Latest / 'Bone Up' / BoneUP Live @ECTS 2024 - Part 2

Transcript

BoneUP Live @ECTS 2024 - Part 2 · 'Bone Up'

0:00
Hello and welcome to another very special episode
0:03
of Bone Up, the podcast. Richie and I are still
0:07
in France at the ECTS Congress in Marseille and
0:12
we're going to bring you another selection of
0:15
interviews that we did with both senior and junior
0:19
researchers and all sorts of interesting people
0:21
here in France. Listen, as we've got some great
0:26
guests for you in the second episode, we spoke
0:29
to some more ECTS Academy members. We spoke to
0:32
the IFMRS about the work they're doing to bring
0:35
all of the societies around bone research together.
0:38
Big friend of the podcast, Cassia Vaid, and some
0:41
young prize winners from around the world. Enjoy.
0:44
So if you're interested to hear more about the
0:46
latest research on your infrastructure of calcified
0:50
collagen, this is Bone Up Live. So we're delighted
1:21
to have another prize winner with us. Oribe?
1:26
Yeah, very nice. I got it. We want to hear about
1:32
your research. I know it's to do with osteoclasts,
1:34
but you tell us a bit more about it. Yeah, so
1:37
I've been working on a funny gene. It's called
1:41
SLC37A2, so a bit of a mouthful. But we're looking
1:45
at what it's doing in osteoclast lysosomes and
1:50
how just this tiny little thing on this osteoclast
1:53
lysosome can actually regulate the function of
1:56
the cell and then the thickness of bones. And
1:59
we know that osteoclasts are the cells responsible
2:02
for essentially removing bone. And in most osteoporosis
2:09
that I would see at the clinic, it's excessive
2:12
bone loss is the problem, particularly after
2:14
the menopause. So you were looking at how that
2:16
cell works and how it's regulated. Yeah. So tell
2:20
us a little more. The lysosome you mentioned,
2:22
what's that in this cell? the trash can or the
2:30
bin of the cell. It's a little pocket of membrane
2:33
and inside this membrane is a bunch of enzymes
2:37
and a lot of acid. And the reason why it was
2:41
seen as the bin is because cells just send whatever
2:44
they don't want into there to get degraded. But
2:47
what we've learned with more modern techniques
2:50
in cell biology is that this little sack of enzymes
2:53
is doing a lot more for the cell than we previously
2:57
thought. And this is especially true for the
3:00
osteoclast. And you've been looking at a gene
3:03
that controls it? Yeah, yeah. So we've got this
3:07
SLC30. 3782 that we've worked on is like a little
3:11
gatekeeper on them that this little sack on the
3:15
membrane of the lysosome and what it's doing
3:18
it's regulating the exit of sugars from this
3:23
little bag and I don't know if you remember your
3:26
high school bio but the sugars are really important
3:31
in osmotic pressure And so when this protein
3:36
is on the surface and allowing these sugars to
3:40
come out, the osmotic pressure changes all of
3:43
a sudden. And rather than this little lysosome,
3:47
this little sack of membrane being really inflated
3:51
and having a lot of tension in its membrane,
3:55
just like a full balloon, it sort of softens.
3:59
and that allows then for other proteins to come
4:02
and then pull on it. And then we see what's happening
4:05
in these cells is we see a little tubulated lysozyme
4:09
starts to form. So rather than being a balloon
4:11
that's like a round one, you get the long ones.
4:14
It becomes the long sausage balloon. Is there
4:17
a difference in function between the balloon
4:19
and the sausage? Yeah, so... In other cell types,
4:24
it does different things. But in the osteoclast
4:27
specifically, and now I need to sort of talk
4:30
about the anatomy of the cell a little more.
4:32
That's what we're here for. So what the osteoclast
4:35
does, it kind of like sucks itself onto the bone.
4:39
And then it has to actually spit all these enzymes
4:43
and acid onto the bone. And that's where the
4:46
lysosome comes in. So in that region that's against
4:50
the bone, these lysosomes come in. and they fuse
4:53
with the membrane of the cell to release all
4:57
of this acid outside onto the bone. But what
5:00
this creates is a lot of membrane all of a sudden
5:03
that's all in one place, and then we call this
5:06
the ruffle border. And it does look like ruffles.
5:10
And you see this when you look at the cells in
5:13
bone, actually, with some microscopy. And because
5:17
this... This lysosome is now tubulated. What
5:22
it can do is it can infiltrate deep into this
5:26
set of membrane ruffles, and it can continue
5:30
to deliver the acid and the enzyme really close
5:32
to the bone rather than far away, and then it's
5:37
way more efficient. For the benefit of the tape,
5:39
Richie and David are staring in wonderment at
5:41
this. So I've heard about the ruffled border
5:44
so much in the past when I learned about my cell
5:46
biology, but I didn't really understand this
5:49
complex mechanism that led to the formation of
5:52
it and then the release of the acids and enzymes.
5:55
Yeah, it's really crucial for the osteoclast
5:58
function. So depending on whether you have a
6:01
balloon or a sausage. for the lysosome does that
6:05
change the way that the ruffled border forms
6:07
or the way in which the acid and the enzymes
6:10
are spat out yeah yeah exactly so when we've
6:14
got this slc on the lysosome this little gatekeeper
6:18
we get this tubulation and then the lysosomes
6:23
that are all tubulated like the sausage balloons
6:25
they can go deep into this they can deliver all
6:28
they need and then you get this really nice mature
6:31
ruffle border and then the bone gets resolved
6:33
really well but what we have in our knockout
6:37
cells so this is where the gate has been removed
6:39
and there's no possibility for the balloon or
6:44
the lysosome to go from a normal balloon shape
6:46
into an elongated shape And you can imagine that
6:50
trying to get this big vacuole to come fuse with
6:55
this really delicate and ruffled membrane is
6:59
going to be much harder. And also moving it through
7:02
the cell is going to be harder rather than moving
7:05
some, you know, very precise, thin little tubule.
7:11
So in terms of then to come back to the clinic
7:14
and osteoporosis, I suppose we sometimes imagine.
7:17
There's just more osteoclasts or they're working
7:19
harder in osteoporosis. So it may be that you
7:22
could different qualities of osteoclasts. Some
7:25
are really good at resorbing bones. Some don't
7:27
resorb bone. Maybe I'm simplifying things a bit,
7:31
but sort of where you're in that area that the
7:33
control of the lysosome might affect how. how
7:37
well the osteoclast works to resolve bone? Yeah,
7:41
so that's true to some point with osteoporosis,
7:45
but it's even more true with the opposing disease.
7:48
So there's another disease, and the technical
7:53
term is sclerosing bone disorder or osteopetrosis.
8:00
I kind of like the more friendly term of stone
8:03
bone disease. Stone bone, yeah, we hear, we've
8:06
mentioned a few bone thickening diseases before.
8:09
Yeah, and this is really generally because of
8:14
osteoclast lysosomes not working properly. So
8:17
now then, you think you may have a potential
8:20
target? Yeah, that's the hope, is that it can,
8:24
you know, in 15 years' time become some new drug.
8:28
We still have a lot of checks and balances to
8:31
go through, but we think it may well be a powerful
8:36
target. And even more so because in this mouse
8:40
that we've taken the gene out, we've got reduced
8:44
osteoclast activity, but we also have increased
8:48
osteoblast activity. So it would actually, if
8:53
it turns out, this would be a dream, but if it
8:56
turns out to be something that we can use in
9:00
patients, we could prevent osteoclast function
9:03
and resorption and we can actually increase osteoblasts.
9:07
So it would be like a dual action type of system.
9:11
That's very exciting. I'm going to say it again,
9:13
you heard it here first on the Bone Up podcast.
9:17
Thank you, Amy, for joining us today. That was
9:18
absolutely fabulous. So well explained. Thank
9:21
you. Thanks. Yeah, it was really good fun. Thank
9:23
you. We're very excited to have our next guest,
9:27
Jack de la Villa. Welcome to the show. Thank
9:29
you. Thanks for having me. Where did you come
9:31
from, Jack? Where have you flown in from? From
9:34
Perth, so quite a journey. How long was your
9:38
flight? I spent about 27 hours, I think, in transit
9:41
on the way. It's great. Even though this is the
9:43
European Congress, it's great to see people from
9:46
right across the world here all talking about
9:47
bone. It's great. And this gives us the opportunity
9:51
to talk to you about your prize. Congratulations.
9:53
Thank you. You won the clinical prize for the
9:56
best paper. And that is a hard prize to get.
9:59
There's some good clinical research here. Yeah,
10:01
thank you very much. Have you told your lab back
10:04
home about it? Yes, a few of them are here, fortunately
10:07
enough, so yeah. Oh, fantastic. So would you
10:10
tell us about the research then that you won
10:11
the prize for? Yeah, so what we looked into was
10:15
something called abdominal aortic calcification,
10:18
which is sort of a measure of calcified walls
10:21
of the artery that runs sort of in the abdominal
10:24
in front of the lumbar spine. So we've shown
10:27
that previously that this is associated with
10:30
all sorts of negative health outcomes relating
10:32
to cardiovascular disease, cognition, musculoskeletal
10:35
health. But one of the key limitations to actually
10:38
using this in practice is how long it takes for...
10:42
to actually be assessed from images. So what
10:46
this paper did and what our team have developed
10:48
is a machine learning algorithm to automatically
10:51
score AAC from DEXA lateral spine images. And
10:56
we showed that these automatic scores were associated
11:00
with fall and fracture risk in a cohort of older
11:03
Australian women living in the community. So
11:07
I guess implications of this work is that we
11:10
see that... this algorithm could be incorporated
11:14
into routine clinical practice. So for any woman
11:17
that has a bone density test and has a lateral
11:20
spine scan, we can automatically assess their
11:23
AAC immediately and rapidly, and then that can
11:28
provide really important prognostic information
11:30
to their clinician and sort of identify those
11:33
at the greatest risk. And is that a software
11:37
program initially that you're using? Yeah, so
11:41
we developed the machine learning algorithm or
11:43
our computer science colleagues we worked with
11:45
using images from a cohort that they then sort
11:50
of developed and trained the algorithm that ultimately
11:54
we see being sort of incorporated into DEXA software
11:58
for clinicians to be able to use. But we've got
12:01
the algorithm to use on cohort data at the moment.
12:05
I know all the radiographers listening will be
12:07
shouting at the computer, ask them about the
12:11
effect on DEXA scanning, because one of the things
12:15
when, as a clinician, when we see a calcified
12:18
aorta, it sort of ruins the quality of the DEXA
12:21
scanning to some extent, because all that calcium
12:24
absorbs radiation, and what happens is we do
12:27
a DEXA expecting to find low bone density at
12:29
the spine, and the result comes back showing
12:31
quite good bone density, but we know it's not
12:33
a proper result. is there any way in which you
12:36
could somehow extract from the DEXA result the
12:41
fact that there's calcium in the aorta? Could
12:45
you use your software to do that? Could you sort
12:47
of clean up the DEXA for us? Possibly. Yeah,
12:51
it's a really good question, an important issue
12:52
that we can speak to our computer science colleagues
12:56
about maybe applying the machine learning sort
12:59
of approach to that problem. You heard it here
13:01
first, folks. Research live on bone up. What
13:05
are the challenges do you think about taking
13:07
this technology now into clinical practice and
13:09
applying it to a lot of people? Yeah, so one
13:12
of the key things that we're working on at the
13:13
moment is verifying the performance of the algorithm
13:16
in independent cohorts, so not the same cohort
13:19
that it was sort of trained and tested on. And
13:21
we're using the cohort in Manitoba with Professor
13:25
Bill Leslie to verify that, and that sort of
13:28
work is underway. So that's being presented here
13:30
at ACTS, and there's a paper under review at
13:33
the moment, or yeah, just recently accepted in
13:35
JBMR. sort of verifying the algorithm works in
13:38
an independent cohort, which is a really important
13:40
step before it's then put into clinical practice.
13:43
It's really nice to see prize -winning research
13:45
that really feels like it's going to impact patients'
13:48
lives and quite quickly. It seems like a really
13:51
wonderful use of AI in healthcare. It's a really
13:54
good example. You're impacting patients' lives
13:57
in other ways, I think, because you've broader
13:59
interests. Tell us a little about the prostate
14:01
cancer work you've been doing as well. Yeah,
14:04
so my background's in exercise science, and my
14:07
PhD was in men with prostate cancer. So we looked
14:10
at men on androgen deprivation, so who have...
14:15
basically reduce testosterone. So that comes
14:19
with a whole range of side effects impacting
14:21
musculoskeletal health. So they lose bone really
14:24
quickly and muscle really quickly as well. So
14:28
we looked at an exercise training intervention
14:29
to try and offset that bone loss. So we randomised
14:35
men to receive a 12 -month exercise training
14:37
program as well as protein, calcium and vitamin
14:40
D supplementation and compared that to usual
14:43
care. and then we measured DEXA and PQCT outcomes
14:48
over the course of that 12 months. And does that
14:51
exercise program start before the man starts
14:54
the testosterone -lowering treatment, or does
14:58
it wait until after that's happened? Yeah, so
15:01
ideally, yes, they would start sort of as soon
15:03
as possible with, obviously it's quite a niche
15:06
population, so recruitment -wise, practical.
15:09
practicalities we sort of recruited people once
15:11
they were on treatment predominantly um but yeah
15:14
we so we tried to get them to do i guess the
15:17
exercise type is really important when it comes
15:19
to bone health so we had resistance training
15:22
as well as what we call impact loading so little
15:25
hops and jumps to provide some stimulus to the
15:28
bone um because we know that sort of aerobic
15:31
exercises aren't as effective for bone um so
15:34
yeah that was sort of what we aim to do Unfortunately,
15:38
the results sort of weren't as positive as we
15:41
had hoped and a large reason for that when we
15:44
did per -protocol analyses looking at those who
15:47
were adherent to the intervention, we saw better
15:49
effects. So it just highlighted that an exercise
15:54
program doesn't necessarily suit everyone. Did
15:58
you find that predominantly older men, obviously,
16:01
with prostate cancer, did you find they were
16:03
keen to exercise? Because people often come to
16:05
me with osteoporosis and say, well, what can
16:07
I do? Doc, what food can I eat? What exercise
16:10
can I do? Did you find them keen to participate
16:13
or maybe not? Anecdotally, it was interesting
16:17
to see the... that some of the men, there was
16:21
a real buy -in and they loved coming into the
16:23
gym. They trained together. They'd go for a coffee
16:25
afterwards as well. They sort of checked up on
16:28
each other if someone wasn't at a session. So
16:31
there was a core group that really loved the
16:33
gym environment and coming in for supervised
16:36
sessions. But on the other hand, there were some
16:38
that were barely adherent at all. So I think
16:41
that's something that I'm really interested in
16:42
now is how can we tailor these interventions
16:45
to each individual so that we can... consider
16:49
what they enjoy what they're you know what they're
16:53
going to benefit from and sort of try and meet
16:54
in the middle a little bit so some we might not
16:56
prescribe the perfect intervention for their
16:58
bone health but if they're going to actually
17:01
stick to it and adhere to it then it's better
17:03
than yeah get the patient to help design their
17:06
own exercise program exactly my other thought
17:08
then is what about women with breast cancer also
17:10
on aromatase inhibitors There's a study for you.
17:14
We're giving you lots of ideas. No, exactly.
17:15
And we've done qualitative work in men with prostate
17:20
cancer and women with breast cancer discussing
17:23
sort of what exercise and diet support they receive
17:26
and what they would want to receive. And that
17:28
was one of the clear messages was they want individualized
17:31
supports that are tailored to their comorbid
17:34
conditions, what they're interested in, just
17:36
their... life situations so you know diet wise
17:40
people women with breast cancer often are cooking
17:42
for their family so they're you know they have
17:44
to factor in what their kids enjoy eating so
17:46
it's just so many just things that we might not
17:49
think about but it's what makes it interesting
17:52
and engaging and rewarding seeing patients isn't
17:55
it you know because human beings are all different
17:57
exactly yeah it's really impressive to see the
18:01
depth and the breadth of your research I'm really
18:04
impressed. Thank you very much for coming and
18:06
talking to us today. And listeners at home, I
18:09
think Jacques Delaville is one to watch. Thanks
18:12
very much. Thanks for not mentioning the ashes
18:14
as well. Thanks for having me. So we're delighted
18:20
to have a friend of the podcast who has spoken
18:24
to us a number of times in the past, Professor
18:26
Kasim Javed from Oxford. I feel if we were a
18:29
comedy quiz panel show, you would be one of the
18:32
sort of team captains for Bone Up. Would I be
18:35
Ian Hislop or Paul Mercer? I think my hairstyle
18:38
goes one way. That's a good question. So thanks,
18:41
Kas, for making the time to come and speak to
18:43
us again. We're always excited to speak to you,
18:46
and we will have a mug for you. eventually um
18:49
we were going to ask you about your takeaways
18:52
from the from the congress here but just before
18:54
that we're both very excited aren't we clinicians
18:57
practicing in the uk about the news we've heard
19:00
in the last last 24 hours yeah it was it's it's
19:03
really a culmination of over two years work well
19:07
over two years of all of your pro society to
19:09
actually take the top -down approach for FLS.
19:13
Fractured liaison services make clinical sense
19:16
and they are cost -effective. We weren't just
19:18
getting that traction with hospital managers
19:21
because it wasn't mandated by the NHS. So through
19:24
the all -party parliamentary group, over 200
19:27
MPs across the party said it was a good idea.
19:30
First achievement. Second, we went, well, we
19:34
didn't. Craig, the chief executive of the IRS,
19:38
takes credit. He had the vision to push and push
19:41
and push, meeting with number 10, health policy
19:44
advisors, the OBR, the Treasury, to what would
19:48
it take to make sure no patient is left behind
19:51
after a fracture. idea of a transformation fund
19:54
a national implementation group using data to
19:59
say the job is done rather than just making the
20:02
fund and letting people apply but really working
20:04
on the detail of phased approaches and the advantages
20:07
of the new structure of the of england we got
20:10
so close with the major condition strategy till
20:13
july the fourth happened We were nervous. I was
20:16
very nervous because that was a very strong Tory
20:19
push. And they actually went on the record to
20:22
say they would have funded an FLS transformation
20:24
fund. And the fantastic news is that Labour are
20:28
at least going to match it. So whatever happens
20:31
on July the 4th, we've got it in writing. There
20:34
will be a transformative. approach to making
20:38
sure no patient's left behind. And so we can
20:40
look forward to genuinely every patient in the
20:43
UK, Scotland, England, Wales, Northern Ireland
20:46
having an FLS? Well this is an NHS England transformation
20:49
fund but it will really leverage the other nations
20:53
to do that because the... Well, you know, Wales
20:57
we don't have to worry about. Inder Singh got
21:00
a million pounds for FLSs across Wales. Not as
21:03
much as maybe he might need, but it's enough
21:05
of a leverage to really move it forward. So that
21:07
model where policymakers say it's too expensive
21:11
to let people fracture again. But I realise the
21:14
healthcare system needs a little bit of kickstart,
21:17
pilot funding, just for the first two years to
21:19
set it all up. And then once it's embedded, the
21:22
local healthcare system take ownership of the
21:24
process, seems to be the way forward. And we've
21:27
got coverage in Northern Ireland and Scotland,
21:29
so it's great to see you're catching up in England.
21:31
Yeah, we will catch up. But, you know, I think
21:34
that's what we need. And then we can really move
21:35
on to the complicated stuff. This is just now
21:38
moving from... osteoporosis experts, DEXA experts
21:45
to actually project management, implementation,
21:48
behavior change. This is about implementation
21:51
now, not science. Yeah, isn't it great? You open
21:53
a clinic, you treat 100 patients, you change
21:55
government policy, you treat millions of people.
21:57
Spot on, and that's why I do this. I mean, there
22:00
are over 500 ,000 patient records in the FLSDB.
22:04
That's incredible. So, a really exciting Congress
22:08
as well. What going home from here, what are
22:12
you going to remember in a week's time? What's
22:14
going to change what you do in a week's time,
22:17
let's say, or a month's time from what's going
22:19
on today? Quite a lot. It's been a really nice
22:22
meeting. Very deep science, but also very clinically
22:25
applicable. One thing is the artificial intelligence.
22:28
Lots of talk about it. We're running a study
22:30
with the ADOPT study through NIHR. I'm being
22:33
plugged a lot, which really gives me the motivation
22:35
to really get those results out. But the other
22:38
issue is around... common diseases. So diabetes
22:43
and bone health is not sorted. We don't know
22:48
why diabetics have fractures. And the really
22:50
concerning thing is the new transformative treatment
22:55
for diabetes are really bad for bone. Yeah, yeah.
22:59
I mean, they did a randomized controlled trial
23:01
in people who didn't have diabetes but had fracture
23:05
risk. And over one year, they lost 3%, almost
23:08
3 % of the bone density at the hip. That's a
23:11
lot. And if you have risk factors for osteoporosis
23:14
and then you add that on again, I mean, that
23:17
is a concern. And we are not... We can take two
23:22
approaches. We can be reactive and we see the
23:25
fracture data do something about it. But I think
23:27
the BMD data and the QCT data is enough. We need
23:31
to be more proactive and say, actually... What
23:34
are we doing about this? What are the studies
23:35
we need to do now to see how do we mitigate that
23:40
risk? Is it through lifestyle? Is it through
23:42
muscle preservation? Is it through bone or a
23:45
combination? But hasn't there always been a bit
23:47
of a black hole in diabetes and osteoporosis
23:50
where we treat? diabetics with osteoporosis not
23:52
really knowing if the drugs work or there's very
23:55
little data there? There is and I don't know
23:57
why that is. I mean we've really been very passionate
24:01
about aromatase inhibitors, steroid induced osteoporosis.
24:05
I think because diabetes is so complicated because
24:07
it doesn't match any of our models. They have
24:10
low bone turnover. They have higher than you'd
24:13
expect BMD. And they're fracturing. And it's
24:16
kind of like, oh, that's really complicated.
24:18
What are we going to do? Is it age -related glycosylation?
24:21
Is it something more fundamental going on at
24:22
the cellular level? Is it a matrix effect? It's
24:25
very complicated. But I think the new treatments,
24:28
they're going to say, well, actually, we've removed
24:31
the diabetes. Now we could now deal with it.
24:35
It's a golden opportunity. And I think it will
24:39
be really... Important to prioritise that. Look,
24:43
thank you for taking the time to speak to us.
24:44
Not at all. It's super. Well, you owe me the
24:46
mug on my bookshelf. I owe you the mug. We'll
24:49
get the photograph and we'll Photoshop the mug
24:52
in. I should probably say the mugs were posted
24:55
here a week ago and have not arrived. So that's
24:57
part of the problem. But we will promise we'll
24:59
get a mug to everyone we've spoken to at the
25:01
podcast. And Cass, I think you're going to be
25:04
the only person to have every mug. I've been
25:07
diligent with you guys. Yeah, yeah, yeah. I've
25:10
been diligent. plugged you and I have to listen
25:13
to more of your podcasts but I think it's really
25:15
important because it's a new way we're going
25:17
to communicate and I'd love patients to listen
25:18
to these as well. We really appreciate your support
25:22
and your friendship. Thanks very much. Thanks.
25:24
Thank you. So we're delighted now to speak to
25:28
some of the team from the IFMRS who are joining
25:32
us today. And I'll ask you just to introduce
25:34
yourselves and say a little about your role.
25:36
And then we'll get into some of the interesting
25:39
things the IFMRS are doing. Hi, my name is Federico
25:43
Moscagiuri. I'm the CEO of IFMRS. Hi, my name
25:48
is Ralph Muller. I'm the secretary of IMRS and
25:51
my interest in the International Federation of
25:54
Moscow Excluded Research, so that's a very important
25:56
part. I'm glad you said that, Ralph. Exactly.
25:59
It's also to bring people together, of course,
26:02
and an alliance is really there. With Federation,
26:05
we do that. It's something that we can really
26:07
bring people together on board. That's my interest
26:10
to be as a secretary also connecting to the society.
26:13
This is the umbrella body for... bone research
26:16
and bone health organizations around the world?
26:19
It's really musculoskeletal, so we're really
26:22
trying to include, you know, everything that
26:25
is musculoskeletal to bring the musculoskeletal
26:27
space forward and not be bone specific, although
26:30
we certainly have origins. Many of the societies
26:32
have bone origin, but we also have societies
26:35
like the Orthopedic Research Society. We have
26:37
societies that are dealing with rehabilitation
26:40
and everything to do with that. But Federico
26:44
can say more about these kinds of things. And
26:45
our third guest. My name is Aline Bozek and I'm
26:48
Editor -in -Chief of IFMRS Hubble, which is a
26:51
platform for young investigators and I'm here
26:55
to promote young investigators and as well to
26:58
promote the MSK field. And Hubble is a platform
27:02
for education and for young investigators across
27:05
the world, is that right? Yes, exactly. That's
27:08
why it's part of IFMRS as well. Great. Yes, so
27:12
as Ralph was saying, the IFMRS is a global alliance
27:15
of musculoskeletal research societies, and our
27:18
purpose is to advance... musculoskeletal science
27:20
through collaboration. We are here really to
27:23
bring everyone together to help the whole global
27:25
community work better together, to share knowledge,
27:28
to join our voices in influencing at the global
27:31
level, to change the fact that despite their
27:35
huge impact, musculoskeletal conditions across
27:38
the board are almost universally under -prioritized,
27:41
and therefore research is also under -prioritized.
27:44
So we feel that needs to change. We want to work
27:46
together to influence at the W. WHO level to
27:50
make that policy change, but we also want to
27:52
support the whole community in terms of building
27:55
a network of knowledge so that we're enabling
27:58
conversations to happen, organizations and individuals
28:01
can learn from each other, and also providing
28:05
resources for individuals like the one that Aline
28:08
is leading. which is a really useful, unique
28:12
resource that is primarily aimed at young investigators
28:15
but also has a very wide appeal to a much broader
28:20
range of researchers. What kind of content do
28:23
you host then on Hubble that will support young
28:26
scientists and researchers? So we host an interview,
28:29
we host as well commentary, we host protocol,
28:32
if they have any specific protocol in MSK research
28:35
or in clinical research, and we hope to host
28:39
as well new podcasts and so on. Fantastic. What
28:44
kind of opportunities do you think are there
28:46
for the IFMRS to sort of change the game for
28:49
musculoskeletal research? Well, I mentioned the
28:52
WHO, and we are seeing a shift happening slowly
28:56
but surely to recognize the importance of dealing
28:59
with the burden of MSK conditions. So I think
29:02
on one hand, we have to make sure that our voice
29:04
is heard within that wider agenda, that we can
29:07
demonstrate why it's important to invest in MSK.
29:10
in the sense that it's going to enable people
29:13
to remain independent, pain -free, have a better
29:16
quality of life, remain in work. These are the
29:19
big things that policymakers are interested in.
29:21
And so by joining forces and by having a really
29:24
strong, clear message around that, I think we
29:26
can start to shift the dial a little bit. And
29:28
we are seeing more interest, as I said. But that's
29:31
only at one level. Then there's much that we
29:33
can do to support the global community, to upskill
29:36
researchers in low - and middle -income countries,
29:38
for example, where we're doing quite a lot. of
29:40
work and so it's it's multi -layered um but ultimately
29:44
it's up to all of us to to pool our forces pool
29:47
our resources and and really get that uh combined
29:50
influence going yeah i was wondering is it more
29:54
about getting availability of drugs and all this
29:57
wonderful research we see in low and middle income
29:59
countries or is it more about changing policy
30:01
so that people are more aware and educated in
30:06
in lower and middle income countries Maybe I
30:10
saw something to that. I think that's quite an
30:12
important part. It's really about when you do
30:14
that. So it's really important to empower. people
30:17
locally and so we want to include them in our
30:20
future young leaders future leaders programs
30:25
so that they also participate also on the round
30:29
so it's something that the federation has a system
30:33
of council and so all our member societies which
30:36
also incorporate societies from low middle income
30:38
communities have a voice and so it's very important
30:41
that we unite all of these voices in one voice
30:45
and I think you speak I think that's starting
30:48
to reflect now more with the societies that they
30:51
see like trying, you know, each individual society
30:54
that is a big society will try to influence even
30:57
worldwide because they have international members.
30:59
But it's very difficult, right? Because you're
31:01
not an honest broker at that level anymore. But
31:04
we can be that honest broker. We can be the one
31:06
voice. It can come through us. We can be the
31:09
contact person because we may be representing
31:11
20 ,000 individual researchers in the end, you
31:13
know. So that's the dream, right? So have that
31:15
one voice. voice and be in these countries but
31:18
you have to be there right you cannot just invite
31:20
them to be part you really have to give them
31:23
a voice you have to give them equity and inclusion
31:26
it's a very important part right so that's what
31:28
I see and we still work more on that actually
31:31
to have the people here yes and today we have
31:35
27 member societies from all over the world including
31:37
from Africa Latin America We're increasing our
31:41
numbers all the time. We've also got six affiliate
31:44
organizations that align with what we're trying
31:47
to do. And we're building partnerships all the
31:49
time, particularly with organizations that are
31:52
not just working in bone, but in muscle, in rehabilitation,
31:56
as Ralph mentioned. So we're really spreading
31:58
out, and we're starting to really see, as you
31:59
say, that critical mass. The other thing that
32:02
we do is we provide resources, I think I mentioned,
32:05
like the one that Aline is leading up. We also
32:08
have the knowledge. portal, which is a repository
32:11
of genetic and genomic data. Yesterday we had
32:13
a great session here at the ECTS Congress, which
32:16
demonstrated a real good practical use of the
32:19
portal in making links between mouse data and
32:21
human data. So that's also a resource that we've
32:24
built for the community, which we continue to
32:26
build all the time. And we have a virtual library,
32:28
which is also a place where people can go to
32:31
find really useful resources from all our member
32:34
societies. Can I ask you, Helena, is Hubble responsive
32:37
to what people want? Is it just... you putting
32:42
on it what you think people ought to hear? Or
32:44
are you listening to people in different parts
32:46
of the world asking for resources? No, it's a
32:50
back and forth, as you said. So we are listening
32:52
to people, what they need, and we are happy of
32:55
receiving anything that they want. Of course,
32:59
we have editorial boards to check the quality
33:01
and to check what we put on the platform, but
33:04
everything is welcome. It's everything about
33:06
MSK. Even people that want to promote themselves.
33:10
are looking for a job everything that makes them
33:13
prone to go in their future's career as well
33:16
is very cool for a bird so yes it's a real platform
33:19
for the bone and muscle world yeah that's that's
33:22
great if you're a young scientist out there and
33:25
you're interested in checking it out ifmrs will
33:27
put some links in the podcast it seems like a
33:29
one -shot musculoskeletal research shop thank
33:33
you everyone absolutely thank you thank you thank
33:36
you Welcome listeners, Bone Up Live 2024, Marseille,
33:41
and we're here with Anaheit and Peter. Welcome
33:44
to the show. Thank you. So you both have a role
33:47
on the ECTS. Peter, would you tell us about what
33:52
you do? So until recently, I was a member of
33:56
the ECTS Academy, which is a group of young researchers
34:00
trying to... further advance the field and empower
34:05
young scientists in the ECTS. And I have also
34:08
been the editor -in -chief of the newsletter,
34:11
which is a monthly letter that every ECTS member
34:15
receives. And I was also working on the Central
34:18
Eastern Europe Action Group, trying to attract
34:22
more people from these countries to the ECTS
34:25
and to make ECTS more relevant to them. Yeah,
34:28
I was particularly interested to know what your
34:30
priorities were with the sort of Central and
34:32
Eastern European group. Do you feel there's a
34:34
demand for more interest in bones in that part
34:38
of the world? Yeah, actually this part of the
34:41
world is not sufficiently represented in the
34:43
ECTS and the ECTS tries to take, to have, you
34:47
know, entire Europe involved as much as possible
34:49
and also considering some special challenges
34:53
in this. part of Europe. I mean, there are challenges
34:56
obviously everywhere, but some are, let's say,
35:00
more pronounced in this area than ECTS was thinking
35:02
how they can help the region to get more integrated.
35:07
And is the gap more in clinical services or is
35:10
the gap in research, do you see? I think both.
35:13
I think both in clinical services, there's also,
35:16
I mean, there's treatment gap everywhere. But
35:19
in some of those countries, you don't have really
35:21
the newest drugs that are available. For example,
35:23
in the Netherlands, you have some that we don't
35:25
have in Serbia. But there's also, I think, a
35:29
gap in research. There's not so many people working
35:32
in bone. And even if they do, maybe they're gravitating
35:35
to some other societies, not DCTS. And also there
35:39
are issues, you know, with the finances and so
35:42
on. And DCTS came up with a reduced fee. for
35:46
people from those countries. And I think this
35:48
really contributed to attracting more people.
35:51
And what do you do when you're not working for
35:54
ECTS? And where do we find you on Monday morning?
35:57
Monday morning? Yeah. Well, not this Monday because
35:59
you'll be here in Marseille. But where do we
36:00
find you next Monday morning? What do you do?
36:02
Yeah, next Monday morning, I think this is the
36:06
end of semester. I'm professor in human anatomy
36:08
at Faculty of Medicine in Belgrade. And next
36:11
Monday morning will be... I think the end of
36:14
semester and probably the start of examination
36:16
period. So you're on holiday next Monday. That's
36:19
nice. Thank you. Something like that. And Anachreit,
36:22
what's your role in the ECTS? Well, I have also
36:24
been a member of the academy and I've even had
36:26
the pleasure of chairing the academy for two
36:29
years, which was really a great experience. And
36:31
I've been on the scientific program committee
36:33
and I've been also on the financial committee.
36:35
I think both are also very interesting roles
36:38
I could have had in ECTS. And what about your
36:41
research? Well, my research focuses on bone marrow
36:45
adiposity, which is basically the fat cells inside
36:48
the bones. And we more and more think that they
36:51
have an important role also in bone metabolism
36:53
and in energy metabolism. And that is what I'm
36:56
looking at, basically. Excellent. Thank you very
36:59
much, both. Thank you. That's great. You're welcome.
37:01
Bye -bye. Thank you. I'm delighted to say we
37:04
have our next guest, Martha Blank. Welcome to
37:06
the show. Thank you. I'm very pleased to be here.
37:10
I saw you give your excellent talk today in the
37:14
basic science session and I thought I'd grab
37:17
you and get you in to tell us about your research.
37:19
But before we get started, which institute are
37:22
you from? I'm from the St Vincent's Institute
37:24
of Medical Research in Melbourne. Oh, fantastic.
37:28
And that's not an Australian accent? Where are
37:30
you from? It's absolutely an Australian accent.
37:33
It is an Australian accent. Okay, fair enough.
37:35
This is why they kicked me out of Austria. Austria,
37:38
okay. Well, you've brought the lovely weather
37:39
with you anyway from Australia. I tried. I packed
37:42
everything into my luggage. Big suitcase. Big
37:45
suitcase, yeah. Two, actually. So can you tell
37:50
us about the research that you presented in your
37:53
excellent talk today? Yeah, absolutely. So I've
37:56
been starting actually my PhD with a mouse model
37:59
which has a brittle bone phenotype, and that's
38:01
the DMP1 -Cree FMB2 mouse model. And in this
38:05
mouse model, we really showed that the bones
38:08
are significantly weaker, so they break more
38:11
easier, but there's no change in the amount of
38:14
bone that really could be the reason for this
38:17
bone strength defect. So where do you think the
38:20
bone strength defect arises from? Yeah, so we
38:23
thought about this as well and with some discussion
38:26
with collaborators, we really thought that the
38:28
bone material quality was deteriorated. And we
38:31
followed up with some measurements and we looked
38:34
at the mineral phase and the collagen phase,
38:36
which are the two dominant parts in bone. And
38:39
we found that we have both more mineral and more
38:42
collagen in the bone, which makes them break
38:45
easier. So how can having more collagen and more
38:48
mineral make the bones break easier, it actually
38:51
sounds a bit counterintuitive. Yeah, but you
38:54
have to consider that just because we have more
38:57
doesn't mean that the geometry of the bone is
38:59
actually ordered. So the geometry was the same,
39:02
but it's just a more dense... and compact material.
39:07
And the more mineral, it's like with a dry stick,
39:11
you can break it really easy because you don't
39:14
have the flexibility anymore of the collagen
39:16
to prevent the fractures. This is something we've
39:19
come across before. Speaking to other researchers,
39:23
we've talked a little about the effect of diabetes
39:26
in bone and how often I see patients with what
39:29
look like typical osteoporotic fractures, but
39:31
you measure their DEXA scan and their bone density
39:34
looks quite good. Often those are patients who
39:36
have diabetes. And we then wonder, the drugs
39:39
that we use that are sort of based on the premise
39:41
that we're giving people more bone, do we know
39:44
they work on people who fracture despite the
39:47
fact their bone is already quite dense? So presumably
39:50
your work will... Give us some insights into
39:53
that. Yes. So it's also quite interesting if
39:56
you think already, if you treat someone, I don't
40:00
know, who's prevalent maybe to have osteoporosis,
40:02
to have a fracture, if you are really inhibiting
40:06
the cells that are eating away the bone, which
40:09
is what you want because you want more bone to
40:11
form. But that also means that the bone is not
40:14
turned over as much. So you will get more bone
40:17
material, which is older, which is also probably
40:20
more prevalent to break it. actually, yeah. And
40:23
why will that older tissue be more prevalent
40:25
to breakage? What happens to the tissue as it
40:28
becomes older? Yes, so we do know from very much
40:33
the first phase how mineral crystals nucleate
40:36
in the collagen matrix, and that's very well
40:38
clear defined. But the maturation afterwards,
40:40
which is really the really long phase, we don't
40:45
really 100 % know how the two phases change during
40:49
this period. Yeah, we don't want to send out
40:53
the message that bisphosphonates don't work if
40:55
you have diabetes. That's important. But there
40:58
was, I noticed, a presentation this morning,
41:00
someone looking at giving anabolic agents to
41:02
people with diabetes. And that seemed to be actually
41:05
to work better in an interesting way. So I think
41:08
that's a big area of growth that we need to look
41:10
at how to treat people who have. better bone
41:13
density, lots of bone, but the quality is just
41:16
not as good. Yes, yes, absolutely. But the limiting
41:19
factor is just that we would need biopsies, and
41:22
that's just, you can't really take out the bone
41:25
and give it to us, unfortunately, to look at.
41:27
Before we started, you were talking a little
41:29
about osteocytes, and that's something that's
41:31
come up a few times here. Most people, well,
41:34
I hope most people know about osteoblasts and
41:36
osteoclasts, because I spend my life explaining
41:38
about them to people. The third cell that people
41:41
don't know as much about. as the osteocyte. And
41:44
you've done some work on how the osteocyte can
41:47
sense how dense the bone is around it. Is that
41:49
right? Maybe not 100 % sensing, but we think
41:53
that the osteocytes, which are terminally differentiated,
41:56
they are actually the main cell population in
41:59
the bone. So they must be very important. So
42:02
they sense changes in the environment because
42:06
they have an extensive network, which basically
42:08
almost covers all of the centimeters in there,
42:11
which is quite fascinating. that they are able
42:14
to respond to this maturity effect of collagen
42:20
and mineral as well. Any ideas about how they
42:24
might sense the density around them? This is
42:27
probably really just with fluid that they have
42:32
in their canal so when you when you compress
42:35
they sense the mechanical stimulus and that might
42:39
change as well and that would be very interesting
42:41
to see in those fractures who do not have any
42:44
change in bone mass whether they have a different
42:47
fluid stress. Wouldn't it be great if we had
42:50
some measure of how osteocytes work then so when
42:53
I saw that patient who seemed of normal bone
42:55
density but was having fractures maybe there's
42:58
some problem with the osteocyte. Yes. Absolutely,
43:01
that would be fantastic. Osteocytes almost struck
43:04
me as the dark matter of osteoporosis, that everyone
43:07
knows they're there, but our understanding of
43:09
how they work is really very limited as compared
43:12
to the other cells. I think it's also because
43:15
they're not the active part of resorption and
43:20
bone formation, that they have been a little
43:22
bit left out, and people have been focusing on
43:25
just bone formation and bone resorption. agree
43:30
with that, that suicides play an incredible part
43:34
in this scenario. A new frontier in bone research,
43:39
listeners. You heard it here first. Thank you
43:41
very much, Martha. Thank you so much for having
43:43
me. Thank you for taking the time and bringing
43:45
the lovely weather. Always. For the benefit of
43:48
the tape, we're standing on the roof of the conference
43:50
venue in the beautiful sunshine, listening to
43:53
foghorns and car sirens. Listeners, the conference
44:02
is over now and it's nearly time to leave sunny
44:04
Marseille and go back home again. We hope you've
44:08
enjoyed the conference as much as we have and
44:10
we hope you've learned as much as we have. I've
44:13
certainly learned lots. Richie, we learned that
44:15
neither you nor I are particularly gifted at
44:17
Patag, but apart from that, we did get lots of
44:20
new insights into various aspects of bone health.
44:24
and bone disease and in fact a few new things
44:26
that i'm quite excited you know to go back to
44:28
my clinic and talk to patients about and see
44:30
if it can make a difference to what i do every
44:33
day and the other good news i think is we've
44:35
heard that not just these episodes but our our
44:39
archive of episodes on bone up will soon appear
44:42
on the online learning environment called hubble
44:46
which is facilitated by the ismrs the international
44:52
federation for musculoskeletal research so we're
44:56
very appreciative to frederico and his colleagues
44:59
for facilitating that and we hope that our archive
45:03
you know can be of use to more people around
45:06
the world so um thanks for listening and we hope
45:09
to see you again soon bye everyone