Bill Klaproth (host): This is OMS Voices, an AAOMS podcast. I'm Bill Klaproth. And with me is Dr. Eric Carlson who is here to discuss medication-related osteonecrosis of the jaws or MRONJ, what is it and how an OMS can help. Dr. Carlson, thanks for being here.

Eric Carlson: Thank you, Bill. Thanks very much for the opportunity to talk to you about this fascinating disease. So, medication-related osteonecrosis of the jaws that comes by the acronym of MRONJ is a truly mysterious disease that we've been talking now for about 19 years or so, I would say. What this represents in fairly simple terms is exposed bone of the upper or lower jaws or both.

The real part of that diagnosis, medication-related osteonecrosis of the jaws, that we should focus on are the medications. They really come in a couple of different classifications that are well-known to many patients in international society. And they include the bisphosphonate medications. For example, they're represented by well-known drugs, such as Fosamax, Actonel and Boniva. These are most typically indicated for primarily women with osteoporosis or osteopenia. There are other diagnoses that they are used for, but these are the primary diagnoses. So, women with osteoporosis and osteopenia. Certainly men can develop those diagnoses as well, but it’s typically about 20 years after women do.

So, we also have a set of intravenous bisphosphonate medications that are Zometa primarily, but also Aredia. And these are indicated in patients who have cancer and often metastatic disease; patients, for example, with multiple myeloma, metastatic breast cancer, some patients with metastatic lung cancer or kidney cancer, for example.

Bill Klaproth (host): So MRONJ, basically, it’s an area of bone in the jaw that has become exposed. What are the other signs and symptoms of this?

Eric Carlson: Yeah. Interestingly, many patients with MRONJ are in fact asymptomatic. They don’t have pain. They merely have the recognition of exposed bone. The important thing here is that bone be dead. And that is a proclamation that can be made based on clinical exam by a healthcare provider, for example, a dentist or a medical oncologist, a primary care physician or what have you, to examine it and identify that it's been present for at least eight weeks and it has taken on the character of dead tissue. That's the important element of this diagnosis.

Bill Klaproth (host): So, when we say an area of bone in the jaw that has become exposed in the mouth, does that mean like literally in the gum, there's a little bone, like "I'm feeling a little bone sticking out of my gum"? Is that what we're saying?

Eric Carlson: Most commonly, that is the case, Bill, yeah. And that patients can see it or it's brought to their attention. But there are some instances actually where patients who have MRONJ of the lower jaw will have such extensive disease that they'll have a hole in the skin underneath the lower jawbone that is a portal for infection, for example, without actually being aware of exposed bone in the mouth.

Bill Klaproth (host): You've kept me checking out my mouth, where my tongue is going, "Okay. Am I feeling anything? What's going on here?" So, you mentioned osteoporosis. People with osteoporosis potentially are at risk for this. Are there other risk factors of MRONJ?

Eric Carlson: Yeah. There are many, really. So, it's the primary disease processes that place patients at risk for the development of MRONJ. And those are in non-cancer patients, as we say, primarily osteoporosis, but then also the cancer patients. So, patients who've taken these medications for a long period of time will potentially be predisposed to the development of MRONJ.

But here's the real, real important thing, and that is that this diagnosis is very rare, meaning that in cancer patients, in patients who have been exposed to Zometa or Xgeva, for example, we know from experience and also the international literature that only about 5 percent of patients exposed to those medications will actually develop MRONJ.

On the osteoporosis side, and this is really good news, we know that only about two to five in 10,000 patients who are taking Fosamax, Actonel, Boniva, for example, will ultimately develop MRONJ. So, how does this happen? Not uncommonly, patients who require the removal of a tooth, for example, who are taking these medications will be the ones who develop this disease. And we know that about 75 percent of patients with MRONJ have actually undergone the removal of a tooth as a minor surgical procedure.

Bill Klaproth (host): So, if a patient is on one of these drugs, should they alert their dentist to this before going in, so the dentist can check to make sure that everything is okay and ask if there any signs and symptoms of potential MRONJ?

Eric Carlson: Yeah. It's a great question, Bill. So, really there are two ways to prevent this disease. One is before initiating these medications. And the second scenario is during the administration of these medications. So, what you said is very true. When patients are going to be exposed to, as we say, antiresorptive therapy – so that is Fosamax, Actonel, Boniva, Zometa, Xgeva, these classes of medications – they should meet with their dentist before doing so and make sure that non-restorable teeth, as we say, bad teeth are removed to eliminate that inflammation that exists that can help promote the development of MRONJ. It's important for these patients before initiating antiresorptive therapy to have just immaculate hygiene and have a dental recall schedule that will keep their remaining teeth in good condition, so as to not help develop the onset of MRONJ and also to potentially assist in not having to remove a tooth.

It's the patients who are already exposed to these medications that also represent a real opportunity. And that is that when patients need to have a tooth removed while they're on these medications, that can certainly be done without causing MRONJ. It just has to be done in a very specific way from a surgical perspective. And also, to make sure that the patient's other medical problems, such as diabetes, for example, and that their social habits, such as smoking, for example, are addressed optimally so as to help reduce the chance of a wound healing problem afterwards and the possibility of developing MRONJ.

Bill Klaproth (host): So, that's interesting. Oral hygiene is really important, as you mentioned. Also, you know, checking yourself. "Hmm, am I feeling anything?" Any lifestyle changes are important as well to possibly prevent this.

Eric Carlson: Absolutely. As I mentioned earlier, this is just a complex wound. For example, the exposed bone and the expressed purpose then of dental procedures such as removal of teeth or biopsies or what have you during their antiresorptive therapies to reduce the chance that they might develop this complex wound or MRONJ related to those procedures.

It's always best for patients undergoing even minor surgical procedures to curtail their smoking, for example, to cut back significantly. And in patients with diabetes who are being prepared for even a minor surgical procedure, it's best to make sure that their blood sugars are under proper control and that their A1C, which is a reflection of their blood sugar over the last several months, reflects a good level of blood sugar to help promote proper healing postoperatively.

Bill Klaproth (host): So if someone is found to have MRONJ, how is it treated?

Eric Carlson: Yeah. So, this is the real exciting element, I believe, of this disease, is the treatment. In the 19 years that we've been talking about this, so since September of 2003, one of the areas that we've debated highly is how to properly treat these patients. There are many in our specialty of oral and maxillofacial surgery who believe that surgery is the proper method of treatment of all of these patients. And there are other members of our specialty who believe that we should conservatively manage these patients.

The recently published fourth edition of our position paper on MRONJ reflects a greater contribution towards surgical removal of patients with this diagnosis. The real question then is when to do it and how to do it. In healthcare in the 21st century, we frequently speak about shared decision-making. And what that means is that no longer is a procedure or any intervention in healthcare forced on patients. We don't tell patients what they need to do per se. But we introduce their opinions and their concerns in a shared decision-making. So, they're making conscious decisions about what's important to them and what their expectations are and the like. And we take this very seriously in the management of MRONJ. That shared decision-making not only involves the surgeon and the patient, but also their family, and other health care providers, their dentists, their medical oncologists, for example, in the case of cancer patients and certainly their primary care physician. So, shared decision-making is really a large group of people who are determining what would be best for that specific patient rather than forcing decisions on them.

In terms of surgical procedures for this, we recognize that this is dead bone. This is dead tissue that's present in the jaws. And like dead tissue elsewhere in the body –  for example, a gangrenous toe in a diabetic patient, for example –dead tissue frequently predicts the value of performing a surgical procedure. So, we remove that dead tissue. In the case of MRONJ and involving the jaws where function is potentially at risk, one of the real important features of offering a surgical procedure to patients with this diagnosis is to continue to predict favorable function afterwards, that is their ability to chew and to swallow and the like. So, these are some of the things that we consider in the management of these patients.

Bill Klaproth (host): So, does MRONJ ever go away on its own or does it always have to be treated in the method you just described?

Eric Carlson: Yeah. That's a great question, Bill. So in fact, some patients do experience resolution of their disease without a surgical procedure. So, that area of exposed bone, for example, might just fall off. We call that sequestering or sequestration. In my experience, that tends to be somewhat rare. And what's real important in evaluating these patients and creating a treatment plan for them is the X-rays that we obtain to determine the extent of their disease and also what it looks like on the X-ray. When patients have very dense dead bone, it's unlikely for that bone to just fall off and heal properly. But when patients have dead bone, dead on an X-ray shows dark areas and the like, there's probably a greater chance that it might sequester and that patient might not require a surgical procedure. So, this is why in our treatment recommendations, when we identify patients with this diagnosis, that we manage them somewhat conservatively for about two months. And that is we talk about hygiene, about keeping that area of dead bone clean. And we talk about the use of antibacterial mouth rinses, for example, and sometimes antibiotic pills and the like, occasionally intravenous antibiotics when patients have severe infections. But we do that for a period of time to permit patients perhaps to heal on their own. When they haven't, then we certainly enter that shared decision-making protocol and consider those patients for a surgical procedure.

But just as I mentioned a moment ago, when we prevent MRONJ from occurring in patients who are going to have a tooth removed, for example, when they have exposure to these medications and we modify their social habits and we modify their other medical problems such as diabetes, it's also very important when treating these patients that we encourage them to cut down or completely quit smoking to help them heal properly. And that we manage their diabetes in such a way that we promote healing as well.

So, this is a multifactorial disease, meaning that there are many, many things that can go into the development of this disease and then, also into our decision-making in terms of how to properly treat it.

Bill Klaproth (host): Well, this has been a great discussion of MRONJ and it's been very informative, Dr. Carlson. As we wrap up talking about MRONJ, is there anything else you'd like to add?

Eric Carlson: Yeah. I think this is a disease that we're going to be talking about for a long time. And I think it's very important for patients to understand that these medications associated with this disease are very beneficial to their overall health. So, we know that osteoporosis is a terrible disease. And when patients develop a fracture of their hip or their backbone related to it, that it can be very problematic for patients and their ability really to survive that. We also know that when patients have cancer, and that they have fractures or other problems related to that diagnosis and that their administration of these medications is also very beneficial to them.

So, I think what's really important for patients to understand is that when their doctors recommend these medications to them, that they are primarily beneficial to them and that patients should take these medications. But it needs to be a conversation that they have. And so, they need to be educated in terms of the potential risks, but also the tremendous benefits that exist in taking these medications and then keeping up with their dental health and their overall health while they're taking them.

Bill Klaproth (host): Well, this has been very informative, Dr. Carlson. Thank you so much for your time. We appreciate it.

Eric Carlson: Great. Thank you, Bill. Thank you very much.

Bill Klaproth (host): And once again, that's Dr. Eric Carlson. And thanks so much for your time today. We appreciate it. For more information and the full podcast library, please visit MyOMS.org. And if you found this podcast to be interesting, please share it on your social media and don't forget to subscribe. Thanks for listening.