritated for a few weeks and then calm down, and typically it’s not a long-term problem. We do use ultrasound guidance so we try our best to avoid the structures and you know when they’re visible on the screen and in the image we avoid them. They’re not always clear and visible, but certainly ultrasound reduces the chances we’re going to run into something we don’t want to hit. With fat aspiration or fat stem cell procedures, because it is really a mini liposuction, there are risks to liposuction that have been well publicized with problems that patients run into. But these are liposuctions that involve removing high quantities of fat often in the several liter sort of amount. When you remove several liters of fat from a person with that classic cosmetic liposuction, there are different risks that that patient will face, there’s no doubt about that. They are to do with the idea of removing those massive quantities of fat, and the procedure that you need to go through in order to do that. With stem cell procedures that are using fat, this is called a mini-liposuction, we’re removing 30 to 60 cc’s of fat, this is 2 to 4 tablespoons, far, far less than the quantities that we see harvested with a cosmetic liposuction. So while the theoretical risks apply to a mini-liposuction as we may see in a cosmetic liposuction, I’ve never seen any of these risks result from one of these mini-liposuction procedures.
KY: Are there any patients who you would not give an injection to, for example because they had a lot of comorbidities or something like that?
You know that’s the beauty of the injection level is that it is a safer approach versus surgery and there are patients that aren’t great candidates for surgery because they do have other illnesses where you don’t want to put them under general anesthetic for instance because the risk of them having a problem is too high. The injection level, because it’s very safe and the risks are relatively low, there’s very few patients that don’t qualify from a medical perspective in terms of getting injection therapy. There are some patients where you may say no due to the idea that you don’t think you’re going to be able to help them. For instance a complete tear in a rotator cuff tendon, a shoulder tendon. So far we haven’t had much luck with injecting those, they usually need the surgeons if a patient has ongoing pain. In time that might change as our techniques improve, but a person with a complete tear in their rotator cuff I would say “I’m sorry but you’re not a great candidate at this stage for this type of intervention”, but from a medical perspective that’s one of the nice things about the injection level of things is that there’s very few people you rule out due to comorbidities or other health related problems. You also may say to a patient, look you’re not the best candidate because you smoke or you have diabetes, and we think that those things will affect your ability to heal after this type of injection. Or you have thyroid disease where, you know, were not confident that they have the same healing capacity as another individual, but that doesn’t mean we can’t try the injection, it just means we have to tell the patient that the chances of success in you will probably be less.
KY: What are you noticing clinically with your outcomes of these injections?
We are seeing about an 80% response rate, so 80% of patients get some positive response ranging from a tiny bit of response on one end where they might say “well I can get up out of the chair easier” or “I can lift my arm above my shoulder easier to brush my hair but I’m still feeling some discomfort but it’s not like it was”, all the way to the other side of the continuum were patients feel like “wow this is amazing and I’ve not felt this well in years”. So 80% are getting positive response, 20% of patients at this stage are not getting a response and we wait six months to analyze this because it can take six months for the regenerative process to finish, especially with stem cells. But 20% of patients at the six month mark have not responded in the way that we wanted them to. We don’t yet know why, and were still trying to understand that. But again these are typically patients that are trying their best to avoid surgical intervention and they’re willing to try and embark on this injection process even with a 20%, you know, risk that they’re not going to respond the way we would like them to.
KY: How do you determine whether an injection is successful? Is that largely based off of the patients’ report of pain levels and function?
Primarily yes. So we do, pre-injection, a survey of pain and function, and every body part has scientifically validated questionnaires where we can develop a score for that patient’s pain and function. We then repeat the score three months and we repeat the score at six months. So far that’s as long as we have taken out our surveys, in the near future we hope to actually start surveying our patients longer than that in getting scores at, you know, one and two years and even beyond if we can, to try and see what happens to these patients over time. But right now we do a pre-injection, three-month, and six-month score, which helps us understand how they’re feeling. Imaging sometimes can be used pre- and post-injection to quantify changes in tissue, but this is a little more tenuous as far as the results that we can rely on, and sometimes imaging does not really help us with assessing the response of these individuals, but the scores definitely give us a pain and function assessment based on a bunch of questions that have been filled in.
KY: We spoke a bit about cortisone, and you said you don’t really use it much in your practice. What is your opinion on the use of corticosteroids in sports medicine?
I think as much as possible we need to keep them at a minimum. In my view there are very select reasons we may choose to use a corticosteroid or cortisone. Because they’re a very strong anti-inflammatory there are very good at killing inflammation. Inflammation is a very common cause of pain, especially in acute injuries. If someone has been struggling with an acute injury where we think inflammation is the culprit and nothing is settling them down, for instance an oral anti-inflammatory medication combined with some therapy, relative rest from an activity that’s causing pain, dietary changes which we’re recommending more and more toward anti-inflammatory diets, compounds in our diet that can be anti-inflammatory. If a patient has been through those steps and we really believe it still inflammation that’s causing pain, because it is not always the case, but if we believe that, then a low dose of cortisone injected into the target tissue can be helpful in quickly reducing pain. The challenge there is that it doesn’t mean the pain is not going to return or the inflammation is not going to return, but it is a way of giving people some quick relief because it will do that usually. However in a lot of pain that is associated with musculoskeletal injuries there is actually very little inflammation, and we know that based on tissue biopsies. And these are areas and situations where the body actually has degenerative change in the tissue, rather than inflammatory change. Degenerative change is not something we really want to put cortisone in and around if we can avoid it, because the pathology in that situation is not inflammation. So we may inject, patient might feel temporarily better because there might be some very low level inflammation even with degenerative change, but in those situations invariably pain will return because the degenerative change has not been looked after or addressed. On top of that you’ve added a drug that can be degenerative to tissue that already is degenerative, and for that reason again I’m reluctant to use cortisone in most situations.
KY: For a patient who did have more acute pain and got a cortisone injection and came to you couple years later saying “oh this worked for me before, but now my pain is back” and wanting another one, would you direct them more towards the regenerative injections?
That’s a really good question because it happens a lot, you know, and patients are still getting a lot of cortisone injections. Sometimes they’ve worked satisfactorily because it was an inflammatory problem. Sometimes it just gave them temporary relief, but they’re very desperate to get more temporary relief. So if it’s a long-standing injury where normally we can assume it’s a degenerative process that is causing this long-standing pain, then I will definitely steer them away from a repeat cortisone injection, and we start trying to understand why that tissue is still painful, is there a degenerative component because often there is, and if there is we really need to start working on the regenerative injection approach with these individuals versus more cortisone.
KY: With any of these injections do you do imaging before to find out the condition of the tissue?
Absolutely, you know you can usually with accuracy assume that a chronic injury, and that usually something greater than three months, has some degree of degeneration associated with that injury, and the longer you go beyond three months of being in pain the more likely you’re going to have some degenerative component. Imaging can help confirm that, for sure. It’s not always needed, for instance, a 60-year-old person with knee pain that’s been present for five years that swells recurrently and may have feelings of instability is 99 times out of 100 osteoarthritis. We know that that’s a very common affliction of middle aged and older individuals and with the story very consistent with what we know of osteoarthritis. We can usually with pretty good confidence say this is an arthritic knee. We may at times want to confirm that so we might send them for an x-ray for an example. With tendon injuries I like to use ultrasound prior to moving along any pathway with the individual. Ultrasound is a good test for tendon injuries, it can see degenerative changes, it can also see tears. Tears are important to know because that is often a reason why a person has chronic pain coming from a tenant is due to a tear. So I like ultrasound exam prior to injecting any tendons, A- to document degenerative change yes, but more importantly I’m looking for tears. And the tears will help me advise the patient what’s going on in that tendon and why is probably causing ongoing pain, and what injection we should choose, or surgery depending on the situation, based on those results and the clinical picture of the patient and what they’ve already tried.
KY: I know there’s a bit of skepticism around PRP and stem cell injections because they’re still consider new and there’s not a ton of research on them and they haven’t been proven in clinical trials. So what are your thoughts on this?
So we’ll start with “is it experimental?” and I would say that these injections are long out of the laboratory, long beyond the experimental phase. We have practitioners internationally who have been doing these injections for a decade or more with a vast accumulated body of experience with what would have to be hundreds of thousands of patients internationally. So it is most definitely not in the experimental phase, and I think that’s an important thing to let people know because there are still thoughts that it somehow still confined to the laboratory and animal research and, you know, we should not to be using these injections in humans and my opinion is that is definitely not accurate. Number two: “what evidence is there to support the use of these injections?” In fact there is a lot of published research on these injections. As in any part of medical progress, it really takes 20 or 30 years for research to reach the conscious level of most of the profession because unless you’re specifically looking for these articles and following the research in a specific area you’re just not going to be aware that they exist, but there is a lot of research being published on a regular basis in this area. There’s even been meta-analyses of randomized controlled trials in the area of stem cell injections, as an example, say for say arthritic knees. So you know the gold standard in research, which is a randomized controlled trial, has being done many times analyzing stem cell injections and meta-analyses is another additional level of investigation to come up with results. So this research is ongoing, you can search clinicaltrials.gov, which is a storehouse of all the projects, research projects, in the world being done on any topic. And if you plug in stem cells and arthritis as an example in clinicaltrials.gov, you’ll usually come up with a hundred to 200 studies that are currently ongoing that have been registered with this website, and then if you search a website like pubmed, the website for the National Library of Congress in the US, which is again a storehouse of all published research to date, you’ll find hundreds of articles on these topics. So there is a very strong body of research that supports the use of these injections. There is some concern at the academic level and the policymaker level that maybe these injections aren’t ready yet to inject humans. Those of us that a been doing them for years, and have done hundreds of them have observed an excellent safety profile, as I said an 80% chance of improving and have not really had any side effects or untoward results that would concern us that these are injections we should not be offering to patients.
KY: Are there any regulations around the field of regenerative injections?
Every country has their own approach, with stem cells I’m talking about because platelet rich plasma really isn’t stirring up too much controversy, but stem cells are because they’re associated with a lot of potential situations that people are concerned about. We go back to say the use of embryonic stem cells in research and in human health and, you know, this creates some controversy for sure. In our injections were using adult stem cells or at least non-embryonic stem cells. We may inject a person who’s, you know, 12 years old with this procedure, but we wouldn’t call him an adult, but at least they’re non-embryonic stem cells, and there are autologous meaning there the patient’s own stem cells. And then the other thing is, is that most first world countries have stipulated that we are not allowed to grow or expand stem cells. We can’t reproduce them in a laboratory and turn their numbers, you know, let’s say we take out a million stem cells from a patient we can grow them in a lab and make them into 10 million stem cells, which is called expansion. Expansion has been associated with some potential problems with the quality of the stem cells and because we are expanding stem cells, which are very important cell of the body, most first world governments have said you cannot do that. So we can’t expand those stem cells, we can grow them in laboratory, we cannot add a drug to them, we can’t change them in any material way. All we can do is take them out, we could clean them and concentrate them, which is what we do with our procedures, but within an hour we’re putting them right back in again into the target tissue. So these are called minimally manipulated procedures and with these types of procedures there are no current guidelines that suggest we cannot do these procedures, because again they are minimally manipulated. In this in my opinion is where it should be, we should not be restricted in giving these types of injections because they are minimally manipulated and simultaneously the concern around using minimally manipulated injections in my opinion should not be, you know, the levels where it is, because it they are minimally manipulated. Expanded procedures where we’re growing stem cells, adding drugs to them, etc., those are definitely different category and I believe that guidelines and restrictions in those areas are needed and are useful to guide, you know, the profession, medical profession, academics etc., but not minimally manipulated procedures.
KY: Where do you see the future of these types of injections going?
Well they’re here to stay, that’s for sure. The results we’re seeing, the patient satisfaction were seeing, and the goal of helping the body heal itself, which still remains in my opinion the primary goal in medicine, is for us to be able to take any ailment that we face as people and to understand how to help the body heal itself. We specialize in musculoskeletal injections: tendons, joints, ligaments, and cartilage, but this field is gone so far beyond that. You know, neurological illnesses, things like multiple sclerosis, ALS, really cruel stuff that people have to, you know, live with and unfortunately succumb to. Cancers of all types, heart disease where a person has damaged their heart due to a heart attack and us being able to regenerate that damaged heart muscle, type 1 diabetics with pancreases that don’t work with making insulin, being able to regrow and stimulate healing in that person’s pancreas. This is where it’s going and this is where were at now, so there’s a lot of excitement in this area and it’s only going to evolve and we’re going to get better and better at using these technologies to help patients.
KY: What is the training like to be able to provide these services?
Well as doctors, you know, we’re all trained early in our careers to inject things, you know, we’re comfortable with needles and it’s second nature. Musculoskeletal injections need to have another level of training to be good at it and that’s ultrasound training, where you’re comfortable guiding a needle into a target in the body using ultrasound to guide you. So there is a whole other level of training and experience needed to help you become a competent and confident musculoskeletal injector, if you’re going to be using these techniques. Otherwise as I said physicians, you know, come out of medical school pretty happy and comfortable injecting things, this is just another next level of injections needing some ultrasound training and experience.
KY: Where can people find out more about you?
Well our website specifically for injections is www.regenervate.com and all the information but what we do and what we inject is on that website with contact details and phone numbers as well, but that’s www.regenervate.com.
KY: Ok, thank you.