Dr. Daniel Kaplan:
Welcome to the Arthroscopy Journal Podcast, I'm Dr. Daniel Kaplan from NYU Langone Medical Center in New York City. Today, I have the pleasure of speaking with Dr. Brian Cole, chair of orthopedic surgery at Rush University, managing partner at Midwest Orthopedics, past president of AANA, head team physician for the Chicago Bulls and about 10 million other titles but we're supposed to keep these episodes under five hours so I'm going to cut it there.
Dr. Cole is the senior author of the article titled, Bone Marrow Aspirate Concentrate May Decrease Reoperation in Osteochondral Allograft Transplantation, a prospective randomized double-blind Investigation which is currently in press on the Arthroscopy Journal website. He's also one of my personal mentors from fellowship and a world leader in cartilage restoration so I could not be more excited to speak with him today. Welcome, Dr. Cole, it's a privilege to have you on.
Dr. Brian Cole:
Thanks, Dan, and I appreciate you guys featuring this article. And Dan, I also want to take a moment to make sure I acknowledge my co-authors as part of this paper related to bone marrow aspirate concentrate as an augmentation to osteochondral allografts and that most importantly includes Drs. Yanke, Dandu, Bodendorfer, Haneberg, Darwish, Zavras, Forsythe and myself. Without their hard work and their commitment, we would've never accomplished this very difficult study which is a double-blind randomized controlled trial so important to make sure they get the recognition that is deserved.
Dr. Daniel Kaplan:
So, let's just start with some basics as our listeners will be coming from various backgrounds and experience levels. So, to start, can you just help us understand what an osteochondral defect is and how this may be different from osteoarthritis?
Dr. Brian Cole:
Yeah, sure. I think that's a good idea just to set the foundation. So, an osteochondral defect is a form of cartilage and bone loss and, most commonly, we're talking about the knee but we certainly see this in any diarthrodial joint. But an osteochondral defect is an area devoid of cartilage and I would say, maybe even back it up a bit and say cartilage defect because these same treatments, an osteochondral allograft, can be used for cartilage loss without significant bone loss. So, it's for cartilage, cartilage and/or bone loss and there's a variety of treatments for this but an osteochondral allograft is one common treatment performed and, as mentioned, most commonly, these are problems within the knee.
Dr. Daniel Kaplan:
So, if someone has an osteochondral defect, what are the type of symptoms they might be experiencing?
Dr. Brian Cole:
Depending upon the chronicity or how long an individual's had this problem, I would say the most common complaint will be weight-bearing or load-related discomfort. There may be other symptoms such as activity-related effusions, achiness, things of that nature but, unlike osteoarthritis, it's less likely to be individuals who predict weather change, who have that toothache feeling and so forth but rather their chief complaint is often activity-related pain that is elevated with loads with or without swelling and, very rarely, locking, catching or mechanical symptoms. But, otherwise, their exams and so forth are usually pretty innocuous, it's usually subjective complaints in the face of activities.
Dr. Daniel Kaplan:
Got it. And then, once a defect is identified, so they're presenting with that toothache, that swelling, that weight-bearing pain, what's your typical algorithm? Does everyone who has that needs surgery? Are there non-operative treatment options?
Dr. Brian Cole:
I think it's important to understand that these are very common things. In fact, probably 40% or more people in adults are walking around with some type chondrosis or cartilage loss, not necessarily overt arthritis, but areas of cartilage demise and we will ... The first thing is actually assigning appropriately the symptoms to that problem because there's lots of reasons to have joint pain. So, making sure that the problem is indeed coming from the source which is a cartilage or bone and cartilage problem.
And then, secondarily, there are often opportunities to treat these without surgery, sometimes it's what I call skillful neglect is educating the patient that these are common, that there's not a lot of data that shows that neglecting them will lead to defect progression and that, if symptoms can be tolerated or even modified with simple things such as anti-inflammatories, sometimes even some type of very safe injection, weight loss therapy, things of that nature, we often take that course depending upon the individual rather than jumping right to surgery.
Dr. Daniel Kaplan:
Skillful neglect is an incredible term and something I'm going to adopt for sure. That's better than watchful waiting.
Dr. Brian Cole:
Oh, so that's a first for you?
Dr. Daniel Kaplan:
I think so. That's a great one.
Dr. Brian Cole:
I love it, I love it.
Dr. Daniel Kaplan:
Yeah, I'm going to back pocket that.
Dr. Brian Cole:
All right, we never stop learning. I love it.
Dr. Daniel Kaplan:
That's why I do these podcasts, for pearls. All right. So, let's say we're now moving a little bit into the surgery realm, what's the rationale for cartilage restoration? So, when you think about this, and this was something I thought you emphasized in fellowship really well, are you thinking more about symptomatic treatment or is there more long-term benefits? Are you telling them you're preventing future arthritis by restoring their cartilage?
Dr. Brian Cole:
Yeah, and I think the interesting thing is there's definitely been a paradigm shift. I would say, even since you did fellowship, which wasn't that long ago, I've spent a good part of the first part of my career looking at ways and collaborating to figure out how we can restore cartilage when the reality is this is probably a bone-cartilage problem more than anything else. So, I think that the big challenge is how do we alleviate symptoms and most patients make decisions for today, not necessarily tomorrow. So, as I intimated, the natural history of these is somewhat poorly understood, it is not always associated with an actual progression so we're really looking for symptom relief. And what's fascinating is that we don't necessarily have to have perfect cartilage restoration or perfect joint restoration to get patients to achieve symptom relief.
So, there are lots of different options that we use and not all of them are perfect but, amazingly, patients can actually feel better and I think that's because we're paying much more attention to the osteochondral unit and there's a lot of things that can actually treat that, that can relieve a patient's symptoms without actually restoring it perfectly as we started before some type of degeneration or damage that occurred. So, that's a little bit of a paradigm shift as opposed to what we used to speak about which was, hey, there's cartilage loss, that's the cause of symptoms, you got to make it perfect and that's going to give them a long-term outcome. The reality is I think we have a fair amount of variability that could otherwise lead to success in terms of reducing the patient's symptoms in improving their activity levels.
Dr. Daniel Kaplan:
Yeah. I really like that and I just saw your and Dr. Yanke's article coming out for AGSM talking about the success of even chondroplasty and second stage MACI.
Dr. Brian Cole:
Right.
Dr. Daniel Kaplan:
So, that's something that I've taken into my practice too, that treating more the symptom that are now problems.
Dr. Brian Cole:
Yeah, agree.
Dr. Daniel Kaplan:
Related to that, so if we've reached the point of surgery, they have a cartilage defect, let's say, it's unequivocal, a medial femoral condyle, what are your thoughts on staging scope first versus directly treating with cartilage ... like an OCA plug?
Dr. Brian Cole:
Yeah. So, it's very rare that I would start with my first line treatment if it's surgical with, say, an osteochondral allograft. There will be occasion but I would say the most common scenario is that, because we've identified a group of patients either with tibiofemoral problems or patellofemoral problems that might be responsive to arthroscopic debridement, and I'm not just saying general just take a shaver and clean up flaps of cartilage and things of that nature, we've taken a more aggressive approach that, at least I have, especially in high level athletes, that it's not marrow stimulation formally but it almost approaches abrasion arthroplasty. What I mean by that is that we do a very ... A lot of these individuals will complain of these biologic symptoms and effusions, for example, and that's taking them out of the game and it's the biologic debris that leads to that.
So, we've had a lot of success with initial treatments being fairly intentional debridements where we're getting rid of flaps and things like that if there's truly degenerative tissue within the lesion, I will now curette it, create vertical walls, get rid of all the debris, do a thermal synovectomy, things of that nature that can titrate the joint to make someone feel better and it's amazing what kind of outcomes we can get with something very simple. So, again, it's a little bit of revisionist history because that's what we ... In some fashion, we used to do some of those things but I'm not doing it the same way as I used to which was, yeah, we'll just get rid of the flaps and things of that nature and hope that the patient doesn't have mechanical symptoms. A lot of these patients don't have mechanical symptoms, they have load-related symptoms so I think we do two things by modifying the defect with lesser treatment.
One is we basically can change the anatomy of the defect itself to make the problem area less relevant because the biomechanical loads are more tolerated because it takes the healthy stuff that's surrounding it, it makes it more opportunistic if you will and then we're also getting rid of the biologic load that can lead to effusions and achiness and things of that nature. So, the point is you can sometimes get surprising mileage out of doing less and I don't think it should be overlooked. It's a little like the paradigm where people are rushing to these high-level procedures with massive rotator cuff tears, let's just jump right to tendon transfer, let's go to some type of augmentation when the reality is, is in many instances, we were getting good results with just partial repair of massive rotator cuff tears.
But as soon as we get these new, sexy technologies, we evolve, we forget our past, the reality is there's some mileage, as I mentioned, that can be obtained by doing less but figuring out who that patient is can be very difficult. Probably the best example is an osteochondral defect that's due to OCD. OCD on the lateral aspect of the medial femoral condyle becomes symptomatic because the individual's walking on a pebble in their shoe, they've had it since they've been an adolescent and they present as an adult and, when that happens, they then become symptomatic. And when that piece is removed, for example, those patients uniformly will feel better. Yes, a small subset will have persistent symptoms and a small subset will get recurrent symptoms but the majority of them will actually feel very well. And if you ask your colleagues to do knee replacement, when the last time I did a knee replacement for someone who had OCD, especially a lateral aspect medial femoral condyle, they'd be hard-pressed to come up with one patient.
So, it's a really interesting area that people just at least have to be thinking about. So, a longer answer than you probably want but I think it's important to understand that we don't just jump right to ... I don't just jump right to definitive treatment because I think we get a lot of mileage with less than that.
Dr. Daniel Kaplan:
Yeah. And just for our listeners, from my own experience in seeing Dr. Cole who's, like I said, the Godfather or one of them of cartilage transplant, I have brought that into my practice and it's worked surprisingly great and maybe annoyingly great because it's forced my OCA transplantation rate to plummet compared to other people because everyone seems to do fine. Yeah, a lot of them anyway.
Dr. Brian Cole:
Yeah, exactly.
Dr. Daniel Kaplan:
So, just talking a little bit now about specifics of, we've been dancing around it, what is an osteochondral allograft transplant and and how does that compare to maybe a cell base? Those are the two buckets we pull from.
Dr. Brian Cole:
Yeah. So, if we get to joint restoration, we're really ... There are other options now that are coming on the scene, coral hydroxyapatite cardio and so forth, there's other options on the medial side of the knee, a so-called shock absorber unloader device. But the reality is, when we're talking about biological restoration, the two most commonly known and talked about will be either MACI, Matrix-associated Autologous Chondrocyte Implantation, or osteochondral allografts which is basically a fresh, it's not frozen, it's a cold preserved piece of cartilage and bone that comes from a donor tested to be free of disease and, typically, it's implanted within 24 days of asystole. So, those are the two most common options that are currently used to treat and restore the joint when other things should fail.
So, one is cell-based where we take, it's a two-stage procedure, we take a biopsy, we culture those cells and then come back and implant it with a collagen membrane, it can be done now arthroscopically which is a tremendous evolution. Then the other alternative is an osteochondral allograft, as I mentioned, which is donor cartilage, typically relatively young donors where the cartilage tissue and bone is tested to be free ... The donor is tested to be free of disease and that's implanted typically in a cylindrical graft into a socket with a shallow amount of subchondral bone and living viable articular cartilage.
Dr. Daniel Kaplan:
So, when you implant an osteochondral allograft plug, what are we hoping for in terms of integration? So, what's the end goal process?
Dr. Brian Cole:
What's interesting is that the cartilage is what we have the least amount of problems with typically in bone cartilage transplantation. You can go all the way back to the tumor literature where structural grafts were commonly literally structural cortical bone and sometimes with the joint and the joint would take years to degenerate on the articular cartilage side even though that was frozen tissue with no viable chondrocytes but the bone would have trouble with either creeping substitution or integration and so forth and even fracture as the healing response is happening. So, I think what we've learned is that we do pretty well with the cartilage even if we don't maintain perfect self-viability with some of our cold preservation techniques but the bone is the challenging area, that's where the immunogenicity lies.
Cartilage is relatively immunoprivileged because the cells are buried deep within the matrix but the bone is probably where we have the inflammatory meters, which is where we have the marrow, it's where we have a difficulty in some instances with creeping substitution. And we don't have, we're still trying to, we're evolving right now, we're actually studying ... We're spending our time now studying the subchondral bone in terms of how it gets either replaced or integrated within the host. So, the major goal there is to have the least amount of bone necessary and, when grafts fail, typically we start to see things by imaging which might be relevant such as cyst formation, clefts, a lack of bony integration and we think that that may be the substance of why some of these patients will fail and it might even have to do with some type of low level subclinical immune response.
So, our efforts have really been focused on reducing immunogenicity to these grafts through lavage with saline, through high pressure CO2 and then augmenting with some type of orthobiologic, which is the subject of this paper, to see if we can reduce downstream consequences of bone to bone healing.
Dr. Daniel Kaplan:
Yeah. So, let's stay on that line there and let's pivot to our last segment of setup. Talking about biologics, you mentioned a few, what are biologics broadly?
Dr. Brian Cole:
I would say, broadly speaking, there are either inductive or conductive elements that we can harness. In this case, we're typically talking about autologous, coming from the same patient. I like to stay away from the word regenerative even though there might be features of, quote, regeneration. I think the problem is it's a loaded term that provokes a lot of perception that may not be reality but, in fact, there might be some regenerative qualities of these growth factors that are provided. But the things that we typically, the things that are available to us that have bioactive ability are tissue that is already present in our bodies.
It could be platelet rich plasma which has platelets which produce tons of growth factors, maybe a few of them which are very potent, that can recruit other growth factors into the area that they themselves can manufacture growth factors. It can be anti-inflammatory, immunomodulatory and so forth and, similarly, this bone marrow aspirate which has a few stem cells but it has, actually, a significant fold increase in platelets. When we obtain bone marrow aspirate and we process in the centrifuge, there's up to a nine-fold increase in platelets.
So, you're not just dealing with what I would call stem cell preparations and it's probably best to stay away from the cellular aspect and focus on biologics or what I'd call orthobiologics and think of them as pharmacies of inductive and maybe even conductive effects of the growth factors that they produce. I think that's probably the healthiest way to think about it rather than the activity coming from the cells themselves.
Dr. Daniel Kaplan:
So, with that background, how might biologics help with the integration process? So, what were your guys' thought process when you took on this study?
Dr. Brian Cole:
So, bone marrow aspirate, ironically, I think the only on-label use for bone marrow aspirate is actually to augment allogeneic bone and bone healing. And that means most of what we do is actually off-label when we use bone marrow aspirate and bone marrow aspirate concentrates. So, there's data that it has a positive biologic impact at the level of bone in terms of a healing response. So, our objective was to see if the use of bone marrow aspirate to saturate the graft, so to hydrate the graft just prior to implantation after cleaning it, with either high pressure pulse lavage and/or deep cleaning with carbon dioxide then saturating it and then implanting the graft would make a difference, most importantly, structurally based upon CT scan and then, secondarily, in terms of PROs or patient-reported outcomes.
We've been using it for years but we just didn't have much in the way of data. Intuitively, it had some face validity but we never really got beyond that and this was a ... The study is a prospective randomized trial in patients undergoing osteochondral allograft transplantation with the primary endpoint being CT scan in an early time point because we will occasionally get CT scans and they occasionally show findings. The big challenge with this study and other studies looking at structural anatomy is that we don't have strong correlates with graft survivorship based upon imaging findings so we have to be a bit careful. But we did in this study, as we'll talk about, show differences between the two groups in terms of those who did and did not get bone marrow concentrate.
Dr. Daniel Kaplan:
Got it. So, to summarize, it was a randomized control trial where one group was receiving OCAs without any control or augmentation and one was receiving OCA with BMAC and you followed them for PROs and then CT evaluation of integration. Is that a fair characterization?
Dr. Brian Cole:
That's correct. Yeah, that's exactly what we did.
Dr. Daniel Kaplan:
And then one thing you mentioned that I wanted to touch on is the idea of pulse lavage or pressurized carbon dioxide. Can you just tell us what are the purpose of that and then what are your thoughts on ... Pressurized carbon dioxide is a newer augmentation, what are your thoughts on that?
Dr. Brian Cole:
Yeah, sure. So, if people want to read, we were very fortunate last year, we received the OREF Clinical Research Award which is given in tandem to the Kappa Delta Award at the academy in the ORS. And this is a group of researchers that were well over a hundred different authors, I think we were approaching, honestly, 200 authors for over 120 papers over the last 25 years and that's what we ... The award was for a body of work and it's important, it's not about a single individual, it's about all the multidisciplinary collaboration that goes on to study such a problem and osteochondral allograft is a perfect model to look at virtually every aspect of the procedure, as we walk through graft harvest and donor specific situations all the way up to patient related variables, how do we do the best for our patients.
One specific area is the potential for immunogenicity in these grafts, as I've already alluded to, and we think, if they do have immunogenicity and it has some subclinical effect that could be detrimental, it's probably at least associated with the bone. And that's because there's donor marrow elements, that's where all of the immunogenicity or most of it would likely lie. So, the area of research that we and others have looked at is what are the effects of high pressure pulse lavage, so the same type of pulse lavage you'd use for arthroplasty when you're prepping the glenoid for glenoid replacement and so forth, we use this to also maybe enhance cement integration but also clean the area of marrow elements. So, how can we reduce the amount of marrow elements and we have shown that there's a reduction in marrow elements when you hit the graft with high pressure pulse lavage.
Then there's another device which is high pressure CO2 which is called CarboJet and we use the CarboJet to basically expose the graft to high pressure CO2 to further eradicate marrow elements do we've shown that. And then, secondarily, we just recently published a study with Seth Sherman in collaboration at Stanford showing that the volume of orthobiologic uptake will increase if you basically ... It almost causes a cancellization of the graft. So, in other words, once you just blast it with CO2 on the bony surface, it creates this cancellization phenomenon and, when you add the orthobiologic, it just absorbs like a dry sponge. So, the volume of orthobiologic that can be applied will increase dramatically if you deep cleaning with the CO2 after you use pulse lavage.
So, those are two things that are inexpensive that we could use in the operating room that don't appear to have any detrimental effects that can actually improve, we believe, the potential for graft integration and now we're starting to show it.
Dr. Daniel Kaplan:
Yeah. Just for our listeners, I've seen that both done with pulse lavage and CarboJet and the amount of PRP or BMAC that it just immediately absorbs after the CarboJet is amazing.
Dr. Brian Cole:
Yeah. No, it's a fun thing to do because it's so satisfying visually when you do it in the operating room, yeah.
Dr. Daniel Kaplan:
One drawback for BMAC is it's expensive. So, for this double-blind study, not everyone can pay for it, was there industry support? Do you have a partner to help with this?
Dr. Brian Cole:
This one we funded ourselves. So, we're very fortunate that we have philanthropic donors that help with these types of investigator initiated trials. So, industry did not support this trial. It's expensive vis-a-vis the capital equipment required for it and the disposables, it doesn't take a ton of time but it does take operating room time and some capital equipment has mentioned so there is a cost but no. And I think that's the problem with orthobiologics, in general, there's a socioeconomic impact and there's a fairness factor based upon economics, if you will, in terms of access and equality. So, that's one of the challenges we have because the reality is insurance doesn't cover it and so this is an out-of-pocket expense in the real clinical world but, for this particular study, it was self-funded and patients had no economic burden and we didn't have any industry support.
Dr. Daniel Kaplan:
That's great, yeah, and that's always the bias you have to weed out when you're reading these orthobiologic papers that it's supported by the reader of-
Dr. Brian Cole:
Yeah, yeah. I think ... Yeah, I know you're right. There's a whole litany of literature on the pharmaceutical industry and pharma trials and so forth. I would argue that our obligation is, first, disclosure and then people have to make their judgment but, if you have objective outcome variables, then you have to trust the process. And Arthroscopy is a peer-reviewed journal, there are very knowledgeable reviewers, it's probably got one of the most diligent editorial processes of any journal that I've been involved with, just look at its impact factor on a yearly basis.
So, I would argue that you have to be mindful of it, you should be aware of it and the reader can make his or her decision. But if you understand the peer-review process on top of the disclosure aspect, you can get around it. But you're right, it has to be talked about it, it can be the elephant in the room.
Dr. Daniel Kaplan:
Yeah. So, let's start getting into the results. What were some of the main findings?
Dr. Brian Cole:
I would say the take home is that we showed at six months CT scan that the degree of cyst size was ... The frequency of smaller cysts was higher when bone marrow aspirate was used versus larger cysts, that was one finding. So, cystic formation after allograft transplantation as seen by CT scan is not uncommon. So, the main finding that I ... The elevator pitch is we saw a reduction in large cysts and an increase in smaller cysts in individuals who had bone marrow aspirate augmentation of their osteochondral allograft at the time of implantation. The secondary finding which is interesting is the subsequent surgical procedures, we saw a higher rate of subsequent surgeries performed in those who did not get bone marrow concentrate. That one was a tough one, it wouldn't have been part of the hypothesis, to be honest with you.
I think it's important to understand that reoperation rates in all cartilage transplants can approach 30 percentage in the first five years. So, I would be ... I don't know if I can hang my hat on saying that's an independent variable that was based upon the dependent variable being bone marrow concentrate that we had a several fold increase in re-operation rate, it was it one versus five or one versus six or something.
Dr. Daniel Kaplan:
Yeah. I think it was six versus one or something.
Dr. Brian Cole:
Yeah, yeah. So, it was a number that-
Dr. Daniel Kaplan:
Hallmark.
Dr. Brian Cole:
... if you asked me, I wouldn't ... But it wasn't a huge number of patients so I wouldn't anticipated that to be the case. So, it's something I want to be a little bit careful of. And even when I speak to patients, while I tell them the findings, I say, "Look," I always use this term face validity, "Does it make sense intuitively and it doesn't to me but I can't explain it a way yet." And I think the important thing will be honed in on, we need probably longer term follow-up to see what's happening with this same patient group so we'll circle back to them. It'll be one of our future fellows, they have the opportunity to look these patients up again and see ... Maybe you'll send us one of your residents who's going to be a fellow and we'll figure out if it's having a long-term impact. But those are the basic two findings-
Dr. Daniel Kaplan:
PROs were about the same.
Dr. Brian Cole:
Yeah, they trended. They trended but they weren't statistically different.
Dr. Daniel Kaplan:
Right. So, yeah, there was a difference in MCID but just missed significance. But it was 88% reach in MCID versus 55% without.
Dr. Brian Cole:
Yeah, yeah. If we had-
Dr. Daniel Kaplan:
Numbers.
Dr. Brian Cole:
Right. If we had more numbers, you would argue that that might come as being statistically significant but I think the take home is what I said. The first is CT scan findings that seem more beneficial in favor of using bone marrow concentrate. The second one was a re-operation rate which we don't fully understand why. If you said, "Well, why do you think that's the case?" I don't know. Because, if you look at the reasons for re-operation, clefs and symptoms and things of that nature.
I'll tell you what, here's one thing I know from another study we did, okay, it was ACL reconstruction with BTB allografts with and without bone marrow concentrate and that was an article in HASM, I believe. And we showed by MRI at three months that the bone-tendon-bone allograft looked more like the native patellar tendon in the recipient than those who did not so graft maturation was higher. But what's interesting is we also showed PRO differences in nine months in those who got it and that was a blind study.
So, it's the same thing, it's not something you would expect at nine months out and these are good studies. When I say that these are blinded studies, that much I can tell you, I know these patients are blinded. So, you could argue that there's some, who knows, subjective there part of a study so that bias is, in general, by at least 35%. But if you do a good job blinding, the patients really don't know what they have because we do ask them if they know and they have to follow up and they don't know so we do a really good job at that. So, anyway, I'm just telling you that was another study that showed a PRO difference with bone-tendon-bone allografts with the use of bone marrow concentrate times zero and we showed a PRO difference at nine months which doesn't make any sense but we did and we're still trying to sort through that intellectually.
Dr. Daniel Kaplan:
So, you kind of alluded to it but this is a study through two years. I know we have to actually run it but what do you think ... Is this going to be predictive of five-year or 10-year outcomes or too hard to say without more data?
Dr. Brian Cole:
I think it's too hard to say, I'd be hard-pressed to predict. I like the idea that they're smaller cysts. I do think, when you have bigger cysts, that's a bigger problem. I think the cysts in general have been looked at for conditions like osteochondritis dissecans, larger cysts. For example, the natural history of juvenile OCD is better in patients who have smaller cysts versus larger cysts in terms of its ability to heal. So, if I had to pick what I'd like to see in my grafts, I'd say smaller cysts or no cysts at all. So, at the time ... And then when we talk about cysts, I'm talking about cysts at the bone-bone junction just for our listeners. So, if you do a CT scan, it is not uncommon to see at the donor bone, at the flat surface of it in the recipient socket and in the recipient bed, in the host to see a bipolar cystic response in both the graft and the patient.
So, I would say, hypothetically and from a hypothesis perspective, that having fewer or smaller cysts might bode well for graft degeneration long term. But I'm just guessing and that's why you don't ever want place it on this stuff, we'll just have to look at it again because we get surprised all the time.
Dr. Daniel Kaplan:
Well, that's face validity so I'll give you that.
Dr. Brian Cole:
Right. Exactly, exactly.
Dr. Daniel Kaplan:
So, to my review, this was the first randomized controlled trial, at least that I saw, evaluating BMAC and OCAs. So, the million-dollar question would be, how are you going to use these results in your practice and, by extension, how should we? So, how are you counseling your patients?
Dr. Brian Cole:
Yeah, yeah. So, the difficult issue is access because it is a cash solution for patients because insurance doesn't cover it. So, the conversation is basically as follows. I encourage every patient to consider it, I explain to them our study and our experience, I tell them that it isn't mandatory, I tell them that it has an out-of-pocket expense. There are three groups of patients, there are patients where money is just not an issue and they're like, "Just do whatever you have to do and I don't really care what it costs."
There are patients who's, you can see as soon as you mention out-of-pocket expense, their eyes roll to the back of their head and they're like, "There's just no way I'm ever doing this," and I don't want them to feel badly and otherwise, I get it and this is never a high pressure discussion. And then the majority of people, including myself, are value shoppers, they want to understand does this make sense. And I give them articles, I give them references, we created a reference sheet. I have a video on my website that I put together that just talks about the science. I stay away from the term stem cell, I stay away from the term cellular activity and so forth when I talk about the growth factors and I just present the data objectively.
So, it is an ethical challenge in the office because we're in a strong position of influence when we interact with our patients and we're considered credible sources and, presumably, we're unbiased. So, when we present this discussion and in the midst of it as this economic concept, it becomes difficult. So, it's a whole different discussion on how to have that conversation but I would add that we all have to be extremely unbiased when we present it. It should be presented very objectively, I think we have to be very careful about making patients feel badly or judged if they don't, if they can't afford to do such a thing. And I've done situations where, basically, we will discount or we figure out any way for them to get it because this is one ... Given what's at stake, the average number of surgical procedures that these patients have had is 2.5 in my practice so they've been through a lot.
And patients will spend $10,000 to fix their dog's ACL but, when it comes to something for their own health, they're often, like anything else, they're shopping it. So, it's a cogent discussion that tries to be sensitive to the fact that everyone has different economic challenges and being very careful for the interpersonal aspect to manage that properly and maintain that professionalism and try to keep bias out of it. That's a lot and that's a whole different thing and it's a lengthy discussion but that's just my general paradigm.
Dr. Daniel Kaplan:
Yeah, no, it is really challenging but I actually still use a lot of the words and stole a lot of your phrases within my own practice now that I saw in fellowship. So, thanks for that was helpful
Dr. Brian Cole:
I'm glad I had some impact.
Dr. Daniel Kaplan:
That was it though. As a brief aside as we're wrapping up, what about PRP for this? Does that factor into your algorithm for OCAs? How do you think about that versus BMAC?
Dr. Brian Cole:
Yeah, it's interesting. So, the bone marrow aspirate that we prepare takes 60 ccs and it's prepared at 7% hematocrit. So, you dial in to get a 7% hematocrit in the bone marrow concentrate after you spin it down. It actually has a 9.2 fold increase in platelets. So, people forget that that's part of what you're injecting. So, I would argue that platelets are probably an important part of it. The challenge is, whichever PRP system you use, may not have a abundant increase in PRP fold, in platelet fold.
So, I think platelets are important and I think you could argue that maybe there's a less expensive option that doesn't take bone marrow, that you could use peripheral blood and make PRP. So, I think I wouldn't discount it, it hasn't yet been studied, something we could study and maybe we should because maybe there's a less expensive option here. But I would argue that that platelet fold increase is just probably more growth factors and we think that the growth factors are probably related to this phenomenon.
And the one thing that we shouldn't forget is that MSCs and platelets will draw other MSCs that are endogenously present within patients into the area. So, it may have some paracrine effect in the patients, in the host that's not directly or immediately affecting the bone but actually pulling other things into the area. So, we clearly don't know, what we do know is we're not seeing any downside. Other than the economic impact, we're not seeing any downside biologically and we think that it either doesn't do anything or, more likely than not, may have a positive impact.
Dr. Daniel Kaplan:
That's great. As we start to conclude, what's next on the horizon in the biologics and OCA space? Is there anything you and your team are working on you're particularly excited about?
Dr. Brian Cole:
Yeah, there is. The thing that now i, I think of the last quartile of my practice, if you will, and the things that I want to do scientifically is the bone, is paying attention to the bone. I think that this study and some other work that we've done has helped us pay attention to that. Maybe the bone is as much of the culprit as is the cartilage and, when you think about when patients present to us, how often do you actually see someone who has ... Well, think about osteoarthritis, that's probably the best one. The epidemiology and the prevalence of osteoarthritis is far greater than what we're talking about, these localized areas of cartilage loss. And when patients come to us, they're usually well beyond the phase of losing cartilage, they often have radiographic changes, flattening, bone osteophytes, subchondral sclerosis, bone marrow edema, subchondral insufficiency fractures, things of that nature.
And if we just focus on ... And we know in the cartilage world, when we've ignored the bone, and when I say ignore the bone that means load, osteotomy and the presence of malalignment, that would be ignoring the bone. In the end of the day, metal and plastic for arthroplasty is the quintessential load sharing operation and we're actually probably treating the bone. It's not the absence of cartilage, it's the downstream phenomenon of what happens in the bone. So, most of my current interest as it relates to orthobiologics or some of which, I should say, is going to really start focusing on solutions that address the bone because I think that's at least as big as the cartilage problem. Because, until we can get the disease modification where we can prevent cartilage demise that would secondarily lead to bone changes, we're still going to be faced with huge numbers of patients who have bone problems.
So, that's today, even though we'd love to prevent it from happening, we're still going to have that problem today. So, let's think about how we can have an impact on our patients with that problem because that's what's walking in our office. What's walking in our office is not necessarily patients of little areas of cartilage loss, when they come to our office, they're coming because they have a bone-cartilage problem and I think we have to at least focus on solutions that address that including how orthobiologics may impact it.
Dr. Daniel Kaplan:
That's perfect. That's exciting and definitely something we're seeing so I'm excited to see what research you guys pump out.
Dr. Brian Cole:
Yeah, likewise.
Dr. Daniel Kaplan:
And then just as we wrap up now, any closing thoughts to share with our listeners?
Dr. Brian Cole:
I would say ... Yeah, first of all, thanks for having me, Dan, and thanks for doing this. Arthroscopy is very fortunate to have you and the team who do these podcasts including Matt McNutt who are contributing to these. This is a great way to ... This is easy for people to digest, they can listen to in the car, they can listen to it on the treadmill, another way to get media and knowledge across so thanks for doing it. I would say the following. Osteochondral allograft is a great model of basic and clinical research. And if you have the ability to do research, whether it's basic science or clinical and you have simple questions to ask that are translational, this is a great example of how you can ask hundreds of questions, take it to the laboratory, work collaboratively with basic scientists whose livelihoods depend upon grants to support the research they do which is sometimes high-risk high-reward work but isn't fundable, this is an area that, given our current landscape, that is great to focus on.
So, as a resident or fellow who's coming out into practice and if you choose to go into an environment where you have the opportunity to research, identify simple questions, don't go for the hardest stuff up front but ask the simple questions that can actually make a difference for a patient within six months and this is an example of that. We just said, "Okay, does it make a difference?" and we showed something as an early primary outcome that we believe was a valid construct for long-term success in a procedure that we do on a pretty frequent basis. So, if you put yourself in this situation, this is for our young people to really study the simple questions and bring it to the lab and bring it back and it allows you to have a really good, cogent conversation with a patient in the office about how you can impact their lives and that's what, I think, help create a meaningful career for those people who are interested in this type of thing.
Dr. Daniel Kaplan:
Dr. Cole, thank you so much again for your time and your insights, it was a pleasure speaking with you.
Dr. Brian Cole:
Likewise, Dan.
Dr. Daniel Kaplan:
Dr. Cole's article titled Bone Marrow Concentrate May Decrease Reoperation in Osteochondral Allograft Transplantation, A Prospective Randomized Double-Blind Investigation is currently available at the Arthroscopy Journal website at www.arthroscopyjournal.org. Thank you for joining us. This concludes this edition of the Arthroscopy Journal Podcast. The views expressed in this podcast do not necessarily represent the views of the Arthroscopy Association or the Arthroscopy Journal. Thank you for listening, please join us again next time.
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