Having a pain in your knee? A hitch in your hip?

It may be time for a joint replacement.

Fortunately, the field has seen major recent improvements, with better outcomes for the 1.2 million people a year who get joint replacements in the U.S.

We spoke about it recently with Javad Parvizi, professor of orthopedic surgery at the Rothman Institute of Thomas Jefferson University.

What's one new development that's really making a difference?

One is genomics. We are individualizing care. In the old days, we would do the same thing for everyone. But we have come to realize that everyone has a unique genetic make-up, which makes them prone to some diseases or respond differently to different treatments.

Sequencing the human genome took 13 years at a cost of $3 billion. At the same time, there was sequencing of other organisms. By now, most of the bacteria have been sequenced. That's important, because one of the issues we have struggled with in orthopedics is identifying the responsible organism in cases of infection.  It's difficult to isolate the infecting organism because the bacteria are attached to biofilm – basically, the slime that organisms live in. They can attach themselves to an implant and we may not be able to detect them.

Javad Parvizi, professor of orthopedic surgery at the Rothman Institute of Thomas Jefferson University.
Courtesy of Jefferson
Javad Parvizi, professor of orthopedic surgery at the Rothman Institute of Thomas Jefferson University.

Typically, if you suspect an infection, you'd get a sample and culture it. But the culture technique — agar in a petri dish – is technology from 1886.  And in the U.S., about 40 percent of samples come back culture-negative.  If you don't know what the organism is, you don't know what antibiotic to treat it with.

Now, you can send samples to companies that look at the DNA and run the data through a computer.  In 90 percent of cases, they are able to tell us what's infecting that particular joint — or for that matter, that brain, that heart valve.  We are refining the technique further and further.  It is possible that in time we will have 100 percent isolation of these organisms.

Is it usually just one organism?

Next generation genomic sequencing has created a very interesting finding for us: It usually isolates more than one organism.  What I believe is that infection is not caused by one organism. It is usually a group of them, with one leading the way.  When the circumstances are right, the other organisms then come to the surface and cause another infection.

If the patient has infection of their joint, they have to undergo surgery, usually two surgeries.  But 20 to 25 percent of those patients, despite having two surgeries, still get infected down the line.  In a third of the cases, it's by the same organisms. In two-thirds of the cases, it's a different organism.  We call it re-infection, but I think it's infection by an organism that was there from the beginning.  The culture wasn't able to identify it, but genomic sequencing can.

What's another significant development?

The science of microbiome is another exciting area.  Our body has three times more microbes than cells.  Each of us has 37 trillion cells in our body, and 100 trillion microbes. It's fascinating how they live in harmony with our body and don't destroy us. They are actually very important for our body. But if there is a disruption in that equilibrium, a state of dysbiosis arises. And dysbiosis leads to disease.

A few discoveries in recent years are fascinating. First of all, we now know that microbes can be present in areas of the body that we used to think of as sterile — such as the joints.  The list of diseases thought to be caused by infective organisms is growing by the day. What if osteoarthritis is caused by dysbiosis? What if the organisms that live in our bodies could over time result in damage to cartilage? That happens to be the case. There are signals showing that patients with osteoarthritis have more microbes in their joints than those that don't get osteoarthritis.

So, potentially, once you know what causes the issues, you could design a therapeutic strategy that could change the microbiome of a person's joints. This isn't really a long way off.

And now, with the microbiome, we are linking it back to next-generation sequencing.  Through that, we have found that in 28 percent of osteoarthritis patients without infections, there is a strong microbiome signal in the joints. Critics might ask, how do you know if that organism is really an infection or is part of the normal biome?  We're extremely close to getting that answer.

You've also mentioned plain old aspirin as a new improvement.

When a patient undergoes an operation, and we cut into their body, the body has to try to stop the bleeding. A coagulation system gets activated. But how does that system know whether to just stop the bleeding at the surgical site, or could it result in blood clot formation in other areas of the body? It does. It's often in the legs, and usually in the veins, where the blood is flowing slower than in the arteries. It's called a venous thromboembolism, or VTE.

In orthopedic surgery, if a patient undergoes a procedure, in particular total joint replacement, they are at risk for VTE and should receive anticoagulation therapy. Different types of anti-coagulation drugs have been introduced over the past 30 to 40 years. One of the most well-known is Coumadin, or its generic version, warfarin.

The balance has to be exactly right. If you give too much of the anticoagulation drugs, the patient can bleed at the site of the surgery. And there are other potential complications.

But now, we have begun giving patients simple low-dose aspirin.  To see if aspirin is as good as the other agents in patients undergoing total joint replacements, we did a randomized study and came across a very interesting finding. We found that patients who received aspirin had a lower incidence of VTE than on Coumadin. We were surprised. We figured it would be as good, but it was actually better. This is partly because Coumadin takes a few days to reach full effectiveness.

We found that aspirin had other beneficial effects. It doesn't cause hematoma. It doesn't cause bleeding from the wound. It doesn't cause persistent drainage from the wound. And then, interestingly, aspirin also reduces the incidences of fever in the post-operative period.

Aspirin doesn't need blood monitoring and testing like Coumadin does. Also, after surgery, patients are at risk of developing heart-related issues and strokes. Aspirin helps protect these patients.

And it's extremely cheap.  Here's the math: We do 1.2 million joint replacements a year in the U.S. Many are initially prescribed low-molecular-weight heparin, a drug that costs roughly $100 a day, for 30 days. It's a massive cost for a drug that is no better than aspirin. Plus, heparin has to be injected. Imagine the convenience of going home with aspirin, instead.

Each year, we take a survey in our annual meeting of the American Association of Hip and Knee Surgeons, asking how many surgeons use aspirin for their patients undergoing joint replacement. Ten years ago, it may have been 5 percent.  In a recent survey, more than 86 percent of surgeons said they were using aspirin as the main modality for prevention of VTE after joint replacement surgery.

Now, let's link back to genetics. Patients who develop VTE have a genetic predisposition. What if we could identify which patients are at higher risk of VTE after joint replacement?  Maybe we will give them aggressive anti-coagulants. But for patients who don't have high risk of VTE, what if we don't give them anything? That individualization is going to happen fairly soon.

What does all this say about the future of joint replacement surgery? 

We will be moving toward individualization of care. Genomics will come to our aid in the first place by helping us know who is at risk of developing diseases. We will know more about what causes arthritis of the hip and knee and perhaps have measures to prevent people from developing the disease in the first place. We will know more about the microbiome makeup, and that may allow us to manipulate it and prevent disease. Knowing the microbiome will also give us better ability to deal with infection of the joint, when it arises. Then it will allow us to monitor the response of these patients to therapies that we implement.