Dr. Ron Falk and Dr. Maya Styner discuss Dr. Styner’s recent research in bone marrow fat. Topics of discussion include the importance of marrow fat, the effects of exercise on marrow fat, and the significance of Dr. Styner’s recent publication.
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-Maya Styner, MD
Falk: Hello, this is Ron Falk for the Department of Medicine at the University of North Carolina. Welcome to the Chair’s Corner.
Today I’m going to be talking with Dr. Maya Styner. Dr. Styner is an Assistant Professor in the Division of Endocrinology and Metabolism. She is an expert in the relationship of bone fat, or marrow fat, and bone health. It is this topic that she has published substantially on, and just recently had a study in the prestigious journal Endocrinology, for which her article was honored, by having the cover of that edition. Dr. Styner, welcome to the Chair’s Corner.
Styner: Thank you very much.
Falk: So you have spent much time now learning about marrow fat. Why does anyone want to care about marrow fat? I only care about fat around my midriff, I thought that’s where fat was important.
Styner: Yes, it’s an interesting field and really one in which we are only beginning to understand its true importance. I first came into thinking about marrow fat thinking about bone health and how to improve bone health. Osteoporosis, which is very wide spread, affects a lot of elderly individuals in our society and causes them to have failure of their bones and fractures. For this reason I started to become interested in how the bone cells are being formed, and it turns out that bone cells come from the same progenitor cell as fat cells do, and there is a very close relationship between bone and fat formation. That’s how I initially became interested in marrow fat was thinking about the bones, essentially.
Falk: So you’re trying to tell me that my bone cells- my osteoblasts, emanate from the same kind of cell that can become marrow fat? They’re related?
Styner: Yes, they’re very related. It’s fascinating, actually, because these cells can form a lot of different tissues. They can form fat, they can form bone, they can form muscle. There are a lot of different signals that help those cells decide which way to go: to make a bone, which we think of as being beneficial, or making fat, which we traditionally thought as being harmful. Now it’s really not so clear whether that fat in the marrow is harmful or whether it’s such a strict inverse relationship that if you had more fat you might have less bone. There might be situations in which that fat is actually helpful.
Falk: Describe marrow fat. How do you get to see marrow fat in the first place?
Styner: It turns out that when we are young we have very little marrow fat in our bones, and as we age, we progressively have more and more of the fat filling, that cavity, that yellow marrow that you can clearly see, when you eat chicken, and it’s very well known—orthopedic surgeons will tell you when they operate on elderly patients they see a ton of this stuff in the bones of an elderly person as opposed to a young person, which has very little of the marrow fat. But it’s basically interspersed inside of the bone with other components of the bone, with bone cells and blood-forming cells and lots of other bone components.
It was previously thought to be just a supportive function—the fat was just there. It might be there because the cells didn’t make bone, they made fat. Nobody really understands very clearly why those cells are there and if they affect the bone, or if they affect the blood forming cells as well.
Falk: So I should exercise. Is it aerobic exercise or is it weight-bearing exercise, or don’t you quite not know because it’s hard to get mice to lift weights?
Styner: Exactly. It’s very hard to tease apart, and that’s a question that we get a lot, especially in the exercise field. We work with what we can with the mice. The mice like to run, it’s a very easy exercise intervention, but we can’t really tease apart what component of that intervention is causing these changes in the bone and the fat within the bone. What we do know very clearly that several different types of exercise in humans have been shown to increase bone density. Weight bearing, as well as less so, non-weight bearing. Swimming, of course notorious for not doing much for bone health as opposed to running or walking, which very significantly increases bone density.
Falk: So if I want as a human based on an extrapolation of the studies that you have done in mice, I ought to be walking with some kind of weight on my arm or around my legs. Those people that walk with weights on them, maybe that’s a good thing.
Styner: Yes, I think that weight-bearing exercise has clearly been demonstrated to improve bone density in humans and in mice too.
Falk: So, wait a minute, I’ve been told that running’s bad for my knees. How do I reconcile those two things?
Styner: That’s very interesting and that’s related to joint health, which is I guess an altogether different topic. But clearly there might be a diminishing return, especially on the very vigorous running, when it comes to the health of the joints as opposed to the health of the bones. That individual that’s running a lot or is a marathoner might have amazing bone density because of the impact that those bones are seeing, but their joint health might be really poor, due to the negative effects of that on the joint.
Falk: You published a study in Endocrinology that actually was selected as the cover story with a pretty picture on the cover. That study describes exercise regulation of marrow fat in the setting of a drug commonly used in diabetic management. The PPAR gamma drugs, the glitazones of one kind or another. Can you briefly describe what you found and the significance of that observation?
Styner: In this particular study, we knew that this drug which had been used for a long time to treat diabetic patients and really significantly reduces blood sugar levels in diabetic patients. We knew that drug alters fat distribution in the body significantly. So it decreases fat in the areas around the abdominal which we all think is a good thing. It increases fat in some other locations, like under the skin, the subcutaneous fat, and also we’ve known that it increases marrow fat. It hasn’t previously been rigorously quantified, to what extent the marrow fat is increased, with this drug.
Our first aim was to look and see just how much is this drug increasing marrow fat. Then we wanted to know whether our exercise intervention could additionally increase this marrow fat, which is probably going to be much more increased by this drug intervention than it would be from something else, like a dietary intervention.
We were fascinated to see that the marrow fat was very highly increased with the drug, more than six-fold what it would be otherwise. The bones were chock-full of fat. We used an imaging technique in which we applied micro-CT imaging to look at the marrow fat with a special stain. This also allowed us to also get a very nice image, and this is probably why it made the cover, because the images were pretty dramatic, of the bones being so filled with fat. It really gives you an impression that this drug is very powerful in its redistribution of fat. What it does to the bone is pretty significant.
Then we were able to show that exercise was able to overcome the drug a little bit, not fully, but it was able to decrease the marrow fat even in the setting of taking this powerful drug.
Falk: So these studies have been done in mice, in order to extrapolate these findings in humans you would have to show at least, to a certain extent, the same observation occurred in patients on these drugs.
Styner: Human studies have shown an increased fracture risk of these drugs, so we know and we’ve known for a long time that these drugs are affecting bone health. Also, there are some MRI studies that have been done in humans but not large-scale studies to show that there’s an increase in fat in humans. I think that our data in mice makes sense, looking at the human studies, but it would take a very large-scale trial to really confirm our results in humans.
Falk: As a patient, should I be worried about taking a glitazone based on these findings, or just encourage myself to exercise?
Styner: The glitazones as a class have fallen out of favor for other reasons, not really for bone reasons because of effects on the heart, so we are tending to reach for them less and less as diabetes doctors and tending to look for other agents to treat, especially Type 2 diabetes. Even though they still remain pretty powerful, and there are some patients who really need them. And yes, I would be very concerned in my patients who are older women, I am very cautious about glitazones. If they’re on glitazones, I have a discussion with them about bone health. It’s absolutely something to think about.
Exercise is always a great way to treat, or to supplement treatment for bone health and for diabetes, so I continue to encourage all of my patients to engage in exercise in various forms.
Falk: What future studies are you contemplating? What’s next?
Styner: We have one major study looking at obesity and bone health in mice right now and it’s a long-term study. We’re feeding the mice a high-fat diet and looking at the effects of fat in the marrow on the bone, in a more detailed fashion so that we would be able to determine the true effects of having increased volume of marrow fat on the bone in the setting of obesity. Everybody is interested in answering these questions more precisely about-is obesity bad for bone or good for bone? We as endocrinologists have quite a vigorous debate on that right now.
A second line of work that we’re doing right now has to do with muscle fat, and we do think there’s a relationship between the fat in the muscle and the fat in the bone, especially in the setting of exercise, that’s another area of interest for me right now. It turns out that athletes have increased fat in the muscle, which we think is beneficial for them in terms of supplying the muscle with required energy that it needs. I’m interested in looking at the relationship between the muscle and the bone fat in the setting of exercise.
Falk: Fascinating studies. A whole interrelationship between marrow fat, exercise, obesity, and drugs. Dr. Styner, thank you so much for spending time with me today and telling me about your fascinating work.
Styner: Thank you.
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