Regenerative medicine has a quality problem. I see it every day. We have medical doctors and chiropractors who hear about a stem cell-based therapy being effective and then take a weekend course to learn about the treatment. However, they soon cut corners and costs and distill it to its most basic form, reducing its efficacy until it no longer bears any resemblance to the original treatment. This morning I’ll use a bone injection therapy used to treat arthritis as an example, but it really could be any therapy we offer.
The bone therapy has many names. We use the term “bone aug,” and technically it’s an intraosseous injection. There are a number of ways it can be done. One (the method we use) is labor intensive, technically demanding, and requires expensive equipment. The others are cheaper and easier but, as I’ll show you, likely not nearly as effective. Despite this, we have now seen a movement of physicians who have decided they can perform this procedure by cutting corners. Let me explain.
Multiple studies in recent years have shown that pain in the knee joint with arthritis is more reliably due to bone marrow lesions (BMLs), NOT knee cartilage loss or meniscus tears. This is a game changer, as it shifts the focus from our obsession with repairing cartilage to trying to treat bone. Let’s review for a minute what a BML represents to see how we may want to treat the problem.
On MRI, a BML (aka BME for bone marrow edema) is an area that lights up in the bone. On certain MRI sequences, it’s a bright spot (when the bone is dark on water-weighted T2 sequences), and on other sequences, it’s a dark spot (when the bone is bright on T1 fat-weighted sequences). It’s thought that this area most often represents tiny microfractures in the trabeculae (the microstructural “struts” that support bone). Hence, healing the area is a good idea.
Outside of providing more protection to the bone itself, a healed BML may have other important implications. Turns out that our penchant to name structures in the body as separate machines has allowed us to miss the big picture of what happens between bone and cartilage. We have always viewed these as two separate things, but in reality, they are one tissue with the bone half being more specialized for structural support and the cartilage part being more specialized for cushioning. Because they are one tissue that shares cells back and forth between the two specialized halves, what happens to one part impacts the other part. So a BML represents an area where both the bone and likely the cartilage are dying or in trouble.
Since a BML represents tiny fractures, one quick way to fix a fracture is with bone cement. An intraosseous injection procedure involves injecting bone cement into these painful bone marrow lesions to shore up, or stabilize, these areas and reduce knee pain. The problem with the procedure is that we have now seen a number of cases of side effects from the bone cement. Hence, there’s likely a better way to address these lesions.
A common-sense thing to do with BMLs is to inject bone marrow concentrate (BMC). This is the stem cell fraction of the bone marrow that is concentrated to improve stem cell content. The pioneer of using BMC in bone was Philippe Hernigou, an orthopedic surgeon from Paris.
Hernigou was the first to perform bone marrow concentrate (BMC) injections to treat bone diseases like avascular necrosis and nonunion fractures back in the ’90s and early 2000s. He has also been performing intraosseous injections for knee arthritis and patients with shoulder rotator cuff tears with good reported results. Hence, his early results support the idea that we can both heal nonhealing bone and also help the interplay between bone and pain in chronic joint diseases with BMC.
In 2006, we began injecting the bone with culture-expanded stem cells and BMC. We’ve recently completed a case control trial in which patients with knee osteoarthritis were injected with BMC either inside the joint only or both inside the joint and into the bone. Those who received injections in both the joint and bone (as opposed to the joint only) actually had better outcomes if they were under 60 years of age.
Our focus in treating bone marrow lesions, in this study and always in daily practice, is on precisely injecting contrast under X-ray guidance into these BMLs and then chasing that with the orthobiologic we’re using (e.g., BMC, culture-expanded cells, PRP). By using radiographic contrast with fluoroscopy, we can follow precisely where our orthobiologic is going live, or in real time, as it is injected into the bone or joint. The rationale is that if we’re not in the BML area, we can see that and adjust our injection technique to get there.
Recently, some European authors have begun injecting BMC more blindly, either by using ultrasound or fluoroscopy but without any contrast—in other words, without specific targeting of the lesion. The assumption being made is that by injecting high volumes of injectate (the material being injected), it will eventually work its way where it needs to go, making up for their lack of accurate targeting.
So is it really that easy? Can you override the importance of accurate targeting just by injecting a lot more stuff? Let me answer these questions by walking you through one of my patient cases this past week. Be sure to watch my video above for much more detail and to view the injection images.
My patient had bone marrow lesions in the bone right underneath the knee joint. I mark these clearly for you to see on the knee images in the video. These BMLs are the specific spots I wanted to target for the patient’s injections, so I placed two microtrocars there, and injected contrast. You will see in the video the contrast isn’t making it to the lesions; they are down a bit lower than where the contrast is filling in. In the video, you will see the result after I tried the “inject more stuff concept.” Meaning I inject more contrast in the same location; however, the increased volume of contrast still doesn’t make its way to the BML.
I then redirect my needle down lower, figuring that the contrast will now certainly fill the spot I want. However, the contrast just leaks back to the old location, nowhere near where I need it to go. I then redirect my microtrocar a little deeper and inject, and that does nothing. I then just try to add volume, figuring that maybe I can just inject enough to fill up the first space and then the contrast will fill up the target. That also doesn’t work; in fact, the contrast then just fills up the blood vessels connected to the local bone in the area I don’t want.
So while it might sound logical that just injecting a whole bunch of stuff will allow the injectate to hit the target, in effect by attempting to flood the space, you can see clearly in the video that it’s simply not that easy.
Physicians who don’t have extensive experience with this procedure view the task like filling up an empty gas tank with the inside of the knee representing the empty tank. If that were the case, you would expect the tank to fill up, and injecting more would eventually hit all areas inside the knee. However, in reality, the bone marrow space is connected to the peripheral circulation. So injecting more can mean that extra stuff bleeds into blood vessels that hook up around the knee. In addition, there are blood vessels inside the bone. Hit one of those and all of the stuff you’re injecting never makes it into the bone but is immediately whisked away into the peripheral circulation.
So the answer to our initial question is, yes, technically you can inject orthobiologics into the bone with ultrasound, and without fluoroscopy with contrast—if you aren’t concerned with precisely targeting bone lesions and are content with potentially producing suboptimal results in your knee arthritis patients. If, on the other hand, you want to take the guesswork out of it and be sure you’re precisely injecting those bone lesions, fluoroscopy (real-time X-ray) guidance with radiographic contrast is the way to go. Meaning, until proven otherwise by clinical trials, the right way to do this procedure is the more labor-intensive and expensive route.
The upshot? Injecting without contrast or with ultrasound means there’s a good chance you’ll miss the lesion you’re attempting to treat. In turn, this likely risks suboptimal results due to a suboptimal technique. As providers, we can’t do what’s convenient for us just because we don’t happen to have fluoroscopy or access to the proper technologies—we need to do what’s best for the patient! Even if that means the procedure costs us physicians more time and money.
*DISCLAIMER: Like all medical procedures, Regenexx® Procedures have a success and failure rate. Patient reviews and testimonials on this site should not be interpreted as a statement on the effectiveness of our treatments for anyone else.
Providers listed on the Regenexx website are for informational purposes only and are not a recommendation from Regenexx for a specific provider or a guarantee of the outcome of any treatment you receive.
About the Author
Christopher J. Centeno, M.D. is an international expert and specialist in regenerative medicine and the clinical use of mesenchymal stem cells in orthopedics. He is board certified in physical medicine as well as rehabilitation and in pain management through The American Board of Physical Medicine and Rehabilitation.…