Update on Diagnosis and Management of Avascular Necrosis

Transcript

• 00:02Go ahead and get things started while
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• 00:08For those of you who have not
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• 00:12internal medicine conference that we
• 00:15hold weekly on a variety of topics
• 00:18and mostly focused to people who
• 00:20practice outpatient clinic medicine.
• 00:22And our goal is always to learn
• 00:25something new in practice medicine
• 00:28slightly different that day.
• 00:30And so, Tony, can you share our slides?
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• 01:17academic hospital who presented our
• 01:20update on hospital medicine last year.
• 01:23Next slide, as you all know there
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• 01:33Next slide,
• 01:37we are excited to bring you Doctor Varty
• 01:41next time for a talk on advances in spine
• 01:44surgery for the primary care clinician.
• 01:46I don't know about you,
• 01:47but many people with spinal stenosis,
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• 01:57OK, you can stop sharing our slides
• 02:00and we will let Doctor Wisnia and Dr.
• 02:03Oslam share theirs while I
• 02:06review their introductions.
• 02:08So I'm not going to go through
• 02:10them in in their entirety.
• 02:11You have it in your e-mail.
• 02:12But we're really delighted
• 02:14to have Doctor Wisnia and Dr.
• 02:17Oslam here with us today to
• 02:19talk to us about diagnosis and
• 02:22management of avascular necrosis.
• 02:25Dr.
• 02:25Wisnia,
• 02:26through various training at Yale
• 02:29and Weill Cornell and specialty
• 02:33fellowships at Institutes of
• 02:36Orthopedics and Sports Medicine,
• 02:39is now Associate Professor of
• 02:41Orthopedic Surgery and of Mechanical
• 02:44Engineering and Material Science who
• 02:46specializes in reconstructive surgery
• 02:49for the hip and knee and as well
• 02:53as revisions with a major clinical
• 02:55focus on AVN and osteonecrosis.
• 02:58Dr.
• 02:59Oslam comes to us through various
• 03:04different trainings but completed
• 03:06her fellowship in this area at Johns
• 03:09Hopkins and is now also Associate
• 03:12Professor of Orthopedics and the
• 03:15Director of Wound Care at Yale New
• 03:19Haven Health's Lawrence and Memorial
• 03:21Wound Care and Hyperbaric Medicine program.
• 03:25And we are thrilled to have you and
• 03:28I will turn the podium over to you.
• 03:30We used to do this in person and
• 03:32keep it real mellow and casual,
• 03:35so we still encourage people to do that.
• 03:38So people will pop things in the chat
• 03:40throughout your talk and as appropriate,
• 03:42I'll just interrupt you and ask you
• 03:44questions as if we were in a small
• 03:47conference room eating food and and
• 03:49just talking and learning together.
• 03:51So don't feel any pressure
• 03:52to to monitor the chat.
• 03:55Thank you.
• 03:57Thank you so much, Doctor Puglisi,
• 04:00for inviting us and having
• 04:03Doctor Aslam and I here.
• 04:06I'm Dan Wisnia.
• 04:08I'm an orthopedic surgeon and Doctor Aslam,
• 04:12she's a physical medicine
• 04:14rehabilitation specialist.
• 04:15We are gonna give you a talk today
• 04:19about what's new in avascular necrosis.
• 04:22So about two years ago,
• 04:26Doctor Aslam and I were at a departmental
• 04:29picnic talking about our passion.
• 04:33Mine in particular was
• 04:35treating a vascular necrosis,
• 04:37hers hyperbaric oxygen therapy.
• 04:39And the more we spoke,
• 04:42the more we realized we had a shared
• 04:44passion in which we could work together.
• 04:46And over the last two years,
• 04:48we've put together an assembled
• 04:52Yale's a vascular necrosis program.
• 04:54So we see a lot of patients with a
• 05:01vascular necrosis from across the
• 05:03country who come to Yale with a vascular
• 05:07necrosis primarily in their hips,
• 05:09but also in other joints.
• 05:11And we help them preserve their joints so
• 05:13that they don't need a joint replacement.
• 05:16And for those of you who are curious,
• 05:18you know, if you end up with a
• 05:20patient with a vascular necrosis,
• 05:22how would you refer them to our program?
• 05:25You'll go into EPIC in the
• 05:28chart in the order section,
• 05:31you can type in a,
• 05:33a VN or a vascular necrosis or
• 05:36osteonecrosis and then select
• 05:39the a vascular necrosis program.
• 05:41That will be the first in your list.
• 05:45And you can always feel free to e-mail us.
• 05:48You're never a bother,
• 05:49so always feel free to e-mail us as well.
• 05:55Now, a little bit of background about
• 05:59a vascular necrosis. What, what is it?
• 06:01So it's essentially an injury to the
• 06:05blood supply to the femoral head.
• 06:09And the femoral head, which is made of bone
• 06:13every day is remodeling. So as you walk,
• 06:16little micro fractures occur in the bone.
• 06:19And every day your body repairs those
• 06:22little cracks and it requires it,
• 06:25the bone to be alive.
• 06:27And when the blood supply is injured,
• 06:29the bone dies.
• 06:30Those cracks aren't able to heal.
• 06:32They propagate, they get bigger and
• 06:35then unfortunately the hip can collapse.
• 06:38And we do see this, I always tell, give
• 06:41the patients an analogy of a China plate.
• 06:43If you have a China plate,
• 06:47over time that China plate develops
• 06:49cracks and the cracks get bigger.
• 06:51And as the China plate ages,
• 06:52it then breaks.
• 06:54So it's really important for us to try
• 06:57to restore that blood supply to prevent
• 07:00the femoral head from collapsing.
• 07:03Over time,
• 07:04the name for a vascular necrosis has
• 07:09changed and some common names are
• 07:12osteonecrosis of the femoral head.
• 07:14That's primarily the term you'll see
• 07:16used in a lot of your pub Med searches,
• 07:20but also a historically ischemic necrosis.
• 07:24Subchondrially,
• 07:25vascular necrosis and aseptic necrosis
• 07:29have also been used in the United States.
• 07:34There's about 10 to 30,000 new cases
• 07:37that we're seeing every year and this
• 07:40is primarily in younger patients.
• 07:43So the patients who worsening with
• 07:47avascular necrosis can range from
• 07:49sometimes even in their teens
• 07:52to about 55 years old.
• 07:54And about 50 to 70% of them will
• 07:58go on and experience a hip collapse
• 08:01and need a hip replacement.
• 08:03And one thing that's really not
• 08:05well known is that 10% of all hip
• 08:07replacement due to a vascular necrosis.
• 08:12So when when we think of hip replacement,
• 08:15we think, well,
• 08:16that's because the cartilage has worn down,
• 08:18the patient has bone on bone arthritis.
• 08:21But actually 10% of all hip
• 08:23replacements are due to this disease.
• 08:25And it can be a very significant
• 08:28surgery for a young patient to have
• 08:31and then live with the potential
• 08:33risk and complications of the hip
• 08:36replacement for their entire adult life.
• 08:40What causes a vascular necrosis?
• 08:42The most common causes are trauma to the hip,
• 08:46alcohol abuse, high dose steroids.
• 08:50There is a correlation with COVID-19,
• 08:52which we'll talk about in a second.
• 08:54HIV,
• 08:55primarily the medication from HIV
• 08:58can be very toxic chemotherapy and
• 09:01then blood disgraces like sickle
• 09:04cell disease and clotting disorders.
• 09:08Now the thing that we really want to
• 09:11emphasize is that if we can catch a
• 09:15vascular necrosis early that it is
• 09:18possible to prevent or delay a hip collapse.
• 09:21So it's important that we catch these
• 09:24early because a hip replacement can actually.
• 09:29If you have a hip replacement at a young age,
• 09:31you may ultimately need a revision
• 09:33as the bearing surfaces wear out.
• 09:37And you could have a multitude of
• 09:40complications with the hip replacement,
• 09:41as I'm sure you've all have seen.
• 09:43And the best thing to do is
• 09:45try to avoid a hip replacement.
• 09:48And the therapies that we're
• 09:49going to talk to you about are
• 09:52relatively safe and a lot safer
• 09:54than having a hip replacement.
• 10:00So first I want to share with you a study
• 10:03in which this is a a big meta analysis.
• 10:07This meta analysis was looking to see how
• 10:12patients did with a total hip replacement.
• 10:16And they looked at patients who had
• 10:18a vascular necrosis and arthritis
• 10:20and they wanted to see the outcomes.
• 10:23How did these patients do after surgery?
• 10:26And they used national registry data.
• 10:29So this is really good dated.
• 10:30It's coming from countries like Australia
• 10:34and the United Kingdom that have really
• 10:37nice total joint replacement registries.
• 10:40And they found that AVN patients
• 10:44were 1.6 times more likely to have a
• 10:47revision after their hip replacement
• 10:49compared to patients who had arthritis
• 10:51who had a hip replacement.
• 10:53And they found that there is a higher
• 10:56risk of infection in these patients
• 10:58and also fracture around the implants.
• 11:01So this is something just to keep
• 11:03in mind that these patients even
• 11:05after they have the hip replacement
• 11:07have a higher risk of complication.
• 11:10Yeah. And I'm going to stop you
• 11:11there for a SEC. So question,
• 11:13what do you think that's from?
• 11:16So I mean, is it that this is a more
• 11:18systemic vascular process that we
• 11:20fail to realize as such and thus you
• 11:24have poor healing even around the,
• 11:26let's say, the implant,
• 11:27the site of the implant, etcetera?
• 11:30Or are there other factors at play?
• 11:34There's a few factors.
• 11:35One is these are younger patients.
• 11:38So you're having a 40 year old
• 11:40patient get a hip replacement compared
• 11:41to a 65 year old or 70 year old.
• 11:44So that younger patient is just
• 11:47going to be harder on the implant.
• 11:49They're going to be more active,
• 11:50they're going to engage in activities
• 11:53that maybe a 6570 year old wouldn't
• 11:56engage in that could lead to a fracture.
• 11:58The 2nd is that these patients
• 12:00have a lot of other comorbidities.
• 12:02You know, we went over the risk factors.
• 12:05They have HIV or a transplant or or
• 12:10sickle cell disease, alcohol abuse.
• 12:14So there's other reasons that that
• 12:17they're sicker that so they're
• 12:19higher risk for infections and
• 12:21that that that's another reason
• 12:23why they have more complications.
• 12:28So Doctor Asim and I have seen a lot of
• 12:33patients with a vascular necrosis who
• 12:37suffered of severe COVID-19 infections.
• 12:43And the reason for this is the relationship
• 12:48between COVID-19 hospitalization and
• 12:50being placed on high dose steroids.
• 12:53In this meta analysis,
• 12:55they looked at case reports, case series,
• 12:59they collected 104 patients who were
• 13:02diagnosed with avascular necrosis
• 13:04after being hospitalized for COVID-19.
• 13:07And they found that patients who had
• 13:11higher dose steroid use or prolonged use
• 13:14of steroids were at the highest risk of
• 13:17a developing a vascular necrosis. And
• 13:25this is not a reason not to give steroids.
• 13:29So I think the most important thing
• 13:32is steroids can be life saving.
• 13:33That if these patients
• 13:35hadn't received steroids,
• 13:36they may not have survived.
• 13:38So we're definitely not
• 13:40saying not to give steroids.
• 13:41There's many instances where you
• 13:43definitely have to 100% give steroids
• 13:47and if you think it's warranted,
• 13:50I wouldn't hesitate to follow the
• 13:54protocols that you currently follow.
• 13:56When you give a Medrol dose pack or
• 13:58if you or someones hospitalized and
• 14:00you're giving them high dose steroids,
• 14:02I think that is very reasonable
• 14:05because steroids have a lot of benefit,
• 14:09life saving benefit.
• 14:11But there is a correlation we're
• 14:14seeing in these COVID-19 patients
• 14:16who some of them were on steroids
• 14:17for a very long time,
• 14:19and we're seeing multifocally
• 14:20vascular necrosis in these patients.
• 14:25If you are interested in doing some reading,
• 14:28this is a terrific article
• 14:30written by one of my mentors,
• 14:33Doctor Lynn Jones at the Cleveland Clinic.
• 14:35It's a review article all about
• 14:37osteonecrosis of the femoral head.
• 14:39And we just want to share
• 14:41this article with you.
• 14:42So if you want some supplements
• 14:46reading after a talk,
• 14:48this article's available.
• 14:49So let's start with a case presentation.
• 14:53This is a typical patient that
• 14:55we'll see in the avascular Necros
• 14:58Avascular Necrosis program.
• 15:00A 29 year old female presents
• 15:02to our clinic with hip pain,
• 15:04complaining of three months of
• 15:06worsening groin pain and she was
• 15:08recently hospitalized about eight
• 15:10months ago with a severe asthma
• 15:12exacerbation in which she was given
• 15:14a course of high dose steroids.
• 15:17On exam she has groin pain and thigh
• 15:20pain and we obtained X-rays in the
• 15:24clinic and the X-rays are normal.
• 15:27This is very typical of a vascular necrosis.
• 15:30Early stage of vascular necrosis,
• 15:32you will not see signs of it on X-ray
• 15:35and that's why a lot of these cases are
• 15:38missed because patients get X-rays.
• 15:40The X-rays are normal and then for
• 15:44the work of it is delayed because
• 15:48because the X-rays are normal,
• 15:50folks don't pursue additional
• 15:53more advanced imaging.
• 15:56Well,
• 15:56Dan, let me just stop you there
• 15:58for a minute because if I'm the
• 16:00internist who this woman is coming to,
• 16:02which is the most classic place she would go,
• 16:06I'm not having AVN very high in my
• 16:08differential given that she just
• 16:10had a brief course of steroids.
• 16:12I tend to think of it more with
• 16:15prolonged steroid courses.
• 16:16Am I wrong in thinking about it like that?
• 16:18Is it, are you seeing this clinically
• 16:21even with brief burst treatments like
• 16:23an asthma exacerbation is Pred 40 for
• 16:26five days it are you seeing AVN and
• 16:29young people after a a course like that?
• 16:33So
• 16:34what we know is that there is a
• 16:38relationship between the length
• 16:40of the steroid use and the dose,
• 16:42but we also know that any amount of
• 16:46steroid use can lead to a vascular
• 16:49necrosis and certain patients are more
• 16:52prone to a vascular necrosis than others.
• 16:56So in fact, as an example,
• 16:58Doctor Asim and I have a have two
• 17:01brothers who each of them were
• 17:03put on a Medrol dose pack for
• 17:06back pain about a year ago.
• 17:09They both got AVN and we've
• 17:11done genetic testing,
• 17:13hematologic testing to try to figure out,
• 17:17you know, why would these two brothers,
• 17:20you know, with such a small
• 17:21amount of steroid use get AVN.
• 17:23So everyone,
• 17:24the way I think about it is everyone
• 17:27has a risk of AVN with steroid use.
• 17:30You know,
• 17:31there are some rheumatologic patients,
• 17:33they're on steroids every day
• 17:35for their entire lives and they
• 17:38never get AVN with other patients
• 17:40who they have one Medrol dose
• 17:42pack and they'll get AVN.
• 17:44So
• 17:44yeah, there's something genetic
• 17:46that we're not able or we don't
• 17:48know how to pick up on that can
• 17:51put people at differential risk.
• 17:52And so it sounds like even
• 17:54though it shouldn't be high,
• 17:56like very high on your list, this,
• 17:58this sort of scenario can lead to AVN
• 18:00and that's really helpful to know.
• 18:03I, I would definitely have it on the,
• 18:05on your differential diagnosis and
• 18:08some other potential diagnosis you
• 18:11should have on your list besides
• 18:14osteonecrosis of the femoral head would
• 18:17be a femoral neck stress fracture,
• 18:19a subchondral insufficiency fracture,
• 18:21a hip dysplasia.
• 18:23So labral pathology, early onset arthritis.
• 18:28And then sort of lower on the
• 18:29list would be septic arthritis.
• 18:31But if there's other,
• 18:32you really need to get a good history too.
• 18:36So if there's a history of other
• 18:38joints that are also painful,
• 18:40maybe a rheumatologic etiology that
• 18:43really comes down to getting a good HPI
• 18:49in terms of the work up,
• 18:50you want to get a good history.
• 18:52So Doctor Asim and I,
• 18:54we have a checklist that we go
• 18:56through of all the potential risk
• 18:58factors for avascular necrosis.
• 19:00So we really try to identify over the last
• 19:04few years if there were any potential risks.
• 19:08And then we want to understand the
• 19:10onset of the pain and where it is.
• 19:12And patients who have hip pain may have
• 19:14referred pain to the buttock or the knee.
• 19:16So if they're complaining
• 19:18of knee pain or pain,
• 19:19you have to really make certain you,
• 19:22you don't ignore the hip because
• 19:25I've had a few patients who
• 19:26come in saying my knee hurts,
• 19:28my knee hurts and I say,
• 19:30oh, by the way,
• 19:31your knee is hurting because
• 19:33you have hip avascular necrosis.
• 19:35So that's you always have to keep
• 19:37that in mind on physical exam.
• 19:40They're gonna have pain with thigh rotation.
• 19:42One classic sign is pain with a log
• 19:45roll where they're lying on their
• 19:47back and you rotate the leg and they
• 19:49have pain in their thigh and groin.
• 19:52And you'll start with X-rays.
• 19:54So you'll get X-rays of both hips.
• 19:56And then if the X-rays don't show anything,
• 19:58you'll move on to more advanced imaging.
• 20:01If you find a vascular necrosis in
• 20:05one joint and they're complaining
• 20:07of pain in other joints,
• 20:09that's when I would consider a skeletal
• 20:11survey and get X-rays of the knees,
• 20:14the ankles and the shoulders 'cause
• 20:16that's those are other joints in
• 20:19which we'll see a vascular necrosis
• 20:22in terms of which X-rays to order.
• 20:24So I would order these three X-rays.
• 20:27I would start with an AP pelvis.
• 20:29This allows us to see the hip
• 20:31joints and also the femoral heads.
• 20:34And then I would get dedicated
• 20:36AP right and left hips.
• 20:38This is where the X-rays focus right
• 20:41over the femoral head and we're able
• 20:44to identify if there's any signs
• 20:46of a vascular necrosis in the hip.
• 20:50And then we get a frog leg
• 20:52lateral right and left.
• 20:54And the value of this X-ray is
• 20:56that it allows us to get a 90°
• 20:59orthogonal view of the femoral head.
• 21:02Now in a bunch of patients,
• 21:05we will not see any signs
• 21:07of a vascular necrosis,
• 21:08especially in in AVN early on in the disease.
• 21:12So if the X-rays are negative,
• 21:14then you want to consider
• 21:17high resolution imaging.
• 21:19So first thing I tell everyone is before
• 21:22you rush and go ahead and order something,
• 21:25look in their chart and see if
• 21:27they've already had ACT scan
• 21:29or MRI over the last year.
• 21:31Because there are many times a
• 21:33patient has gone to the emergency
• 21:35room and the emergency room just
• 21:38reflect reflectively just gets ACT
• 21:40scan of the abdomen pelvis and
• 21:42we can see AVN on the CAT scan.
• 21:44And if it's already been done,
• 21:46there's no reason to repeat the the study.
• 21:50The gold standard is an MRI.
• 21:52So we'll get an MRI of the
• 21:54bilateral hips without
• 21:55contrast. You don't need contrast.
• 21:58And if they're not able to get an MRI,
• 22:01then you can get ACT pelvis without contrast.
• 22:05And this is what you'll see.
• 22:07You'll see edema in the femoral head.
• 22:09You'll see signs of a vascular necrosis
• 22:14where there isn't any perfusion.
• 22:15You'll see areas of dead bone.
• 22:19In this particular patient,
• 22:20we're able to tell that the
• 22:22femoral head does not collapse.
• 22:24We have a nice round femoral
• 22:26head to This patient is a great
• 22:28candidate for therapies to try to
• 22:31prevent femoral head collapse.
• 22:35So when a patient comes to
• 22:37our vascular necrosis program,
• 22:39we categorize them into two categories.
• 22:42Has your hip collapsed or not?
• 22:44If it hasn't collapsed,
• 22:45then you're a candidate for therapy
• 22:48such as medication, surgery,
• 22:51such as cord decompression in
• 22:54which we drill into the femoral
• 22:56head to remove some of that dead
• 22:58bone and then we will put some
• 23:00stem cells into the region and
• 23:04also hyperbaric oxygen therapy.
• 23:07But unfortunately,
• 23:07if the femal head has collapsed,
• 23:10then our only option is a hip replacement.
• 23:14We don't have a way to restore the
• 23:16femal head once that round spherical
• 23:19architecture has been destroyed.
• 23:21A
• 23:21couple questions here if you don't mind.
• 23:24One is what is the timing between
• 23:26taking a course of steroids and the
• 23:29development and symptoms of AVN?
• 23:30Is that predictable in any way?
• 23:35What I'll tell you is a lot of
• 23:38patients will say that during their
• 23:40course of treatment of the steroids,
• 23:43they will notice symptoms of joint pain.
• 23:49So it's likely the AVN is occurring
• 23:52as they're taking that medication.
• 23:55And then in terms of when during the
• 23:58course will the femoral head collapse,
• 24:00that timing is really hard to predict.
• 24:03It depends on the size of the
• 24:05lesion and where the lesion's
• 24:07located within the femoral head.
• 24:09So sometimes the lesion can be
• 24:11located in a more of a weight
• 24:13bearing region of the femoral head.
• 24:14That's higher risk of collapse.
• 24:16It's a larger lesion that's
• 24:18higher risk of collapse.
• 24:20Got it. That's helpful.
• 24:21And I think you said this,
• 24:23but just to confirm,
• 24:25if somebody already has existing
• 24:27significant hip arthritis away,
• 24:30will it be harder to
• 24:31see the AVN on imaging?
• 24:35It's a good question it it shouldn't be,
• 24:37but in patients who have underlying
• 24:41arthritis, they probably would not
• 24:43be a candidate for any of these
• 24:45preventative therapies for hip collapse.
• 24:48And we would probably recommend
• 24:51a hip replacement because if
• 24:53you have arthritis in the hip,
• 24:55then again, you know,
• 24:58what we're trying to preserve with
• 25:00these therapies is that round shape
• 25:02of the hip and the cartilage.
• 25:04But if you the cartilage is already damaged,
• 25:06it would most likely make sense not
• 25:10to do these preventative therapies.
• 25:13OK, And then one more and just humor
• 25:15me 'cause this one's a little bit
• 25:16out there and it's my own question,
• 25:18so I'll own that. But like, you know,
• 25:20this is an ischemic process.
• 25:22So if you have ischemia to the heart,
• 25:24we have a troponin that
• 25:26that can be our marker,
• 25:27our biomarker in addition to more
• 25:30rudimentary tests like an EKG.
• 25:32If you have ischemia to the gut,
• 25:34we have a lactate we can check as a marker of
• 25:37ischemia that can point us towards, you know,
• 25:40whether that process is, is occurring.
• 25:42Is there any such biomarker
• 25:44with ischemia to the bone?
• 25:46Because it seems like this imaging like
• 25:49it's like by the time the imaging changes,
• 25:51you already have some some
• 25:52big problems going on.
• 25:54You're not catching it early.
• 25:55It doesn't sound like with an X-ray per SE,
• 25:59probably something's happening before
• 26:00you can even see it on an X-ray.
• 26:04And so I wonder if there's work in the
• 26:06field on biomarkers of bone ischemia
• 26:08that can point you towards that.
• 26:12It's a great question.
• 26:14And there are certain biomarkers
• 26:16that can be elevated.
• 26:18These are markers that show
• 26:21osteoclast activity and they're
• 26:24just not sort of traditionally
• 26:28ordered or available in our lab.
• 26:31And, and, but there have been a bunch of
• 26:34papers looking at different biomarkers,
• 26:36different products of bone resorption
• 26:42that that in which you will see a spike,
• 26:45but I'm not aware of them being
• 26:50used for for a diagnostic purpose.
• 26:52Got it. Thank you.
• 26:56So in terms of medical
• 26:59therapies, there are certain
• 27:03there's certain comorbidities
• 27:04that place a patient at higher
• 27:07risk for avascular necrosis.
• 27:09So one are patients with thrombophilic
• 27:12or hypo forbidinolytic disorders.
• 27:15And there are some studies for this
• 27:19particular subset of patients that have
• 27:22found that Lovenox or heparin can be helpful.
• 27:27And there is another subset of patients
• 27:31with lipid metabolism disorders and
• 27:34hypercholesterol disorders in which
• 27:36statins have been found to be helpful.
• 27:40There are a number of studies looking at the
• 27:43use of bisphosphonates and bisphosphonates,
• 27:46specifically allodronate therapy.
• 27:48It's known to slow osteoclast activity
• 27:53and there's very strong evidence to
• 27:55show that it does slow the progression
• 27:58of the disease of avascular necrosis
• 28:00and it can also help with hip pain.
• 28:03So the bisphosphonates are a good
• 28:08medical therapy to consider,
• 28:10but not every patient is a candidate
• 28:12and they do have side effects and not
• 28:15every patient is really open to this.
• 28:17And the one thing about bisphosphonates is
• 28:20that while it it slows the progression,
• 28:23it doesn't help with angiogenesis,
• 28:25It doesn't help with revascularizing the hip.
• 28:29So it will delay the rate of progression,
• 28:32but it doesn't halt it.
• 28:37One particular surgery that has demonstrated
• 28:40a lot of effectiveness is cordee compression.
• 28:43So this is where we drill into the
• 28:46femoral head directly into the
• 28:49lesion and remove the dead bone.
• 28:52And the one big value of this surgery
• 28:55is that it reduces the swelling and
• 28:58pressure within the femoral head.
• 29:01So that provides some pain relief and also
• 29:04by reducing the pressure in the femoral head,
• 29:08helps with revascularization.
• 29:09The second thing is,
• 29:12is that a sclerotic margin of bone
• 29:15develops around the dead bone.
• 29:17This becomes very thick.
• 29:19And as a surgeon,
• 29:20I can tell you as I drill through it,
• 29:22it's almost like I'm drilling through rock.
• 29:24It is so thick and hard.
• 29:26And there's no way that new capillaries
• 29:28or blood vessels can cross that
• 29:31barrier into that region of dead bone.
• 29:33So the core decompression,
• 29:34another reason we do it is to
• 29:37provide a pathway for those new
• 29:39capillaries to grow into that region.
• 29:44There are many, many clinical studies
• 29:46that have been done over the years
• 29:48looking at core decompression.
• 29:501 challenge in comparing all these
• 29:52studies are that there's many different
• 29:55techniques drilling with the eight or
• 29:59nine different drill pins different
• 30:03removing certain amounts of bone.
• 30:06But they have all shown very good
• 30:10success with with smaller lesions
• 30:13and less advanced stage lesions
• 30:15and they really show a remarkable
• 30:18improvement with pain control and
• 30:20core decompression has been found to
• 30:23delay the need for hip replacement.
• 30:28One big question we had here at
• 30:30Yale is that if a patient has
• 30:32a core decompression surgery,
• 30:34does it then make their the hip replacement?
• 30:38If they need a hip replacement down the road,
• 30:40does it affect the outcome
• 30:42of that hip replacement?
• 30:44And what we demonstrated in the
• 30:48Journal of the American Association
• 30:50of Orthopedic Surgery is that if
• 30:52you have a cord decompression,
• 30:54it does not affect your outcome if
• 30:56you eventually go on to femoral head
• 30:58collapse and need a hip replacement.
• 31:00So that's a really reassuring finding
• 31:04to tell patients is that, you know,
• 31:07we're not closing any bridges or making
• 31:08if you need a hip replacement down the road,
• 31:11we're not increasing your
• 31:13risk of something happening.
• 31:16So according compression is very challenging
• 31:20because it's directed under fluoroscopy.
• 31:22So these are X-rays.
• 31:25So you try to see the lesion on X-ray.
• 31:28It's really hard.
• 31:29I don't know if you can see
• 31:31the lesion on this X-ray,
• 31:33but it's in, in my opinion,
• 31:34it's almost impossible to see on X-ray.
• 31:38So what traditionally is done is the surgeon,
• 31:42instead of just drilling in once,
• 31:43they'll drill in eight or nine times
• 31:46through different tracks to really
• 31:48ensure that they are hitting the lesion.
• 31:51But every time you drill
• 31:53through the femoral neck,
• 31:54you increase the risk of a hip fracture.
• 31:56So in the traditional sense,
• 31:58when these cord decompressions are done,
• 32:00most surgeons don't allow the patient
• 32:02to weight bear for three to six months
• 32:05because they're destabilizing the bone
• 32:07and they're removing so much bone.
• 32:12We also at Yale used stem cells.
• 32:15So what we'll do is we'll take bone
• 32:18marrow aspirate concentrate and then
• 32:19we'll spin it down with a special
• 32:21centrifuge system in the operating room.
• 32:24And then we'll give these stem cells back
• 32:27during the surgery through those drill tracks
• 32:30to supplement the core decompression surgery.
• 32:33And this procedure has a term,
• 32:36it's core decompression with adjuvants.
• 32:38And there's many different
• 32:39adjuvants on the market,
• 32:40bone marrow aspirate, concentrate,
• 32:43platelet risk rich plasma.
• 32:45There's even studies where they take
• 32:47patient stem cells and grow them in the
• 32:50lab for a few weeks and then and then
• 32:53inject those into the femoral head.
• 32:55But, but very good evidence has
• 32:59been demonstrated using these
• 33:01adjuvants and and improving the
• 33:03outcome of core decompression.
• 33:06One thing I want to emphasize is that a
• 33:10vascular necrosis has very different,
• 33:14very different in shapes and sizes.
• 33:18So these are four 3D models that we created
• 33:21on patients with avascular necrosis.
• 33:23And here you can see that some of
• 33:25the lesions are very small.
• 33:27Some of the lesions are very large.
• 33:30And this is just to emphasize that
• 33:32when you do a cardiac compression,
• 33:34you really need to customize the surgery
• 33:37for the patient and target the lesion.
• 33:40So we developed at Yale a 3D technique
• 33:44and we use computer navigation
• 33:47stereotactic techniques where we
• 33:49create the 3D model during the
• 33:52surgery and then we're able to guide
• 33:57during the surgery in 3D,
• 34:00our drill guide right into the lesion.
• 34:03In the panel A you can see the
• 34:06patients in the CT scanner and panel
• 34:09B you can see I'm holding a drill
• 34:13guide that has an optical array on
• 34:17it and the patient's thigh bone,
• 34:19the femur has an optical array.
• 34:21And then in 3D in the third panel,
• 34:23you can see that I'm able to move the
• 34:26drill guide and target the lesion directly.
• 34:30So with this technique, I'm usually
• 34:32able to do it with just one drill pass.
• 34:35And I'm not, I, I, I do not have to
• 34:39do eight or nine different drill paths.
• 34:40I'm able to do the surgery just
• 34:42with one drill path.
• 34:44And this is a technique that
• 34:46we developed here at Yale using
• 34:49our stereotactic techniques.
• 34:54And, and just quickly here,
• 34:57you can see we're drilling
• 34:58into the femoral head.
• 34:59We've targeted the lesion.
• 35:01We've deployed a flip cutter
• 35:03drill to remove the dead bone.
• 35:06We're inside the lesion,
• 35:08removing the dead bone,
• 35:09and then we're going to inject
• 35:12the stem cells into the lesion.
• 35:14Right now, I'm going to
• 35:15hand off to Doctor Aslam.
• 35:18Thank you, Doctor Bisniya.
• 35:20So I'm going to talk about my role in
• 35:23this program is providing hyperbaric
• 35:25oxygen therapy as an adjunct
• 35:28treatment to the procedure the doctor
• 35:30Viznia is doing for ABN patients.
• 35:33This is like a boost to what he does
• 35:36and I'll explain in the next few slides
• 35:40so you can advance the slide to that.
• 35:44Oxygen used in high concentrations
• 35:46of hyperoxia is actually a drug
• 35:50with many therapeutic effects and
• 35:52hyperbaric chamber is the dosing device.
• 35:56The definition of hyperbaric oxygen is
• 35:58not just hyperoxia, but it is hyperbaric.
• 36:01So it is 100% oxygen intermittently
• 36:04breathing by a patient breathing.
• 36:07So that's a systemic effect under
• 36:10pressure and the pressure that
• 36:13hyperbaric oxygen is defined at is at
• 36:17least 1.4 atmosphere absolute above
• 36:19sea level where one is at sea level.
• 36:23Most of the outpatient therapies
• 36:25that we provide with hyperbaric
• 36:27oxygen like wound healing,
• 36:29treating osteomyelitis,
• 36:30keeping radiation injuries is
• 36:32anywhere between 2 and 2.48 year
• 36:37absolute atmosphere pressures.
• 36:39That's the normal range and each
• 36:43patient would have about 30 treatments.
• 36:46That is five days a week for about 6
• 36:50weeks and each treatment is 2 hours in
• 36:55the chamber getting this 100% oxygen.
• 36:58With this therapy,
• 37:00the arterial PO2 raises to about
• 37:041000 to 1500 millimetres mercury,
• 37:06whereas this oxygen is not the
• 37:09oxygen bound to the hemoglobin.
• 37:11This is dissolved oxygen in your plasma.
• 37:14With that high pressure,
• 37:16this oxygen can diffuse out of the
• 37:18vascular system into ischemic tissues
• 37:20and in tissues we raise the high.
• 37:23We raise the oxygen tension to about
• 37:26300 to 400 millimetres AG with two
• 37:29to three atmosphere pressures of
• 37:32hyperbaric oxygen and that is the
• 37:35concentration where oxygen has
• 37:37the therapeutic effects.
• 37:38So oxy hyperbaric oxygen,
• 37:41the therapeutic effects are mostly through
• 37:48through you know generation of reactive
• 37:51species of oxygen and nitrogen and
• 37:54then these reactive oxygen and
• 37:57reactive nitrogen species will then
• 38:00lead to many signalling pathways which
• 38:02all have these therapeutic effects.
• 38:05So the biochemical pathways where hyperbaric
• 38:09oxygen improves neo vascularization
• 38:12or antibacterial effect of collagen
• 38:15synthesis and regulating inflammation,
• 38:18these are all biochemical pathways that
• 38:21have been established beyond, you know,
• 38:24with very good evidence for decades now.
• 38:27But what is now emerging is the
• 38:30mechanism of hyperbaric oxygen for
• 38:32avascular necrosis and how does it
• 38:34promote osteogenic process promotion,
• 38:36which I'll talk about in a few
• 38:38minutes next time please.
• 38:43So this is our oxygen hyperbaric
• 38:46chambers at the Lawrence and Memorial
• 38:48Wound and Hyperbaric Centre.
• 38:50These are monoplace chambers.
• 38:51These are more commonly used
• 38:54for outpatient therapies.
• 38:55There are multi place chambers which
• 38:58actually have many patients sitting
• 39:00in a big room and they actually wear
• 39:04hoods for the hyperbaric oxygen.
• 39:06Whereas in monoplace chambers
• 39:07which are very common in many
• 39:09hyperbaric outpatient centres,
• 39:11one patient goes into one chamber and
• 39:15stays there for about 90 minutes getting
• 39:19hyperbaric oxygen and next slide please.
• 39:22The patient lies on a stretcher.
• 39:25The stretcher,
• 39:25the top part of the stretcher
• 39:28goes directly into the chamber.
• 39:31The patient is given 100% oxygen, sorry,
• 39:34clothes that are safe for 100% oxygen.
• 39:37So they're 100% cotton and cotton sheets.
• 39:40These are all hyperbaric safe linen
• 39:43that goes in when the patient
• 39:45is in the door is closed.
• 39:47But there are all these diets and
• 39:49mechanisms to change pressure and be
• 39:52able to communicate with the patient.
• 39:54A hyperbaric physician is supposed to
• 39:56be in the center at all times when the
• 39:59patient is in the hyperbaric chamber.
• 40:01And a hyperbaric nurse and a
• 40:03technician is in the room at all times
• 40:05to communicate with the patients.
• 40:07Next slide, please.
• 40:09So I'm going to talk to you about
• 40:11a little bit about osteo radio
• 40:13necrosis of the mandible or ORN.
• 40:16This hyperbaric oxygen protocol
• 40:19for ORN was established like about.
• 40:22More than four decades ago by
• 40:24doctor Robert Marks and it's called
• 40:27the Marks protocol.
• 40:28The interesting thing is that
• 40:31the pathophysiology of ORN,
• 40:33how it affects the jawbone is actually
• 40:36an avascular necrosis which was
• 40:38established by Doctor Robert Marks
• 40:40like in 1980s that he established
• 40:43by by sampling bone from necrotic
• 40:47bone that they were no bacteria.
• 40:50So he said this is not an infectious process,
• 40:53this is essentially an avascular necrosis.
• 40:57Who gets this is patients who have
• 41:00radiation for head and neck cancers.
• 41:02They because of late effects of radiations,
• 41:05get fibrosis of blood vessels and
• 41:09develop this necrosis of the jawbone.
• 41:12The protocol that Doctor Marks came
• 41:15up with decades ago and it is actually
• 41:18the earliest use of hyperbaric oxygen
• 41:21and it is actually the most frequent
• 41:24use of hyperbaric oxygen that we see
• 41:27that we use in medicine today as well.
• 41:32So the protocol is 20 treatments
• 41:36of hyperbaric before the surgical
• 41:39treatment for the necrosis or the
• 41:41when the oral surgeon removes the
• 41:44necrotic bone and the decayed teeth.
• 41:46So you give 20 treatments before
• 41:48and the idea of those 20 treatments
• 41:50before is to condition the bone
• 41:52to decrease inflammation in,
• 41:54improve some neo vascularization
• 41:56so the bone can then withstand the
• 41:59trauma of the surgery, the wounding,
• 42:01as well as the metabolic need of
• 42:03the surgical intervention.
• 42:05And then you do the oral surgeon
• 42:07takes out the teeth,
• 42:09cleans out the bone and then you
• 42:10do 10 more treatments after that.
• 42:13So that has been an established
• 42:15protocol and then 10 more treatments
• 42:17after the surgical procedure is
• 42:19to heal the
• 42:20surgical bone and heal the bone.
• 42:22In my last 15 years of doing hyperbaric
• 42:26oxygen, this has been a very successful
• 42:29treatment of all ORN using this protocol
• 42:32and Doctor Marks has on many papers on this
• 42:36where they've shown complete resolution
• 42:38and really huge success of this procedure.
• 42:42Now the question that Dan and I were asking
• 42:45like if this is the same path of Physiology,
• 42:48so why isn't hyperbaric approved for AVN?
• 42:51And that is our mission now to get it
• 42:55approved for AVN because believe it or not,
• 42:57the European Council of Hyperbaric
• 42:59Medicine has included AVN and approved
• 43:01it for a condition treated that
• 43:05will benefit from hyperbaric oxygen.
• 43:06But we need large randomised controlled
• 43:09trials to get it approved here.
• 43:12But we do believe and this is our,
• 43:14our hypothesis or I think we have,
• 43:18we have done some cases that we think
• 43:20have suggested that the concurrent use of
• 43:23hyperbaric with core decompression that
• 43:25Doctor Viznia is doing with stem cells.
• 43:28This will all have a collaborative and
• 43:30enhanced effect on, on healing of this bone.
• 43:33Next slide please.
• 43:36So improved neo vascularization
• 43:38by hyperbaric is not only through
• 43:41angiogenesis, which is you know,
• 43:43takes a hyperbaric effect,
• 43:44endothelial cells and new blood
• 43:46vessels sprout in areas of ischemia,
• 43:48but also through vascular vascular genesis,
• 43:53which is basically de Novo
• 43:56synthesis from stem cells.
• 43:58So as I said, hyperbaric oxygen,
• 44:01the therapeutic effects are through reactive
• 44:04oxygen and reactive nitrogen species.
• 44:06But because hyperbaric oxygen is interrupted,
• 44:09so it's like daily for two hours and we
• 44:12do five days a week and interruption.
• 44:14This protocol has shown that hyperbaric
• 44:17oxygen will give enough oxidative stress
• 44:20to drive all these processes of neo
• 44:24vascularization and tissue regeneration,
• 44:26but it is not oxygen toxicity.
• 44:29So this is very important to understand
• 44:32about the mechanism of hyperbaric
• 44:34oxygen and its efficacy that the
• 44:36oxidative stress by hyperbaric oxygen
• 44:39is not synonymous with oxygen toxicity.
• 44:42Doctor Steven Palm has done extensive
• 44:45research on hyperbaric oxygen and
• 44:48shown that hyperbaric oxygen does
• 44:51mobilize stem cells from stem cells
• 44:54depot in the body from bone marrow,
• 44:57not only mobilizes them but enhances
• 45:00the recruitment of stem cells in
• 45:03ischemic tissues or areas of injury.
• 45:06Not only that,
• 45:07it also improves and stimulates
• 45:10the differentiation of pure pure
• 45:12reputant potent stem cells.
• 45:14So with Doctor Viznia putting
• 45:16the stem cells there,
• 45:18we believe that it is going to
• 45:20enhance a lot of effective stem cells,
• 45:22not only mobilizing the stem cells,
• 45:24but stimulating the stem cells that
• 45:26have been put there by Doctor Viznia
• 45:28so that they have their effect sooner.
• 45:30So the oxidative stress needs to hit 1A,
• 45:35which is hypoxia inducible
• 45:37factor stabilization,
• 45:38growth factor production.
• 45:40And there's a whole mechanism of
• 45:42many cytokines and growth factors
• 45:45that are affected.
• 45:47And these studies were done not only
• 45:49in mice but also in human volunteers
• 45:52and patients where samples were
• 45:54taken of blood at beginning of
• 45:56hyperbaric at 10 treatments 20 and 30.
• 45:58And they were shown that there was
• 46:01increasing stem cells circulating in
• 46:03the bodies. Doctor Kemporesi and Dr.
• 46:06Vizani have done extensive research
• 46:08and published widely and now have
• 46:11come up with these new indications of
• 46:14hyperbaric and have shown evidence
• 46:17that hyperbaric oxygen suppresses
• 46:19the activity of osteoclast.
• 46:21So in dead bone or ischemic bone,
• 46:24the osteoclasts are activated and there
• 46:26is more bone reduction than bone generation.
• 46:29So what hyperbaric does is
• 46:32it reverses this process.
• 46:34So it suppresses osteoclast
• 46:36differentiation and activation,
• 46:38it stimulates osteoblast differentiation,
• 46:41drives down the inflammation by decreasing
• 46:46amounts of TNF alpha Illinois 6.
• 46:49So it decreases the bone edema,
• 46:51it decreases pain.
• 46:52That way it tips the balance towards bone
• 46:55regeneration rather than bone resorption.
• 46:57But underlying mechanisms are
• 47:00still largely unclear as we are,
• 47:03and we hope to have more studies
• 47:05to elaborate on these effects.
• 47:07Next slide please.
• 47:09What are the side effects of hyperbaric?
• 47:11Basically,
• 47:12hyperbaric is one of the safest
• 47:14treatments in modern medicine.
• 47:16All the side effects that we see in
• 47:19our practice is they are temporary.
• 47:21So the most common are the
• 47:23patient can be claustrophobic,
• 47:25but once they get into these chambers,
• 47:27because their glass chambers is a person
• 47:30outside, they can watch TV outside.
• 47:33Most people are not claustrophobic
• 47:35like they would be in an MRI machine.
• 47:38Some oftentimes if they have
• 47:40significant claustrophobia,
• 47:41we give them a little anxiety
• 47:44medicine and they do fine.
• 47:47The other very common side effect
• 47:49which is also temporary can
• 47:50be middle year better trauma.
• 47:52So our our sinus squeeze because
• 47:54these cavities in our scalar airfield,
• 47:58airfield and can have the pressure if
• 48:02middle year starts bothering the patient,
• 48:05they can get a meeting guard and
• 48:06meet you by an ENT which equalizes
• 48:08pressure on both sides of the tympanic
• 48:11membrane and it's very comfortable.
• 48:13I've never had in my 20 years have
• 48:16anybody blow out the tympanic membrane.
• 48:19Those have been reported very,
• 48:21very rarely,
• 48:22but those have been in cases where you
• 48:24really have to increase the hyperbaric
• 48:27pressure for life saving emergencies
• 48:29like carbon monoxide poisoning.
• 48:31But again,
• 48:32are very rare and most patients
• 48:35do not even need a tympanic,
• 48:37you know, maryngotomy.
• 48:39They're fine by decongestant,
• 48:42you know, treatment by sprays.
• 48:45Progressive myopia sometimes happens.
• 48:47It's seen after many treatments
• 48:50like 20 or 30 treatments,
• 48:51but it gets reverted and gets normalized
• 48:54after we stop hyperbaric treatment.
• 48:57Any toxicity in the lungs,
• 49:00which can be like half or some
• 49:05inspirational burning or any CNS toxicity
• 49:08which we might think would happen with
• 49:12oxygen toxicity like seizures or nausea,
• 49:16vomiting.
• 49:16These are very,
• 49:17very rare.
• 49:18And these will happen after 100
• 49:21treatments or high pressures which
• 49:23are not really used in in any
• 49:26treatment protocols that we use.
• 49:28So it's very safe treatment.
• 49:31Next slide, please.
• 49:34This is an RCDA randomized controlled
• 49:36trial that was done by doctor Cam Borussi.
• 49:40When he compared this was a small trial,
• 49:42but it was very the evidence are very
• 49:46good with he took 20 patients and
• 49:50randomized them to either hyperbaric
• 49:53oxygen or just hyperbaric air.
• 49:55And these are patients of AVN stage two
• 49:59AVN and he did pain scores also did
• 50:06MRI imaging showed that after about
• 50:0920 treatments the pain got better.
• 50:11The range of mission got better between
• 50:1320 and 30 treatments and this is
• 50:16exactly what we are seeing with the
• 50:18patients that we have done so far.
• 50:21It is amazing that after 20 treatments
• 50:23these patients were walking with a
• 50:25cane and these are young patients
• 50:27were walking with a cane or limping.
• 50:29They come in without their cane in
• 50:31the centre and not limping anymore.
• 50:33So these are patients we get very
• 50:35attached to because they come every day
• 50:37and the staff gets attached to them.
• 50:39So when they come without a cane,
• 50:41you should see the excitement in
• 50:43the wound center.
• 50:43It's like, whoa, what happened here?
• 50:45Look at this patient now he's walking.
• 50:48So that we have noticing at
• 50:51about 20 treatment that happens.
• 50:53And in this trial they followed the
• 50:55patients for about one year and
• 50:58seven years with imaging and they
• 50:59found that none of them needed a hip
• 51:02replacement and there was complete
• 51:04resolution in at least seven patients
• 51:06of the ischemic necrosis.
• 51:08Now these did not have surgery,
• 51:10they were just treated with 30
• 51:13treatments of hyperbaric.
• 51:15Next slide,
• 51:16please.
• 51:17So we have come up with a protocol
• 51:19and we are still trying to design
• 51:22A protocol for our study.
• 51:23But most of these patients are coming
• 51:26from out of state and we just want
• 51:28to make sure that we have something
• 51:30that that is practical for them.
• 51:33And this is a protocol I came up
• 51:35with and with Doctor Viznia looking
• 51:38at the evidence,
• 51:39looking at the Marks protocol.
• 51:40Now where is Marks protocol is
• 51:44based on conditioning for 20
• 51:46treatments before the surgery.
• 51:48Now those surgeries are a little extensive,
• 51:50whereas Dr.
• 51:51Wisnia surgery is the patient
• 51:53is up and about and walking.
• 51:55It's so minimally invasive.
• 51:58And then he's putting stem cells.
• 51:59So we said,
• 52:00OK,
• 52:00let's just do about two weeks or
• 52:0310 treatments of conditioning,
• 52:05then do the core decompression because
• 52:08I felt the healing should happen
• 52:11after with the neo vascularization
• 52:13that we think is happening.
• 52:15So we are doing four weeks after.
• 52:18So far this is showing good results,
• 52:20but we are designing a clinical trial
• 52:23where we'll do different doses for
• 52:25hyperbaric to compare really what works.
• 52:28We don't know yet.
• 52:29Next slide please.
• 52:33So this is our program.
• 52:35Our mission is to provide integrated
• 52:37care to all avian patients.
• 52:39These are patients pre collapse
• 52:41and we hope to coordinate with
• 52:45other medical specialties.
• 52:47We want to catch them early.
• 52:49We want to minimize the risk of having
• 52:52them undergo hip replacement surgery.
• 52:54So, so far this is the program and it
• 52:58is Doctor Viznia's Co decompression.
• 53:00And then the hyperbaric is I've done
• 53:03under my supervision at the Lawrence
• 53:05and Memorial Munden Hyperbaric Center,
• 53:07which is part of the New Haven Health.
• 53:11And this is the core orthopaedic surgery team
• 53:16because we do have other joints
• 53:19with AVN, so happy to offer
• 53:22them hyperbaric if they need it.
• 53:25And Doctor Vizio, do you want to
• 53:28talk about the last slide, this one?
• 53:32Yes. So yeah, but we've been,
• 53:33we've been ramping up over the last
• 53:36year and we're now at the pace of
• 53:39doing about 60 core decompressions
• 53:42a year and dozens of hyperbaric
• 53:45oxygen therapy treatments at L&M.
• 53:48And a few months ago,
• 53:50we had a patient with a vascular
• 53:52necrosis of their talus and we did
• 53:54the first total talus replacement in
• 53:56the health system for that patient.
• 54:02Again, if you need to get in touch with us,
• 54:05feel free to e-mail us.
• 54:07And you can always put an order in Epic.
• 54:10Just type in AVN or osteonecrosis
• 54:14or avascular necrosis and we'll
• 54:16try to help your patients.
• 54:19And if you have any questions at all,
• 54:22don't hesitate to reach out.
• 54:26Thank you. Thank you guys so much.
• 54:28Really interesting stuff in a topic
• 54:29we have not had in the past 10 years
• 54:32I've been directing this course.
• 54:34So really, really interesting to
• 54:36hear about what's going on at Yale.
• 54:38Certainly stuff we have I'd say
• 54:40more commonly in the outpatient is
• 54:42historically perhaps before your
• 54:44program was people on chronic pain
• 54:47medications for non operative AVN,
• 54:50which becomes quite a conundrum.
• 54:53And it's, it's really great to hear that
• 54:56there are other approaches going on now.
• 54:59A really great question in the chat by
• 55:02Doctor Banatowski asking can you talk
• 55:04briefly about how alendronate is both
• 55:06a potential cause of osteonecrosis
• 55:09and a treatment for osteonecrosis?
• 55:13It it's a great question because it's known
• 55:16to cause a vascular necrosis in the jaw.
• 55:19So why would you think it
• 55:21would help in the femoral head?
• 55:24Well, the architecture is different
• 55:27in terms of the blood supply.
• 55:30And in the femoral head,
• 55:32the epiphysis of the femoral head has a very,
• 55:35very poor blood supply.
• 55:37It's supplied by small little capillaries.
• 55:40You have to remember that the
• 55:42cartilage is not perfused at all.
• 55:44So you have small little capillaries
• 55:47that are very prone to injury.
• 55:50And the thought is,
• 55:53is that the the halodronate in that case
• 55:57is really preventing osteoclast activity.
• 56:01So just the progression of the collapse.
• 56:04Whereas in the jaw again you have
• 56:09different architecture and it's thought
• 56:12that the osteo the the reduction of
• 56:16osteoclast activity may be impacting the
• 56:19capillaries in that micro environment.
• 56:23We don't know specifically the mechanism of
• 56:27how the allodronate causes AVN in the jaw,
• 56:30but the way I would think about it is
• 56:32they are different micro environments
• 56:34that are perfused differently.
• 56:38That makes a lot of sense
• 56:40and is very helpful.
• 56:42Unless there are other questions,
• 56:44I don't see any in the chat right now.
• 56:46I just want to thank you
• 56:48for a fantastic talk.
• 56:49I think your your message went far and wide,
• 56:52so hopefully you will be
• 56:54getting some communication and,
• 56:56and it's great to know that you guys are
• 56:59here and this program is here as a resource.
• 57:01I think it's really intriguing.
• 57:03I'm still going to make a
• 57:04plug for the early biomarker.
• 57:06I think there's some,
• 57:07some work in the field to be
• 57:09done that I will not be leading,
• 57:10but I think it's really fascinating,
• 57:12right?
• 57:12Like we're treating everything
• 57:14at the way margin of once the
• 57:16the horse is out of the barn.
• 57:17It's I think it's a a fascinating
• 57:19and hard to diagnose condition
• 57:21and we will stay tuned.
• 57:23Thank you guys so much and
• 57:24hoping you have a great day.
• 57:26Thank you and thank you reaching
• 57:28out. Thank you so much
• 57:29and lots of thank yous in the chat.
• 57:32Thank you, thank you. Take
• 57:35care.