Spine surgeon Michelle Welborn, MD, has spent years researching a collagen X biomarker that she hopes will change how physicians approach scoliosis care.
Dr. Welborn began working at Shriners Children's Portland in 2016 and is researching the biomarker with William Horton, MD. She spoke with Becker's about her work and what's ahead for her newly endowed professorship.
Note: This conversation was edited for clarity and length.
Question: What are the challenges with determining skeletal maturity in patients? Is there an age where this gets a little more difficult to figure out?
Dr. Michelle Welborn: Skeletal maturity is a rough estimate of how much longer somebody is going to grow for. The reason why we like skeletal maturity is because there are early bloomers and late bloomers. Theoretically, skeletal maturity helps us to differentiate between those kids that are going to be done growing at 10 versus those kids that are going to be done growing at 17. The problem is that skeletal maturity doesn't tell you how much they're going to grow. How much they are going to grow is growth potential. Currently, there's no way to tell what growth potential is. So, we extrapolate it based on the skeletal maturity, which is based on radiographs of our extremities. This presents an additional problem, as the growth of our spine doesn't happen at quite the same time as the growth of our limbs. Since we can't visualize the growth plates in the spine easily, that is our current gold standard. The combination of these means that there's a large error range because, while the time frames are similar, they're not the same.
Q: I assume this is where the collagen X biomarker comes in. Can you talk more about the process of finding this?
MW: Collagen X has been something that we've been pursuing here for 40 years. This is a huge effort that started with Mike Sussman, MD, who was just this incredible guy. Back in the early '80s, he, among other people, helped to delineate the structures of growth plate and the mechanism through how our bones get longer. That's important because our bones — even though the same building blocks are used — get wider through a different mechanism than how they get longer. The fact that they use the same building blocks in different ways is part of why figuring out growth potential has been so hard. And then he and William Horton, in the late 1980s and early 1990s, helped to delineate the structure of collagen X. This is important because collagen X is found anywhere where there is a cartilaginous model of bone or where soft bone is converted to hard. This model is used in processes where you need to grow bone quickly, like the growth plate or a healing fracture. These were monumental steps.
Using this in a clinical way was the challenge. We had an idea of what we wanted to use, but not how to use it clinically. But they needed some advances in technology before they were able to utilize this clinically.
After they identified collagen X, they needed to break it down with endogenous collagenase (enzymes found in our body) and see which of these degradation products could be found in the bloodstream. The amount of these products seen in the bloodstream basically indicate how fast we turn that soft bone into hard bone, or how fast we're growing. And it was basically at about that point where I started working here at Shriners. Shortly after that, we started our collagen X biomarker study that looked at the impact of growth on the progression of scoliosis.
Q: Can you talk about the actual application of this? How much have you applied all this knowledge in your practice?
MW: I have not applied it yet. And the reason is that anytime I do something that will directly affect patient care, I need to prove it beyond a shadow of a doubt. I can't say, "I think this is a better idea." I have to know it's a better idea, and to know it's a better idea takes years.
We have been working for about seven years now, following kids through their growth. We look at the radiographic measures of maturity, their anthropometrics (things like height, length, and weight and their biomarker levels). I have to follow kids through their entire growth spurt to see if what we're doing with collagen X is as good as what we have been currently doing. Only if I can show that it is as good, can we then start to apply it.
Q: What are your goals with the professorship? Are you planning more research and trials to bring this into mainstream spine care?
MW: That is exactly what the goals of this are. We just received a major grant as well, and while the exact amount of the grant is to be determined, it should hopefully be about $1 million. As part of the professorship and the grant, we've expanded this study to include genomics and AI. Our long-term goal is to incorporate this into mainstream spine care. But this is a slow process. So, for now we are working on being patient and making sure to hold our research up to the highest standards.
Q: Are there any other areas of spine that you're researching?
MW: Our biomarker study is just one of many research projects that we have been working on. In addition to our work on translational research and rare disorders, our team has done a lot of work on just trying to better understand indications for different procedures so that we can improve their safety and efficacy. These have included publications on magnetic growing rods, halo gravity traction and on vertebral body tethering. There are a lot of different procedures out there, and we see the incredible successes and we see the incredible failures. In order to improve the care of all kids, we need to try to better understand what contributed to those successes and what contributed to those failures.
I have a special place in my heart for all those kids struggling with rare diseases. We've recently published on osteogenesis imperfecta and myelomeningocele and I'm currently working on a study on neurofibromatosis. But these kids with rare bone and soft tissue disorders are some of the bravest, most amazing kids I've ever met. Anything that I can do to help to lift them up and make their lives a little bit better is worth it to me.