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Marie Williams: So we're going to go on to the next lecture. And I'm Marie Williams and I'm going to be giving this lecture over the next 30 minutes on how to treat nonunions and I have no financial disclosures. The most important thing about this lecture is truly understanding the types of nonunions, being able to identify a nonunion versus a delayed union, knowing and understanding the different multiple modalities for management of nonunions, understanding the various biologics that can be used to help you in healing these nonunions.

Nonunion basically is a fracture that has an incomplete healing for at least nine months and no sign of healing in three months. That was in the FDA in 1986 actually made that statement. I think it holds true today for when you're actually trying to figure out what type of modalities you're going to use for treatment. A lot of times, you'll say, how long has that delayed or nonunion been there? You're usually documenting up to three months.

General signs and symptoms consist of chronic and persistent pain, swelling, inconsistency with the clinical healing timeframe. When you have someone healing, you always expect the four to six-week timeframe for healing, and sometimes is very inconsistent, it takes a little longer. Now you're looking at things where you might have a fibrous union where you have a pseudarthrosis and you'll see on radiograph sclerosis of bone fragment ends.

The fifth metatarsals are very common area especially the base of the fifth metatarsal where you can see many of these signs and symptoms. It's not the only place but very common. Here are your risk factors. You have people who are chronically taking non-steroidal, anti-inflammatory, smoking. Smoking is a really big topic and it becomes more and more valid as we go.

[02:03]

Early on in the days, people would say smoking and then move on to that subject very fast. And now, when you have a patient who comes in and they're smoking and you're planning on having a surgical procedure, this is a topic that you must discuss with them, quitting, cutting back, and lowering their risk for nonunion, malunion of bone healing. Infection is a common risk, someone who has previous infections or has a post-op infection.

Vitamin D deficiency and actually that is becoming more and more common. I don't know if you found that but many people come in now with vitamin D deficiencies, taking vitamin D and I've never seen so many people in Florida with vitamin D deficiency. Thyroid imbalance, hyperparathyroidism and people on glucocorticoids, the rheumatoid patients, many of the arthritic patients are on many steroids that can lead to and have dramatic risk factors for non-healing.

Other risk factors include antibiotics, bisphosphonates, chemotherapeutic medications, excessive alcohol, high and low level trauma. Someone falling off of a height from 30 feet with complete disruption of ankle has a high risk of a nonunion or a malunion as an example. Bone loss and/or soft tissue loss, open and close fractures are some of your higher risk factors for nonunion.

When you look at the classification, Webber put out a classification that actually shows you two types, the vascular and the avascular. It's funny that we learn this in podiatry school and it just keeps coming back at us but you can see in the actual side in the front here at number A is your hypertrophic elephant foot type vascular – there we go, vascular nonunion. And then B is the normotrophic nonunion.

[04:03]

And C is actually where you have a hypotrophic avascular component but hypotrophic because you don't have large bone callus. When you get in to the vascular sides, D, E, F and G, you start to see fragmentation so you see here you have a torsional type wedge. And then E becomes more involved where you have multi fragments and then you have separation, and then you have atrophy at the bond ends. So these are the types of pseudarthrosis or nonunions according to Webber.

Types of nonunions again, vascular, the hypertrophic or hypervascular, the oligotrophic which we'll talk about, avascular or atrophic nonunions, and also you have then in types of comminuted, large defects and torsional wedges that don't heal well. So the hypertrophic nonunions are absolutely rich in blood flow to the fracture ends. They form excessive callus formation. They can result from insufficient stability with possible fixation or movement in an area that is not well-fixated via screws, plates, casts. It doesn't really matter.

You can have a result from premature weight-bearing. We've had many of those patients that appear to be noncompliant that start to walk on their fracture sites and then all of a sudden you're starting to see hypertrophic callus and delayed healing. And if you do a bone scan, you will see a very hot bone scan with proliferative activity in bone. In the oligotrophic nonunion, you have very absent callus formation.

[05:58]

You might have a displacement of the fracture but you do have intact blood supply to the bone ends, which is a little bit different than your avascular nonunion where you'll – when you do a bone scan, you'll see a positive bone scan or hot spots, which show that there is active blood flow and potential for healing. When you get to the avascular atrophic nonunions, the bone is usually more osteoporotic, atrophy at the bone ends. The bone ends are cold on a bone scan and very much avascular.

They're common with the internal fixation or internal hardware many times where you have poor fixation. Radiographic examination will show signs of eburnation, osteopenia and/or sclerotic bone ends. The comminuted ones that have defective bone fragments is comminuted and defective nonunion, avascular to the necrotic bone fragments. Sometimes multiple in nature depending on the level of trauma.

The injury will cause a devitalization of the fragments by disruption of the internal vessels, as well as a loss of periosteum. The key when you lose the intact periosteum to bone, you lose its vascular blood supply and have a higher risk of avascular necrosis, and one of the proponents when I'm fixing an ankle not to denude much of the periosteum, because I believe it gives you the most blood supply in healing to that bone.

This is just an example where you have a positive stress view where you have – you can see sclerotic bone ends, absence of the trabecular pattern at the fracture side, a failed and/or broken hardware. The deformity that was a fusion of the first metatarsal now has a worsening of the deformity and you don't have bone callus.

[08:00]

So if you will take a look at this a little bit closer, so you have here, you have increased deformity. You have a plate with a broken screw. You also have absence of any trabecular patterns across the fusion site. You have the failed hardware and also you have sclerotic edges along the bone. So here's a situation where you know once you see something like this, it is vital that you go back and repair this surgically. Maybe a bone stimulator might be indicated.

But at this point when I see increased bone deformity and no bone healing, I know that it's time to go back in and maybe reevaluate, surgically remove the hardware, replace the hardware, maybe a bone graft and we'll talk more about that in a little bit.

This is actually a gentleman who had a very well-fixed ankle. When you've finished it, you went, "Wow, this looks great." I don't have that before but I'm just showing you this picture because it's very destructive. You have a fractured hardware. You can see the screws are fractured, fragmentation of bone. Well, the fibula looks quite good but what that whole medial ankle? There is no medial ankle. He has Charcot joint disease along with a fractured ankle that went really bad.

The point is, is that here is a person who had all the risk factors for failure in repair and yet the repair looked well on X-ray until he started walking on it right after surgery. So here's a gentleman that was weight-bearing, didn't feel anything. The ankle was very swollen when he came in. So what are we left to do on something like that? We have to repair it. There wasn't much to repair because the bone was fragmented and also non-healing, so we elected to put a ride in there with a screw and clean up some of that bone and fuse that ankle.

[09:58]

And also we use a lot of the information that we had with regard to his Charcot so we really wanted to immobilize him and stabilize him, and that was the best way we could think of. There are other ways of doing that but here we repair this nonunion, which came because of all the risk factors that he had and all of the early ambulation. Maybe the fixation could have been better. There's a lot of things that I – you know, you look back at and think of but this was a good alternative.

When you see hypertrophic nonunion, this is a gentleman who came to my office with an already fractured ankle. This is three months post injury. He said, "I broke my ankle three months ago and I seem to have a little pain, and I'm not healing." And you can see where you can see a little bit of the bone callus but you have separation. Six months later, you can see more bone callus. Interestingly enough, he has a fibrous union here. He has no pain and no real deformity.

Now, if you're going to treat the X-ray, the right thing to do would be go in, debride the bone ends, freshen them up and maybe put a plate on that fibula. The realistic thing is that if you have no pain, no deformity, the X-ray doesn't quite look so good but you as a patient are able to run, jump, do all your activities, as a physician, the dilemma is to go, I would really like to fix that. You're not really going to fix that.

So what is happening here when you look at it is you get a nice fibrous union of bone even though – and maybe over time that may heal in maybe six to nine months but right now, no pain, no bone motion and no movement. Therefore, you leave it alone even though it doesn't look quite good.

Nonunions of the fifth metatarsal I think are one of the more common problems that we have. So you look at the bone ends and you can see where you have different types. In this picture here, you have a gap and that's just not healing and it's painful. You may have to go in and refracture the bone, debride the bone ends and put a plate or screw on that.

[12:06]

If it's not painful, you leave it alone. Whether it heals or not, you're not going to take something that's not painful and make it look better on X-ray. Now, this one on the other hand is you have complete sclerosis of bone on both ends. That's bone death. This where you have avascularity. You need to debride that bone and reattach. So two different types of nonunions, two different types of approaches. The patient with the sclerotic bone ends has pain. The patient that has that little wedge has no pain so you're going to actually treat the patient that has the avascular nonunion.

Another example of a delayed union requiring further surgery, this is actually a nightmare of a case as you can see just from the first case. This is one of my colleagues who showed me these pictures and I said, "I got to show this," because it's interesting, you put in all these hardware, right? You have all these plates, pilon fracture, and right here, the medial mal with all the screws and all the fixation, didn't heal.

It's interesting to me. I mean, you have some osteopenia of the bone. You don't have any real broken hardware. It looked like it was going to heal well and yet that medial mal was very painful, long-term disability, couldn't walk and so the doctor elected to go back in and repair it with what we call a hook plate. Freshened up the bone ends and used a large hook plate to actually put the medial mal back into its right appropriate anatomical position.

Now, interestingly enough, you could have used a cerclage wiring, hook plates, and other couple screws, but that was what she elected to do and that patient went on to healing.

[14:04]

You think to yourself, why does this happen? And I remember listening to one of my colleagues once and he said, "It's the failure of the surgeon because the hardware wasn't appropriate or wasn't fixated appropriate." And I used to think about that a lot because when you're putting in all these hardware, you think you're doing a great job. You would never think in a million years that one small area where you have a comminuted tibia, a comminuted fibula, and you have the medial mal as your area of complete pain and inability to allow this patient to walk.

So you look at the hardware and the hardware actually is good. I mean, you look at that and you want to kind of evaluate that. But what happened was, is the early active movement in walking on this made that fracture move some, and then you have the deformity that occurs and further repair for surgery.

Here's another example of ankle fracture where it goes into malunion. Once again, this looks pretty good. You have a nice fibular fracture that's repaired. The ankles joint looks well. The medial mal is attached. Sometimes when you get these fragments, you may need two screws or a cerclage wire or tension banding because they're very small. So the chance of the medial mal becoming a malunion or disruption is great.

So that is where we have to take that screw out and then do something other to get that medial mal to attach. This patient had a lot of pain. This is about eight weeks post-op and was unable to ambulate. So that patient had to return back to surgery for repair. Not all have to return back to surgery and sometimes they may look, like I said, radiographically not exactly the way you wanted to see but the patient has no pain or disability, you leave that alone.

[16:00]

So when you're looking and thinking about your diagnostic tools for evaluation, bone scan is one of your best tools to find out whether you have an area that is hot or cold. Whether it's a hypervascular or it's avascular. And so we'll use the bone scan to help us determine whether you have a biodynamically active area of bone or you have a synovial pseudarthrosis and actual no bone healing. You can use the Technetium 99, Gallium-67 and/or the indium labeled if you think there are some infectious process as well.

The other thing that I like is the 3D scan. This is just an example of a 3D CT scan where you get to see the bones and their – you miss sometimes without 3D all the fragmentations that's going on within that fracture site. So that's a good diagnostic tool to see what you're going to deal with. When you have hardware in there, you can't really do an MRI so a 3D CT scan might help you to determine how much separation there is in bone.

And then MRI is also another good tool. It gives you the blood flow to the area and will help. Some of the management of the nonunions consist of bone grafting, bone stimulators. You need sometimes the BMPs, the bone morphogenetic proteins. Stem cell therapy is actually something that we have now as a tool, bone marrow aspirates, PRP, dynamic casting, surgical ORIF, external fixation, internal fixation and ultrasonic treatment or ultrasound. So we'll go over a couple – the areas of management.

When you do bone grafting, you have an auto graft. Osteogenic precursor cells for bone growth, you need something that's osteoinductive with bone matrix protein and growth factors to stimulate bone growth, and you need something that's osteoinductive, which is a scaffolding.

[18:04]

So it's best to have products that are both osteoinductive and osteoconductive that is osteogenic for your best grafting material. You can get bone grafting from the cortical iliac crest, the tibia or the fibula. If you want cortical cancellous bone, the iliac crest, and the tibia and fibula are also a good area for that. And then cancellous bone, again, your iliac crest but also the calcaneus and the femur, and also the tibia. You can get good bone for cancellous bone.

Also with bone grafting, right now, the industry has grown so much with the types of bone material, both the autogenous and also all the types of grafting. But remember in bone grafting, you don't want something just osteoconductive only. You want something that's osteoconductive and osteoinductive. So when you have a cortical or cortical strut, you might have only osteoconductive unless it uses the BMPs in conjunction.

Electrical stim or bone stimulation is actually very vital now in all our nonunions or delayed unions. I think that you have to be careful with – I'm always checking, will the insurance cover? They always ask, how long has it been delayed? You can find out that sometimes on fresh fractures with high risk, it's covered. So you just have a lot of work to do to find out whether it's a covered procedure or not, but bone stimulators are very, very vital.

Electrical stimulation is used to induce the osteogenesis, stimulate bone growth and promote fracture healing. There's invasive electrical stimulators which deliver direct current to the fracture site through a complete implanted system. And I can tell you that with the new technologies and things that are happening now, I very rarely use an invasive one but it's definitely there for you to have.

[20:08]

Then there's a semi-invasive electrical stimulators which deliver the direct current via percutaneous electrode and anode placed in the contact site with the skin. And now you have also the noninvasive elective electrical stimulators which are external and deliver current to the fracture site via pulsed electromagnetic field and it actually is combined with a magnetic field technology. I am not a scientist but I find that the noninvasive ones are most palatable for the patients.

This is just a little schematic drawing of both the internal, the percutaneous and the external stimulators, and they developed an increased bone growth to the fracture site. Ultrasonic bone growth stimulators deliver mechanical stimulation to the fracture site through the application of a low intensity pulsed high frequency acoustic pressure wave. It produces integrins which enhance the production of COX-2 and prostaglandins, and it also is associated with mineralization of osteoblasts in culture.

And now, many of the products out there talk about this one thing which is the increase of the COX-2 and prostaglandins. This is just – shows that there's – with ultrasound, 20 BMPs have been found, six of which are capable of bone growth. BMP-2 is the most studied and also they used – they're approved for tibial surgeries and most commonly been, and it used to be very expensive and I don't think expense is really an issue at this point. But you can see here in this little scheme here what happens over time.

[21:58]

When you have an injury, you get your hematoma formation and then you have your intramembranous bone formation. And then, you end up with as you come down, you have – it's just the way a bone – an injury heals with – you got chondrogenesis and then you increase with your bone callus information. And then what happens is you have your platelets, your BMPs, and they increased to – come to this one factor called bone healing. So it's actually really a big, large function of the body – producing the body's BMPs and platelets, and growth factors for healing.

Now, one of the things that I've actually used quite a bit is the amniotic membranes. Just a quick, this could be a lecture all by itself. But amniotic fluid contains factors amniotic epithelial and mesenchymal stromal cells, collagens 1, 2, 3, 4 and has – and 5, and has other products RNA that help to heal, as well as has bactericidal effects. It's preserved and prescreened from C section. There's two types. There's chorion and chorion-free and if you remove the chorion, it lessens the chance for an immune reaction.

Some companies say chorion is good. You just have to read that and decide for yourself. Many are cryopreserved. The indications are for soft tissue and bony procedures although early on, bone was just – when it was used in bone, it was off label. This is just a picture of how the cell becomes multipotential and then divides into certain stem cells for nerve, bone, tendon, ligament and that just helps to see how the stem cell is a very versatile tool.

[24:00]

I like to show this picture because it was an unexpected result where patient had a wound on the medial aspect of the first metatarsal and the wound healed very well. But what happened on – as in the side was that the bone completely filled with new bone formation over a 52-day period where the amnion was placed.

Some of the special techniques, bone marrow aspirate, you don't want any more than two CCs. It can be aspirated from any single anatomic site. It becomes very painful and I think with the advent of the amnions, you may not need to do bone marrow aspirate. But if you do, you're going to take it from, as I said, the iliac crest, the tibia, the calcaneus and you can draw that out. It's easy to harvest. It doesn't take much time. You need about 30 mLs of blood and it's platelet-dependent. That's PRP.

Now, the surgical ORIF and external fixation is also another tool you have to help with early range of motion, anatomic reduction. You need to have stabilized fractures and preserve the blood flow to the fracture site. External fixation is really good in an infected nonunion or defective nonunion where you're not – you actually can preserve some of the skin tissue. It's good for comminuted nonunions, poor healing and osteoporotic bone. So you have the AO principles as well as external fixation to help you for those very difficult malunion and nonunion cases.

Remember, prevention is your best medicine for anything that we do. Remember that good patient selection for any kind of surgical procedure is important. I can tell you that sometimes I miss on that and I think that's going to be a very compliant person. And now they're out there riding their motorcycles after you fixed their fifth metatarsal and you go, "How did that happen?"

Anyway, remember that patient selection is important. Good principles, AO principles for any kind of fracture reduction to reduce your chance for a malunion or a nonunion, and knowing your comorbidities, malnutrition, diabetes, thyroid problems, smoking or just a few that can help.

[26:09]

I wanted to give you just a little bit of an overview. I could probably spend an hour just on the topic of surgical healing of a non or a malunion, but to understand the mechanics of it was important to me so I hope I delivered that in a short period of time that we had. Thank you.

TAPE ENDS [26:30]