We're on time. I want to greet you to BONESUPPORT's Capital Markets Day for 2026. It has been around two and a half years since we last met in November 2023. Here we are today. A warm welcome. My name is Charlotte Stjerngren. I will be the moderator of today. We have a full agenda with people from the management team, BONESUPPORT's CEO, and also clinicians who are going to talk about the fantastic products of BONESUPPORT. We are very many people here in the room and also on the web. You can ask questions here in the room, or you can send them on the web and we will post them to m anagement and the clinicians. Without further ado, please, Torbjörn, the floor is yours.
Thank you, Charlotte. Great to see you here. A warm welcome also from me to BONESUPPORT's Capital Markets Day 2026. It's a privilege for me to kick off the first session. Before I do that, I just wanted to put today's Capital Markets Day into a bit of perspective and into a bit of conte xt. Here you see the topics of previous Capital Markets Day, and what I would like you to take home after today is really these four points of the focus that we will go through today. Number one, strategy update. BONESUPPORT strategy remains right, remains very strong. What we're doing is that in order to fully unlock the potential of CERAMENT and BONESUPPORT, we want to become even more segment specific in foot and ankle, trauma, arthroplasty, and spine.
We'll talk more about that. Second topic that I want you to take home is that we are making an upward adjustment of the market potential that we see in the U.S. for foot and ankle, trauma, and arthroplasty. Third topic that I want you to take home is around clinical evidence. Clinical evidence has been a core part of our strategy ever since 2018. It continues to be. We are announcing that we are continuing to invest in evidence across all four platforms, most notably so in spine, wher e we plan to conduct a multicenter study to introduce and start selling antibiotic eluting CERAMENT in spine in the U.S. That study we estimate to cost somewhere around SEK 80 million over three years. That is in line with what we have communicated before.
We are also announcing that we are going to invest in a study in arthroplasty. That is not to get any market approval. We already have market approval with arthroplasty, but we're investing in a study to further penetrate the arthroplasty market. That study we estimate to cost somewhere around SEK 40 million over three years. Last topic is that we will talk, that I hope you take home with you is that in spine, we see a clear unmet need for antibiotic eluting CERAMENT in spine, and we're going to show you what our research in this field indicates, why we think it's an attractive space to be in, and also our plan to not only get regulatory approval but also start penetrating that market.
Those are the four topics that I hope that you bring with you home after today's session. My part will cover four areas: strategy, the unmet needs, current standards of care, then the moat, meaning what protects CERAMENT. If we look at BONESUPPORT, the company has really transformed over the last couple of years. In the last five years, revenue has grown almost sevenfold. Cash flow has gone from negative to actually generate more cash than we actually need. We've stayed focused, we've stayed small. That is in order for us to continue to run very fast. Qualitatively speaking, our evidence has gone from interesting to actually challenging the standard of care. Our brand has gone from actually no brand awareness whatsoever to now actually be a serious market challenger.
Our penetration, if we look back five years ago, CERAMENT G was not approved for use in the U.S. We almost had no penetration. Even today when we look at the market and we have grown, but still our penetration levels are very low. We're very early on our growth journey. The strategy that we currently have and that we will continue to apply was really formulated in 2018. It's based on three pillars, innovation, which is the core of CERAMENT, this unique technology that focuses on bone healing and infection management. Next pillar in our strategy has been evidence. If you have something innovative in orthopedics and you want it to get traction, you need the evidence.
Not just to convert the surgeons who use it, but you have to convert the multidisciplinary teams that are around them, as well as the payers. T hird part of the pillar is around commercial execution. Once you have innovation and once you have evidence for that innovation, it's very simple in orthopedics. The only thing that you have to do is be very disciplined and very systematic, commercially get that product into the hands of surgeons so that it reaches patients. Those three pillars have been the strategy for BONESUPPORT since 2018. It will continue to be the strategy for us going forward. However, we are taking the strategy, we're making it more segment-specific in these four segments that I mentioned earlier. Foot & Ankle, Trauma, Arthroplasty, and Spine.
Why is that important? Simply because it's different customers, different clinical settings, different needs. In order for us to fully unlock the potential of CERAMENT, it's the same product, we need to be more segment specific and cater to the needs that the respective customers have in these four segments. The needs are there's no doubt about it. If we look at bone infections, they are among the most complex, costly, and consequential complication in orthopedics, and the incidence is increasing. In foot and ankle, one in five diabetic foot infections progress to bone infection, which is a leading non-traumatic cause for amputation. In trauma, the incidence is more than 30% of fracture-related infections after open fracture fixation. In arthroplasty, periprosthetic joint infections carry a five-year mortality that rivals many cancers.
Not only the consequences for the patients, but also for the healthcare systems. I think since I joined, I read this quote from late Richard H. Rothman, a very famous orthopedic surgeon in the U.S. I think the way that he describes it in this one sentence actually describe the potential or the need for our products. Telling an orthopedic patient that they have an infection is like giving them a diagnosis of cancer." This quote is 25 years old. More than that. It was recently repeated at the latest international consensus meeting for bone infection in Istanbul. Bone infection still is a massi ve clinical unmet need, and CERAMENT has a role to play to deal with that. If we look at the three segments that we focus on now, here and now, Foot & Ankle, Trauma, and Arthroplasty.
Despite that these segments are different, the patients are different, the clinical settings are different. The failure pattern is the same. You have a bone defect, you have an infection, but there's no single solution that addresses it. CERAMENT is really the first one. When you don't have a single solution, what happens is that you have multi-stage care. You have high recurrence of infections, so patient come back, infections don't go away, and there's a lot of costs. We believe that some of that cost, a lot of that cost, not all of it, but a lot of that cost can be avoided by using CERAMENT because it addresses the unmet need clearly. If we want to look at the scale of this, how big is this?
We will talk about the market adjustment, that's on sort of on the micro level. What I'm painting here is the macro level. What's behind, the pool of patients are behind. It's millions of patients. 38 million Americans have Type 2 diabetes. In trauma, 54 million Americans have osteoporosis or low bone mass. That's not the only pool that pushes patients into trauma. In arthroplasty, 2 million primary hips and knees on average are done every year. It's very clear about this cascade. It's almost an inevitability that some of these patients, more and more, will end up with a bone infection. What is it then that CERAMENT does? Here we have a very simplified picture of a femoral fracture, it's a broken thigh bone.
You can get a broken thig h bone, a femoral fracture from a car accident, you can get it from tumor, you can get it from many different things. Essentially, the surgeon meets this patient with a bone where they have to fill a void, and they are afraid of infection. That rectangle to the left describes the starting point where you have filled that void with some white stuff with purple dots. The white stuff is CERAMENT BVF, the bone void filler . It's a mix of calcium sulfate and calcium phosphate. Hydroxyapatite, which is a subcategory of calcium phosphate. The purple dots is the antibiotics. What happens when you inject this into the bone? Two things start simultaneously. First, that white stuff helps the human's own bone to regrow and replace the BVF.
After six to 12 months, the body has reabsorbed the CERAMENT and transformed it into its own bone. The second thing that happens simultaneously is that in the first 30 days, you have these purple dots, which is the antibiotics that elute in a predictable, controllable way to kill bugs. We'll get more into the details of how that works. That's essentially what CERAMENT does. It heals fractures as effectively as autograft, eliminating the need for bone transplants. Why is it so important with this local elution of antibiotics or the local application of antibiotics? Well, you see it on the picture. To the left, you see when you go target it only to the part where you want to manage the infection, with CERAMENT, you get a local concentration of around 90 milligrams per liter.
Compare that to the standard of care, which is systemic antibiotics. You get a concentration level, in soft tissue that is, of 15 to 20 milligrams. A large difference. Bone is not soft tissue. It's even worse. It has much worse vascularization. Clearly, you're able to kill the bugs where you want to kill them. There's no problem with patients' compliance when you have local antibiotics like CERAMENT. The patient cannot pull it out. The patient can decide to not take the pills with antibiotics when they do it systemically. Systemically, you can get intravenously, or you can take pills. There's no patient compliance risk. Very important. This picture here really shows, and I would say that start looking at the graph to the bottom right .
This g raph really shows this picture that you have a controlled elution curve of antibiotics. The x-axis is time, the y-axis is concentration. It's a logarithmic scale. You can see that it's very predictable over time. That's one thing. Even more importantly, it is above that red line, which is called the minimum inhibitory concentration level. You have to stay above that line for a long period of time to kill the bugs. It's easy to throw in a lot of local antibiotics in the short term, and then it reduces down to zero. That's not what you want, because then some of these bugs will actually learn to deal with these antibiotics and become resistant. This is one crucial part of CERAMENT, combined with the picture that you see up there, which is the bone resorption.
Here you have a fracture. It's a picture of a knee. You want to repair that fracture. You use plates and screws. That's standard. Then in this case, you also use CERAMENT in the middle picture. In the picture to the right, you can see that actually CERAMENT has been resorbed and human's own bone has been reformed. Why doesn't everyone use CERAMENT? Well, the current standard of care has been used for decades, and it's largely based on organic bone grafts and systemic antibiotics. There's a lot of pros with all of those. If you look at autograft and allograft, autograft, that's the human's own bone. Typically, you cut up here on the hip, and you carve out bone from the iliac crest. It's great. It's a standard procedure. It's very biological.
The nose recognizes the bone. Somewhat similar on allograft, but allograft is donated bone from other patients. Biologically works really well, but there are limitations. Part of the limitations is on autograft is that there's only so much bone th at you can take out if you have a big injury to repair. Also, you get a scar. It's a different surgery. It's another surgery, and there's a risk of infection. Clearly, there are limitations with autograft. On allograft, there are other limitations, not as good as autograft, and also there's an inherent risk of disease spreading from one patient to the other. Clearly, CERAMENT addresses the limitations on both those two, autografts and allografts. If you look at systemic antibiotics, why is that good?
Well, it's proven. Everyone uses it all the time, you can use a broad spectrum of whatever antibiotics that you want. The limitations you see on the slide, also what I said earlier. You don't reach the therapeutic level where you want to. It's long treatments, four, six, 12 months. You have a toxicity risk. Patients that get systemic antibiotics, they're not happy. Just the other week, I was in Denmark, walked around with the surgeons in the ward, one of the main things that two patients said was that, "No, I really don't want to continue on the systemic antibiotics. It's awful. Makes me feel really bad." CERAMENT G and V really addresses that. It regenerates bone, and it delivers local antibiotics in a predictable, controllable way.
That's the current standard of care when it comes to organic bone graft. Since decades, there are many alternative synthetic bone grafts, and I grouped them all together. This is actually a table that I took. I copied it completely. I didn't change anything. I put those boxes at the bottom below. This is a picture from the Oxford Bone Infection Conference with Matthew Scarborough. He put this overview together. I think it's a brilliant overview that sort of indicates, so what does the playing field look like? You have calcium sulfate to the left. Biphasic, so that's the category where CERAMENT plays. You have calcium sulfate, and then you have Bioglass and PMMA. All of these solutions have existed on the market for decades.
Calcium sulfate was actually clinically documented already in the 1890s in Germany. A great product in many ways. It resorbs very fast. To get that controlled antibiotic elution curve is very challenging for pure calcium sulfate. If we go the other side of biphasic to calcium phosphate, it's actually on the other extre me. It takes too long. It almost doesn't turn into bone, or it's not resorbed. The last large segment is maybe not to be entirely accurate, but PMMA stands for bone cement. It's typically used when you want to fix primary or implants to the body. The big difference with PMMA and the other categories is that it doesn't resorb. It is, in Swedish, plexiglass that you put into the body.
If you want it out, you have to have a second surgery to pull it out. In terms of the antibiotic elution, not as well documented and controlled as we believe CERAMENT is. That's really the current standard of care, and call it a competitive landscape. These technologies have existed for decades. It's nothing new. CERAMENT is a biphasic, and we introduced this product in around 2000. We're in this category. We've talked about what makes it unique, what is it that makes it so difficult to copy and replicate what we've done with CERAMENT? As with all difficult questions in life, it's not one simple answer, it's multifactorial. The way that we look at this is that the CERAMENT moat consists of six distinct interlocking barriers.
We have the patents, 30 core patents valid until 2034. We have the evidence with more than 350 clinical papers and abstracts published. Essentially, it's a proprietary experience-driven formula that you cannot really figure out just looking at the patents. It's the knowhow that we've built up. I'll go into more details soon. We have the regulatory barriers. We're the only FDA-approved antibiotic-eluting bone graft in the market. Reimbursement, I'll also talk about. It's not just the fact that we have IDN, GPO, and NTAPs. It's about how the DRGs are assigned. We got some really positive news a couple of weeks ago related to the CMS proposed ruling on that. Then the last barrier is our go-to-market in the U.S.
It's a non-exclusive call point-based independ ent sales rep model that we started when we split from Zimmer Biomet in 2017, 2018. I would argue that's one key part of the success that we've had and that we plan to continue to have. It makes it very easy for us to penetrate the market, move fast, and focus on this unique technology. A bit of deep dive into this moat 3, the secret formula. What we mean here is that this is stuff that you cannot really read it in the patents. It comes separately. Essentially, it is a combination of advanced material science, years of bone biology research, manufacturing and production experience at scale.
I say at scale beca use one thing is to manufacture and produce this in small batches a couple of times, but to do it at scale, at the volumes that we've done, you don't want to know the production yields that BONESUPPORT had a couple of years ago. Most of the stuff that we produced just had to be scrapped. Now we don't have that issue anymore. Of course, it's the combination of all those things plus the clinical evidence, both from a theoretical point of view and a practical point of view. This secret formula is part of the moat, and it's not so easy to copy. Another moat is the regulatory barriers. I would argue that this barrier or moat is probably the least understood or least appreciated by the investor community.
Essentially, it goes to the fact that, as I said earlier, CERAMENT G is the only FDA-approved antibiotic-eluting product in the market. If you look at the category of bone grafts, calcium, we didn't have the wording here, but synthetic bone void fillers and resorbable calcium salt bone void fillers , it falls in this category. Since 1996, there are around 400 to 500 product indication combinations approved. That means between 10 to 20 approvals every year in this category. CERAMENT BVF is in that category. New products all the time. We created the category together with FDA, of course, that is called resorbable calcium salt bone void fillers containing a single approved aminoglycoside antibacterial. Gentamicin is an aminoglycoside.
We were the first one in that category in 2022. It's been open for everyone to use it as a predicate device for four years. No one has done that. Is that because the space that we're in with CERAMENT G is not very attractive and not commercially viable? We don't really think so. By setting the standards, you see that in the box below. We set the standards in terms of the clinical settings and special controls that all future products will need to live up to enter the space. It's not only what you see here on the slide, but there's a lot of different things that future products will need to live up to. I'm sure they will. I'm not saying that it's impossible, but it's part of the barrier .
I think this is my second last slide and relates to the last part of the moat, which is around reimbursement. As I said, reimbursement is not only on NTAP, IDN approvals, GPO approvals. Those are important. As part of running the business, you have to get them in order to grow. We've grown, so we've got them and we continue to work on them all the time. This example relates to DRG assignments. The CMS came recently with a full year 2027 IPPS proposed rule. If you simplify it, you can say that this proposed rule increases the payments to support the standard use of CERAMENT G in the U.S. It's a lon g document. I think it's 1,600 pages. Of course, not all relate to CERAMENT G, but there's quite a few pages that relate to CERAMENT G.
If we simplify it and we do our calculations based on the data that is in this proposed ruling, we see that the payments, the way that we interpret this, for CERAMENT G DRG codes, meaning codes where CERAMENT G can be used, will increase somewhere between $5,000-$11,000 per procedure. It's not just one simple list, and it's not very easy to sort of draw simple conclusions on what this means. We took an example here and looked at fracture-related infections. You see three DRG codes, 492, 493, 494. They exist already, so there's nothing new in that. What is new is what we've marked in blue. That's top level. That's the most complicated. MCC stands for major complications and comorbidities, I think.
That's the most complicated, and that category remains the same, but the proposal is that they change the wording of it or the title to include or insertion of antibiotic-eluting BONE VOID FILLER . There's only one antibiotic-eluting BONE VOID FILLER approved in the U.S. market. Essentially, that DRG code can only be approved or used when CERAMENT G is used. What happens? Well, there's not a lot of extra money from $26,700-$27,700. Yes, it's an improvement. The key thing here is that it's a proxy or instead of using the lower codes, whenever CERAMENT G is used, they can code it fully with this 492 code. In this specific set that relates to fracture-related infections, the average payment increase for the hospital would be $7,900.
Of course, what you all ask is, "Well, what does this mean this quarter?" Nothing this quarter because it doesn't have any impact this quarter. This is a proposed ruling. We expect the ruling to be announced firmly beginning of August and come into effect starting October, but how fast and how much this will impact us, we don't really know. What we know is that it's very positive. What we focus now more on is to prepare ourselves and prepare our customers to take advantage of this. This clearly reduces one of the barriers that we have. Sorry, I ran over a bit, but we're okay. That concludes my presentation. I've taken you through the strategy, the unmet needs on a more of a macro level .
I went through current standard of care and competition. Lastly, we went through what are the components that protect CERAMENT. I'm happy to hand over to Annelie that will talk more in detail about what does it mean to take a more segment-based approach with CERAMENT. Thank you.
Thank you. Good afternoon, everyone. Today, I will cover three areas. I will go more into detail around how we apply this segment-specific strategy and the value proposition. I will also take you through the market opportunity and how we have updated our market model since the last time that we met. Finally, I will also provide some more insight to market research we have done in arthroplasty and spine. Need to be a little bit more firm there. Yes. The CERAMENT strategy applied. At the core of our strategy is a very straightforward and powerful idea. As Torbjörn talked about before, we have the same core technology, but we apply it in different types of segments. As Torbjörn also said, CERAMENT combines two essential capabilities, the bone healing and also trying to control infection.
As you can see on the picture here, there you basically have the recipe for how we work. We start with early adopters. We start to make clinical evidence in the form of first case series. We expand to clinical data and longer studies, driving adoption and further on coming up with standardized techniques, which helps also for hospital protocols and finally, guidelines. That is what we also aim for. Importantly, we are also expanding from surgical treatments into prevention, and we look for adjacent market segments to move into. Most lately here, arthroplasty and spine. If we look at the different values, basically it's the same value all over. Heal bone, repair bone and protect from infection. There are some different surgeons to work with and the basic problem is a bit different.
When it comes to foot and ankle and diabetic foot, the most important thing is there to save the limb. It's to secure that the patient can stay mobile and preserve the function of the body. That really helps to prevent amputation. An amputation is really a disaster for pat ients where the survival rates are really bad. Within five years, there is a horrible situation for patients with large amputations. We are also translating. If we can do that, we can translate the value into health economic value with fewer surgeries, lower complication rates, and then reduce hospital stays and which also positively impact costs. Looking at trauma, the most important thing there is to protect from fracture-related infections or reinfections.
Which helps to faster recovery and shorter hospital stays as well. Trauma is a large under-penetrated market. I didn't touch anything, I think. Trauma is a large under-penetrated market, and you will see that also when we come to the market model. In arthroplasty, which is the latest segment where we have really made a big, strong foothold in, we see here a strong growth driver and preventing periprosthetic joint infection will really be a benefit. We have the opportunity to also listen to Dr. Meller here, who have done the CeraHip study later on, and he will give you a much more deeper insight to how it is for these patients. Lastly but not least, spine. Here we see a future big growth opportunity.
We have just stepped our toes into this segment, and right now we're focusing on CERAMENT BONE VOID FILLER, but at the same time, we are preparing for market expansion and to have CERAMENT G and CERAMENT V approved there in that segment. I will come back to the spine. As I said in the beginning here of our recipe, standardizing procedures is super important for this. Here you see some examples of different types of surgical procedures and appl ication techniques that have been developed by our surgeon community, KOLs around the globe, which also have been published, and that is what we aim for. That really helps to expand into new segments and sub-segments. I will now move into our market model.
For you that were at the Capital Markets Day 2023, you recognize this picture and maybe also when you have been meeting Håkan and Torbjörn at other different types of meetings. At the Capital Markets Day there, the data was triangulated by multiple data sources, including market reports, surgeon society data, CMS codes, and primary research. Data coverage was relatively strong there for synthetic bone grafts and allografts, while the data we had on auto graft was less transparent and often excluded from available data sets. This is important, as Torbjörn earlier talked about. CERAMENT covers all areas, both synthetic and organic, both autograft and allograft, and therefore we need to have the whole full picture.
Since then, more comprehensive and higher quality data has become available, enabling us to refine the underlying assumptions and improve the accuracy of our market segmentation and total addressable market. Here I will just give you a brief update on what is the most significant updates we have done. When it comes to the bigger changes we have done, revision arthroplasty is larger than we modeled earlier. Our ear lier work underestimated procedure volumes. New data shows that it was bigger and it also has grown over the years since we were last here. Second, I will go back to that also. At the same time, infection has emerged as the leading cause of arthroplasty revisions, which also helps bring up the numbers. Basically, we go from around 70,000 cases in 2022.
Now we estimate the market to be around 120,000. Second, local antibiotics are already widely used in clinical practice. This was also underestim ated. There we have also done some updates, which you will see. We have also sharpened our strategic focus. In the previous picture you saw four segments. Now we focus mainly on three segments in extremities. This slide shows our updated U.S. market view for 2025, covering the three core segments, foot and ankle with diabetic foot, trauma, and revision arthroplasty. The biggest update there is in revision arthroplasty, but all have been upgraded due to growth over the years. In the total number of 460,000, we also include tumor, but we are not focusing on that area.
The infection incidence before we also tried to differentiate between prevention and infected cases, and here we now take a more overarching view on it. The use of local antibiotics is quite high. You will also see some numbers in the market research that I will show that this is the case, this is wha t surgeons say. Spine, we have not done so much. We have upgraded the number a bit and the total estimates are quite in the similar situation as in 2023, but we will do more rese arch on those moving forward. At the bottom, you see how we expect our market shares to be within the different segments. As you can see, although we think that we are very successful on the U.S. market, we are still just scratching the surface.
In diabetic foot and foot and ankle is where we have the highest market share, while in trauma it's still very modest. There we have a big opportunity for future growth, as well as in revision arthroplasty. Spine, we have just, as I said before, just dipped our toe in. Torbjörn was talking also about that this is the current serviceable market that we are addressing, but there is a lot of other factors that will continuously increase the market size. We talked about the diabetic patients. They get diabetic foot ulcers. These result in that bone also getting infected, where CERAMENT has a good place hold. Surgical trauma, we see a growing amount of people with osteoporosis, which will also eventually increase the number in the trauma segment.
Primary arthroplasty, osteoarthritis is also growing. It is also increasing the number of primary arthropla sty procedures. That will also give a lot of more revision arthroplasty in the future, which will also come and help increase the market size. Market dynamics is there. We estimate the biggest growth of the market between now and 2030 to be in foot and ankle diabetic foot and in revision arthroplasty, while a bit modest still in trauma. Very much in the foot and ankle will be diabetic foot, and we hope to be able to prove that earlier intervention can help even more patients in the future, which will grow that segment quite drastically. We believe that it can reach around 100,000 procedures per year.
Today, we calculate that around 40,000 of the 80,000 is diabetic foot. Now I will go into a bit more of our segment deep dives, and we will start with arthroplasty. We are continuously doing market research to stay alert and to stay informed about how the market situation looks like. This is the latest study we did for arthroplasty. Here we were looking at revision arthroplasty and also a bit into prevention in primaries. What do the surgeons do? I previously showed that there are around 120,000 revision arthroplasties made in the U.S. each year where bone grafts are used. Our quantitative research shows that 96% of surgeons consider infection prevention challenging. Recent separate data from the structured registries from 2025 shows that the most common reason for revision of a primary arthroplasty is infection.
The use of local antibiotics in septic revisions is very easy to understand, but what we saw also in this research is that the surgeons are applying local antibiotics already in revision surgery, 54% in hip and 60% in knee. PMMA and antibiotic powder were the most common application forms. When telling about the technology that we had without not mentioning the name of CERAMENT, 82% found the concept compelling to very appealing, and this is a very high number for a product like that. On the next slide here, the top section there is from the same research, and that was primary arthroplasties. In this survey, it showed that local antibiotics is used in 40% of the cases already. Which for the future leaves a possible segment for us as well.
We believe that this is primarily in high-risk patient and reflects the growing burden of comorbidities as diabetes and obesity. In the bottom section is from an earlier survey we did in Europe and U.S., and it was specifically looking into prosthetic joint infection. Here we saw that surge ons are very concerned about prosthetic joint infection. Use of local antibiotics is critically important, and the current administration is through either PMMA and in spacer or beads or as antibiotic powder or also, sorry, also mixed with bone graft, synthetic or organic. Yeah. One other thing that was also seen was that the surgeons were also worried about microdefects in bone. That is something that can occur in routine surgeries, fractures, primaries, and revisions.
This also open up a significant use of CERAMENT G with the possibility of its injectable form. Not just for larger defects but also for small defects. Yeah. The biggest challenge with prosthetic joint infections are recurrence of infection, bone loss, and implant biofilm. 93% of surgeons expressed that PJI is a challenging condition. 84% of the surgeons expressed lack of available technology and techniques that would enable the transition to one-stage proced ure, things that CERAMENT can meet. Leave the arthroplasty segment and go into spine. In 2023, when we were here, we said that we were going to start looking into the spine as well. What have happened since this? Yes, we have obtained clearance for CERAMENT BVF use in interbody fusion. We have done preclinical studies, specifically looking into application methods.
We have done a lot of research and talks with customers in the spine market to understand the unmet clinical need. We have also started a targeted CERAMENT BVF launch, which is ongoing. We have also initiated and established a plan for how to take antibiotic CERAMENT to the US market. This is from the latest research we have done in spine. This is also telling about how big the need is for antibiotic-eluting CERAMENT. Everywhere in the body is a problem if you get an infection, but it's sup er hard if you get an infection in the spine. You can't take away the spine, you need it. Therefore, these surgeons are even more prone to use local antibiotics to prevent infection and, or to find a lot of different ways to not make this happen.
In the research, 86% of the surgeons are already using local antibiotics prophylaxis in at least some patients, specifically if there are comorbidities. 75% of surgeons use local antibiotics for surgical treatment if there is an infection. The most usual way to do this is to dumping antibiotics, although almost all of them believe that it's not an optimal way to do this. Even though they do it, 82% of the surgeons consider the approach suboptimal. When we thought about how CERAMENT G is working, 78% expressed a need for that kind of a product in this area. It's about the same for arthroplasty. We see really high unmet need and really high numbers for wanting to have a product like CERAMENT.
This is my last slide, and this is telling about what we are right now doing and have initiated when it comes to spine. We are starting with a lead focus indication, posterolateral fusion, which is the biggest segment and the most intuitive and also where local antibiotics is actually going over those numbers I showed you in this area. This is the segment that is really driving up those numbers, so they are even higher than the ones that I showed. The idea is to build the foundational spine data across the full CERAMENT portfolio. We are starting right now pilot studies to guide model selection and study design, and in the next phase, we'll do pivotal studies that could be used for pre-submissions and then finally also submissions to the FDA.
The timing for that is around 2026 and 2027, we hope to be done with that. The clinical strategies has also started to take form, and we plan to do basically two studies initially. One single center case series, around 20 patients, around CERAMENT BVF, and then a multicenter PLF study on antibiotic-eluting CERAMENT versus standard of care. The estimated cost there is expected to be around SEK 80 million-90 million, as previously said, and timing starting in 2027. Regulatory pathway strategy, we believe it will be a De Novo pathway, likely due to the novel spine indication and the claims, and we expect that to be done no later than 2031. Overall, what w e see is a large and growing market. From the market models that we saw, we have gone from 380,000 procedures to 460,000.
We see that there is a need and a future where this serviceable market will continue to grow in all of the segments that we have now decided to focus on and to build upon. We believe that CERAMENT have and solves a really unmet need for both patients and surgeons, and we hope that we will help a lot of patients coming back to life, avoid amputation, and stay healthy. With that, I leave over to our Chief Medical Officer, Michael Diefenbeck.
Thank you, Annelie, for the kind introduction. I will continue with the clinical update, the clinical update will follow the already established market segments. I'm sure that you're all really well familiar with the market segmentation, to me as an orthopedic surgeon, it was somehow new how easily you can apply market segmentation to medical topics. If we look at the definition, we just have to exchange users with patients. We will share similar characteristics, this would be specific diagnosis or specific diseases. Here are our four market segments, as mentioned before, foot and ankle, trauma, arthroplasty, and spine. I will go through all four segments, following basically the same structure, I want to start with a patient case, then I'll follow with publications since the last Capital Markets Day, then we look into ongoing and future clinical studies.
Let's look into foot and ankle. This is a case of a patient, male diabetic patient in the age group 51 to 60 years. He has a diabetic foot osteomyelitis, or in short, as we say, DFO, and he has a Charcot deformity of the midfoot. Maybe you're not so familiar with the Charcot deformity, but basically what you see on the top is the normal anatomy of a foot, and the bones are kept in place by ligaments, tendons, muscles, and the muscles are innervated by nerves. With the progression of the diabetic disease, all these structures are weakened. The ligaments are weakened, the tendons, the muscles are not innervated anymore by the nerves. The whole architecture of the foot collapses, which you can see here on the right side in the middle.
For example, in this case, the midfoot, the talus, the bone in the middle, points down and pushes out this part of bone. Now the arc that you usually have on your foot is reversed into a bump, which you can see on the clinical picture in the right corner. If the patient walks on this bump, of course, the pressure increases on the sole of the foot. It creates a pressure ulcer or a diabetic foot ulcer, which leads to contamination, infection, and a DFO. In this case, a Charcot deformity correction was performed by doing bone osteotomy and wedge osteotomy, so basically parts of the bone are cut out, and then the architecture is restored and internal fixation used, which you can see on the fluoroscopy.
This structure here is the intramedullary nail locked with some screws and plates and screws, and the debrided bone voids are filled with CERAMENT V. CERAMENT V is quite well visible in black and in the middle picture. We use a new software where we can mark the CERAMENT, and it's marked here in purple color, so it's easier in the follow-up to find the region of interest, which is here at six months. CERAMENT starts remodeling into bone. Here in the follow-up at nine months, the architecture of the foot is well in place. The hardware is not broken, has not moved, and CERAMENT has remodeled into bone, now marked in green. CERAMENT V has here protected bone healing and promoted bone healing. This is the first publication I wanted to mention.
It comes from the group of Professor Hans Gottlieb from the Herlev Hospital in Denmark, Copenhagen. It is called CLOSE-UP: A Favorable Protocol for Limb-Sparing Surgery in DFO. Here are the highlights of the study. It is a one-stage procedure with local debridement or minor amputation, CERAMENT G and CERAMENT V, and primary wound closure in 92 patients. For systemic antibiotics, the OVIVA protocol was followed. This means a short duration of intravenous ant ibiotics followed by a five-week duration of oral antibiotics. If you look at the results, failure rate 13%, with only four patients who had major amputations. Please keep in mind the benchmark, the amputation rate from the literature is up to 24%. The conclusion of this study was that a defined protocol with CERAMENT leads to favorable results.
The second study I want to show to you comes from Anand Pillai's group from Manchester. The title is Adjuvant Local Antibiotic Therapy in the Management of DFO. Here come the highlights of this study. It was 105 patients, all had surgical treatment. The group was divided into two groups. One group received CERAMENT G or CERAMENT V, which is called the local antibiotic group, and the other group had the conventional treatment without local antibiotics. If you look at the results, reinfection rate almost 20% in the CERAMENT group versus almost 50% in the non-local antibiotic group. The major amputation rate, almost 2% in CERAMENT versus 12.3%, a huge significant difference. As I mentioned before, the benchmark, 24%. The conclusion is very similar to the conclusion before from the Herlev group.
Defined protocol with CERAMENT leads to favorable results, now in direct comparison to a group which did not receive local antibiotics. On the next slide, I wanted to show you an overview of ongoing and future studies. I have this slide for all four segments, I want to introduce it to you first. In the top, you can see the timeline in short term and midterm and long term, starting over 0-2 years, 2-5 years, and 5-10 years. Starting at 2026 and then adding up to 2036. We have the studies color-coded here. This is the normal progression of a study. You start with a planning phase, then comes after the study protocol has been finalized, the agreement signed, the enrollment, follow-up data analysis, then a manuscript is written, submitted to a journal, and published.
Here we have four studies in the foot and ankle segment. I have an individual slide for each of them, I just give you the overview here first. PRESERVE, that's an ongoing DFO study on the forefoot in the Netherlands. CERAMENT 2 is done at the moment in Basildon in the U.K. Again, DFO of the forefoot, here with a short duration of systemic antibiotics, they already applied the early findings from the SOLARIO study in this study. METAMAT in Spain, in Madrid, focuses on a special surgical technique to introduce a new, third technique, you could say, of how to treat special anatomical locations of DFO in the forefoot.
In the planning phase, not written in stone yet, very far advanced in the planning, is a randomized controlled trial, standard of care versus standard of care plus CERAMENT G in the U.S. Let's have a deeper dive. The first is the PRESERVE study, a prospective case series, DFO on the forefoot on 53 patients. The technique was a debridement and bone void filling with CERAMENT G, that was done in 10 hospitals in the Netherlands. The first results were already presented at OBIC, the Oxford Bone Infection Conference at Oxford this year. From a starting point, 107 patients were treated with conservative treatment, systemic antibiotics and wound care for DFO, 50% failed this initial conservative treatment.
This is really an interesting finding on its own in the beginning because it shows that the standard of care at the moment in DFO leads to a failure rate of half of the patients. They needed to have surgery and would have benefited if they had earlier surgery. These 53 patients were included into the trial, and after a follow-up of 20 weeks, there were 15% revision surgeries. If you remember from before, that's in line with the Herlev data, with 13%, or the data with 18% from Manchester. There were no major amputations, which is really great for the patients, of course. The wound healing was around 70%. Here it is that CERAMENT promotes bone healing, protects bone healing. For the ulcer healing, that's more dependent on the deformity, reconstruction, and on the wound care.
The second one I mentioned is the study going on in Basildon in the U.K., London area. 25 patients enrolled. They are now in the follow-up phase. This is the one with the short duration of systemic antibiotics. The six-month results are submitted for presentation at the European Bone Infection Society meeting this year in Porto. METAMAT, this is the surgical technique. 20 patients enrolled. They are now in the follow-up phase. It's a quite established technique. It is called resect ion arthroplasty, where to correct the deformity, a part of this bone and the joint is resected. Then CERAMENT is used to fill the bone and ar ound the bone. The idea of this study is to establish a new surgical technique which can be used exactly in these very common cases of the diabetic foot infections on the metatarsal heads.
Finally, last slide on DFO, is the planned randomized control trial. Here, the planning is quite advanced. I can share some more details with you. It's on the DFO on the forefoot. Oh, why always forefoot? 90% of the osteomyelitis we find in diabetic patients is on the forefoot. This is why our focus is on the forefoot. 100 patients, 50 versus 50. Standard of care versus standard of care plus CERAMENT G. The study will be done at the University of Texas at two sites, UT Southweste rn and UT San Antonio. Follow-up will be 12 months. I said we are quite far with the planning, so the study protocol has been finalized. We are in the phase of signing the agreement. Fingers crossed, we hope we can enroll the first patients until the end of the year.
This was foot and ankle. Continuing to trauma. Foot and ankle is our largest segment, so the other segments will be a bit shorter. In trauma, I have included some slides for SOLARIO, so maybe about the same size of foot and ankle. Starting with a patient case. This is a patient, 30 to 40 years old, fracture-related infection of the right tibia after a gunshot injury and fracture fixation with an intramedullary nail. The case was provided from a surgeon in South Africa. The nail was removed, the bone was debrided and filled with 10 cc or 10 milliliters of CERAMENT V, systemic antibiotics started. You can see on the right hand, in this bright white color now, where CERAMENT V was placed, again, color-coded down here.
If we follow up the patient now at eight months, CERAMENT remodels into bone, creates new bone, which we can see quite good here. This is the area where CERAMENT was placed, here you can see how nicely new bone is built, color-coded on the lower side. The 13-month follow-up, full weight bearing. The patient doing well. If you ask yourself maybe what these little white dots are, this is shrapnel, which is left from the bullet, so that will stay with the patient. Looking at the publications since the last Capital Market Day, the first one comes from Dr. Sandilands from Florida. It is on intramedullary nailing with CERAMENT G in fracture-related infections and osteomyelitis. Here come the highlights of the study.
It is a case series on seven patients with fracture-related infection where the RIA irrigation aspiration system was used. This is a tool where you can clean the inside of the bone and at the same time flush it or irrigate it, and at the same time remove the debris so that nothing stays behind. CERAMENT G is injected via the 2-CAN. When necessary, in case of instability, a new nail is introduced. Mean follow-up was 14 months. No recurrence of infection, no major complications or amputations. Here the benchmark, the recurrence rate usually is around 13% from the literature, and the 13.3% was the same benchmark we used for the FDA approval for CERAMENT G. The conclusion of the study, I just put these two images here.
This is exactly, they show how the 2-CAN is used to precisely inject CERAMENT at the place where it's needed, at the fracture site or where the infection is. We heard that seven patients is not a large number. It's a small case series. This is exactly what the surgeons in the U.S. are interested in, to see how CERAMENT G can use, in a minimally invasive technique here, how it can be used successful, coming from one of their colleagues to describe this technique. Of course, this is perfect promotional material for our sales force in the U.S. to show how to use CERAMENT. The next publication is quite similar. Same author. Now it's on the intramedullary nailing, but now for fracture-related infection prophylaxis. This is now open fractures and to prevent infection after open fracture.
Same setup, a case series on nine patients with severe open fractures using intramedullary nailing with CERAMENT G through the 2-CAN again. Mean follow-up of nine months. All fractures were healing, achieved union, and no case of fracture-related infection and no amputation. The conclusion, again, on this slide, a practical guide how to use CERAMENT with this instrument, the 2-CAN, which you can see here. The 2-CAN is basically a cannula inside a cannula, and you inject through this and place exactly the CERAMENT inside the bone where the fracture is and a bit around. Then a nail is introduced to stabilize the fracture. Final publication on open fractures. This is a publication you might be more used to, a bit more heavier on the science side. It comes from Professor Anand Pillai's group in Manchester.
"Do you want local antibiotic prophylaxis in these difficult-to-treat IIIB open fractures?" With a 10-year follow-up. The highlights, it's a retrospective evaluation on 76 patients with these Gustilo-Anderson IIIB fractures. Infection rate 5%, with four cases of osteomyelitis after a follow-up at 88 months. If you do the math, that's about a bit more than seven years. The benchmark is here around 15%, far beyond the benchmark of infection from the literature. The conclusion that CERAMENT G is a safe and effective option for local antibiotic delivery to prevent infection. This is the slide on the evidence pipeline now for trauma. You are used now to the setup. The SOLARIO study, we talked about this before previously. It's close to publication.
There is a combined study where it's done in Gothenburg, here in Sweden, where CERAMENT G and CERAMENT BVF is applied together in a bone void. The CERTITUDE study in the U.K., that's a post-market surveillance study going on at Oxford. The CONVICTION trial , a randomized controlled trial in France. I go through this in detail, starting with SOLARIO. I took this picture at the EBJIS 2024 meeting, where Professor Martin McNally is presenting the first results on SOLARIO. Just to remind you, SOLARIO stands for short or long antibiotic regimes in orthopedics. The design was a multicenter randomized non-inferiority trial. Indications were a wide set of orthopedic infections with osteomyelitis, FRI, DFO, PJI.
It was done in 500 patients randomized in two similar-sized groups, 249 patients, the standard regime, which means at least four weeks of systemic antibiotics, and 251 in a short regime, which was a maximum of seven days of systemic antibiotics. To the treatment. All patients had debridement, and all patients in both groups had licensed antibiotic-eluting bone defect fillers. Initially systemic antibiotic therapy after surgery and at seven days the patients were randomized. In half of the patients, the systemic antibiotics were stopped, and then the other half continued up to the suggestion or advice from the ID physician. The follow-up was at 12 month. These are the top-line results. The endpoint was met. The short regime was equally good in infection eradication as a standard of care.
If you spin it around, the short duration of systemic antibiotic was non-inferior to the long duration of antibiotics. If we look at the numbers, the shorter systemic usage was five days versus 37 days, or an average reduction of 47 antibiotic days and a total reduction of more than 11,000 days just inside this trial. The SOLARIO team did a calculation. If you take the weight of a small antibiotic pill, how much antibiotics were saved just in this trial, and it is 15 kg. Now vacation time comes, a huge suitcase, 15 kg of antibiotic pill was saved just in this trial. This has, of course, a huge impact for the patient because this short regime reduces the adverse events.
This is shown here on the right-hand side. You have on the Y-axis, the patient numbers, and you have the adverse events, and the dark blue is the no adverse events. 80% in the standard, in the long group, had no adverse event, and up to almost 150 in the short had no adverse events. If we look into the adverse events, moderate adverse events, 70 in the standard group, and this was reduced to 35 in the short arm. In the severe adverse events, the reduction was even more significant. Why is SOLARIO so important for CERAMENT and for BONESUPPORT? This is explained on that slide. As mentioned before, all patients had local antibiotics and empiric systemic antibiotics, and 19 different products were used in this study.
About 80% were resorbable, like CERAMENT G and CERAMENT V, and 20% were non-resorbable, so that's the PMMA, the bone cement. 81% of the resorbable products were CERAMENT G or CERAMENT V, which means 64% of all the procedures. This study relies heavily on the results from CERAMENT G and CERAMENT V. In summary, on SOLARIO, the advantages of using CERAMENT plus short antibiotic regime, it promotes patient well-being by re ducing the side effects, the adverse events. It reduces the antibiotic costs. That's clear by saving the systemic antibiotics. It reduces costs associated with adverse events, and that's quite important because the adverse events are a cost driver in these studies. This would be readmission of patients, maybe even be admitted to intensive care unit, and then the costs really go up for these adverse events.
It improves the patient adherence. Torbjörn already talked about that. The surgeon or the physician does not need to rely on the patient taking his medication. The medication is basically implanted by the surgeon. It improves antibiotic use because it's placed at the site of infection, at the right site, at the right time, in the right dose, and it decreases the risk of creating antimicrobial resistance. With this excourse on SOLARIO, I come back to the other planned and ongoing studies in the trauma segment. This is the study where CERAMENT G and V are used together in the same bone void. On the right-hand side in pink, you can see the size of the bone void where the products are placed, and then in the follow-up, the bone healing.
The study has been finalized, and the manuscript is submitted to a journal. The CONVICTION trial in France, which is run and organized by the CRIOAC centers in France. It's a randomized controlled superiority trial. The indication is chronic osteomyelitis. The aim is to enroll 200 patients. At the moment, 48 are enrolled. It's the two groups, debridement without dead space management versus debridement with CERAMENT G. Eight sites are now enrolling, but the enrollment is, as you could see, far below the forecast. The CRIOAC group will probably need to come together, they are driving this study, and to decide if all these 200 patients can be enrolled. The next study is CERTITUDE.
This is a post-market surveillance study with a very long follow-up of three years, and this was demanded from BONESUPPORT from FDA in the De Novo approval. It is a consecutive case series, fracture-related infections. 121 patients planned, 20 enrolled. It's done at Oxford, so the Oxford protocol is followed at the invention place, basically. It's a long study, but we're happy to do it for FDA with a three-year follow-up. The last patient included around end of 2027, three years follow-up clinical study report in 2031. For these results, we have to wait a bit. This was trauma. Now coming to the third segment, arthroplasty. This is a 54-year-old patient with a PJI or periprosthetic joint infection and an osteolysis of the right hip.
If you have a close look at the radiographs on the right, you can see this is the prosthesis, the shaft, the neck, the head, and the cup. You can see around these translucent lines here and this hole. These are characteristics of a bone infection. The surgeon would do a joint aspiration and see if he can or she can find bacteria. When bacteria are found, then it is an infection, like in this case. The one-stage exchange with CERAMENT G was done. This is how the surg eon is applying the CERAMENT G. He's augmenting the cup and the stem. By this, the CERAMENT G is transported or delivered into the bone voids around the cup and around the stem, and then by implanting the cup and the stem.
Here are the follow-up radiographs of this patient with this one-stage exchange, only one surgery for this infected hip. One study I wanted to mention on arthroplasty, and this is coming from Charité, Berlin. Its first authors is Dr. Meller and Dr. Khakzad. Dr. Meller will present after the coffee break online. I will leave this presentation or the details of the publication to his presentation. Here are just the highlights. It's a prospective study on 20 patients with confirmed PJI. Recurrence rate 0%, no recurrence in the follow-up of 3.3 years. The benchmark here for the infections is around 15%. All the details of the study and of the surgical technique then with Dr. Meller after the coffee break. An overview of the ongoing and planned studies.
The overview, CERACHANGE, a 2-stage study in Germany with CERAMENT G is used in the first stage. CeraHip 2.0 is a continuation of the CeraHip study at Charité. It's in the planning phase. In the planning phase, not written in stone, the CERAMENT in arthroplasty, a heavier lift, a multicenter RCT. The details. This one is the CERACHANGE study. It's a pilot study, a small pilot to gauge the differences in the results in a treatment in the 2-stage hip exchange. In the first stage, Interesting. I would suggest, I'm not going to touch this. I just continue with my presentation. I wanted to show you because you're experts now with the radiographs. You can see here again, these radiolucent lines, which shows that the prosthesis is loose and probably infected.
Usually in the 2-stage, the prosthesis is removed, and this PMMA spacer, so bone cement spacer, introduced. In this study, in the CERAMENT group, no spacer is used, but CERAMENT is injected into the cup or into the acetabulum, where the cup is placed in the proximal femur. It's done at the University Hospital in Munich. I have some more slides on this. The first stage is the removal of the prosthesis, the placement of CERAMENT, which can be seen, CERAMENT G and V here into the proximal femur and into the acetabulum. Here is the acetabulum, the look. After six weeks, when the revision is done, CERAMENT is still in place, the bone healing has already started, and the huge antibiotic elution led to the eradication of the infection, and the new hip is implanted.
This is the continuation of the CeraHip study, CeraHip 2.0. It is PJI of the hip, 30 patients. There are two new things. One is that this one comes with two retrospective control groups. One is CeraHip on its own because this new one has a shorter duration of systemic antibiotics. Again, following the SOLARIO results. The second is a control group where no local antibiotics have been used. Final slide on arthroplasty. This is the plans. Again, not written in stone. International multicenter RCT, PJI of the hip, of the knee. We're probably aiming around 300 patients, but that has to be confirmed in a statistical sample size estimation. It's a single stage exchange.
The idea is to have one group with CERAMENT G and a short duration of antibiotics systemically versus the standard of care, which is no local antibiotics and the long duration. This will be done at, we think, about 20 hospitals, and we are in the planning phase with our advisory board and with intern ational experts in the field. The costs have been estimated, as Torbjörn said, with SEK 40 million. Finally, spine. My colleague Annelie Aava Vikner has already talked about spine and the strategy here. I just jump right into the planning slide. Two studies are planned in yellow. The first one is a single-case series on posterolateral fusion. It's for deformity correction. This image, it's not a standard approach, usually you have just a tiny incision.
This here is to correct scoliosis, to reconstruct the shape of the spine. It's 20 patients are planned. The treatment is the combination of CERAMENT BONE VOID FILLER plus autograft and instrumented posterolateral fusion, and it will be done in a single center in Canada. Why Canada? Because in Canada, all three CERAMENT products are approved to be used in spine. The second study, the heavier lift, the multi-center study, posterolateral fusion in high-risk patients for infection. This is to show the prevention of infection, to reduce the risk of infection. Around the same number of patients as an arthroplasty with antibiotic-eluting CERAMENT plus autograft, multi-center, and again, in Canada. Estimated cost, around SEK 80 million.
With that slide, I hope I gave you a good overview of the market segments and the clinical update. I would hand over to Charlotte to moderate the Q&A session. Thanks for your attention.
Perfect. Thank you very much, Michael. Please stay on stage, and Annelie, perhaps you want to come up as well. We have microphones in the room. Could we get a microphone immediately, please, because Kristofer here has a question. Please, Kristof. It has come this way. Other side. Just there. Thank you.
Is it on? Can you hear me?
Yeah.
Okay, great. A question on the market model. The 430,000 procedures, you think that you could penetrate all of that eventually with CERAMENT G and V? Also, I'm looking at the figure 115,000 ongoing infection, and then you have 190,000 for the use of antibiotics. Is the difference there prevention, just to make sure I understand it, or should we add them on top of each other?
I'll start with the first one in terms of what's reachable for us. If we look at those numbers, you saw the penetration levels depending by segment. It's a couple of % on trauma and arthroplasty, and it's slightly higher on foot and ankle.
Could I just interrupt? That was my second one. When you talk about penetration, is that out of 430?
Yes.
Okay.
Yes. When we talk about penetration, I prefer to use penetration, but you can argue market share. Penetration is that we define the number of procedures where we believe we can be in as a bone graft and/or with antibiotics. That's one piece. Then we always count procedures. We don't count value. We always count procedures. Then, of course, in some procedures, more CERAMENT is used. In some procedures, less CERAMENT is used. We start with that procedure count because that's important for us. What's reachable? I think in the U.S., the reason why we say that we're still early on the growth journey is simply because if we look at the U.S. where we are now, number one, it's only a few years since we actually launched CERAMENT G. Just a couple of years. It takes time in orthopedics.
That's number one. Number two is that if we would achieve, let's say, the same level of penetration in the U.S. that we have achieved in certain regions and countries where we've been much longer, then we will get not 100% of that potential in the short term, but a long runway. We know that we have data points where we reach 60%-70% of the penetration. In some countries where we haven't been as successful, we've only reached to 30%-40%. We definitely think that that range is definitely doable in the foreseeable future. Longer term, we expect this total addressable market to expand. We talked about the cascades of patients. We're not overly concerned that there is room for us to growth. We just focus on making sure that we get that penetration day by day, quarter by quarter.
Let's say in two or three years, do I think that the market size will have expanded even more? Yes. This is the data that we have today. Also, that is what we see today, everything else equal. Annelie showed also the so-called preceding segments. I think that is a very interesting dynamic for us to follow in the medium to long term. Exactly how that will play out, we don't really know. It's of course a very strong tailwind for us. If that answers your question.
The difference between 190,000 and 115,000, is that prevention?
Well, the way that I would think about it is that first of all, you have a total number of procedures where bone graft is used, and some of these bone grafts are used with antibiotics and some of them without. Whether prevention or not, yes, you could draw that conclusion, but there are also other nuances that we should take into account. I don't know, Annelie, if you have more?
No, I think in principle you're right there.
There could be ongoing infections where you're not using local antibiotics today.
Absolutely.
Yes, absolutely.
Great. Thank you.
Sten, did you want?
Yeah. Hi. It's on the same topic. I'm just trying to understand the model. Previously, you talked about infected patients, osteomyelitis around 50,000 and some 90,000 in prevention. How do we go from those numbers to these 115,000 and 190,000?
From my perspective, I prefer to talk about the segments as they are, meaning foot and ankle, trauma, arthroplasty, and stick to the definitions of in foot and ankle, you have the diabetic foot osteomyelitis. In fractures, you have fracture-related infections, and in arthroplasty, periprosthetic joint infections. Using the term osteomyelitis is a bit confusing, and different data points interpret the term osteomyelitis differently. That's why we try to stick to that. That would be my starting point. Then, Michael, I don't know if you can share why is that use of these different terms different in the different categories around osteomyelitis, fracture-related infections, and periprosthetic joint infections.
I think over the last probably 10 years in orthopedics, we got more focused, and we have now all these definitions on these specific infections, which we didn't have before. Before, everything was thrown into one bucket, which is osteomyelitis. Sometimes it was even called surgical site infections, and the numbers were a bit all over the place, and now it gets much more specific. Publications coming up with definitions of these infections and treatment regimes, and this is another way which we follow with this market segmentation as well.
I cannot answer directly on your number, but maybe Annelie.
I can give a little bit more flavor also because what we say is that these preceding segments are now coming in with more patients that we were not counting on being able to provide treatment before. We see more and more in diabetic foot. You can preserve more and more of the foot, and we believe that those are numbers that have come in and grow our infected size number. Also in the revision arthroplasty or in the periprosthetic joint infection, we very much underestimated the use of local antibiotics together with the bone graft there. That has also increased this number.
Okay, the SEK 190,000. Is that the preventive use?
That is total use. That is both infection and prevention, and also based very much on this market research that we have done that shows that there is a much higher use of local antibiotics already preventatively.
Thank you.
Torbjörn, you started your presentation today also mentioning the cost of these studies, and Michael reiterated them. Can you talk a bit about why you put so much more money in one of these segments and how you distribute it over the years?
Yeah. I'll talk more strategically how we allocate the capital, and then Michael can provide the assumptions behind why is one costing more than. On spine, we want to achieve two things with doing the study. Regulatory approval, surgeon buy-in or being able to use it. That's number two. In arthroplasty, we have all the regulatory approvals. We're not doing it for regulatory approvals. It's all about creating more science, more evidence to convert more surgeons and increase the penetration. That's really important. When we look at the total potential of these two segments, arthroplasty is much more here and now, closer to us, less risk. It's just to go out and get it, so to say. Spine, we're not there yet.
New indication, new regulatory approvals, but both of the segments, to us, look very attractive, independent how we see them. That's why it's almost a no-brainer to do the investments at this stage. The two studies that we, at this point, preliminarily look at, they are designed slightly differently, and that's also the cost. Michael, feel free to share what are the thinking around the studies.
Yes, thank you, Torbjörn, and you mentioned some of the parts. The spine study, as you mentioned, will be used for regulatory approval. This needs a higher scrutiny. This has to be perfect to be used with the regulatory authorities in the U.S. In spine, we are not so far in the process compared to arthroplasty. In arthroplasty, we have an advisory board. We have a lot of surgeons which are interested in doing the study and which want to contribute to the study. In spine, it's a starting point. We have to go out and find the interested surgeons. Concerning the costs, the calculation is that in spine, we need a CRO, a clinical research organization, which we have to rely on heavily to get the study done to all the standards for regulatory approval.
With arthroplasty, with the key opinion leaders, it's not written in stone, but it could be driven by one of the key opinion leaders, meaning that we don't need the cost for a CRO. The cost for a clinical research organization for these studies are significant. These are the two differences.
You're saying significant, but not as much as has been speculated in the market.
What's being speculated in the market is up to the market to sort of answer to. On spine, let's be honest, the number that we communicate today here on spine is exactly the same number that we've communicated all the time. There's nothing new on that. For those of you who have been in meetings and been in presentations, when we get these questions, what we say now is exactly how we have answered that question. Around SEK 80 million-SEK 90 million. If other people have better or other estimates on how much studies cost for BONESUPPORT in CERAMENT, it's up to them to answer that.
Keith, where's the microphone? Yeah, good.
I have it already. I have three questions. The first one is, I guess you implicitly shared a volume split between the three focus segments in the U.S., it implies a quite clear major representation in diabetic foot, of course. Two questions there. In your opinion, is it any factor we should account for that suggests a lower market share in trauma and revisions long term that we should consider? Also, I think what would be helpful is if you could share the sort of volume split in Europe between these three segments, where you've been before in certain markets.
Okay. Good. First question, no. I don't see that there's a different sort of threshold that we can reach in foot and ankle versus what we can reach in trauma versus arthroplasty. All of them look very attractive. At this point, we don't see a ceiling that one is going to be drastically different than the other. They will be different, but we don't really know yet. Foot and ankle has been a fantastic segment for us. Trauma is fantastic for us, but it's early days. It takes time. Arthroplasty, again, we're just scratching the surface. All three of them are very important for us in absolute terms.
It's easier for us to provide this level of granularity for the U.S. simply because we have much more granular data, and that comes from the go-to-market model that we have in the U.S., which I said earlier. It is non-exclusive, call point-based, independent sales rep model. That call point-based, what that means is that we get data. For 80% of all the procedures done in the U.S., we know what is the individual surgeon, who is it, who is he or she, what is he or she using it for? We have that level of granularity in the U.S. In Europe, we don't have the granularity. It's more anecdotal, and we can make estimates. It wouldn't be fair to give an exact number for OUS because we simply don't have it.
Do I think it will look completely different OUS than the U.S.? No. That would be my estimate.
Good.
Those were two questions. What was the third one?
No, I think maybe it's four questions here.
Oh, okay.
The next one is how big a factor is the ability to plan the procedure when it comes to the decision of the surgeon to use CERAMENT G or not? I think maybe some words on, yeah, then diabetic foot versus trauma, for example, would be helpful.
I think it's a great question that we can ask Dr. Matuszewski when he presents. Park that question. You hear it right from the surgeon. I think from our perspective, the principles are the same. Number one, you have to have an innovative product. We do that. Number two, you have to have the evidence. That depends a bit on which procedure you're going after. Third, you have to do it surgeon by surgeon. You have to convince surgeon by surgeon. You could argue, well, are the trauma docs easier or harder to get in front of versus the foot and ankle docs? Some say yes, some say no difference. For us, we don't draw any sort of major conclusions on that. The principles are the same.
You have to convert surgeon by surgeon with an innovative product and with the evidence. So far, I think it's still too early to tell, and we don't have enough data to say that, yes, one is absolutely more difficult than the other. We have enough demand on all three segments as it is today.
Good. In years here post 2026, let's say 10 years out in time, how much faster do you think the local antibiotics patient cohort will grow compared to the total procedures? A question to that is also, do you think SOLARIO is yet to help to age these patients higher? Also, do you think SOLARIO could have an impact on the U.S. behavior?
What do you think of SOLARIO?
It's a very good question, and it is basically the orthopedic community has been waiting for this study. It has been waiting for these results, and it has been waiting to reduce this long duration of the antibiotics. I think if you can avoid these problems for the patients by reducing the duration by local antibiotics, this is a driver towards the local antibiotics and to CERAMENT G and V. I think it has a high impact. The question in Europe, it's a European study. In the U.S., it will probably take some more time to make it public and to get the adoption, because, yes, in the U.S., it's quite known for the long duration of antibiotics. They kind of will stick to their rules first.
On the other hand, if you compare it to the OVIVA trial, the OVIVA trial is where it was shown that oral antibiotics pills are as good as intravenous antibiotics. This was adopted quite fast in the U.S. because they immediately saw the benefit and said, "Oh, then we don't need these six weeks of intravenous antibiotics, the special application cannulas," and so on. It could go both ways, but I think it would be more conservative in the U.S. for the adoption of the SOLARIO. What we see starting now, and I mentioned this a bit in the clinical studies, that there is a huge interest now to prove the SOLARIO concept in the segments. We hear a lot about, "Oh, diabetic foot, can we do a study on a shorter duration like it's done in Basildon now?"
This topic is coming more and more and will help to get even more evidence behind the large SOLARIO trial.
Thank you very much.
I think a key point, which I am not really sure, and I cannot really quantify, but I think it will have a significant impact, and this is actually something that is over the last, I would say, year, has been referenced in relation to the SOLARIO study. One of the key things that Professor McNally says when he presents this is that this study gives more decision power on the orthopedic surgeons. They don't have to rely as much on the infectious disease docs and the systemic antibiotic regimens. It gives them more evidence, more decision power, and I think it's not only good for society and the patients as such, I think it's also going to benefit us. Exactly when, how, we don't really know.
How important is the full publication? Do you expect to get an extra boost from that? It's already published the top line?
Yeah. Top-line results are published in 2024. Every conference that I go to or that we go to, SOLARIO is mentioned. It's been talked to, it's been referenced. They talk about the results, and every time McNally and his team are out presenting, they're presenting the data. From an orthopedic surgeon perspective, it's already getting traction. It's already talked about. That's one thing. However, in many hospitals and hospital systems, or actually the topic that we're in, it's not only a decision for the orthopedic surgeon. It is a multidisciplinary decision involving the infectious disease docs. What that means is that they, in several areas, in many cases, they say, "Well, great study, love it. We're definitely going to go with this. Where's the publication?"
Last time when I was at, was it NÄL on the west coast of Sweden. This was exactly this. "This is great, I will use it, but I cannot start using it because I need the publication. Where is the publication?" Yeah, it will have impact, but exactly how, we don't really know. We have really good reasons to believe that it will come soon, but it's out of our control.
After following you for many, many years, a couple of years ago, you did this booster program to get sales up. Now it seems you are today talking a lot about the clinical side. Isn't there a potential still to do some type of booster programs? What is, hampering would be the wrong word, but what is holding your growth back? Is it the clinical side or could you have the money to do booster programs as well.
You know what Johansson tells me all the time? We're doing all of this booster. We're doing a lot of booster recently. What has been announced has been announced. If you look at 2024 and 2025, we've invested a lot in the hybrid markets OUS. We've invested heavily in the U.S., in 2025 and also since I joined. We invest a lot in the back office functions to support the organization to drive more sales. The good thing, as we grow, we build a stronger base, larger base. We're not shying away from investments and commercially in the U.S. as well as OUS. Actually, the good thing is that they pay off. If you look at the Håkan, we'll talk about the investments in the hybrid markets after the break. It looks really good.
We continue to invest in the U.S. In the last two years, we have invested to boost production. We have doubled the capacity of the business. That's something that we've done over the last two years. Cannot really see it on the balance sheet, cannot really see it on the P&L. We continue to do that. The reason why we put so much emphasis on this is there's a lot of exciting stuff on evidence around CERAMENT, and this is part of the strategy. We have an innovative product, but in order to get it into the hands of surgeons in a segment-specific way, we will continue to invest in evidence. We don't really change the strategy. We just continue to what we've done historically, and it's more of the same, really.
We have a question from the web on CERAMENT G covers Gram-negative organisms and CERAMENT V, Gram-positive . How is the determination between when to use G and V made? Are there an increasing amount of procedures where G and V together would be appropriate?
These are very good questions. CERAMENT G with the gentamicin as the broad spectrum covers Gram-positive and Gram-negative. This is basically the go-to product, I would say. This is especially for the one-stage procedure where you are not 100% sure which bacteria you are facing, you could use CERAMENT G. CERAMENT V is more focused on the Gram-positives, not for the Gram-negatives, and this is a good choice if a patient, for example, is transferred, where already a surgery has been done somewhere else and they found Gram-positive bacteria, maybe even resistant to gentamicin. This is a really good case to use CERAMENT V, so when you know that the bacteria are there and that they would react really good to vancomycin. The go-to is CERAMENT G.
CERAMENT V, for the staphylococci, the Gram-positives, and there's one part which is interesting for the PJI, the periprosthetic joint infections. Here, the surgeons are doing this joint aspiration, so they find the bacteria even before they do surgery. There are a lot of Gram-positive bacteria, and vancomycin works really well against them. I think there's a really good space for CERAMENT V in PJI.
I hope they are happy with that answer. There's one thing that you have announced lately that we haven't covered at all, and it's the buybacks. There's also been some questions from the web. Why aren't you addressing this matter at all today? Perhaps Håkan will, now we have you on stage, Torbjörn.
Håkan for sure will address it when he shows his favorite slides relating to cash flow. We're in a fortunate position. We're generating more cash than we actually need to do this. We have plenty of cash. Also, please bear in mind that the board proposed to the AGM to give approval for a buyback program. The AGM gave that. We didn't only do that for fun. We did it because we think it's adequate and relevant to do. Exactly when and how, we will announce that in the correct ways. Now the focus for us is to continue to operate the business the way that we want to invest in the business that we have done and that we show now that we want to continue to do.
I'm sure Håkan soon will give more information about how we start executing on the approvals that we have received now from the AGM.
In a while. Before that, we're going to have some coffee and just please remember the A, B, or C that you got when you entered the room. Now there is coffee, but please, as soon as possible, go to your A, B, or C, and then we're going to rotate, so you get to see two of the product demonstrations before we are back here at 3:30 P.M.
We have the eminent and great support of Karin, who's the Director of Medical Education in Euro. She is responsible for the foot and ankle demo. For trauma, we have flown in Candice Maxwell, who runs m edical education in the U.S. For arthroplasty, we have the eminent Pia Walby, who's the Director of Product Management. Take the opportunity. You get to feel the stuff. It's really fun. You get to feel the product and a sk a lot of questions. Thank you.
[Break]
Is going to be moderating this part. Please, Michael.
Thank you, Charlotte. Welcome back from the coffee break. I hope you had some time for good conversations and some time to experience the product. We continue now with the clinical experience session. It's an honor for me to introduce two surgeons who will present now. We have first Dr. Sebastian Meller. Dr. Sebastian Meller is a consultant for orthopedic surgery. He is the head of the Department of Hip Arthroplasty and Infection Surgery at the Charité Universitätsmedizin Berlin from Germany. Of course, he will present on the arthroplasty market segment. He will have the first presentation now online. After that, Dr. Paul Matuszewski will present. We brought him over from the U.S. for this presentation in person.
He's Associate Professor of Orthopaedic Surgery, Chief of the Trauma Service, and Chief of the Trauma Research at the Department of Orthopaedic Surgery and Sports Medicine, College of Medicine in Kentucky, University of Kentucky. Of course, he is presenting on trauma as the expert for trauma. With that, let's continue and see if Dr. Sebastian Meller is online. Sebastian, can you hear us?
Yes. I can hear you, Michael. Hello. Can you hear me as well?
Yes, we can hear you here in the room.
Perfect.
Now we can see you, and we can see your presentation. Wonderful. Thank you for spending the time with us, and we are now looking forward to your presentation on arthroplasty. The floor i s yours.
Yes. Thank you. Once again, Michael, thanks again. Hello, everybody, and guten Tag here from Berlin. It's an honor for me to talk here for the investor meeting, and I'm presenting our experience with CERAMENT in our PJI cases. Let's start. PJIs, so periprosthetic joint infections means challenging diagnosis. We have big problems. We have time-consuming surgeries. We have high costs, worse function, worse outcome, and we have a high morbidity and mortality on the sides of our patients. In some cases, we have higher mortality rates than in some cancer cases. That's really a big problem. What means PJI? PJI, it's an infection of a joint replacement and the surrounding soft tissue and bone tissue. It's biofilm-driven, and it's mostly caused by bacterial pathogens.
The diagnosis could be difficult, so this is why we need clear classification systems like the EBJIS or the Charité definition. The PJIs often requires revision surgery, implant exchange, prolonged antibiotic treatment. This is why we have to talk about the treatment in future. Why we doing hip revisions? These are the data fro m the German Arthroplasty Registry, and you can see that almost 30% of all hip revisions are being caused by infections. We are talking about a high number of patients, a high number of cases, which we are dealing with in hip and also knee revision. If we look at the re-revision rate, so these are patients which are revised and again revised after a hip revision. We see that in septic cases, and this is the blue line.
In septic cases, you have 30% of re-revision rates after one year and higher in two or three years. Even in aseptic cases, this is the red line, can you see 10% up to 20% in five or six years. We're talking about not as good results in the real world. This is why we have to improve our results, and we have to talk about strategies to improve these results. This is why I would like to present our surgical treatment strategy for these patients. The goal is to take the less inva sive approach with the best results, and you can see here, this is the treatment algorithm for chronic PJI treatment. In a chronic PJI, you have to remove the prosthesis. You can do it in a 1-stage, in a 2-stage, or in a 3-stage exchange.
Let's talk about the single-stage, so-called 1-stage exchange. For that, you need good patients, you need good soft tissue, good bone, and no systemic infections. These are the indications for a single-stage PJI treatment from our point of view. The current gold standard worldwide and the most frequently used technique is the two-stage. The two-stage means in two surgeries. In the first one, you explant the prosthesis, and in the second surgery, mostly after six to eight weeks, you go for re-implantation and re-implant the new prosthesis. This is called a two-stage surgery. This is the most frequently used technique in the meantime till now. The single-stage is an option, a reliable option, which is getting more and more popular, increasing application, mostly in centers.
The success is comparable between the single-stage and the two-stage in PJI of the hip in selected patients. In good hosts, in sensitive pathogens, this is a point which we have to go if we talk about a single-stage exchange. The treatment failure rate in PJI in single-stage and two-stage rem ains high. We have reinfection rates with strict criteria with more than 20%. It's really important to identify and modify risk factors which can be involved for better outcomes. That means host factors, local antibiotics, defect and dead space management. These are the three key points from our point of view to modify and to improve results in PJI treatment. L et's talk about our surgical approach for a single-stage exchange in these patients.
To illustrate our procedure, I want to present you a case. This is a typical case, 59 years old lady, PJI of the right hip arthroplasty a few years ago. You see also on the right side a CT scan with some holes around the cup and with some defects. From our point of view, a good patient for a single stage exchange. What we did, we did a puncture and aspiration before the procedure. We found a pathogen, a Staphylococcus capitis in this case. We decided to go for a single stage PJI treatment in this lady. We used CERAMENT G with some allograft in the bone defects in the acetabulum. You see it here on the video in the middle.
We fill the defects with CERAMENT and allografts, and then we go and implant the new prosthesis in this new filled acetabulum and then we are happy because we have local antibiotics, we have defect management for the new implant. Let's talk about on detail about our augmentation technique using CERAMENT in these cases. What we do usually in the first step after removing the prosthesis, we absorb blood and fluid, then we go deeply in the femur and fill the whole channel retrogradely without pressure deep into the femur under the stem with CERAMENT G. You see it here. It's quite deep after removing the compress, filled retrogradely. This is step one and step two. The next step is an augmentation of the implant.
You see it here. Every implant surface has some grooves, some notches, some holes, and you can augment this implant with CERAMENT like we did it in this case. Then you go straightforward according to your standard protocol and implant the prosthesis to this position like it's planned. You see here again the augmentation of the surface of the implant 360 degrees on the implant surface, and then you go on with the implantation of the prosthesis. In the next step, it's step number five, we fill and augment the dead space. You see it here in between the prosthesis and the bone. There's always some dead space. There's always some defect.
We go and fill it up with CERAMENT to avoid dead space, to avoid hematoma, because this could be the next position and the next space for bacterial infection. This is why we fill it up with CERAMENT. In the next step number six, we dry the CERAMENT. You see it here. Usually I take a compress and push, compress the CERAMENT 8-10 minutes, wait till it's fully set and hardened, and then you can see it's very nice, hardened, fully set, and then we are happy and can go on with the surgery after the CERAMENT is dried. In the last step, according to your protocol, make an X-ray, check the position of your implant, and you can also check the position of the CERAMENT.
You can see it here in the red marked areas, the CERAMENT in the proximal and also in the distal part of the prosthesis. This is our augmentation technique for the femur site. Sure, we also have an acetabulum, and this is what I have here, the CERAMENT and the cup revision, and this is the same principle. We dry the bone, we absorb blood, use some compresses, use a suction device because you need a good dry area for good visibility and application of the CERAMENT. In the second step, you go on with the application of the CERAMENT. It's applied into bony defects. You see it here. These osteolytic areas, these holes in the acetabulum are filled up with the CERAMENT like it's here shown. You can do it without or with allografts.
If the defect is a little bit bigger, you can also take some allografts, like I will present it in the next second. Again, some CERAMENT. You see it here layer for layer. After the cement, you take some allografts. You see it here, some chips, and then you can put it on the cement, make some compression, go on with a reversed reamer or with a pusher. You can compress it and fill up the holes and the defects very nicely, and you will get a nice osteointegration in this case. In the next step, it is step three. It is again the augmentation on the implant. You see it here. Here on the surface of the implant.
Here, the same like in the femoral revision, you have in the acetabulum also implants with not just with grooves, with holes, and you can fill them with cement. According to your standard protocol, you go on with the implantation of the prosthesis in the prepared acetabulum like you do it routinely. You can complete it as per standard protocol. Here, put the cup inside, then, yes, now it is in. Take the right position and then fix it with your hammer. Step number five, also here, filling and augmenting of dead space and defects. You see it here in between the cup and the bone. There's also remaining dead space, some cavities. You can fill it up and close these defects with cement.
Also in the last step number six, you can compress and dry the cement eight to 10 minutes till it's really fully set and hardened. In step number six, you do the X-ray, and also in the X-ray, you can see the cement around the cup, in the holes, in the cysts. Then this is also ready, and the patient has a new hip after one stage PJI treatment. What are pitfalls in using cement? From my point of view, first of all, the incorrect patient selection. You need a good strict selec tion criteria for a single stage. This is necessary. The further pitfalls from my point of view are insufficient drying of the bone. It will bring a poor adhesion. Dry the bone.
The next point is high pressure application. Don't use high pressure. Make it slowly. Take your time. Otherwise, you will get misdistribution in the system. Number 4, the incomplete filling of these defects or dead space. Residual spaces between implant and bone remained. Again, take your time, fill up the holes, fill up the dead space with the cement. Make an X-ray, check if there are some holes, and you can fill it up with cement. Number five, don't close the wound too early. Wait till the product is hardened at up to 10 minutes. If it's hardened, you can go on with a good soft tissue closure, and then you are happy, and also the patient will be happy.
To verify now the things I told you and to verify our protocol, we performed a prospective study which was published a few months ago. The cementless 1-stage hip revision arthroplasty with cement in infected hips. We called it CERAHIP study. It was a pilot study, and I want to present you the design and the results of the study. It was the first prospective study using cement in PJI cases, and we included confirmed PJIs according to the EBJIS criteria. We involved 20 study patients in this prospective study with a follow-up of at least two years. We used cement with gentamicin in defects and dead space around the stem and also around the cup like I showed you before. We follow up the patients with a standardized protocol, like it's typical in our unit.
The patient's characteristics, we included 20 patients, 10 men, 10 female, with PJI of the hip. The mean age, 66 years. 16 patients were cementless in the previous surgery. Four patients had a cemented total hip arthroplasty. The stem was cemented in these cases. Six patients had one previous revision, it was aseptic. It was no PJI case before. The intraoperative characteristics, we confirmed PJI in all patients intraoperatively. We had positive microbiological or histopathological results. In mean, we used 13.2 ml CERAMENT G per patient. Postoperatively, 19 patients reached the follow-up. One patient had a lymphoma, was not a ble to follow up. We had one aseptic dislocation of the cup. We had no wound complication, we had no drainage after the discharge of the patients. We found 60% of coagulase-negative staphylococci, a typical cohort.
Staphylococcus epidermidis was the main pathogen. Polymicrobial infections, 20%. Culture negative, 20%. A typical microbiological finding in a PJI cohort. The results, the postoperative results for the WOMAC hip score, they improved significantly. The EQ-5D-5L improved. That's a life quality score. The patient felt better after the surgery, were happier, and also the pain evaluation improved in the CeraHip cohort, in the CeraHip study, also significantly. Very good results in this cohort. We can say after now 3.5, more or less four years follow-up, we had no reinfection. We had very good, excellent functional results, good radiographic results. The limitation, longer follow-up and more patients are necessary for future investigations. You can see it works, and our study could prove that it works in our hand. Let me mention that we're also using CERAMENT in 2-stage exchange procedures.
I brought you also to one case for a 2-stage exchange. That means this is a typical case for a 2-stage. You can see it here on the left side. A lot of surgeries in before hip replacement of the left hip, explantation, re-implantation, fracture. Some different pathogens. The patient was referred to our unit. We did an explantation and a Girdlestone procedure, like you can see it here on the right X-ray. You see it's no implant inside. After six weeks, we go and made a re-implantation in our unit, and we decided to use CERAMENT mixed with some allografts for the defects. There were some defects in the bone around the acetabulum, also around the femur. This is why we use CERAMENT also in the 2-stage, in the re-implantation procedure in this case.
Until so far, the patient is good. I wanted to mention that we also use CERAMENT for prophylactic use. That means we have patients which are at high risk, patients after revision, patients with some comorbidities, and this is also the case in this lady. You see it here. She got a nail after a fracture on the left hip. After a few years, she developed an osteoarthritis. You see it on the left side. She suffered from pain and was not able to walk properly. What we did, we removed the implant. In the same session, we cut the neck. We removed the head. We cleaned the acetabulum. We implanted a primary hip arthroplasty like it is shown here on the right side. Because she was very old, she had a surgery before, she had some comorbidities.
We decided to protect the implant with local antibiotics, to do it in a prophylactic way, to save and to hope that the implant will be safe for the future. We used it in single stage, two stage, and also here in prophylactic patients. Let's go to my take-home message. I would like to say that the two-stage is currently the gold standard. The two-stage is the gold standard, but the single stage is getting more popular. We're getting more brave worldwide, more and more surgeons doing single stage in PJI cases. For the single-stage revision procedure, we need a critical patient election. This is mandatory. I showed you our algorithm for these patients. CERAMENT G is, in our department, firmly established in the treatment protocol as a local antibiotic-eluting bone graft substitute for defect augmentation in the PJI treatment.
The CERAMENT G is utilized according to a standard protocol. We do a debridement, a bone preparation, and then we applicate in defects and around the hardware in the acetabulum, in the femur, and also around the knee. The CeraHip study showed good functional and radiographic results, and we also could use it prophylactically in high-risk revision cases like I showed you before. This is my team. I always say thanks to my team and thanks you for the attention.
Fantastic. Thank you. Thank you, Sebastian, for this great presentation. I think, I'm not sure if you could see the audience, but what was really appreciated were the videos, I think. I saw some smiles when you were hammering in the prosthesis. I think this is one of the highlights of each implantation procedure.
All of you are invited to come to my surgery room if you want to see it live. No problem.
Sebastian, we have some time for questions. You just can hear my voice, so I would repeat the questions, and I would ask the audience for questions. Please formulate them short so that I'm able to repeat the questions. No numbered questions like one, two, three, four. Okay, let's start with Kristofer.
Would you say that CERAMENT is as beneficial in the 2-stage procedure as the 1-stage procedure, or is it mainly in the 1-stage that this is useful? Thank you.
Thank you. No. From my point of view, if the indication, if you need local bone graft substitutes, if you need local antibiotics with a high concentration, if you need a substitute for defect management, for dead space management, it's also a good idea to use it in a 2-stage. The CeraHip study was about single stage. We also do it now in some cases, if the indication is right in 2-stage cases as well. Yes.
Great answer. It's fantastic, of course, when you use the microphone, then I don't have to repeat the question, so that was a mistake on my side. Sten, the next question.
Yes. Dr. Meller, approximately in how many percentage-wise or % of your overall procedures do you use CERAMENT G today? Where do you think that that number should be five years from now?
In the moment, we use CERAMENT G in all our single-stage hip procedures. Why? Because we had these good results like I showed you in the CeraHip study. We have a good working system, never change a winning team. This is why we use CERAMENT G in these single-stage exchanges. We will look up how our results will be in two-stage and also in prophylactic patients. I can imagine that if it works and if the results getting also good, we can go and use it also there as maybe standard product if you have defects, if you need a high concentration of local antibiotics.
Thank you. My second question would be, would it make sense to use it prophylactically in primary hip procedures?
The question is if there is some space for the CERAMENT. Normally, there are no bone defects. There is not much dead space, so you don't use it. Some primary cases are difficult. In some primary cases, you have osteolysis, you have defects, and there it could make absolutely sense. Make sense to use it in these cases. Yes.
Thank you.
That's a great answer, it really depends on if there are bone voids. CERAMENT is, as you of course know, BONE VOID FILLER . If there are bone defects to fill, it makes sense. Sometimes there are no bone voids, the application is tricky. Great answers. I think we have time for one more question, if there is interest. No further questions. Sebastian, once again, thank you so much for presenting from Berlin all your experience from the Charité. Well done.
Thank you. Have a nice day. Bye. Good luck.
Thank you. Now it's an honor for me to introduce Paul Matuszewski, Dr. Paul Matuszewski, Associate Professor at the University of Kentucky, presenting on trauma. I come down and make space for you.
Thank you. All right. Well, it's a privilege to be here to talk to you guys today and all the way coming from the U.S. and certainly good to share our perspective. My job that I wanted to impart to you all today was essentially to get a little insight into how we use it and how it's been helpful for us, but also understand really what the burden is. I think that you can talk about market share and things like that, but I think it's really important to understand from the patient's perspective and a worldwide perspective how big of a problem infection is for us. The socioeconomic effect in the treatment of fracture-related infection is quite high. Some of the prior speakers talked about this.
The rate of infection has largely been unchanged, and is anywhere between 1% to 30% in patients. Why is that? It turns out that we're getting better at taking care of patients. It used to be that patients would have traumas and they would die. With advances in automobile safety and also some of our trauma care, we're able to keep these patients alive. When these patients survive their injury, then they become the broken man, so to speak. That's where I come into play. As these patients survive more, we have a higher rate of complex injuries. When you have complex injuries, you have a higher rate of infection. When you look at it from a worldwide perspective, the burden is huge.
Each year, there's about 178 million new fractures, and that corresponds to about 1.8 million fracture-related infections, which is quite a bit of infections every year. Treatment for infection is expensive. It could be anywhere from up to six and a half times more expensive than it would be for the original cost of fracture care. In an older study published, they said about $108,000 per case, but it's likely more. A lot of that cost comes from staying in the hospital. These patients get admitted with their problem, and they stay in the hospital, and they're there for several days, and often multiple times. That's followed by the cost of the implants and the pharmaceuticals. As these patients become more sick, older, so on and so forth, that expense increases.
When you think about that worldwide, extrapolating those numbers, if you're spending about $100,000 U.S. per infection, and you have 1.8 million, you're talking about upwards of $200 billion a year spent on taking care of infection. When you look at a society, that number is probably a little bit lower than what we really expect because the cost is tremendous. In the U.S., you have about a 45% increased odds of requiring some type of governmental supplemental financial support, meaning patients are on disability and receiving benefits from the government. What about the actual individual? I just talked about the numbers to society. The cost is tremendous, and you have to think about it and look at it from the perspective of how good we are at taking care of infection.
It turns out that for infections, we're about 60%-70% successful for the early infections. When someone has a fracture, they get the surgery, they wind up with an infection, we can treat them with a debridement, washing things out, retaining what they have, and they get antibiotics. That's about a six-week timeline, give or take. If you have a later infection where the infection is set more into bone, that's when we talk about removing implants and debridement, cleaning things up, giving antibiotics, and returning to the operating room potentially for another stage, not dissimilar to the PJI literature. Similar success rate, but now the timeline is increased. Now we're talking about three months. These timelines are really only if it's successful on the first try. That's historical data.
We've looked at this at my institution, and I have to say, as an egotistical surgeon, this was prior to my tenure, so I don't know how much better it is now. Only 43% of patients were successfully treated with two stages, 29%, three stages, 27%, four or more stages. That's with an overall success rate, including those stages, of about 60%, and with 32% of having recurrent infections, and with those recurrences happening between eight and nine months, with multiple complications, patients receiving amputations, and complications associated with the IV antibiotics, delayed wound healing, and things like that. Getting back to the patient, I love this picture. This is a perioperative care pathway from our preoperative unit at my hospital. It shows how straight line everything is in a hospital.
We talk about primarily the diagnosis, and we talk about eradication. There's a lot going on during that time. I just told you that some of those timelines are six weeks, three months, six months, nine months. A long time goes by. Think about yourself. If you were out of work for that amount of time, what would happen? Upon first diagnosis, patients are frustrated. It's like they've heard cancer. We heard that earlier. Then they're out of work. They can't go to work. Maybe they have some benefits from the government. Maybe they do, maybe they don't. They have pain. Divorce happens during that time. They have problems in their family. They lose their job, and they develop chronic pain, and all sorts of things happen before the eradication.
The effect is tremendous on these patients. They can be devastating. Patients have problems with mobility. They get amputations. They have complications from antibiotics, like we talked about. They lose function. They don't get back to where they were. Some of them go down the path of substance abuse disorder, where they're addicted to certain substances, and the emotional and mental impact is tremendous. Anxiety, sleep disturbance, pain, concentration problems, depression, even suicide is associated with this. The long-term impact, though, is even worse. Once that eradication occurs, those problems still exist. They get past the infection. They move on. They're not in the hospital anymore, but they have decreased quality of life, and the psychological burden persists even beyond four years. As that time increases, those themes, they worsen.
The more time for longer treatment, the more complications, the more problems, the higher psychological burden, and so on and so forth. Where does that leave us? Well, the fractures are increasing, and patients are becoming more complex, and these complications and infections are increasing in prevalence, but not necessarily incidence. More and more patients, even though we're getting better at taking care of these patients. How do we do better, and what have we learned, at least in the trauma space? Well, we can actually take some of the data from the joint literature folks because they've shown in revisions that there's certain things that we can do. In the joint arthroplasty space, they have moved, at least in the U.S., more towards outpatient procedures.
Patients are no longer staying in the hospital for three or four days. They're staying maybe one day or even less than a day, and they're going home. Guess what. Patients do better. They have less complications, and they just overall mentally feel better. When we look at infection revisions, my colleague talked about this a little bit, but when you take a single versus a dual-stage procedure, it's a big difference for a patient. I just told you about all that time, right? You go to the office, and you get diagnosed, and they said, "Okay, we're going to take out all of your implants, and then we're going to come back six weeks later, three months later." Think about how you'd feel while you're sitting there waiting to find out to get your next surgery.
There's a lot of anxiety associated with that, a lot of problems. When you change that to a single stage, the mental impact is tremendous, and patients feel so much better. If we take that to the FRI, the fracture-related infection side of things, we can easily, if we decrease the number of procedures, decrease hospitalization stay, and also the length of stay, logically, we'd think that we'd have the same effect. Can we do it? Well, I think we're working our way towards it, and I think that some of the evidence that was presented earlier helps frame this and give this context for us, and it all has to do with recent improvements that we're taking advantage of and combining those techniques. Number one, local antibiotics. Local antibiotics are a huge thing in the treatment of infections.
Historically, IV antibiotics, we give them to patients, they get a via an IV, they go home with this. Every day, someone delivers a bag of antibiotics to their house, and they have to administer and sit there for 30 minutes. The problem with IV antibiotics is you can only have a small dose that's in your system, because if you get a higher dose, it will kill you, or you have severe complications. We can only give so many antibiotics, whereas if you flip the script and you give it locally, you can give orders of magnitude increased concentration. Instead of 10 units, you can give 10,000 units, so to speak, which is like a battlefield approach to things, if you think of overwhelming force in a war.
If you hit everyone with everything that you've got, as opposed to a little bit at a time, you tend to be more successful. We look at some of the guerrilla warfare and strategies that have been used in the past and how it just takes a long time for these conflicts to go on and on. If you have an overwhelming force, things tend to deescalate pretty quickly. What is the clinical evidence? There's actually a lot of evidence that's available. You can use it in both prevention and treatment, and some of the prior speakers have talked about that. In the prevention space, there's been a couple trials in this looking at vancomycin and tobramycin, which is another aminoglycoside not dissimilar to gentamicin, and showed decreased infection rates when we use this in the initial treatment.
For treatment, and we've talked about this before, there are multiple studies also that have shown that if you use local antibiotics, it benefits the patient. Okay. What about the decrease the reliance on IV antibiotics? I talked about this a little bit. IV antibiotics are problematic because there is a high cost of delivery, it is inconvenient, and there are lots of complications. One of the prior speakers talked about some of the findings of the SOLARIO trial, which I will touch on, but if you have an indwelling PICC line or an IV line in your arm for three months or six weeks, there is a high probability you will wind up with an infection that usually is a bloodstream infection, which is a big problem for patients.
That can create all sorts of systemic issues and can even cause sepsis and death. It is a really serious thing. When you treat patients with IV antibiotics because of that, the guidelines aren't clear. There's a lot of disagreement. Should it be for six weeks? Should it be for 12 weeks? There's confusion surrounding that. Oral antibiotics are very attractive alternative, because it's easy to give. It's a pill. It's lower cost. You don't have the complications. Actually, there's plenty evidence now. In the U.S., there was the POvIV trial, which demonstrated that oral antibiotics are non-inferior to IV antibiotics in the treatment of fracture-related infection, and the OVIVA trial, which was mentioned earlier, shows a non-inferior result, meaning it's as good. Okay. What about single stage treatment?
Well, historically, I talked about the dual, the single or the multistage treatment, but a more modern version of this capitalizes on this. If you use local antibiotics at the site of infection, you can actually be better than if you don't use it. Now when we use those local antibiotics, we can take advantage of that in a single-stage scenario because we don't have to rely on those systemic antibiotics as much. The biggest thing is really a combination of all three, and it was sort of the our powers combined. I chose this graphic here because this was popular when I was a child, and I read it was popular in Europe, too.
I don't know if you guys recognize the cartoon "Captain Planet," but it's all about combining the forces together to create this guy, Captain Planet. The SOLARIO trial is a lot like that, so you combine the local antibiotic therapy plus the short course of antibiotics, and they showed that it was non-inferior to a longer course, which we heard about that, with a decreased rate of adverse events. If we combine these improvements, it changes the landscape dramatically. Local antibiotics, oral antibiotics, single-stage therapy treatments, changes that paradigm completely. CERAMENT G plays a tremendous role in this because in the U.S., that's the only thing that's available and approved to be a BONE VOID FILLER that's combined with antibiotics.
That means that you get the local antibiotic delivery to help improve the eradication of infection, and then you get the bone graft substitute to fill the hole. All right? That's the single-stage part. Before, we'd have to go in, take everything out, and there's a big hole, we put something temporary in, and then we come back later once the infection is eradicated, and we put something back in. CERAMENT G allows us to do both at the same time. Here's a clinical example for you that I think can be illustrative to kind of make these points. This was a 41-year-old lady who came to my clinic, very active lady. She had a prior trauma.
She was treated by another surgeon for her ankle fracture, and she was a long ways out, actually, and she started to develop infection in her leg. This is what her X-rays look like, and if you look at her X-rays, you can see screws at the bottom of her ankle, and if you look really top there's something that's in there. That's actually a drill bit from the surgery, which happens. It does happen. To get that drill bit out in the middle of a surgery is kind of tough. There's a significant morbidity associated with that. A lot of times we leave that in there. If you look really closely, you can see at the tip of that drill bit, there's a little bit of fuzzy stuff there.
What that fuzzy stuff represents is some type of reaction to something. Most likely infection. With this patient, I've got two choices. The traditional treatment is I could bring the patient into the operating room, admit them to the hospital, do my surgery, take everything out, give the antibiotics, send them home, and then bring them back after we've confirmed that the infection is gone for a potential second procedure where we might bone graft. I just told you that in order to get that drill bit out, I have to make a hole in the bone. I have to create a hole. How do I fill that? I have to go back and bone graft that or hope that it's small enough that it doesn't matter.
Maybe take advantage of some of these techniques and use more of a modern strategy where I can do everything in one shot. Bring the patient to the operating room, take it out, and go ahead and put the local antibiotics with the CERAMENT G in it to fill the bone at the same time, discharge them with oral antibiotics, maybe IV antibiotics, and then follow them as an outpatient, and let's see what happens. I chose number two because that was going to be better for this patient. This patient's a mother of three. She's got to go home. She's got to take care of her children. She can't be in the hospital. There's no one else there to take care of her kids. We did her outpatient surgery day one.
We did what we said we were going to do. We removed the foreign body. We put our biphasic calcium sulfate hydroxyapatite, CERAMENT G, and then we took cultures, and we discharged them home on the same day. We gave her two weeks of oral antibiotics. It turned out she did have infection. Her cultures were positive, and we referred her to ID for a referral. Now mind you, if this was the traditional way, those positive cultures that I just talked about on post-op day three, patient still would've been in the hospital waiting for those things to percolate, and then they would get their IV line, which would take another day, and then they could be discharged home, and then all the stuff that's associated with that.
She actually wound up not getting any systemic antibiotics because she had complete resolution, so she didn't need any further treatment. This is definitely a success. Minimal disruption of the patient's life. She's back to work quickly. No additional visits or procedures. How does the hospital look at this? Is there any evidence for improvement? Well, we actually did look at this a while ago. We look at the healthcare economics of this, and it all has to do with time. The more time you spent away from work and the more time that you have to spend on procedures, the worse it gets. When you change to a single-stage procedure, it gives tremendous savings. This is probably a lower estimate, about SEK 30,000 or so, with a large part of that being the surgery.
There's also improvement in life years and quality adjusted life years as well. The bottom line, it's good for the patients and it's good for the payer of the healthcare system. We talked about that. What about the hospital? Well, actually, the hospital's a little bit more complicated. In the U.S., if you have a complication, the hospital still gets paid for it. More procedures, more complications, more revenue, right? Because things aren't really tied to performance. That might be evolving over time, but currently, that's how it is, at least in the infection management space. The hospitals look at these things more on a per case by basis. At least they did at my hospital. What we found is that when you look at the cost of care associated with infections, it's usually a loss for hospitals.
They don't want to treat infections. That's why a lot of the centers in the U.S. that are the academic centers that take care of these complicated patients, they're referred from other outside hospitals to take care of them. Why? Because the government supplements their overall revenue cycle to keep them alive. That's how it functions in the U.S. When we looked at our cases, specifically CERAMENT G, shortly after it was brought onto the market and I got approval at my hospital, they said, "Woo, you're losing money. You're losing about $4,000 a case from these patients." I said, "Well, wait a second. What if we flip this on its side?"
When we flipped it on its side and we took this from an outpatient perspective, all those things I talked about, it turns out that we actually were making a profit. Well, the healthcare administrators love that. My healthcare administrators are split. We have some doctors, and then we have some folks which are more into the finance. The doctors say, "This is good for patients, so you should be doing it." The administrators on the other side say, "We like that, but if you could do it as an outpatient, that'd be better." Which it turns out is better for patients anyway. It's not just the money, though. It's about our ability to take care of these patients a little bit more creatively than we were able to before, because not every patient is the same.
Not every patient can be outside of work, and every patient is a little bit different. I talked about that mother and how she was a little bit challenging to treat because she couldn't get away from home. There's other things that are involved with this, and patients tend to avoid traditional care. They're afraid to go to the doctor because they don't want to have to deal with what's going on, which leads to even more problems before. Consider this case. I had a 48-year-old female. She had a bicondylar plateau fracture . That's a very traumatic injury to the knee. She had an implant infection. She had treatment of the infection. She had removal of the implants. Guess what? It wasn't successful.
She came back, after about six months after the antibiotics were stopped, she had recurrence of her infection. She had drainage, so she had a hole in her leg, and she's draining here. This is a picture of her X-rays on the right where you can see there's a hole. It's pretty obvious that that's there. On the left, that's an MRI sample which shows a white spot. The white spot represents fluid. In this case, that represents infection. She had an infection in the middle of the bone. This patient is a sick patient. She's not healthy. She's someone who has multiple medical comorbidities. The last time that she had IV antibiotics as an outpatient, it was poorly tolerated. She had severe nausea. She had diarrhea.
She had kidney damage, so the IV antibiotics caused damage to her kidneys. She had a really rough go. She said, "I'm not doing that again. I don't want to be stuck in the hospital for three months or six weeks," because she wound up being stuck in the hospital for a while for that. She wasn't interested in following up with our infectious disease colleagues. She didn't like them, but she liked me. What do I do? Do I refuse her the surgery and say, "If you don't do it my way, it's the highway"? Do we take more of an authoritarian strategy and say, "Nope, you have to have this." Will that patient comply, or will there be an issue?
With these new techniques and these ideas and concepts and things that are evolving, we can take advantage of these findings. I can offer her outpatient surgery with local antibiotics and debridement and oral antibiotics. She was okay with that. This is her intraoperative photo, which shows the CERAMENT G that's been placed in the area of that hole that I showed earlier. She had complete resolution of her symptoms. She did great. This is two months post-op, and you can see that the hole is getting smaller and smaller by five months. This was a success story, and she was very happy and able to get around with her life. With this nice lady, 49-year-old female, psychiatric, schizophrenic. Okay? This is someone who's in and out of the hospital, disappears, doesn't come back.
You see them one year, and they might disappear for two, or they might have all sorts of issues and just compliance is an issue. They cannot go to the hospital. They cannot make their appointments. This is a standard problem that I see almost every single day. Okay? She had a prior trauma. She had external pin sites on her arm from an external fixator, and she had a draining wound. She's had this draining wound for years. If you look on the X-rays and the MRIs, you can see in the red circles, you can see where it almost looks like something's exploded out of the bone. What that represents is the infection, and you can see it confirmed on MRI. There's that white spot that I was talking about before.
A chronic localized infection, difficult social situation. What do we do? We do exactly what I talked about. Local treatment, minimally invasive, oral antibiotics, and referral for outpatient antibiotics. That's what we did. Here we are. This is a good example. I'm very proud of this picture. Someone took this with a phone, and it looks like it was part of a CERAMENT G brochure. This is a small incision right here, and there's a cannula, which you might have seen in the presentations in the hallway there, with me injecting the local antibiotic. The incision right here. What that looks like on the X-ray is just that. That's the humerus, that's the top part of the bone, and her infection's on the lower part of the bone.
That wire is introduced, and we use that wire to guide us to put a hole in the bone to sort of enter the middle of the bone. We use cannulas to get all the way down to the site of the problem. That's a chisel that's used to get down to the site of the problem. Once we clean that out and wash it out and core it out, that's the 2-CAN on X-ray. You can see there's a wire over here, which has directed me where to go, and I slide that down into the bone. At this point, this is where I am with it. We put the antibiotics in its path.
This area here where you can see It's hard to see actually on the projection here, but if you look pretty closely, there's a shadow, and that shadow represents the CERAMENT G. I'm able to do that from all the way up here for something that's all the way down here to avoid flaying the arm open. Historically what we would do is we would open this whole arm open, huge surgical approach, and I can do that through a pretty limited incision. That's a big benefit for patients. The patient grew out MRSA, which is a tough bacteria. They were discharged on the same day, and they followed up one to two weeks later. Infectious disease prescribed an antibiotic that happens to be a pretty expensive antibiotic. Guess what? She never got it.
T hat's not ideal, but pretty common, especially for me. The local antibiotics, I could take a deep breath because the patient's still getting treatment, and they're still being compliant 100%. I don't have to worry about her. If she disappears, that's okay. She's taken care of. Here she is at six months. Mind you, I don't have any X-rays before that because that's when she came back, six months later. Normally, we see patients at two weeks, six weeks, three months, six months. She came back at six months. Her stitches were removed somewhere else. Someone else took them out. I don't know who. She did great. In conclusion, the number of infections, they're increasing. The complications in these scenarios and the complication of the patients continue to rise. The patients deserve better. We're not that good.
I just told you that when it works, it works 60% of the time. Guess what? It doesn't always work on the first try. Outpatient pathways can help us do that, and single-stage procedures really improve the quality of care and the cost of care. Thank you.
Great. Wonderful. It's really impressive to see these tough cases and all the complications we maybe sometimes not think about or how difficult it is sometimes to deal with the patients, not just to treat them. Are there questions from the audience? Yes. Microphone is coming.
Thank you for that very good presentation. I have a question. If you could talk a little bit about the process of deciding the risk of a patient potentially developing an infection. How clear is this typically to you after this assessment?
With the question being that how do I decide if someone is high risk? Part of that's already set in stone for the patient. Some of these injuries have a pretty high risk of infection. When you look at open fractures, for instance, the infection risk is quite high. If you look at the risk of what we call periarticular injuries, meaning injuries around the joints, the knee joint and the ankle joint and the foot joints, the risk is anywhere between 12% and 25%. These patients are very high risk, and those were the targets of some of those trials that I spoke about earlier to try and help prevent. We try to identify these patients. What's interesting about that is that.
When you look at that risk, we look at the high-risk injuries, the question becomes is really who's to gain? Is it the high-risk patients or the low-risk patients? The patients that are high-risk, they might actually wind up getting infections anyway from other reasons, whereas even the patients that are low risk, if you have a 1% infection risk and you can take that to a half of a percent, that's actually a tremendous amount because the number of those patients is much greater than the higher-risk patients. I guess to reframe that, I think it doesn't matter really because both groups of patients benefit from some type of preventative treatment.
Good. I had a question before, which I will try again now with you here. I imagine you're in a very stressful environment at work. When it comes to the factor, so the ability for you to plan procedures is not typically there, I guess, when it's acute procedures. I typically get the question, so if that's a decisive or if that's a factor for the uptake of CERAMENT G use compared to procedures that are easily planned and you can plan for weeks ahead.
Well, we see both versions of that in the acute setting and then also in the reconstructive setting. My practice is taking care of acute trauma, but also I have a little bit of a niche where I take care of some of these patients that have had surgeries and infections treated many times over. To your point, does it help having the time to plan? Absolutely. I think that this is something that's on the shelf for us that we can grab whenever we need it, and sometimes these patients come in right in the morning, and then we have to make a decision minutes later. In my institution, we each have a day that we're responsible for. Whatever comes in the night before, we don't know what it is.
It's going to be a surprise, and that's what we have to take care of. We don't have a lot of time to think about that, but certainly this is a great tool to use, and we do use it on the fly. We don't get approval and then wait. We have to treat them right away, and it's used just the same.
Thank you. Then if a patient treated with CERAMENT G returns with an infection, what would you believe had gone wrong?
Well, nothing's perfect, and these patients are complicated, and it depends on the clinical scenario, and sometimes that can happen. Sometimes it can be as a result of an error on the surgeon's behalf or an inadequate debridement. We try to put it on ourselves, but sometimes these things are more complicated. I had a patient that we had treated for infection and had used CERAMENT G, and it failed. They were better off this time around than the last time. The first time I used CERAMENT G as part of a larger, much bigger procedure where they had extraction of implants and all sorts of things done and an antibiotic-coated implant, and the CERAMENT G was used to augment things. The patient came back with a small area of concern of infection.
Now, the big infection had been taken care of. I just took care of this patient right before I came here, actually. We're able to go in and target it, and that's one of the nice things about it is you can take a bigger problem, make it less complex, and then turn it into a small problem. We can address that and still use it again.
Thank you so much.
Thank you. Great questions. Here's a question from Kristofer. We just need the microphone, but yes, pass it on. That's great. It saves time.
Thanks. Considering your discussion here about the cost benefit with the product, I don't know if you were here earlier when there were a discussion about the new reimbursement proposal from CMS and that CERAMENT G use would automatically maybe trigger a higher reimbursement. Is that something you see would drive the use of CERAMENT G or in any way? Thanks.
Absolutely. I think that one of the barriers, and I think the others touched on this too, CERAMENT G as it entered the United States, is the cost. Any time that we add something that's new, there's a significant cost associated with it, and it's not cheap. I just told you that on that one case, and when they looked at our value, that we had a small negative margin. When you talk about infection care is SEK 50,000, SEK 100,000, we lost SEK 4,000. Those are the kind of margins that we're dealing with, and these conversations do occur. The bottom line is that it's a huge burden because the hospitals are looking at it and they say, "Well, does it work?" They say, "Because we're not going to spend the extra money to get it in."
When you add something like that for the DRG and supporting that, it's a big benefit because now in those cases, even in the inpatient cases where you see a reimbursement goes up just a little bit, that's enough actually to turn that margin positive for the hospital. When the hospital looks at it, they say, "Okay, I know it's better for the patients, and it's actually allowing us to make money." It's a big thing for hospitals. That was a big burden for me. That slide that I shared with you was an analysis after we got the CERAMENT G approved. When I went to my board to get approval, I said, "Okay." They said, "How many times are you going to use this?" I said, "Oh, six or 10. I don't know."
About six months later, they said, "Okay. Well, you used it like 40 times. That's a lot different than what you expected to use it." Well, there are other people using it, too. I said, "Well, that just happens to be the way it is." They looked at the cost, and they said, "Wow, this is costing a lot." That board consists of administrators and doctors. The doctors say, "This still works, and this works well, so we're going to give you approval, but you need to be judicious about using it." Well, the administrators say, "Yes, but why don't you use it as an outpatient preferably to try and make that work for you?" That was a big thing. This only adds to it.
At the time when I first started doing it, there was, and you'll have to correct me on the terminology, a new technology code. Where the hospitals got extra reimbursement for the first 18 months or 12 months.
The NTAP. It was called NTAP .
When they said, "Oh, wait. Oh, that's something that exists?" I said, "Yes." They looked back, and they said, "Oh, yes. We actually did get that." Those numbers were even more positive. These things are huge because hospitals are going to be very resistant to approving something like CERAMENT G without that. Now they have that's a big deal. It's wonderful. It opens up the door because surgeons are waiting for it, and that's a common conversation that we have. When I teach other people how to use this at all these conferences, and they say, "Well, I got to get approval." Well, this is how you get it. It just opens up the usage.
Thank you.
That was a great answer and great to hear the feedback from the administrators. You already mentioned it a bit, the feedback from colleagues and surgeons, ID physicians. Did you hear any reactions there on your single-stage approach with CERAMENT G? What are they saying?
Well, I think that one of the things when the conversations and the questions were coming up that I think that everybody's forgetting to talk about is that physicians are very stubborn, especially surgeons. Getting change is tough. The things that I'm talking about, my colleagues, some of the elders that have more gray hair than me, they're very resistant to change. It takes a long time. It's like trying to move an aircraft carrier. It doesn't move very quickly. The same thing goes for the infectious disease colleagues. They'll see one study, and they'll say, "Oh, I saw that, but I don't believe it." "Oh, well, maybe." It's hard to go against dogma that's been around for decades.
When you look at the standard of treatment with six weeks of IV antibiotics followed by a consolidation phase of oral antibiotics, that's something that's sort of been beaten down over the course of many years. To go beyond that takes a little bit of sort of really gestalt of confidence to do that. I think that some of those slides that I shared about those studies, that's what that gives me that, to do it responsibly. When I first started doing this in my practice, I used this in conjunction with the most difficult patients because they had no other choice. I said, "We've got to take advantage of what we know, and how can we do this?
I'm going to use it for the difficult patients, otherwise they're not going to get anything. When you look at it that, then the infectious disease colleagues say, "Okay." I force their hand. I don't even tell them about the patient now. I take care of them in the operating room, and then they follow up with them a couple of weeks later, as opposed to before, they'd be admitted to the hospital, and now they have complete control over what happens in terms of getting antibiotics and staging it. I set the stage now for these patients.
Great answer. Thank you so much for answering the questions. Thank you for your great presentation. I ask now Håkan Johansson, BONESUPPORT CFO, to the stage for his presentation. I think it contains the final conclusions, right?
Well, that I will do also together with Torbjörn later on.
Yes, exactly.
Thank you. It feels like a bit of a challenge after two such exciting presentations, and we're starting to be quite late in the afternoon, but bear with me. I've been engaged with BONESUPPORT for more than seven years, and I promised some new slides today. My ambition is really to use history, use the last few years to hopefully be able to explore more clearly the underlying trend. We have had quite volatile periods in terms of currency, for instance, et cetera. All the numbers I will be sharing today is based on constant exchange rates, whether it's on sales or whether we talk EBIT margins, et cetera, to give a better view of the underlying performance. Again, we've been talking a lot about sales, and sales and revenue growth remains a high priority on our side.
When I joined back in late 2018, we were really in the starting point of changing somehow the focus of the business. We made big changes in the commercial platform in the U.S. We made big investments in our European sales organization. That was really the starting block of this journey. We have, since 2020 to 2025, delivered a 44% CAGR. With the FDA authorization of CERAMENT G in the U.S. back in 2022, launched in October 2022, sales also accelerated. This, as you've seen earlier today, with a lot of market potential remaining. Well, that's looking at the total perspective. If we look at U.S. specifically, because again, U.S. remains a very high priority for us. It's a huge market opportunity.
In the U.S., we have a CAGR of 55% during the same period. With the commercial strategy and the platform that we created in 2018, so already from the start establishing a good growth momentum, and that only preparing for the launch of CERAMENT G later on and helped accelerated that market pickup with CERAMENT G as we launched. As you can see somehow, the incremental growth is increased every single year. In terms of the relative growth in percentage, it's coming down. Again, incremental growth increasing year by year. If we continue to focus the numbers, because again, in all means, some of the sales of CERAMENT G is really the focus point currently in the U.S. How does that market penetration go? This is a slide.
It's a lot of information on this slide, but this is a slide to show for every single year in the U.S., what are we gaining in terms of new access. This is based on surgeons first time use. How much do we gain by adoption? The surgeons that were recruited the year before, how much are they extending its usage? The world is never perfect. You also lose some business, and that is also disclosed on this slide. What is really positive, I believe in this slide, is when you look at how access is growing year by year, as well as adoption. So adoption increasing from SEK 6 million to SEK 11 million to SEK 18 million.
As we have been communicated when releasing Q4 last year, Q1 this year, et cetera, we're in a stage where new access and adoption are equally important. That's why, again, we have been talking so much about the segment-based approach, et cetera, because that's really also a good way to not only drive adoption, because it really helps, but also extend market as new access. That's really U.S., but also when we talk Euro. Europe is coming shy when compared to U.S. for two reasons. One, it's a smaller part of sales, and growth in percentage is so much smaller than in the U.S. Part of the reason for that is also that we have been doing investments lately in our so-called hybrid markets.
Hybrid markets are distributed markets as a revenue model, which means that it's half the price. How to present that to, in a way, come beyond that and make numbers comparable? I decided to look at Euro sales in units because that changed the perspective somewhat. Euro in total for this period, despite quite a lot of headwinds in 2025, shows a CAGR of 17% in total, increased its sales with 2.2 times since 2020. Direct markets, which is a handful, which consist of U.K., Germany, Sweden, Denmark, and the Netherlands, had a lot of headwinds in U.K., Germany during 2025, showed a 30% CAGR. Also very important, if we look at the hybrid markets, where we have done a lot of investments during the last few years.
Starting with Italy and Spain, extending during last year in countries and markets such as Australia, South Africa, Canada, Norway, Austria, et cetera, we see sales accelerating and showing a CAGR of 38%. Turning to some of the OPEX side of things. Well, as been said, we are constantly doing commercial investments. This is a slide showing selling expenses, not including commission and fees, because they are so directly related to the revenue. This is all the rest, meaning this is people, this is marketing spend, et cetera. We can see that we continue to invest commercially because we believe that's the right way also to support continued growth. We have been adding substantial heads, especially the last few years.
Just from 2024 to 2025, we extended with sales and marketing functions of close to 20 people, both in the U.S., but here also in what we call the Euro booster, where we extended ambitions in our hybrid markets. What to keep in mind is that if we just take the 10 additional heads in Europe, we communicated when doing that investment that it takes 18 months until these people are returning their cost in revenue, and it takes at least five years until they reach their peak sales. These are investments ahead of some of the revenue impact that is coming. Again, what else? Well, we're not only investing commercially. Our R&D expenses have been accelerating during the last two years. The main reason for that is that we are investing for the future.
If you look at this slide, you see in 2024 and 2025, colored with a dotted line, some of the amounts that we have spent that is much more forward-looking. This is the investment we have made in terms of our CERAMENT V submission to the FDA in the U.S. This is our investments entering into spine, new market entries, clinical studies to get into new applications, and product development. We will continue to invest in that pipeline because we also believe that this gives contribution to our future sales growth. We've been hearing a lot today about all the initiatives we do in terms of our segment-driven strategies and our ambition in spine and revision arthroplasty.
Despite all of those investments, with the strong sales growth that we're reporting, these costs are down to somewhere around 7% and 8% of revenue. All in all, we've seen when we step out of all the impact of currency and currency volatility, et cetera, a very solid trajectory when we talk operating results. In this case, looking at operating results, excluding the impact from long-term incentive programs. The operating leverage, which is marked as the gray boxes on this slide, we can see that the operating leverage remains extremely solid and stable, and we see a clear trajectory in terms of yearly improved operating result and operating margins. As mentioned a few times, we not only sit on a very scalable business model, we extended production without impacting the P&L.
We can see that the strong operating leverage from the sales growth, we deliver a lot of profit improvements. Investments level low. All R&D expenses are costed and so on. With efficient treatment of working capital, despite the fact that we hold extensive safety inventories to ensure flexibility to the market, we have a very solid cash conversion. The cash conversion is parked steadily over time, around 70% to that adjusted operating profit. This gives us headroom. This gives us flexibility, whether it's investing in those clinical studies, investing in the full R&D pipeline, investing commercially, or using part of that cash in terms of share buybacks as an optional way to create shareholder value. If I sum that up, I believe that just by those limited numbers of shares.
We can show that we have a lot of operational performance delivered during the last few years, still with a material untapped market potential being out there. We've seen in our presentations about the low market share in all of our main segments and the market potential that remains in those segments. I think that we have proven over the last few years that we have a very scalable business model, not only in terms of operating leverage, but also in terms of the lean balance sheet that we're operating with. Not to forget that we have a queue of interesting triggers short to mid-term.
The SOLARIO study that we've been waiting for since fall 2024, and we heard from several speakers that we believe that this is, for the longer term, something that will bring value to our contacts with surgeons, hospitals, and the market. Our CERAMENT V submission. As always with FDA, it's hard to say when, but we have a strong belief that with the experience we have in Europe of using CERAMENT V, we will get there, and we will be able to launch CERAMENT V in the U.S. Geographic expansion. We invested in hybrid markets during the last few years. We made inroads in India early this year. We are working with the authorities in Japan to open up that market. We will continue to open up new markets outside the U.S .
Again, also as we shared today, our plans to get CERAMENT G or V, the antibiotic-eluting properties into spine in mid to long term. With that, Torbjörn, I'll leave to you to round off the meeting.
Thank you, Håkan. You can actually feel free to stay on the stage. We're going to do Q&A later. I promise, last slide for the day. Concluding remarks. I said earlier what I thought you should bring home as take-home message. The way that I would summarize today is our strategy is proven. We're moving into the next evol ution that relates to becoming more segment-specific because customers in the different segments are different. Different needs, we have to cater to that. We have upward adjusted our U.S. market opportunity. Again, underlining the growth potential that we see with CERAMENT in the U.S. We continue to invest in evidence. That's one of the core pillars of our strategy, with special emphasis on arthroplasty. That study is estimated to cost around 40 million SEK.
We believe that we have a role to play in spine with an antibiotic-eluting product for the long term. We're not on label there yet, but we're investing in that space. That study is estimated to cost around SEK 80 million. We hope to, or aim and have an ambition to have a regulatory approval or regulatory submission no later than 2031. Most important thing, however we run the numbers, you looked at the upgraded numbers, you looked at the market potential, you looked at the pools of conditions that there's an inevitability of patients in this space, and you looked at the unmet need. We're very early on our growth journey. We're just getting started.
E ven though it's fantastic numbers that you guys have delivered, I'm absolutely convinced that the best days of BONESUPPORT are ahead of us and not behind us. With that, I thank you all for taking the time to be here, and happy to take any final questions.
Thank you very much. Do we have any final questions to wrap this up? Yes, in front here.
Thank you very much. It was on the adoption versus new access chart, that was really helpful. I wanted to see your thoughts of how that would look like in the future. Could you see maybe adoption sort of start to scale ahead? Then maybe to follow up on that, if you could focus on maybe sort of the ASC channel dynamics, sort of how are you growing there versus maybe other settings, that would be really helpful.
Okay. The way that we split these questions is that I take the easy ones and Håkan takes the difficult ones. Håkan, you take the first one, and I'll talk about ASCs.
No, again, I think that what we believe when we look forward is that new access and adoption will continue to be somewhat equally important. I think that it's also important to say some of what we stated here is lost sales, while in that number you find surgeons retiring from that certain practice. You find surgeons that is moving from a hospital where we have listings to hospitals where we don't have listings, which is in the longer term is not necessarily negative. I think that when looking at that slide, it's somehow a first indication of how this looks. I think that some are being still so early on that commercial journey with CERAMENT G, we need more time until we can see some of the firm underlying trend.
I think that some are keeping 85% of the business that we had with us into the new year is a good level also if we look at comparables in the U.S.
Good. On ASC, I think it's a very relevant questions, especially if you look at it medium to long term. We are a very small player in orthopedics. Honestly, we're like nothing compared to the big guys. The big guys invest a lot in ASCs for the right reasons. There's a lot of patient volume moving in that direction. That's not going to go away. We see that. Where we are in our journey now, our focus is on inpatient, but Dr. Matuszewski had a really good point on that. It's going to move, and we will of course be part of that move. Now we like to keep things simple, straightforward.
Inpatient is more than we can handle at this point, but we stay very close to the trends, because in a couple of years, it's highly likely that it will look slightly different.
Perfect. Thank you. Just a clarification on the sales force. The ROI that you projected, is that based on historical data you've got, or is that based on what you expect in the future?
I will say both. Some of that's the learning we've done, some with the investments done over the years. It's quite steadily around that. It takes 18 months to somewhat recover the cost in terms of revenue. I think that what we saw on hybrid markets very much corresponds to that.
That's U.S. and globally?
That's Europe, because that's really where we have a direct sales force. In the U.S., we don't have the same front-end cost.
I don't know if this is a good or bad last question, probably not, but I want to back things up a bit to just now you've showed us your plan, how hard was it to prioritize this? You've had areas that you could go into, where you could put money into, you could have gone into Japan. Why this, and how hard was it?
I would say saying no to things is the most important task of the CEO and the CFO. We have to do it all the time. Prioritization is always very hard, especially when it comes to CERAMENT as a technology because it's so versatile. There are hundreds and hundreds of things that we could do with CERAMENT, combine it with different things. There are a lot of ideas, some of them really good, quite a few pretty bad when it comes to inorganic activities. There's a lot of things that pull our attention all the time. At the same time, when we compare all of those alternatives, compared with foot and ankle trauma arthroplasty, which is here and now, it's so, I call it easy.
It always comes back to when we look at it rationally, we look at the numbers. We have to continue to focus here until we start seeing other data points that indicate that we need to look outside. Spine is actually an area where we think, we don't know for a fact, but we think that there's a lot of data points indicating that this could be another important leg for BONESUPPORT in the future. That is why we're trying to get into that segment. Yeah, it's hard, but it's part of the job that we do. Especially with the P&L that we have, with the asset-light model, with the balance sheet, it takes a lot to improve on what we already do today.
That's why we're pretty disciplined when it comes to inorganic activities and also moving into other segments . I think this is a very solid and logical and rational plan that we have.
Great. Thank you for a good day.
Thank you very much. Thank you, guys