MJM MedTalks
MJM MedTalks (S02E02): To Boldly Exercise, Where No One’s Exercised Before


Khiran Arumugam1, Leigh Gabel2, Katherine Lan1, Renée-Claude Bider1, Masha (Maryia) Samuel1, Meryem K. Talbo1, Predrag Jovanovic1, Esther SH Kang1, Samy Amghar1, Vanessa Ross1, Carolyne Schumacher1, Jan Pack1, Susan Joanne Wang1 for the McGill Journal of Medicine
Published online: August 14, 2023

1McGill University
2University of Calgary


McGill Journal of Medicine (MJM) MedTalks is a Podcast series where members of the medical and health science communities from McGill and beyond are interviewed on topics related to career, research, advocacy and more. The aim of MedTalks is to open a space where experienced professionals and researchers can share information and advice for trainees in healthcare and medical sciences. In this episode, McGill MSc Candidate and MJM Podcast member, Khiran Arumugan, interviews guest-expert Dr. Leigh Gabel,assistant professor at the Faculty of Kinesiology at the University of Calgary and a member of the McCaig Institute for Bone and Joint Health, on her research on musculoskeletal health in space. This conversation covers bone and musculoskeletal health, imaging tools and biomarkers used to evaluate bone health, the TBone study and some its results, Dr Gabel’s path to academia and some advice for trainees. The show notes include a glossary of terms, links to publications referenced in the episode, and a full transcript of Khiran Arumugam’s conversation with Dr. Gabel.


Content overview


Links and papers

Some relevant articles referenced in this episode:

Additional articles referenced physical activity & imaging techniques specific to bone health:

Dr. Gabel's Links:


0:05 Khiran Arumugam (KA): Hello everyone. Thank you for joining us on another MJM podcast episode. McGill Journal of Medicine MJM MedTalks is a podcast series, where members of the Faculty of Medicine and Health Sciences at different universities are interviewed on topics related to career, research, advocacy and more. The aim of MedTalks is to open a space where faculty members can share information and advice for trainees in healthcare and medical sciences. My name is Khiran Arumugam, a McGill MSC candidate in Experimental Medicine and in this episode as one of MJM podcast team members, I will be interviewing Doctor Leigh Gabel about her countless areas of research focusing on the significance of physical activity and exercise on musculoskeletal health using advanced medical imaging tools such as HRPQ-CT, PQ-CT, DEXA, and more.

0:57: Doctor Gabel is an Assistant Professor from the Faculty of Kinesiology at the University of Calgary and a member of the McCaig Institute for Bone and Joint Health. In fact, she completed her Postdoctoral Fellowship and began her academic appointment in Kinesiology in 2021. She leads her research team through her groundbreaking works on how loading through physical activity and exercise influences bone development and bone adaptation throughout critical stages in life. With over 40 publications, she has made significant strides with her earlier work in the growth and maturation of the musculoskeletal system during childhood and adolescence. And now, following the completion of her PhD at the University of British Columbia and her Post-doc at the University of Calgary, she's actively investigating the influence of spaceflight on the bone health of astronauts. Thank you so much Doctor Gabel, for being here today with us. On top of enjoying the adventure and beauty of the mountain ranges which are within easy reach for you, you have also now become an independent researcher contributing to the advancement of space explorations by connecting something as fragile as the human skeleton with the vast unknown that is space.

2:08: This interview will potentially cover concepts such as bone and musculoskeletal health, bone mineral density, microgravity, spaceflight, physical activity, and so much more. Today's conversation is divided into three parts. First, we have questions regarding the association between bone health, physical activity, and medical imaging. Second, questions focusing on the specific objectives in Doctor Gabel’s TBone research study, and third, general advice for medical research students. The show notes include a transcript of the podcast, a more detailed content overview, a glossary of important terms and resources, as well as references. So once again, thank you so much, Doctor Gabel, for being here today.

2:52 Dr. Leigh Gabel (LG): Thanks for having me. Happy to be here.

2:57 KA: With the rise of physical activity as a component of multi-modal treatment options in primary care practice, improving patient health outcomes, can you briefly explain, in your perspective, the relationship and significance of physical activity in bone health? That is, how does regular exercises such as weight bearing resistance training relative to sedentary behavior, impact bone strength and density, as well as the overall architecture of bone?

3:26 LG: Yeah, absolutely. So, I study physical activity and exercise in relation to bone health and I think the first bit is just to recognize that, you know, bone is a living tissue and it's constantly adapting to the mechanical forces that it experiences. So, contrary to that white inert skeleton, you might think of on, on Halloween sort of as bone, our bone, it's living tissue; it's innervated, lots of blood flow, highly metabolic and it's always sensing changes in your loading environment. So, what bone cells really care about is changes in loading. So anytime they experience increases in loading that actually gives them the signal to add more bone, so that's how bones adapt by by experiencing, by sensing that increase in loading, so we know that kids who are more active tend to have larger bones, so greater bone geometry, cross-sectional area, more dense bones and and stronger bones, and the physical activity benefits that bone experiences during childhood, we do know that it persists across the lifespan as well. So we can look at some really neat studies in athletes where we can see that training that was done in childhood and adolescence actually persists all the way through until older adulthood.

4:59 KA: In many of your studies, when you look at the impact of physical activity on bone health outcomes, they are all usually assessed using different medical imaging tools such as quantitative computed tomography, so Q-CT, high resolution peripheral Q-CT, as well as the dual energy X-ray absorptiometry which is DEXA. So, could you explain how these tools are critical in evaluating growth related adaptations of different bone parameters?

5:27 LG: Yeah, absolutely. I think probably the technology that most would be familiar with, would be dual energy X-ray absorptiometry or DEXA. That's what's commonly used in body composition studies. So, DEXA is used to get a full body scan. You can get parameters such as lean mass, fat mass, and we also derive bone mass and aerial bone mineral density from it. And this is also the type of scanning that's done in older adulthood to diagnose osteoporosis. So, it really is the clinical gold standard. However, there are some limitations and the major one is that it is a planar instrument, meaning it can’t assess bone in three dimensions, and so it has some limitations, particularly during growth and development, where, a longer bone will artificially be assumed to have a greater bone mineral density because this instrument can't account for the depth of the bone.

6:26 So, some of newer technologies, so quantitative computed tomography, it, these are technologies that can assess bone in three dimensions, and your bone certainly is three dimensions. So from these instruments we get estimates of bone geometry, strength and we can get true volumetric bone mineral density. So, in a lot of our work, we use peripheral Q-CT, so these are devices that scan the peripheral skeleton. So, we're not scanning the total body with these devices, but we're usually scanning an ankle, or a wrist and we use, primarily right now, high resolution Peak Q-CT. And this technology lets us see details in the bone as fine as that of a human hair. So, on the resolution of about 60 microns, which is pretty fine. So, we can see the intricate details within both your trabecular bone compartment, some would be more familiar with that is like, the spongy cancellous bones at the ends of long bones. As well, we get really interesting details about the cortical compartment.

7:35 Some really great technologies in the last couple of decades, and I think also important is that, there, these scans are fairly quick. They take a couple of minutes and the radiation dose is quite small. So it is safe for use in kids and in adults.


7:54 KA: So you have recently completed a study that evaluates the influence of microgravity on astronauts' bone loss during spaceflight. Could you just briefly describe the TBone study that you've completed at the University of Calgary, which was actually funded by the Canadian Space Agency?

8:13 LG: Yeah, absolutely. So, the TBone study again is a Canadian Space Agency funded study. The principal investigator is Doctor Steven Boyd at the University of Calgary. I was fortunate enough to come on as a Postdoctoral Fellow to work on this study and continue to be involved. But in brief, we know that bone loss is a consequence of long duration space flight, but we're really interested in understanding what's happening to the bone microarchitecture and wanting to know whether bone can actually recover after returning to Earth. So, the TBone study is unique in that it images, we image astronauts before going into space. We have one of our high resolution PQ-CT scanners down at Johnson NASA Space Center. So before they go to flight, we'll collect scans of the ankle and the wrist and then once they come back immediately upon return, we collect scans as well, so we can look at how much bone was lost, and then we followed astronauts out at six months of recovery and at 12 months of recovery, so that we were able to understand whether or not astronauts could actually recover the bone that they had lost.

9:24 KA: That’s amazing. And what is interesting about your work as well, is its implications for the bone health of earthbound humans. And I mean, not everyone is an astronaut or lives in space. But however, many of them are not aware that space flight can actually be observed as an analog to understanding bone loss that people can typically experience from just a typical injury, disuse, or even aging. So, physiologically, how exactly does microgravity relate to bone metabolism and induces a rapid rate of bone loss relative to an individual's bone loss due to a normal physiological response such as aging?

10:02 LG: Yeah, that's a great question. So, microgravity is such a potent stimulus for bone loss because the body is not being loaded. We're getting that loading we might get at home if we were just lying in bed or or sitting on the couch. So, you really are spending almost 24 hours a day unloaded. So that's why we see so much bone loss. And if we put it into perspective of human aging, roughly the amount of bone that an average astronaut loses over six months would be comparable to what they might lose over one to two decades during aging and older adulthood. So, it is quite a stark loss. We did find in the recovery bit, some of that is recovered, about half of that is recovered. But most of the astronauts had some incomplete bone recovery, so they weren't able to recover back to baseline.

10:56 KA: OK, interesting. And that was actually one of my questions is basically, whether during space flight, how much of it of the bone architecture, could be recovered because upon the return, and or whether or not it's a permanent altering of the bone architecture. And I don't know if there's a lot of evidence out there that talks about bone reforming after bone loss and it's fully recovering its original architecture and strength.

11:21 LG: Yeah. And, you know, there are very few conditions on Earth where we lose bone, a lot of bone and then recover it. Probably the one that comes to mind would be during pregnancy and breastfeeding. We know that that's associated with a lot of bone loss but doesn't necessarily put people at greater risk of fracture. So, there is some recovery happening after weaning. But what's interesting about what we're looking at at the microarchitecture level, is that you can kind of think of your bone, an analogy would be a bit like the Eiffel Tower. So, if you think of a structure like the Eiffel Tower, with a whole bunch of rods and beams that are held together, that gives your bone its overall strength. During aging, it's natural that these rods and beams start to thin and they disconnect and become weaker. And that’s what we see happening, with a long time spent in microgravity in space. So once these rods, or the trabeculae disconnect and they're gone, you actually can't rebuild them. So, bone can only rebuild on the surface of existing bones. So, you might be able to thicken and strengthen the remaining trabeculae that you have, but for the most part, that overall bone structure will permanently change. And I mean these, the changes that we're seeing happen on a really small scale. It's really hard to pick apart these changes in the actual images. But yeah, over a grander scale, you could imagine them kind of disintegrating and collapsing. Yeah.

12:50 KA: Do you believe that there could be some form of plateau threshold or slower rate of bone loss or degradation the longer the duration of the space flight?

12:58 LG: Yeah. And that's what we're hoping, that's what NASA is hoping as well, that eventually you reach sort of a new steady state. So, we only followed astronauts out to one year after recovery. We know from studies and spinal cord injury patients that bone loss tends to plateau between about two or three years. So, we're assuming that a similar phenomenon might happen in astronauts. However, at the moment, the typical duration of space flight is about 6 months. In a new study that's getting started, called TBone II, it's a complement of other studies that NASA is about to launch. We will be following some crew members for up to a year in space. So that will give us a better understanding as to whether or not we see this, you know, continued decline or if we see a little bit of a plateau in bone loss and that's what everybody is hoping that we see.


14:04 KA: Normally well, to minimize the loss of weight bearing bones of astronauts in microgravity, in flight, countermeasures actually involve daily exercises using a treadmill, cycle ergometer, and the advanced resistance exercise device, ARED. Could you explain what exactly is ARED?

14:22 LG: Yeah, absolutely. And it, yeah, ARED is really important component to astronaut health while on the International Space Station. I'll start with just a brief history of exercise in space, so that you get a sense for what it looks like. Before humans were even sent into space, there were concerns about how microgravity would impact health. So, it's not a new concern. Russia launched the Mir space station in the mid to late 80s. They had a treadmill and a cycling [machine] on Mir. So they were, they were already sort of acknowledging the fact that, we should be exercising. We need some loading on the body. But those devices didn’t prevent bone loss. So, then this interim resistive exercise device was developed and it went up to the space station in 2000, and it let crew members load up to about 130 kilos. However, it was also found to be ineffective for preventing bone loss. So, this brings us to the ARED, the advanced resistive exercise device, which has been on the space station since 2008, and it actually provides almost twice the loading of that interim device. So, up to about 270 kilos of loading, which is quite a bit. It stimulates using free weights, but with a bar and cable exercise, and then that resistance force is generated via vacuum cylinders that contain pistons. So, it's that moving of the pistons within the vacuum cylinders that provide resistance. You can do a quick Google of “NASA exercise in space” if you want to see some of the crew members using this in action. But, typically astronauts would be doing deadlifts, squats, heel raises, bench presses, I mean, anything that you can perform in the gym, you'd be able to do it pretty much on ARED. And the astronauts all work with NASA's strength and conditioning specialist to provide them with a strength training regimen. So typically they're working out six to seven days of the week and they have dedicated time every day, not only for cardiovascular fitness - so on the cycle ergometer or treadmill - but also with ARED.

16:35 KA: And, now is there any difference between the preflight versus the inflight exercise programs? Do they change a lot or do they try to keep them consistent?

16:45 LG: Yeah, so all crew members are working with astronauts’ strength and conditioning specialists, particularly during the mission, like leading in the very short time and sort of leading up right before the mission, as well as once they return. However, we don't have really great records of what the astronauts are doing “before space flight” from “in space flight”. We get automatic records from the ARED device, the cycle ergometer, and the treadmill. So we have a really good picture of what we're doing, it's from that preflight phase, that right now, we're really limited to some self-reported questionnaire data that we've been looking at. But it's been interesting to see that at least in our work, what we have seen is that those who are most active prior to going into space, were actually unable to maintain that level of training in space flight and were then those the most at risk of losing bone.

17:47 KA: So, the astronauts who had increased their inflight resistance training volume compared to preflight were able to preserve some of their bone strength and trabecular bone in microgravity. However, the astronauts with higher strength training volumes prior to the space flight did not really increase their training volume inflight and experienced greater bone loss, and that's pretty much one of the huge key components of the findings of your study, as well.

18:11 LG: Yeah, and it was counterintuitive to what we were expecting to see. I was expecting to see, Ohh! You know - the people who were like really preparing and working out a lot prior to going to space, those were the ones who were going to preserve bone the most. But when you think about it from a bone cell’s perspective, all the bone cell cares about is that change in the loading environment. So, if you're heading into space, already, you're going to have that huge drop in weight bearing activity due to microgravity. But then, if you can't maintain a really high level of loading that maybe you were doing in the form of strength training or running or something else on Earth, then that's almost going to be a bit of a double whammy. So, the messaging is a little bit tricky because we don't want to, you know, put a across the message that exercise is going to be bad for you going to space, because certainly, you need to be strong enough to do everything on board the Space Station; you need to be able to prepare in case for our emergency situations; But, I think probably there needs to be a bit more consideration going into the, whether or not an individual is going to be able to maintain a certain level of of exercise training while on the Space Station, knowing that bone really only cares about that change in the loading environment.


19:37 KA: Could you elaborate on the outcome variables and the biochemical markers of bone turnover that were measured preflight and post-flight using some of the medical imaging tools and perhaps talk about the relationship between these markers and exercise with respect to the changes in the measured bone parameters.

19:55 LG: Yeah, absolutely. So, we collaborated with some of NASA's investigators to measure the biochemical markers of bone turnover. So, there are, there, which, there's quite a few of them. So there's a number of markers that you can assess. The two that are used most clinically or most clinically associated with osteoporosis or bone loss would be CTX - it is a measure of bone resorption, and P1NP – it’s a measure of bone formation. Now the neat thing about biomarkers is that, way before we can see changes in any mineralization in the bones through our Q-CT or DEXA techniques, we can detect increases in bone resorption with these markers of bone turnover just in the urine or in the blood.

20:47: So we get data preflight at several points during space flight, astronauts submit samples, and then we can look at the biomarkers after return to flight. And, you see these very stark increases, pretty much in all crew members, that as soon as you get into space, within a couple couple days even, you get rapid increases in bone resorption and decreases in bone formation. So, the interesting bit I guess coming out of the TBone study, is that we found that it was the preflight measure of bone resorption, so preflight CTX, which was most predictive of bone loss. So, if an astronaut went into space with greater bone resorption or a higher level of CTX, they were at greater risk of losing quite a bit of bone on the space station. And that was really interesting because, it was this preflight time point that matters, which means potentially we could identify these crew members ahead of time and say, hey, you know, this crew member might be at greater risk of bone loss, so maybe we should be thinking about some other countermeasures. But the sort of mechanism behind it, is we think, sort of, if somebody's already already has quite active bone resorption then, probably heading into microgravity is just going to exacerbate this.

22:15 KA: So, it's pretty much like the idea of having this preventive countermeasures by using bone resorption biomarkers to predict it all in advance.

22:25 LG: Absolutely. And really, I, acknowledging that there isn't sort of a blanket solution for everyone. I think we can relate to this within medicine here on Earth, as well, and looking at more personalized medicine, and NASA is really interested in that, as well. How can we tailor some of these countermeasures better to the actual crew members?

22:45 KA: According to the results, there were some changes to the level of the radius which were less pronounced relative to the changes at the level of the tibia. Now, could you explain why we noticed a lot of the few differences in those specific results.

22:59 LG: Absolutely. So, pretty much everything we saw in terms of bone loss was at the tibia. And that's because the tibia is weight bearing here on Earth. So going to microgravity, it experiences the greatest change in loading. The radius here on Earth, unless you're, you know, maybe a gymnast or some other sport, you're not using, you're not loading your arm all that much. And, so that change in loading environment wasn't as great for the radius. So that's, you know, one of the reasons why we hardly saw any changes at the radius. And then the other reason is really that, on the Space Station, your arms almost become what your legs were on Earth. So, the arms are used a lot for maneuvering around the Space Station. And if you look at any of those videos of crew members kind of, you know, floating through and almost like flying around, you'll see them using their arms to pull them around. So, we think that's probably a second reason as to why we don't see a lot of loss in that non-weight bearing limb.

24:03 KA: In your sample size, you have 14 male astronauts and three female astronauts. Knowing the physiological differences in bone metabolism between males and females, how would this impact the results when assessing the bone health outcomes or parameters in microgravity?

24:20 LG: Yeah, that's a really good question. And NASA is certainly interested in understanding sex differences in bone loss. And as you mentioned, we only had three females in this study. That wasn't because we only wanted three females in the study. It's sort of the nature of how spaceflight research works. You present the research study to all crew members and whomever wants to participate, can participate. So, this study was, it was started back in 2014. We had the first astronaut, or 2015. So you know, 7 to 8 years ago. And, at that time, there wasn't as great of parity between male and female astronauts as there is today. So in future, we would definitely hope to achieve sort of a better balance there, so we could actually look at sex differences. So, I don't have any sex differences, actually to report from the TBone study. But certainly, if we're thinking about female astronauts sort of over the lifespan, we know that at menopause, bone loss really ramps up, due to the decline in estrogen. So, I could only imagine that microgravity would probably exacerbate that. So, I would expect that we would see some sex differences in bone mass in microgravity were we to look at a sample of crew members who included those who were menopausal or postmenopausal. I can tell you just today I was on a call. We're trying to recruit for our TBone study too, and I see at least as many female astronauts as male astronauts, and that's really encouraging. And I think it's really important for girls and women also to see women in space, and it’s really inspiring for a whole lot of people.

26:07 KA: Following the findings of the TBone study, what are the next steps to mitigate bone atrophy in astronauts during long duration space flight expeditions like you mentioned, and even longer duration space expeditions, such as to go to Mars? So how does that translate into earthbound humans, as well?

26:23 LG: Right. Yeah. Those are all really good questions and going to Mars, it's going to be really challenging. One of, you know, there are a number of challenges. The nutrition part is going to be very challenging, a lot of medical challenges, but one of the pieces is that the spacecraft is going to be a lot smaller. So, ARED, that resistance training device that is so critical for helping to prevent bone loss, is not going to be able to fly on that, that shuttle or spaceship. So, right now people are trying to come up with different ways that we can load the bone, provide some resistance to the body, and I think that's going to be a real challenge, is, how do we prevent bone loss on even longer space missions. And then I think, probably we might see some pharmaceutical interventions, as well. There are osteoporosis medications that might be fairly good at preventing bone loss, at least in the short term. And I think we might start to see some of those studies being conducted in adults and younger adults and maybe even in astronauts at some point.

2741 And then how this will translate into earthbound humans? It's really anybody who is, as you mentioned before, experiencing bed rest due to a condition, immobilized for any period of time. You're going to also experience bone loss, maybe not to the same extent as astronauts, you know, heading out for many, many months or or even a year. But I think what we can learn from astronauts certainly applies to recovering from those conditions here on Earth.


28:24 KA: How did you find your way into academia?

28:27 LG: I would, I would say I sort of wandered my way into academia. I think I sort of decided that I might want to pursue being a professor during one of my last years of my undergrad, when I had a few really fantastic profs. I knew I wanted to teach. I've sort of been involved with instructing, coaching for a long time, so I knew that would be part of my path. So, I decided to pursue a Masters in Pediatric Exercise Science, because my background is in kinesiology and I love working with kids. And that's really when I found out that I also had this love for research and wanting to be able to pursue these research questions and the creativity that comes along with being able to, you know, ask questions and try and find out answers. And then from that point onward it was mostly just a mix of really good timing, hard work and chatting with the right people. And so, then I ended up doing a PhD at the University of British Columbia with Doctors Heather McKay and Heather MacDonald, studying bone health in children. And then as I was finishing up my PhD., I reached out to Doctor Steven Boyd and that's when he said “Ohh hey, I have a study that I'm working on with the Canadian Space Agency. Would you maybe be interested in coming on board?” And I kind of had to hold myself, to you know, shouting out, “Yes!”. And I said, well, I'll get back to you in a week or so. But it wasn't a very hard decision to decide that I would be heading to the University of Calgary to pursue that Postdoc. So, that's sort of my general pathway, along with some time off in between, and some working and travel plans as well, to kind of stay excited with research.

30:16 KA: What advice would you give to a student in healthcare who wants to devote their time towards advocating for important issues while balancing the demands of school and or work on the side? How would you suggest approaching one's work in such a way that it continues to excite them even after 10 plus years in the field?

30:36 LG: Yeah, I would say, it really matters that you're pursuing work that you're interested in. You know, as opposed to acquiring credentials, so to speak. I mean, there is a lot of, it's a time suck. Your grad school, you know, takes a lot of years out of your life. Med school as well. You know, you're devoting a lot of your life. So, you've got to be excited about it. I really think it comes down to working with the right people. So, finding colleagues you enjoy working with. Research is a lot more fun when it's sort of collaborating with others, as well. So, finding good people, recognizing that maybe there isn't this so-called work life balance. You're always going to be tipped to one side or the other and you just do your best that you can to manage it. But really finding something that you enjoy and then working alongside good people.

31:30 KA: Beautiful. And what advice would you offer students who want to pursue a career in research, whether it be to improve musculoskeletal health and overall well-being of individuals through physical activity or just advancing our current understanding of medicine, especially even space medicine?

31:49 LG: Yeah, I think probably you can't overemphasize how key networking is, you know, working hard pays off, but ultimately, often it comes down to timing and being in touch with the right people, who are doing neat things, at that time. So, taking advantage of all of those networking events, conferences, getting to chat with people, even if that puts you out of your comfort zone. And then I think, probably for the long haul, is having something else besides research or work in your life that keeps you excited. And so that work doesn't define your whole sense of yourself and to help keep you grounded.

32:34 KA: Well, everyone, that's all the time we have for today. Thank you so much, Doctor Gabel, for this profoundly engaging and thought-provoking discourse. I'll be putting the links to any relevant papers or projects we've discussed in the show notes, or even perhaps some of the links to ARED exercises we've mentioned, as well. And thank you to our audience for joining us on another episode of the McGill Journal of Medicine, the MedTalks series. This podcast is produced and edited by MJM Social Media team member, Khiran, with input from the entire MJM podcast team. Feel free to reach out to us on Twitter or Instagram @mcgilljmed or by e-mail. We would love to have your feedback and do not forget to join us again for our next episode.

33:18 LG: Thanks so much for having me. Take care.


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