Latest / 'Bone Up' / BoneUP Live 2025 @ECTS - Part 4

Transcript

BoneUP Live 2025 @ECTS - Part 4 · 'Bone Up'

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Hello and welcome to Bone Up, the podcast all
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about bones, how we make them, why we break them
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and if we fully understand them. I'm David Armstrong.
0:11
Hi and I'm Richie Abel and over this series we're
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going to be exploring osteoporosis, bones, what
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we know and what we're yet to discover and we
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hope you will join us on the journey. So for
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anyone keen to learn more about our infrastructure
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of calcified collagen, this is... Bone up. Welcome.
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to the fourth and final installment of our Bone
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Up Live recording at the ECTS conference in Innsbruck
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in Austria. We hope you enjoy the recordings.
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Listeners, we're really happy to bring our next
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guest to you, Dr. Sinja Goldberg, who's a postdoctoral
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researcher in the Department of Clinical Research
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at the University of Southern Denmark. Welcome.
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Thank you. Thanks for having me here. Thank you
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for making the time. It's getting late in the
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day and everyone's a bit tired, so it's great
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that we're still here talking about bones. So
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we met a little while ago at the Danish Bone
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Workshop in southern Denmark. Yes. And it was
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an absolutely fabulous conference, wonderful
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venue, people were amazing, such a welcoming
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atmosphere. And I was absolutely blown away by
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the research at the conference. Absolutely amazing.
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So we've managed to pick up a few people at that
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conference for interviews. One of the things
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that I kind of came across for the first time
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in the conference was something called spatial
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transcriptomics, which seems to be a really big
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and emerging technique in bone science at the
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minute. Would you be able to tell our listeners
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a little bit about it? Absolutely. So yeah, this
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spatial transcriptomics is about... knowing more
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than we already know like it's it's never enough
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we want to do more we want to do it also even
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more fancy so for many years it has been possible
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to actually like take some tissue you can mash
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it and then you can extract whatever component
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you'd like you could have the mrna you could
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have the proteins you could take you could take
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cytokines from the serum so But when we do all
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of this, we would kind of like mass the tissue,
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so we would lose all of their structural orientation.
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We wouldn't see who the cells were sitting next
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to. We wouldn't see how the cells were located
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compared to each other. So we would be able to
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split all of these different cell populations
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without actually knowing where they were located.
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So it's always been like a multi -step process
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to first doing this massed. a bunch of things
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all together and then trying some histology where
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we stay in for one two three factors and say
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oh we see this factor in these cells they are
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sitting right here but we would never really
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know whether all of the genes we see all of the
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proteins we see are in that exact same cell or
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whether we have like parts of the cells that
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are different or that are clustering at some
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place especially within the cancer it's very
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interesting to see what's actually sitting next
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to the cancer cells because we have all of this
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tissue that's surrounding the cancer cells and
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we're talking a lot about that these cells are
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actually helping the cancer or at least parts
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of them are, and we don't really know which ones
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these are. And if we identify a signaling molecule,
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maybe it's not even important if the signal can't
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travel all the way to the recipient cell. There's
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a tendency to sort of destroy the tissue as you're
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examining it up until now, so you're not quite
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sure where it all sat before you took it apart.
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Exactly. So tell us what you've been doing then.
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Well, we have just, in my department at the molecular
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bone histology team, we have just... we were
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so lucky that we got in a nice funding to buy
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some of this fancy new equipment and like when
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i did my phd i think we're almost five years
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ago now we were we heard about this spatial transcriptomics
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it was new it was fancy and it's very hard to
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do so kind of been following it and now all of
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the companies come in and you can buy like a
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machine that's actually doing much of the work
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so we got two of these machines and we've been
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testing them and making them run. One of the
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challenges in bone is that bone is hard to work
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with because it falls off these glasses we have.
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So there's a lot of optimizing. We can see nice
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results from spleen and brain and all these other
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fields of research, but the bone has been hard
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to get. But now the results are actually starting
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to come. People manage to do it right now. So
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what kind of experiments are people doing using
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the facial transcriptomics with bone? So there's
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a lot of things about this fracture healing.
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So trying to track what's happening after a fracture
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and which cells are coming in and which signals
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are appearing, that's what we see pretty much.
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We also see bone metastases from the cancer research
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because people get their biopsy taken because
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otherwise bone research is kind of limited in
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where we can get the bones from. Often you don't
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give a bone sample for research because it hurts
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a bit. And if you're just healthy, not everyone
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is willing to do that. But in these diseases
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where you have a bone biopsy taken as part of
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the diagnosis, that's also where we have things
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available. Otherwise, it would be my studies
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with the fractures or also with cancers. And
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we've already heard a couple of times at this
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conference how sometimes... mice data and human
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data doesn't quite match up. One of the other
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things that really blew me away at the Danish
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Bone Workshop was bone reversal cells. Until
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that point, I hadn't heard anything about it.
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And I feel this is like an enormous discovery.
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Could you tell us a little bit about that? Absolutely.
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So reversal cells were kind of... What I've been
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working on throughout my whole PhD. We have during
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the bone remodeling. Bone remodeling is a process
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where old or damaged bone gets renewed. So every
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10th year we say that our skeleton has been completely
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renewed. Because when we walk, when we run, we
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constantly obtain these micro fractures. And
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to avoid that our skeleton becomes... becomes
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bad because of these small fractures, we have
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to remove them. So we actually have a natural
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process happening in our body where old bone
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is renewed and new will be formed. So actually,
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patients would often say bone resorption or bone
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degradation, that's a bad thing. But in the case
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of bone remodeling, it's not. Because we actually
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just remove something that's no longer sufficient
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and replace it with something new. And in a healthy
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person, this will be totally balanced. So you
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remove something, and then you replace with the
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exact same amount. And earlier it has been like
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we have the osteoclast, they come in, they remove
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the bone, and then magically we have the osteoblasts
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coming in afterwards and forming the bone. But
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when the histologist started looking at the bone
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samples, it appeared that bone resorption is
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quite short, and it actually takes a while until
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this bone -forming osteoblast comes in. So there
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must be some kind of an intermediate step. And
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they started looking into what's happening in
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between. They saw that after the osteoclasts
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have been removing the bone, they're kind of
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sloppy. They remove parts of the bone, but they're
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not leaving a nice surface. So these cells are...
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sitting around the osteoclast and they are kind
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of preparing the bone surface that's what we
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believe now at least these are the reversal cells
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so that the missing link they're a type of cell
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that comes in after the osteoclast is gone before
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the osteoblast arrives they sort of come in at
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night time and tidy the place up ready for the
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osteoblast that's right when they were when they
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were noticed in the beginning people thought
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they were actually just like young osteoclasts
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not not you're not able to resolve bone yet so
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because they took up some of the proteins that
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that's actually associated with osteoclasts but
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it later it was realized that they actually they
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do not produce this protein themselves so they
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are not osteoclasts they are actually young osteoblasts
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so they are the young bone forming cells that
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are not yet ready to form the bone and even though
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they're bone forming cells you were saying they
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actually remove debris or remove bone tissue
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so they're what they're masquerading as osteoclasts
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are they or are they they're able to do both
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presumably they can remove bone tissue and then
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later in their life they can build bone tissue
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yes it seems like that because if also if we
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go through the literature they have been described
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as having these catabolic um what's it called
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these catabolic capabilities they they they have
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some enzymes that's able to degrade bone So some
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papers are focusing on this catabolic activity
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and looking at them in that context. But at the
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same time, they have an osteoblastic signature.
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So they also have this bone forming signature.
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And where do they come from then? Maybe you don't
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know this. Where do they come from? Let's say,
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are they always there? Do they come from osteocytes?
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Are they hidden away somewhere? Where are they?
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It's a good question whether they come from the
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osteocytes, whether the osteocytes are actually,
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since the osteocytes are usually considered like
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the final differentiation, like the end of the
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road. Their osteoblasts have gone out to retirement
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homes, the osteocytes, so possibly they could
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renew themselves as new, young, reversal cells.
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Goodness, that is exciting, because that completely...
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turns in its head our whole understanding of
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how bone turnover works doesn't it exactly but
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most of them are probably coming from the blood
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as mesenchymal lineage mesenchymal stem cells
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are coming from the blood and so they're arriving
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they're just arriving new on the building site?
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We actually do have, even in this compact part
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of our bones, we do have a lot of blood vessels
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coming in. And we also see, if we look at that
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section, we see that when we have the active
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bone remodeling, we can always find a blood vessel.
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So most of them will come from the vasculature,
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from the blood, and kind of serve as a population
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of new cells. But whether the osteocytes can
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come back and become... osteoblastic or reversal
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cells is is one of the things that you use to
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study in this which would be amazing if they
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were sort of born again as reversal cells and
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yeah but it completely changed our thinking about
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things yeah because i don't think we know that
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when when you resolve when you remove this bone
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and then suddenly you meet an osteocyte i don't
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think we really know what's happening to this
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osteocyte but probably they they play an important
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role in actually signaling that it's sitting
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in old bone that the hey i'm This is bad bone.
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Can you please come and remove it? Yeah, yeah,
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yeah. There needs to be some... It's like if
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there's a damaged piece of road, an inspector
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needs to say, that piece of road's damaged, and
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we'll get then the workmen to come and dig a
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hole in the road and get other ones to... But
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you need that signal that the road's damaged
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and you need an inspector to come and look at
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it. So maybe this is what the reversal cells
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are involved in in some way. Maybe. I think...
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I would rather say probably the osteocytes are
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like... the ones telling, hey, we got a problem
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here, come fix me. They have like a lot of, what's
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it called? They have a lot of extensions. Yeah,
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dendritic processes and things. Just as you see
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in the brain cells, they have a lot of processes.
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And they connect with each other, but then they
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may convert themselves into reversal cells and
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go and start the job. They may be, or they may
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just be like adding some signals that will...
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that would recruit the reversal cells and so
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it's kind of important and we've always saw earlier
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we believe that bone was such a dead tissue nothing
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happens in the bone but yeah it's i start off
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a lot of consultations with patients by saying
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you probably think your bone's dead and then
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you've got to convince people that it's alive
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and we were talking to someone earlier richie
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about some of the films that you see you know
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the the films where you They're obviously sped
12:44
up, but you can see the osteoclast moving across
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the surface of the bone and resorbing a pit and
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moving on. And I think if I could show my patients
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that, they would see how alive the bone tissue
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is and how important it is to take your medication.
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Keep taking it because your tissues are alive.
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And remember to tell them that they are not the
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bad guys, these osteoclasts. They are important.
13:05
We need them. But most often we've also been
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considering that osteoporosis is when... the
13:12
bone resorption becomes too much. But actually
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it appears like it's rather the bone formation
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that becomes too slow. Yeah. And maybe the reversal
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cells are actually important in recruiting or
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maybe it's just the replenishment of new bone
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cells that's bad when we become older. And potentially
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a therapeutic target at some stage, I imagine.
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Yeah. We hope that we can find some signaling
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that these reversal cells are like when they
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are calling their friends and saying, hey. It's
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now come and filled the new world. Another classic
13:43
case of basic science leading to the identification
13:46
of physiological pathways that could be used
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as a treatment target. Yes. Xenia, you're an
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early career researcher, and yet you are already
13:55
rewriting the textbooks. How does that feel?
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I think it's kind of nice to see how things change.
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Now you just talked about these osteoclasts.
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move across the bone surface. I was told that
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the osteoclasts are just sitting there, resolving
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and then moving. And then all of these studies
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have been done. And now it's actually been accepted
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that, okay, maybe they do move. So it's a change.
14:24
It's a paradigm that's shifting. And the same
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with these reversal cells. It's also a paradigm.
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And it's so nice to be like in the middle of
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this and also experience going to my first meetings
14:34
that people were a bit like. Really? Are you
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sure? And I'm just like, yeah, not completely,
14:40
but we kind of have a better and better gut feeling
14:45
about it. I feel it's potentially one of the
14:48
most important discoveries in bone research for
14:51
a very long time since the recent discoveries
14:53
about osteoclasts fusing together and forming
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new cells. And when I got back from Denmark,
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I had a meeting with David and he told me he
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was going to go and give a lecture and he's going
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to talk about boner and modelling. And I was
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like, yeah, you're going to have to change it.
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That's true because I gave a lecture in Oxford
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earlier this month and I included the reversal
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cell in my diagram. But I hope no one would ask
15:16
me about it because I didn't really know that
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much about it. No one did ask me about it. So
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now I'm going to be an expert. Now you know.
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Now I know. So that's, yeah, that's great. The
15:26
really lovely thing about doing this podcast
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is we get to sit down with the people who've
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made the discoveries and hear straight from them
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how they did it and ask our own questions. And
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I really love it. yeah it's great in the in the
15:38
science world discovering a new cell is like
15:40
discovering a new species in the in the sort
15:43
of the bigger world so it's really exciting yeah
15:46
i think i think it's also a question about like
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discovering because it's it's always been there
15:51
we just really didn't know what it was we believed
15:54
then we believed it was this kind then we believed
15:56
this was this kind maybe it's just an intermediate
15:58
step on the way towards bone formation and it
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was the spatial transcriptomics technique that
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allowed you that it was a big step towards finding
16:07
this, wasn't it? Actually, we've seen it before.
16:09
So we just wanted to use the technique to look
16:13
into this because we haven't really found a marker
16:16
that would be able to show us this is the cell.
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So kind of like saying this is actually the one
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we're looking for. So we just want to see what
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else does it do. And we can actually see from
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the spatial transcriptomics that it has both
16:30
these anabolic and catabolic functions. You can
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see it in its natural environment where it actually
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is doing its job. Yes, we can see that it's making
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those genes or activating those genes that's
16:46
actually important for these functions. It's
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a really good example of very new technologies
16:52
in the right hands being very disruptive and
16:56
completely rewriting some of our understanding.
16:59
Disruptive in a good way. Yeah, yeah. Disrupting.
17:03
which was incomplete and replacing it with new
17:05
knowledge. The look on your face now is the look
17:10
that I had when I first heard about this as well.
17:12
It's amazing, isn't it? Great. It's absolutely
17:15
wonderful. Thank you so much for coming and telling
17:18
us about your work. It's really staggering. Thank
17:20
you for inviting me. It's been a pleasure. It's
17:22
a pleasure and thank you. Isn't it great? We're
17:24
also enthusiastic about Bones, even though most
17:26
of the rest of the conference have gone home
17:28
now. Everyone's tired. We're still talking about
17:30
Bones with enthusiasm. I don't get to tell friends
17:35
or family the same amount of details. You're
17:40
among friends now. Exactly. It's amazing. Thank
17:45
you very much indeed. It's been great speaking
17:46
to you. Thank you. Listeners, we're really excited
17:58
to interview our last guest for Bone Up Live
18:01
3 2025. It's a friend of the podcast, Kastya
18:05
Vaid. How are you doing? Oh, very well. I'm actually
18:08
honoured. I didn't realise it was the last one.
18:09
I don't know if that's a sign of respect or desperation.
18:13
Have I a filler or am I the cream on the top?
18:15
I'm not quite sure. As I think I said last time,
18:18
if we were a popular television quiz, you'd be
18:20
one of the team captains. Can I be Paul Merton?
18:23
Ian Hislop's a bit controversial. I think we
18:27
normally talk to you about your highlights in
18:29
the conference. and uh get some perspective for
18:32
you so i think it's good to put you at the end
18:34
of the episode because we're kind of like looking
18:36
back at what's happened what were your highlights
18:38
of the conference this year well i you asked
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me about this so i actually took some notes i
18:43
didn't forget anything so i think that what's
18:45
really surprised me is the breadth of science
18:47
and it's really shifted we've got everything
18:49
from the the zebrafish with jaw ache yeah which
18:54
doesn't influence how much it eats uh to um real
18:58
population and public health messaging in low
19:02
- and middle -income countries. And I've been
19:04
really happy to see the real multinational contributions,
19:09
not from the usual Australia and other countries,
19:13
but from China, from India, from Africa, and
19:16
really seeing the ECTS as becoming a global space
19:19
that's very friendly, encouraging, and hopefully
19:24
building the capacity in these... in these countries
19:27
where I think there was an amazing figure from
19:29
Celia where she compared population size and
19:34
then amount of research done. And you could just
19:37
see we need to develop a whole army of researchers
19:40
in these countries. And any way we can help coming
19:44
to the ECT and inspiring them or helping them
19:46
through ECTS would be brilliant. Yeah, that's
19:48
wonderful. I've been impressed by the generally
19:51
high standard of talks and science at this conference.
19:54
I think that's really blown me away is the quality
19:56
of the slides. The images, the diagrams on slides
20:00
are absolutely beautiful these days. I think
20:03
that's from the... I've seen a few AI -generated
20:06
images. I can just check, can you draw me an
20:08
image of a kidney and a bone talking to each
20:11
other? But I do agree. I think it's become much
20:14
more visual and less text -heavy. And people
20:18
are... preparing slides to communicate rather
20:21
than just show data. Yeah, it's a good thing,
20:24
isn't it? You know, the last thing you want is
20:25
someone to just put up a slide with a lot of
20:27
text and then just read the text out. I think
20:30
people are becoming better at communicating.
20:32
And, you know, that comes through. That's not
20:34
just a science thing. Obviously, as practicing
20:36
clinicians, communicating with the patient is
20:38
something we talk about again and again and again.
20:41
And we don't use images much to communicate with
20:44
patients. Maybe we should. Well, we once did
20:46
the draw your bone project. Yeah. So we got them
20:49
to draw your bone and we got them to draw a healthy
20:52
bone and then we got a patient to draw a bad
20:54
bone and then draw a line between them and put
20:57
a cross where they were. And we just basically
20:59
said, oh, no, they're always underestimating
21:02
how bad their bones were. We said, well, your
21:03
bones are really bad. And we drew the cross and
21:06
then it was like, what should we do about it?
21:08
But yeah, that's a really good idea. The first
21:10
time I ever met you was at the ROS con. conference
21:12
where you're on stage doing that and you've got
21:14
us all in the audience to draw a bone. That was
21:16
many years ago. Isn't it amazing how long we've
21:19
been doing this and we're still finding out new
21:22
things about osteoblasts and osteoclasts. It's
21:25
amazing and I think also the additional sort
21:30
of the breadth of bone so I mean we had a section
21:34
on something called CRMO, a very rare auto -inflammatory
21:37
disease. We had a section on mastocytosis sort
21:40
of very Very unusual cause of osteoporosis. We
21:44
had lots of kidney bone disease. It's a massive
21:47
problem with a section on osteogenesis imperfecta,
21:50
rare bone disease, with myeloma. We had other
21:52
rare bone disease. We had that new, not new,
21:56
but sort of update on the anti -FSH story. Yeah.
22:00
The sympathetic system as well. Also, the youngsters
22:07
presenting, they're small bits of research. Not
22:10
necessarily the blockbusters, but the small steps.
22:12
It's also very inspiring. Yeah, and if you were
22:14
here right at 8am on the first day, you got to
22:17
hear about the bone marrow adiposity and the
22:19
really interesting story about that as well.
22:23
Please, you picked up on Mane Zayed. We interviewed
22:25
him yesterday about the FSH and the FSH blocking
22:29
antibody. It's a really fascinating interview.
22:31
I hope you enjoyed it, listeners. Cass, as always,
22:35
one of the busiest humans on the planet. And
22:38
we saw your talk just now on improving FLS with
22:42
AI. And I thought it was really interesting because
22:45
we've seen a lot of people at recent conferences
22:47
talking about how they're using AI to try and
22:50
improve FRAX prediction. And I sort of feel,
22:53
is that kind of reinventing the wheel? Are there
22:56
some bigger things we could be doing with it?
22:58
And I think your project does exactly that. Thank
23:01
you, Rich. That's really kind of you. So basically
23:04
the premise of the project is that actually we
23:06
should find all the people who've already had
23:08
fractures, who've had a CT scan for another reason,
23:11
and are just sitting in our hospital systems.
23:13
And it really came from an observation that we
23:15
had hip fracture patients, and when we went to
23:18
look at them, we always look at their previous
23:19
imaging, and a lot of them had already had a
23:21
CT scan. And of those CT scans, a lot of them
23:24
had vertebral fractures. We've tried everything,
23:28
radiology, reporting, getting a nurse to look
23:30
at the CT scans. And then over the last, it must
23:33
be eight years now, we've built a sort of AI
23:35
program. And then we were very fortunate to be
23:38
funded by the NIHR to do an important grant,
23:41
which has just finished. And we sort of tested
23:43
it in the real world. So not in a lab where you've
23:46
got the person who invented how to score vertebral
23:49
fractures reading all the scans, but just give
23:51
it to a normal hospital. normal FLS and just
23:54
see what happens. And what we found, it works.
23:58
It does create challenges for an FLS. And it
24:01
raises the question, like you said, go back to
24:04
the basics. What's an FLS for? Prevent the most
24:07
fractures. And the way to prevent the most fractures,
24:09
you find the people at highest fracture risk.
24:11
And we've known from the beginning, vertebral
24:14
fractures are where it's at. So the AI gives
24:17
you a sort of very low, low intensity work. to
24:21
find thousands of patients with vertebral fractures.
24:23
And we've shown they live long enough, they have
24:26
low bone density, and the transformation now
24:30
is to move that for less is to be AI -enabled
24:32
so we can really find them. The thing I liked
24:35
about your story there was the beginning, how
24:36
you had the patients with hip fractures and you
24:39
were looking at their other images and seeing
24:41
what you could find. That kind of just thinking
24:43
about what you're doing while you're doing it
24:45
and taking your time over it. leading you to
24:48
that little discovery that then got you thinking
24:49
about, well, hang on a minute, I love that. Just
24:52
being switched on and thinking and applying critical
24:54
thinking as a doctor in your daily practice really
24:58
leads to great improvement of care. It does,
25:00
and I think that's a big challenge we have because
25:02
at the moment the healthcare system is all towards
25:04
productivity. And if we're pushed too hard, our
25:10
curiosity will suffer. So I tell the juniors,
25:13
stay curious. If something doesn't fit... Usually
25:16
it's nothing, but you need to show me it's nothing.
25:19
You know we're so interested in vertebral fractures
25:21
because from the data we've had in the past,
25:24
we know they're a very strong predictor of further
25:25
fracture, a very strong predictor of osteoporosis.
25:28
If there are vertebral fractures just being picked
25:31
up by AI, do we know for certain that those fractures
25:35
would be associated with the same bad outcome
25:37
as the ones that people have turned up with back
25:40
pain and had an x -ray of the lumbar spine? We
25:43
don't know for sure. There is some good work
25:45
from Denmark that's looked at that very question,
25:49
and they looked at AI -detected fractures, other
25:53
inpatients, and then the risk of another fracture.
25:56
And there it was a bit confusing. Just being
25:59
in hospital... makes you more likely to have
26:01
another fracture because you're ill. And they
26:03
couldn't really tell the difference. We've done
26:05
it slightly differently. We've looked at the
26:06
ones with a fracture, then we've done a bone
26:08
density, find the ones who are low bone density
26:10
and then treated them. I'm pretty confident on
26:13
basic principles that they will be a high risk
26:16
of fracture because they've got a vertebral fracture,
26:17
they've got low bone density. The big question
26:19
was, were there other risks of... disease so
26:23
bad that they wouldn't survive long enough. But
26:25
we know about 68 % survive at least two years.
26:28
You mean if you're having the CT because you've
26:30
got lung mets or renal failure or something then?
26:33
It's actually the pulmonary embolus. The CTPAs
26:36
are really... If you're a man and you have a
26:38
CTPA in a hospital, that wasn't a good thing.
26:40
But what we also found, it mattered which hospital
26:43
you were in. And to understand this, having a
26:45
CTPA increased mortality in some hospitals more
26:48
than other hospitals if you're a man. And that
26:51
means... that we can't have one rule for all
26:53
of them. It's either you have no rule and just
26:55
accept it, or you try and do hospital -specific
26:57
things. But it's such a quick thing that AI can
27:01
pick it up really quickly, and it took our nurse
27:03
about 30 seconds to check a scan. So it's a very
27:06
fast way to find vertebral fractures. Yeah, it
27:09
was an interesting presentation, certainly, and
27:11
well -received, I think. Where will you go next
27:13
with that work? Is there going to be any possibility
27:15
to expand it to other hospitals? Yes, so we are
27:18
writing the papers. So we have a paper on what
27:22
happens when you audit it, how do you implement
27:24
it. We've done one on information governance,
27:27
then we've done the health and cost effectiveness.
27:29
We'll then create a business pack that hospitals
27:31
can look at to see if I have this many CT scans,
27:36
this many CT scan patients, this is the expected
27:38
number of fractures I find. This is the impact
27:41
on the service, and this is the impact on the
27:44
patients and saved outcomes. And, Richie, because
27:47
they're vertebral fractures, you don't have to
27:50
treat that many to start preventing hip fractures.
27:52
If you have to pick one fracture that predicts
27:54
hip fracture and survives long enough, it's a
27:56
spine fracture. So the HealthEconom model is
27:58
actually really positive. So we will create a
28:00
pack for FLSs to enhance their services, and
28:04
hopefully that pack will then help the FLSs just
28:06
become more efficient. at finding high fractures
28:09
patients. But no, my journey only finishes when
28:12
every hospital has at least looked at whether
28:14
they need AI. And then we'll also create the
28:17
packages. So putting AI in is not a challenge.
28:21
It's just a stepwise process of ABC. We had to
28:25
create the ABC and hopefully we can make that
28:28
a lot easier. Amazing. We'll watch with keen
28:31
interest to see how you get on and I hope that
28:33
we get an update next year. Definitely, definitely.
28:36
Thank you for joining us. It's always a pleasure.
28:38
Not at all. Thanks a lot, guys. Keep up the good
28:40
work. I'll see you again soon. Thanks. Well,
28:47
listeners, David and I are sitting in the airport
28:49
waiting for our plane home. It's been a really
28:53
busy four days. I'm feeling quite tired now,
28:55
but it was definitely worth it. Yeah, we learned
28:58
a lot about bone, I think, when we come to these
29:00
conferences. and you always go home having learned
29:04
things but also with lots of questions lots of
29:06
ideas as well which is really encouraging and
29:08
again a really good mixture of of clinical talks
29:13
where we as a doctor you learn from other doctors
29:17
about how better to treat patients lots of interesting
29:20
science and new research and then lots of opportunities
29:23
for scientists and clinicians to sort of meet
29:25
together and talk about how we work better together
29:29
Yeah, it was fascinating this year. We learned
29:31
a lot. I felt the talks were very broad and encompassing
29:33
of the bone field. The plenary talks, invited
29:37
speakers gave really excellent talks. I think
29:40
my personal favourite was the talk about the
29:43
relationship between chronic kidney disease and
29:45
osteoporosis, explaining the relationship between
29:48
the pituitary gland, PTH and bone resorption
29:51
and all of the other impacts that it has on the
29:54
rest of the body. What was your favourite talk?
29:57
Yeah, I mean there's a number of things stood
29:59
out. I think right at the very start there were
30:01
some very interesting presentations on bone marrow
30:04
adiposity and the observation that increasing
30:08
bone marrow adiposity, in other words more fat
30:11
cells in your bone marrow, that's not good for
30:14
your bone. That's associated with osteoporosis.
30:16
But interestingly, both as overall body fat goes
30:21
up, adiposity in the bone marrow goes up. But
30:24
in patients with anorexia or patients who have
30:26
lost weight dramatically, even though they lose
30:29
fat elsewhere, adiposity in the bone marrow remains
30:32
or in fact goes up as well in those circumstances.
30:35
So there's something very interesting going on
30:37
there. And that has potential implications, and
30:40
of course implications potentially for developing
30:42
drugs as well. i think the other thing that stood
30:45
out for me was the presentation and i know we
30:48
actually spoke to him and you will have you will
30:50
have heard him talking to us folks um about his
30:54
work on fsh and i think as a clinician that's
30:58
one of those things over many years you measure
31:00
estrogen levels you measure fsh but really it
31:03
was only the estrogen levels we looked at and
31:05
associated with changes in bone the fact that
31:09
actually fsh may itself be associated with changes
31:12
in bone and could potentially be a target for
31:15
treatment and new drugs and and a very direct
31:19
and obvious target for new drugs and treatment
31:21
well that's that's quite exciting and it remains
31:23
to be seen just what comes from from that research.
31:27
Especially in the very early stages of bone loss.
31:30
It feels like it could be a very preventative
31:32
medication. Yeah. I agree. I thought the talks
31:36
around adiposity were really interesting as well.
31:40
And one thing I think is that really the science
31:44
seems to have leapt forward in the last year,
31:46
at last year's ECTS. I remember we spoke about
31:49
adiposity. We spoke to Jeroen Goertz. And we
31:53
learned about, you know, the distribution of
31:54
adiposity in bone, etc. It feels like in the
31:57
last year, that field has really moved forward
31:59
quite a lot. And now, just 12 months, people
32:02
are understanding a lot more about how changes
32:04
in overall body mass and weight relate to changes
32:08
in adiposity in the tissue and how changes in
32:11
adiposity in the tissue in the bones might affect
32:15
osteoporosis. There was always that interesting
32:18
observation, you know, in patients that if you
32:20
saw someone who was... very very light and very
32:23
frail and had a very low body weight low BMI
32:26
well that was associated with osteoporosis and
32:29
with bone weakness but the converse wasn't necessarily
32:32
true people who were very obese and very overweight
32:35
we've known for years that actually that can
32:37
drive osteoporosis as well so there's that interesting
32:39
sort of dichotomy and it may all be related to
32:42
bone marrow adiposity so lots more to to find
32:45
out there and I mean in in the sort of the clinical
32:49
world particularly We were talking or there were
32:52
presentations looking at denosumab, looking at
32:56
teriparatide, you know, the PTH analog, some
32:59
mention of abaloparatide as well, the new TTH
33:04
analog or PTH -related protein analog, and then
33:08
romosuzumab as well. And while I think in the
33:12
last few years people have been thinking in terms
33:15
of... comparing those different drugs to work
33:18
out which is better, to put it very simply like
33:21
that, I think people are slowly moving towards
33:23
the idea that it's actually the sequencing we
33:26
should be thinking about, because actually all
33:28
those drugs work well under certain circumstances
33:30
for certain patients. And the question we should
33:33
be asking is, which do I use first in my patient?
33:36
How long do I use it for? Which drug do I switch
33:39
it to? Do I switch the patient to? Which drug
33:42
do I use next? We were starting to see some discussion
33:45
of that, actually, sequencing as opposed to just
33:48
sort of head -to -head work. And again, I think
33:52
the emergence very much of the concept that we
33:54
have anti -resorptives, which are bisphosphonates
33:57
and denosumab, which reduce bone loss, that we
34:03
have osteoanabolic drugs, teriparatide and abaloparatide.
34:08
And actually, while aromasuzumab is generally
34:11
lumped in with the osteoanabolic drugs, in many
34:14
ways it's a third different type of, because
34:16
it acts on a different pathway, the WNT pathway.
34:20
It promotes bone growth and reduces bone loss
34:23
at the same time. And I think as other work is
34:26
done on that pathway, the WNT pathway, there's
34:29
potential for new drugs to come out targeting
34:32
that pathway. I think it will eventually be considered
34:34
that there are three pathways rather than just
34:37
two. I agree. I feel that maybe romisosomal is
34:41
better described as a bone -forming medicine.
34:44
As opposed to an anabolic medicine? Yeah, it's
34:46
different from the other osteoanabolics, which
34:50
activate PTH receptor. It obviously acts in a
34:53
different pathway, and therefore perhaps we should
34:55
sort of categorise it differently. One thing
34:58
that stood out for me that's quite exciting is
35:01
the possibility of combination drugs. In previous
35:04
conferences in the last few years, drug sequencing
35:07
has been a big topic, and now, as you mentioned,
35:09
all these drugs. They're available. You as a
35:12
doctor have got an opportunity potentially to
35:14
use them in different sequences for different
35:15
amounts of time to get the best outcomes for
35:18
your patients. This conference was the first
35:20
time I'd seen drugs used in combination at the
35:22
same time. And if you do have two or three different
35:25
types of drugs that act on different pathways,
35:28
then maybe by putting them in combination you
35:31
can get better outcomes. It reminds me of taking
35:33
paracetamol and ibuprofen at the same time to
35:36
get... double the pain killing. Yeah that's something
35:38
people have looked at a bit in years over the
35:40
last few years and it would seem obvious maybe
35:43
to give an osteoanabolic drug and an anti -resorptive
35:47
at the same time. Looking at experience across
35:51
many other diseases apart from bone disease as
35:55
you combine drugs to get greater efficacy you
35:58
also run greater risk of side effects of course
36:00
that's always the problem i think with combining
36:03
drugs but certainly it's something we'll be looking
36:06
at a lot more and yeah again another interesting
36:09
area of study and of course we heard about a
36:13
new cell as well it's not often that we hear
36:15
about a brand new a brand new cell in in sort
36:20
of basic biology so what did you make of that
36:22
the reversal cell i thought that was quite incredible
36:25
i thought it's a very good example of how a technological
36:28
leap forward allowed scientists to answer questions
36:33
that had remained unanswered for a really long
36:36
time. And the development of spatial transcriptomics
36:39
and the ability to conduct that in laboratories
36:42
which are associated with hospitals meant that
36:46
for the first time we could get human tissues
36:49
into the systems in large numbers for long periods
36:54
of time, and it allowed the scientists of southern
36:57
Denmark to... really look at that very intricate
37:01
process that takes place between osteocytes resorbing
37:04
bone and osteoblasts putting new bone back. I
37:08
think for a long time we hadn't really known
37:11
what was going on there, but because there wasn't
37:13
really any way of looking at it, we kind of just
37:15
sort of ignored it really. But as soon as the
37:18
technology became available, people got straight
37:20
on it to go back and solve that really interesting
37:22
problem. I wonder how much more we're going to
37:25
hear about bone reversal cells. in the next few
37:28
years as people start to think about what role
37:30
they might have in the etiology of osteoporosis,
37:33
pathophysiology of the disease, and whether or
37:37
not there are some people whose osteoporosis
37:39
might be treated by targeting the sequence of
37:42
events around a bone reversal cell. That's really
37:44
exciting. Yeah, and you heard it here first,
37:47
folks. So I suppose we're going to have to go
37:51
and get ready for our flight now, but we should
37:53
thank a few people before we go. We'd like to
37:55
give a big thank you to the whole... ECTS society
37:58
who supported us not just this year but in previous
38:01
years at the conference the past president Bo
38:03
Abrahamson the current president Peter Peachman
38:06
we should also give a shout out to the ECTS academy
38:09
they've been going for 10 years now they've been
38:11
incredibly supportive Jeroen Goertz who helped
38:13
us get going earlier and a really really big
38:16
shout out to Gonzalo Diffuse Gonzalo if you're
38:19
listening thank you so much for all the help
38:21
you've given us over the last few years finding
38:23
us good guests and we should also thank the IFMRS
38:26
as well they've they've been able to get some
38:27
really good guests for us. And I really enjoyed
38:30
their session on the digital twin. Thank you,
38:32
everyone. And thank you to our colleagues at
38:34
work and indeed our families at home who allow
38:36
us time to come to these conferences as well.
38:39
We've got to put that in, Richie. And thank you,
38:44
listeners, for joining us. We hope you had fun
38:48
listening to the podcast and that you learned
38:49
just as much as we did. And we'll see you soon
38:51
back at one of our conventional episodes. Bye
38:54
now.