Latest / 'Bone Up' / BoneUP Live @ECTS 2024 - Part 1

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BoneUP Live @ECTS 2024 - Part 1 · 'Bone Up'

0:00
So hello and welcome to a very special episode
0:02
of Bone Up. It's one of those episodes where
0:06
Richie and I have got on a plane and we're here
0:09
at the European Calcified Tissue Society Congress
0:13
in Marseille in the south of France to give you
0:16
a little flavour of what goes on here. So Richie,
0:19
bonjour, ça va? Bonjour, ça va? We've come to
0:23
ECTS listeners to give you a bit of a flavour
0:25
of what's happened in bone research in the last
0:28
year, tell you about the highlights, introduce
0:31
you to some of the prize winners at the conference.
0:34
get the voice of some young scientists, the people
0:37
who are doing the research that are going to
0:38
develop the next generation cures. We're going
0:41
to talk to some of the senior profs and look
0:44
back at their lifetime of work and how they've
0:46
developed the drugs and medicines which you might
0:49
be taking. And we're also going to talk to some
0:52
of the ECTS members, the people who run the society,
0:55
especially the ones who... do a lot of work to
0:57
support young scientists. It's very difficult
0:59
when you're starting a career, and the ECTS are
1:02
doing a lot of really good work, and we'd like
1:05
to bring some of that to you. Yeah, so we hope
1:08
if you're a patient, you'll be reassured listening
1:11
to the research, listening to the scientists,
1:14
and if you're a young doctor or a young scientist,
1:16
maybe it will stimulate your interest as to what
1:18
actually goes on at these conferences. And maybe
1:21
you might want to come to one in the future,
1:23
and we'll see you there. So we're delighted,
1:29
and this is an interview I'm very excited about.
1:31
We have Thomas Funk -Brentano with us, working
1:33
in Paris at the moment. And Thomas presented
1:36
yesterday, telling us about the latest and most
1:39
exciting research across the world of bone disease
1:42
in the last year. Thomas, I have to tell you,
1:45
I'm at the conference here. When I go back to
1:47
work next week, my patients will say to me, so
1:49
you've been to the big conference. Tell us what's
1:52
coming up next. What's the most exciting research?
1:55
And you're the man to give us the answers. Wow,
1:58
thank you very much. It was actually a very exciting
2:02
task to review all the exciting science that
2:06
is out there. And of course, we needed to do
2:10
some selections. So I think what I remind is
2:14
the new anabolic agents that there's increasing
2:22
evidence that they're effectiveness in reducing
2:26
fractures is higher than bisphosphonates. And
2:31
that perhaps we really need to reflect on in
2:35
like which position we should give these bone
2:40
agents to our patients. And by that you mean
2:44
drugs like romosuzumab, teripalatide, abalaparatide,
2:47
those sorts of drugs? Yeah, exactly. These kind
2:50
of drugs that promote bone formation rather than...
2:54
you know, inhibiting bone resorption. And I think
2:58
it's really a good opportunity. Of course, it
3:01
is sub -Q injections in general, and some of
3:05
our patients are, well, you know, not so happy
3:09
with that, and we can understand. So this particular
3:14
study that was very interesting is to try to
3:16
capture which patients would respond. the most
3:20
with these agents and looking at genetics. And
3:24
they were able actually to find that if you have
3:28
certain alleles, certain variants, you might
3:30
respond very nicely compared to other alleles.
3:34
So in a strategy in the future, that could be
3:37
interesting actually to try to capture this information
3:40
so that we're really sure that despite the burden
3:43
of the treatment, it will actually turn out to
3:47
be very efficient. That's one of the things on
3:50
a patient, particularly if a patient becomes
3:51
so invested in the condition that they're injecting
3:54
themselves every morning for a year, for two
3:57
years. And I'm able to use bone turnover markers
4:01
and I do contact patients and say your bone turnover
4:04
has increased. That's good news. And people are
4:06
encouraged by that. The idea that we could tell
4:09
people before they started that you have a gene
4:12
profile, which makes you're really susceptible
4:15
to this treatment in a good way. That would be
4:17
very. encouraging, you think, for patients? Oh,
4:19
yes, I definitely think that it is encouraging.
4:23
And on the other hand, if we think that they
4:25
would not respond, that perhaps we would not
4:27
push too much. Yeah, yeah. So that's, I think,
4:30
of course, it's preliminary data. Well, it's
4:34
a big study already, but it needs to be enlarged
4:37
and confirmed with other data before we turn
4:39
it into clinical practice, I think. But I think
4:42
it's a very interesting idea. Because we see
4:44
that a lot with cancer treatments now, where
4:46
the oncologist will do genetic tests to choose
4:50
the treatment but we're not really at that stage
4:53
yet with osteoporosis. That's the global idea
4:56
of that study so I thought it was really interesting
4:58
and needed to be mentioned. Other options to
5:02
try to decrease the burden of these sub -Q injections
5:06
is other routes of administration such as oral
5:10
PTH or transdermal PTH and there are some increasing
5:17
studies a number of studies that are interested
5:20
in that and that's very promising I think. Almost
5:23
the most exciting thing I thought from all the
5:26
work you summarized yesterday was the idea of
5:29
oral anabolic agents because that would make
5:32
it so much more widely available to my patients
5:35
it would make it more acceptable to them and
5:38
I think we would then involve primary care as
5:40
well because We want to get treatment early with
5:44
anabolic agents, but people have to come to the
5:47
hospital to see me, to be weighed, to be seen.
5:49
Whereas if it was tablet form, I could get GP
5:52
colleagues. That could be started in primary
5:54
care, monitored. It would just be a... paradigm
5:57
shift in how we treat things. Yeah, well, I do
6:00
agree. I think the phase two study was giving
6:04
some promising results with increase in bone
6:07
turnover markers for bone formation and increase
6:11
in bone mineral density. Of course, it needs
6:13
to go further in the steps of clinical trials
6:17
to be confirmed that is in fact effective, but
6:20
it's going to be very interesting to follow these
6:22
studies. My fracture liaison nurses would love
6:24
to hear that because it would be less work. for
6:26
them as well. Thinking ahead now, how would it
6:30
be practical to bring in genetic testing into
6:33
healthcare for bone treatment? The kind of equipment,
6:36
I guess, you need to do the genetic profiling.
6:38
Is that something you normally have in hospitals?
6:40
Do you have to send out to a lab? How would it
6:42
work on a big scale? Yeah, so that's an important
6:46
question. I'm probably not fully sure about the
6:48
answer, but what I can see is that genetic testing
6:53
at large scale is getting easier and easier and
6:58
less expensive with time. So I'm pretty sure
7:02
that some companies would be able to do these
7:07
tests, these screenings. So this is a whole other
7:11
question, and I'm probably not the genetic expert
7:13
to have all the pros and cons, but it's going
7:19
to be interesting, I think, to see what goes
7:21
on. upcoming five to 10 years. I think one of
7:25
the other things you mentioned as well in some
7:27
of the studies about denosumab, which we all
7:29
use lots of and it's very exciting, but a lot
7:31
of people are asking, how do I get my patient
7:34
off denosumab again? Should I be getting my patient
7:37
off denosumab again? Yeah, this is a very, very
7:41
important field. There's growing evidence in
7:45
osteoporosis. And actually, the study that I
7:48
mentioned was in a very particular situation
7:50
of end -stage renal disease with patients under
7:56
dialysis. And there was this very interesting
7:59
study that we're able to look at. bone hip strength
8:05
indices using, well, derived from DEXA in 124
8:10
patients treated for up to five years. And, well,
8:16
there were some promising results with these
8:19
indices going up, so improving with denosumab
8:23
treatment. But 11 of these patients discontinued
8:28
denosumab and were followed for another year.
8:33
As we could have expected, but I think it's one
8:36
of the first that actually demonstrates that
8:38
in this population, that these improvements,
8:41
well, they disappear. So then what to do? Because
8:46
you can always give bisphosphonates in non -CKD
8:51
patients to try to... Limit the off effect, but
8:56
not with renal failure. Yeah, exactly. So I think
9:00
the use of denosumab in... is really tricky and
9:04
we really need to improve our knowledge in this
9:07
situation. The second thing that is, I think,
9:10
very important for the community to insist on
9:13
is the risk of severe hypocalcemia in these patients
9:18
with denosumab. And the main message is that
9:22
it's frequent, so you need to know that it's
9:24
a very high possibility and that you need to
9:27
work hands -in -hands with the nephrologist so
9:33
that you can try to prevent this. I don't know
9:36
if you see the same in France, but certainly
9:38
I see maybe five years ago, ten years ago, my
9:41
renal physician colleagues would have used denosumab
9:45
themselves, would have managed that themselves.
9:47
Now they're referring lots of... those patients
9:49
to the osteoporosis clinic to me because they
9:52
perceive it's quite complex and as you say you
9:57
can't You can't really come off denosumab if
10:00
you've got end -stage renal disease because you
10:01
can't use a bisphosphonate. But I did think it
10:04
was reassuring from the paper that you covered
10:08
that showed that it actually was effective. Some
10:10
people would have said if you have very low bone
10:12
turnover because of your renal disease, trying
10:15
to lower it further with denosumab may not help.
10:19
But actually you showed a paper that suggested
10:21
that it did have some benefits. Well, yes. So
10:24
the limitation of this study is that we didn't
10:26
really know. what kind of renal mastodystrophy
10:29
they had. And exactly what, as you said, we didn't
10:33
know if those patients with low bone turnover
10:36
or adenamic bone also responded in this way.
10:42
Thank you very much for speaking to us today.
10:46
Your talk was incredibly well received. I think
10:48
it's one of the best at the conference. Thank
10:51
you very much. I'm very honoured. And thank you
10:54
for answering our questions today. I think the
10:55
listeners at home are going to be really interested
10:57
to hear what you have to say. Yeah, both my patients
10:59
and fractal liaison nurses will be delighted
11:01
to hear all about what you were saying. Oh, well,
11:04
thank you. Well, I was just a storyteller here.
11:07
You were passing on the work of others, but that's
11:09
okay. In this case, we'll praise the messenger.
11:12
The storytelling is the hard bit. And it's such
11:15
a huge volume of information to get across, to
11:18
synthesize everything and put it together and
11:20
pick out the highlights. Just, I suppose, one
11:21
last question. How long did it take? How long?
11:26
Oh, well. So, a few weekends. But I actually
11:33
really started two weekends ago and had a short
11:37
night just before. There you have it, listeners,
11:41
working through the night to bring you the latest
11:44
bone research. Thank you, Thomas. Thanks very
11:46
much, Thomas. Thank you very much. Bye. Listeners,
11:51
David and I have been at the conference for the
11:53
first half day now, and one of the things that
11:55
really seems to be standing out is research into
11:57
diabetes. It really seems to be taking the conference
11:59
by storm, and to prove that, we've got two prize
12:02
winners here. We've got the Clinical Award Prize
12:06
winner, Lorenza Mattia, and we've got the Basic
12:09
Science Award winner, Tessa Crapper. Welcome
12:13
both of you to the podcast. Thank you. Thank
12:15
you for having us. Thank you. So it's really
12:17
interesting that both prizes this year have been
12:19
given out for diabetes research. Lorenza, I wonder
12:22
if you could just tell us a little bit about
12:24
the work that you've been doing. Yes, thank you.
12:27
diabetes is a worldwide disease so this is probably
12:31
it is important to study also from the bone metabolism
12:35
point of view so I'm an endocrinologist and I've
12:41
studied diabetes and bone metabolism since the
12:44
last three four years during my PhD and we know
12:50
that type 2 diabetes is a condition characterized
12:52
by an increased risk of fracture and it's important
12:56
because it is a a huge burden for our societies
12:59
from an economical and social point of view.
13:02
So it is important to increase the research in
13:04
this field. In my little research, I have studied
13:10
some biomarkers that could be involved in increasing
13:16
the risk of fracture in this population. And
13:19
in particular, I focused my attention on growth
13:21
differentiation factor 15, which is a senescence
13:25
biomarker. And I've seen that this increase in
13:28
type 2 diabetes, it might be linked to increased
13:31
risk of fracture. But in particular, I've studied
13:34
the effect of exercise training on this biomarker.
13:38
And we know that exercise training could reduce
13:41
the fracture risk, but we don't know what it
13:44
can do on this biomarker. So we have studied
13:47
this effect of exercise training in a population
13:51
of type 2 diabetes to see which are the changes
13:54
of GDF15 after two years of exercise training.
13:59
So you're following patients with diabetes for
14:01
two years then and you're monitoring the changes
14:03
in the biomarker, which is a biomarker for senescence,
14:06
for ageing and also for the diabetes disease.
14:10
What happens to the biomarkers in the people
14:12
who are exercising? So in people who exercised,
14:18
the biomarkers decreased. and on the other side
14:23
it increased, significantly increased, in people
14:26
who did not do any exercise training. So the
14:32
key result might be that exercise could somehow
14:36
reduce this senescence biomarker, or maybe is
14:41
associated with a reduction of this biomarker,
14:44
and we also think that if DDF15 might be involved
14:49
in the fracture risk in type 2 diabetes, we think
14:53
that his effect might be related not to an effect
14:58
on bone metabolism but to muscle function rather
15:02
than bone. It's something we've come across before
15:05
in other... episodes of the podcast the link
15:08
between muscle and bone so the patients who exercised
15:12
did they get an increase in their diabetic control
15:15
did their glycemic control improve as well as
15:18
their bone health And was there a relationship
15:22
between improving glycemic control and improving
15:24
bone health? Actually, we didn't find this relationship,
15:28
but the glycemic control was improved in those
15:32
who exercised, and it is confirmed by several
15:38
other research on this field, which exercise
15:41
is able to improve glucose control. Actually,
15:46
we didn't find any correlation with the better
15:49
glucose control. and bone outcomes but we had
15:55
a small sample of patients so probably we need
15:58
to do more research in this field. So where do
16:02
you think you go next then? If you could wave
16:05
your magic wand and have all the money and resources
16:07
in the world, what would you like to do? So if
16:10
I were very rich and then have all the findings,
16:14
I think we need to study the changes of these
16:22
biomarkers from baseline and follow up for more
16:27
than two years to check. if there is an effect
16:31
on the fracture risk because you need longer
16:33
time to see the effect of the fracture outcome
16:36
because so far we just looked at the bone density,
16:42
bone turnover and we know that GDF15 is not related
16:44
to bone but it is related to muscle function
16:49
in improvement of muscle function so what we
16:53
need now is to check if there is also an effect
16:57
on the fracture risk but we need more time to
17:00
establish this so let me ask you this if we were
17:04
at a diabetes conference today instead of a bone
17:06
conference would the diabetes experts be talking
17:09
about bone and if not why not yeah this is a
17:14
very unpolite question because i am yeah perfectly
17:19
polite so probably not not enough at least The
17:25
last conferences have been about diabetes. I
17:28
didn't find any talk about bone. I hope in the
17:32
next future I will find more bone metabolism
17:37
talk and topics. Probably I will bring my research
17:42
there. This is my next step for October. People
17:47
with diabetes, patients even need to know this
17:49
as well, don't they? They're educated about kidney
17:51
disease, about eye disease. They're not told
17:54
that they're bone. are at risk of diabetes as
17:56
well. Yeah, you're right. We need to start thinking
17:58
about bone as another chronic complication of
18:04
the disease. So, studying patients is difficult.
18:11
Studying the mechanisms and causes underlying
18:13
disease is very hard. Listeners, as you might
18:15
know, because humans have long and complicated
18:18
lives. with complex physiology, so it's really
18:21
important we have the basic science too, and
18:23
Tessa, this is probably a really good time to
18:24
bring you in. Probably. We had a discussion before
18:28
we started recording about basic science, and
18:30
somebody said, actually, there's probably a better
18:32
word for it, but I've forgotten what that was.
18:34
Fundamental was the word suggested, yeah. Fundamental
18:37
science, yeah. As myself, I'm a basic scientist.
18:41
Would you be able to tell us about your work?
18:43
Okay, I worked with the zebrafish model to look
18:47
at bone formation and bone regeneration under
18:50
high glucose conditions. The zebrafish serves
18:57
as a suitable model to address skeletal complications
19:01
in diabetic research because my findings are
19:04
consistent to those that have been made in diabetic
19:07
human bones. i just did an overview is there
19:16
any differences because uh just two studies um
19:20
have have looked at bone tissue and diabetic
19:24
zebrafish and they just investigated the scales
19:27
and the fins so i was the first one to look at
19:30
the bone wow so and then at the zebrafish lava
19:36
There I could prove that the number of osteoblasts
19:40
were reduced during bone formation and during
19:44
bone regeneration I could also show that the
19:47
number of osteoblasts was reduced. I'm going
19:52
to ask as a clinician who doesn't understand
19:53
this, so these fish are bred to have diabetes
19:56
from birth or you do something to the fish that
19:59
gives them diabetes and then you look at their
20:01
bones, which of the two? I give them diabetes
20:05
by incubating them in high glucose or with a
20:11
nitroreductase mediated cell ablation of the
20:14
better cells. ability where you can enable either
20:20
type 1 or type 2 diabetes. We know that bone
20:24
mineral density differs between those types and
20:27
this would be also a nice topic for further research
20:30
because I looked at both types of diabetes but
20:35
there needs to be more research on the molecular
20:38
level. to look is there a difference also in
20:47
the model organism and not just in humans. Which
20:50
type of diabetes is worse do you think for bone,
20:53
type 1 or type 2? Oh, that's a good question.
20:56
I guess type 1 because there is an absolute lack
21:00
of insulin and we know that insulin is anabolic
21:03
to the bone and we have an autoimmune disease
21:08
with higher pro -inflammatory status and metabolism.
21:14
I guess that will enhance this bone. Inflammation
21:21
enhances bone loss. You get it earlier. You will
21:26
live longer with the diagnosis of type 1 diabetes.
21:30
Diabetes is a disease of long -term complications.
21:35
I will get diabetes and in two months I will
21:38
show bone fragility. It's causing over the years
21:42
not only nerves, the brain or the kidneys. We
21:47
should have asked Lorenza that question as well
21:49
then. So which is worse for your bones from your
21:51
point of view Lorenza, type 1 or type 2? So thank
21:55
you for this tricky question for a diabetologist
21:58
because actually both have lots of problems.
22:06
probably from from the bone point of view we
22:10
have several differences between the two types
22:14
of diabetes of course type 1 diabetes people
22:19
with type 1 diabetes have a longer longer duration
22:25
of disease. So we expect to follow them from
22:30
the early childhood or adolescence to the elderly
22:36
age. So there's a long duration of the disease,
22:45
so bone might be involved. Yeah, because if you'd
22:53
asked me, I would have said, well, in theory,
22:54
it would be type 1. But then when I see patients
22:57
at the clinic, so many people with type 2 diabetes
23:00
perhaps. have been smokers, have taken steroids,
23:04
have lots of other risk factors. Whereas perhaps
23:07
the type 1 diabetics have been careful not to
23:09
smoke, to exercise, to look at their other risk
23:11
factors. So probably at the basic model, it's
23:14
type 1. But at the clinical model, with the real
23:16
human beings making bad lifestyle choices, it's
23:19
type 2. Yeah, probably it's true because type
23:22
2 diabetes have worse lifestyle. They are inactive.
23:27
As you said, they smoke more. cardiovascular
23:32
disease. So yeah, you're right. The listeners
23:34
at home might be thinking it's a bit strange
23:36
that we can be at a bone conference and we have
23:38
clinicians alongside basic scientists studying
23:41
fish as a model. I mean, it sounds a bit crazy,
23:46
right? Yeah, it sounds crazy. Why do you pick
23:49
zebrafish as a model? I think maybe most people
23:51
would think about mice or rats or dogs or something.
23:54
Why fish? um fish because they're easily to hostage
23:59
you can put them in a small tank and they're
24:03
happily together in a big tank and they have
24:07
a short development time and they're very easy
24:11
to do to create transgenic lines there's for
24:18
example there i will i work with a model with
24:22
the insuline mutant with um They have a deletion
24:26
of 60 base pairs and then they are not able to
24:30
create the insulin and get diabetes. Or it's
24:36
possible to easily create fluorescent proteins
24:41
that express the bone to image them and so many
24:48
others. So it's easy to do science? It's pretty
24:52
easy. It's also nice to have because you can
24:58
easily regenerate it in a short time. It's easy
25:02
to handle and they are also invisible in the
25:07
first five days. So live in vivo imaging is possible.
25:13
I wonder if there might be some collaboration
25:16
one day. We saw some great talks about collaborations
25:19
between human and mouse scientists today. Yeah,
25:21
hopefully. I hope zebrafish. We'll become a rising
25:25
star. Well, that's great. Thank you for taking
25:29
the time to speak. Thank you very much. Thank
25:31
you. Thank you. So, listeners, next up, we have
25:38
an interview with the co -chairs of the ECTS
25:41
Academy, Alex and Jeroen. Welcome to the show.
25:46
Thank you for having us. So we'd like to chat
25:49
to you a bit about the ECTS Academy and how it
25:52
fits alongside your kind of work lives and research
25:55
lives, because it must be a big investment for
25:57
you. It seems like the society has really got
26:00
behind the ECTS Academy. Could you tell us about
26:03
your role and what are your hopes for the Academy?
26:08
Yeah, so we're the co -chairs, so our responsibility
26:11
is to kind of organise the group of about 30
26:13
early career academics. do different activities
26:17
from sessions at the conference to we have a
26:21
retreat once a year we also do online mentoring
26:24
we have our own networking sessions etc so we
26:27
are the secretaries coordinators uh chief cat
26:32
ravelers yeah i think the interesting aspect
26:36
is basically because it's such a diverse group
26:38
of of members basically clinicians and basic
26:42
scientists and the mission of ECTS is also to
26:45
bring together these different disciplines although
26:48
to realize that at a conference is typically
26:51
a bit more challenging because sessions are typically
26:55
topic based so having an interaction at a society
26:58
level is a bit more complicated but it's something
27:00
that actually within the Academy something that's
27:02
very prominent because we host several events
27:06
focused on our personal career development and
27:08
that forces us basically to understand what everyone
27:12
is doing and that's a very good experience and
27:15
i would like to add i think what has been very
27:17
useful also in terms of my professional development
27:20
first of all you're leading a group of 30 people
27:22
so it's a big group exactly so your laboratory
27:25
tends to be smaller i mean mostly for us in our
27:28
career stage and and then you also realize what
27:32
the challenges are also dealing with with different
27:34
cultural backgrounds also different disciplines
27:36
working hours and so that's a very good that's
27:40
a very good lesson and Other than that, I think
27:44
it was also really helpful to understand how
27:48
a society actually works and how you can contribute
27:51
to the mission and vision of the society. So
27:54
to interact also with the board, because that's
27:56
decision -making at a different level. It's interaction
27:59
also with sponsors. It's different people and
28:02
members wanting something from a society. And
28:04
it's a very insightful lesson because... along
28:06
our career path, somewhere down the line, we're
28:08
going to end up in these positions also. And
28:10
most of them actually grow into this position
28:13
without being trained to be in this position.
28:15
We have never received specific training for
28:18
management or leading groups. So this is just
28:20
an experience with support of the ECTS. I think
28:24
I'm really grateful for being able to. to experience
28:27
this and can you outline for us just sort of
28:30
exactly what the academy does or just to give
28:33
a couple of headings because some people listening
28:35
to the podcast you know won't won't necessarily
28:37
know what do you do sort of practically week
28:39
by week to achieve your goals so it's online
28:44
meetings through across the year because we're
28:47
based all across europe and then twice a year
28:49
we have the opportunity to get together so i
28:52
mentioned there was a retreat so we have two
28:55
to three days dedicated where we're all together
28:57
and what we really try and do is maximize that
29:01
time and just think what are the things that
29:03
couldn't possibly work online so i think open
29:05
table discussion is very difficult to replicate
29:09
that conference in -person experience so we try
29:11
and make it as interactive as possible and all
29:14
the kind of admin we push off into online meetings
29:19
And then at the conference, we do a lot. There's
29:23
a lot of academy sessions. There's a mentoring
29:25
session where we get senior scientists to talk
29:28
with early career researchers about different
29:30
topics that are relevant to them. So publishing
29:33
in big journals, networking, et cetera. We have
29:36
a couple of sessions that we run where we select
29:39
from the abstracts from early career researchers
29:42
that weren't selected for the main program. And
29:45
we have 18 opportunities for presentation. so
29:48
I think that's a really valuable thing because
29:50
you're very squeezed and it's a very it's a big
29:53
learning curve isn't it speaking in front of
29:55
a couple of absolutely and you get great confidence
29:57
as a more earlier career grade researcher clinician
30:01
coming to a conference and speaking absolutely
30:03
yeah and I think so it serves you know for the
30:06
image of the society as well So it is very good
30:11
to reinforce the mission of ECTS showing that
30:15
we are also there for ECRs. And I've been going
30:18
also to different meetings, larger meetings typically,
30:21
maybe also more clinicians. And the atmosphere
30:24
at these conferences tends to be different. The
30:26
content is different. The speakers are different.
30:28
It's more prominent. It's based indeed on...
30:33
publication status on status in the field seniority
30:37
and I think what ECTS does really well is to
30:40
really emphasize on on the ECR members and Actually
30:44
also leave that in our hands. I think as the
30:46
Academy like they give us lots of tools in our
30:50
hands to to To help help create this program
30:54
basically really for the ECR So I think and it's
30:58
also what they what they like a lot is that they
31:00
will come back for that And this reinforces also
31:03
their connection with ECTS and feeling basically
31:07
at home with a society, which in your professional
31:09
career, this is something that you will need
31:11
to do eventually. And that's really important.
31:14
I really like ECTS. It's a very friendly conference.
31:19
I do feel at home here. I feel that other people
31:21
feel at home here. You mentioned earlier on about
31:23
how sometimes it's difficult to get scientists
31:26
from different backgrounds together, and you
31:27
talked about clinical and basic science. Yeah,
31:30
a lot of conferences only tend to have one or
31:33
the other. ECTS has a very good mix. David, you'll
31:37
know about this. Sometimes it's hard to get clinicians
31:39
to come to conference because they've got really
31:41
crazy, busy lives. ECTS does that very well.
31:45
And I wonder if it's because of this holistic
31:46
approach that you're taking. Being a young scientist
31:49
is so hard. It's so difficult to develop your
31:52
career, get a staff position, and then build
31:55
your profile. It's really amazing that you're
31:57
supporting people through really their most difficult
31:59
years. And if I was a younger researcher or younger
32:03
clinician and I had an idea of something that
32:06
I would maybe want the academy to do, I take
32:09
it you're sort of open to that, responsive to
32:11
sort of facilitate and help people? Yeah, definitely,
32:16
because I think this program was initiated, seven
32:19
or nine years ago. Initially started out with
32:22
a small group of people, I think seven or eight
32:25
initially, and it steadily grew over time. Now
32:28
we are 32 members currently. We already have
32:30
33 alumni. And it means that we actually have
32:34
lots of hands available for different projects.
32:37
So we have the activities that Alex already explained
32:40
that we are running on an annual basis. But we're
32:43
also, every year we're reviewing our activities
32:46
and... trying to think of what is something new
32:49
that we can do, or should we revise our current
32:52
content? We actually did that this year. We did
32:55
an outreach to the different society program
32:57
at the conference previously, and now we decided
33:00
to put a much more prominent slot in the program,
33:05
highlighting our own activities and explaining
33:08
the transparency and fairness behind the recruitment
33:10
process, and also explaining that we are not
33:13
an elite organ operating. by itself, but actually
33:18
we like to collaborate with any ECTS member and
33:21
we're open for input from anyone. I think that's
33:25
an important thing is that when you look at how
33:27
it's building, it isn't just a select few. So
33:30
five to seven people come in to a year, which
33:33
might seem quite restricted, but as you were
33:36
saying, it's now 65 people have... either completed
33:41
or are in the program so we think another 10
33:44
years we're talking 150 people presumably the
33:47
majority at the conference will have been through
33:48
that and there's kind of a kinship you know there
33:51
is a big social element to it as well as a scientific
33:53
element and it's that idea that hopefully these
33:56
are the professors the leaders of the field of
33:58
the future and that you get them working scientifically
34:02
get a good kind of atmosphere collegiality between
34:05
them that makes for a more productive friendly
34:09
approach to the field growing a big family so
34:12
if there's somebody listening to this now a young
34:14
scientist who might want to get involved how
34:16
would they go about joining and applying so there's
34:21
an annual call so this comes up late in the year
34:25
and you will be asked to submit a form which
34:30
kind of indicates how you fit with different
34:32
criteria so it'll be details of your publications
34:34
or details of your grants education etc also
34:38
your service to learned societies because we
34:42
want people who've shown that ability that collegiality
34:45
to go above and beyond papers and money to to
34:48
contribute to the field and then you also write
34:50
a motivation letter that really helps us to understand
34:53
why you want to do this and you will have a references
34:56
so approach us and and ask us for advice about
35:00
this because i think there's also we've we've
35:02
talked a lot about this over the last year there's
35:05
really a i think of perfect point or you know
35:09
perfect points when people could apply I think
35:11
you can technically apply after your PhD but
35:15
I think only very exceptional individuals and
35:18
certainly I wouldn't count myself amongst them
35:20
would be mature enough and have the work position
35:23
where they could best take advantage of it because
35:25
you know you think in your first postdoc you're
35:27
still really learning you probably have a really
35:30
It's a bit difficult to get hold of a project.
35:32
You're getting hold of a project for the first
35:34
time, probably learning new literature. So that's
35:37
quite challenging. And probably you don't have
35:39
the capacity to go and do new projects and commit
35:42
to new things. Whereas in your second postdoc,
35:44
perhaps, or a bit more experienced towards the
35:46
end of your postdoc, you've probably got more
35:49
freedom from your PI or you might have a fellowship
35:52
that you can initiate your own projects. You're
35:55
more confident. You've developed better skills.
35:59
It's not an indication against you if you're
36:02
not successful early on. It may be a better fit
36:08
to you later on in that 10 -year window so you
36:10
can apply up to 10 years after your PhD and perhaps
36:14
think about, you know yourself, and maybe speak
36:17
to mentors or senior colleagues and think, am
36:20
I in the position where I could best take advantage
36:23
of this opportunity? It sounds like a really
36:26
big time commitment that you both have to make,
36:28
the residential weekends, the meetings and things.
36:30
How does this work alongside your day jobs as
36:33
being academics, researchers and clinicians?
36:36
Does it help you? It does definitely help, I
36:41
think. I mean, if you look at the life of a scientist
36:44
nowadays, it's... i would say 80 administration
36:47
anyways so this is just another thing to to administer
36:50
of course but i think the big difference is also
36:53
that because you contribute to the mission to
36:55
of a society it's also quite fulfilling uh to
36:58
do um i think i would like to emphasize also
37:02
on the fact that why maybe you're alluding also
37:04
or asking about the fact how did this help my
37:06
my career also So Derrida has been, maybe it's
37:10
anecdotal, but I don't think so. I think it highlights
37:12
one of the missions of the society. So I was
37:14
working, I'm entering into a new field where
37:18
there's not too much literature basically available.
37:20
And just by serendipity, I was learning about
37:26
clinical colleagues within the academy that are
37:29
working in the diabetes fields and trying to
37:32
use the same... type of drugs that I'm actually
37:36
interested in testing in an osteoarthritis condition.
37:39
And while we were both sharing experiences, we
37:44
did an exercise at the last retreat where we
37:46
said, please, in one line, explain what your
37:48
topic is about and what line of research you
37:50
would be interested in pursuing in a collaborative
37:52
effort. And when you find out that you're basically
37:56
with a person that you would not realize that
37:58
you would share a similar future perspective.
38:03
to go into together. So when that became clear,
38:07
we started thinking about, OK, how can we make
38:09
this work? And what would be interesting? And
38:11
basically, scientists think a lot inside of their
38:16
box, I think. You look at a profile online and
38:19
you would say, okay, this is an endocrinologist
38:22
working on diabetes. I'm a translational scientist
38:25
working on osteoarthritis. These are different
38:27
diseases. Probably we have nothing in common.
38:29
But there is much more common ground than we
38:31
think. And I think that's really what I learned,
38:33
what I appreciate most, I think, in the ECTS
38:37
Academy, that we actually also in terms of career
38:40
development, I think we're much more similar.
38:42
then we are different and and that helps a lot
38:45
and i think what also helped me a lot it it also
38:47
provided me with a support network of people
38:50
that go through similar experiences career -wise
38:53
as we are so from the outside it might seem like
38:56
okay you were elected into the academy because
38:58
you were so successful but success also comes
39:01
with a tall basically and especially for us early
39:04
career stage i think it puts us a pressure on
39:06
you and so we're all dealing with the same with
39:09
the same issues how do you deal with this admin
39:11
having a heavy task how do you balance work work
39:16
work life balance how do you how do you go about
39:19
difficult situations with your with your personnel
39:22
maybe with the dean maybe at your at your at
39:24
your department what if you miss a promotion
39:27
and this is really helpful to to go back to this
39:30
support network out outside of your closer academic
39:34
environment and just have an opportunity to find
39:38
out that you're not alone in this either. And
39:40
I think that's one of the things. I mean, we
39:43
as chairs also talk regularly. I mean, every
39:46
other week we just have a quick phone call. And
39:49
it's really, really helpful also on a personal
39:51
level. Yeah. I mean, you said you were asked
39:53
that you're... people attending to summarize
39:56
what they did in one sentence i won't ask you
39:58
to do that now but if you could give us just
40:00
a very brief summary of what your area alex what
40:03
are you looking at at the moment in your research
40:05
so it's bone mechano adaptation so how bone adapts
40:09
to exercise and disuse and over the last few
40:11
years that's really focused on the earliest stage
40:14
of life so prenatal movements and development
40:17
motor skills and walking in infancy oh that's
40:21
that's really exciting because we have talked
40:23
a lot about getting older people to exercise
40:26
and the benefits of weight -bearing exercise
40:27
in older folk. The benefits of exercise in adolescence
40:31
is also really important. You're actually looking
40:34
at it sort of pre -birth. That's very exciting.
40:37
Yeah, I think so. So yeah, it seems to be quite
40:41
a profound effect that this is the period at
40:44
which the skeleton is growing most rapidly. I
40:46
mean, not even as a relative amount, as an absolute
40:48
amount. You change in body length prenatally,
40:52
and I think you go from a single cell to 45 centimetres
40:56
in nine months, even in the pubertal growth speed,
41:00
but you don't do that. So it's a period of unrivaled
41:03
growth, and it's also a novel opportunity for
41:06
you to be introduced to. to loading so when you
41:09
are an older person you might not do a lot of
41:10
exercise but you were still walking generally
41:12
and loading your bones as a baby it's a big transition
41:15
from being on your back to then running about
41:18
within the space of you know a month or or two
41:21
yeah that's fascinating how do you measure activity
41:23
in in utero so there's a different a couple of
41:28
different ways there are monitors that you can
41:30
put on the abdomen and they can measure measure
41:35
movement we also take different models so we've
41:37
looked at babies that are breech so when babies
41:39
are in breech position they're less able to move
41:42
their legs and some beautiful mechanical modeling
41:44
studies that have shown that the loads that you
41:47
can apply to the womb lining the uterus lining
41:52
and therefore the forces that are acting on the
41:56
legs are much lower in children that have breech.
41:58
And also other conditions like oligohydramoneos,
42:01
etc. So we can use those as kind of reasonable
42:04
models where we can expect the loading is lower.
42:07
And actually there's quite a clear clinical consequence
42:10
that breech position, for example, is by far
42:14
the biggest risk factor for developmental dysplasia
42:16
of the hip. Of the hip, yeah, that's interesting.
42:18
Which in turn is a big risk factor for osteoarthritis
42:21
later on in life. Exactly, yeah. And Aaron? It's
42:25
a nice bridge because I'm actually working on
42:27
osteoarthritis. Well, as soon as he said that,
42:29
I thought, yeah, we'll move over here. Perfect.
42:31
Seamless, seamless, definitely. Good presenting.
42:34
I have a long -lasting interest in subchondral
42:37
bone remodeling in osteoarthritis, and I realized
42:40
that when looking basically at histological images
42:44
of subchondral bone, that there is a tissue component
42:47
there that hardly anyone talks about, which is
42:49
the subchondral bone marrow adipose tissue. Maybe
42:53
I can ask you a question. What do you think the
42:56
function of subcranial bone marrow adipose tissue
42:58
is? So we're talking about fat then? We're talking
43:01
about fat inside of the bone tissue under our
43:03
cartilage surface. And if you'd asked 10 years
43:06
ago, we'd have said the fat just sits about there
43:08
and does absolutely nothing. Whereas now we know
43:10
it's probably the most active, metabolically
43:12
active tissue in the bone and has all these relationships
43:15
with what's going on in the rest of the body.
43:18
Yeah, so it's a really exciting area, so that's
43:20
why we're hoping that you're going to tell us
43:21
about it. Exactly. Well, I'm very happy that
43:23
actually these concepts are better known than
43:25
I expected, because if I write a grant, and I
43:27
typically use this statement as well, I say this
43:30
was considered for a very long time as an inert
43:32
filler tissue. Tell them that at least one clinician
43:34
has heard of it. That's good, that's good. It's
43:37
good to know. But indeed, it's much more dynamic
43:40
than we actually expected, and it also responds
43:43
very rapidly to different nutritional conditions.
43:47
like overfeeding or even being on a low calorie
43:53
diet, for instance. And this induces many changes
43:56
to the actual fat cells. So what we were realizing
43:59
is when we think about conditions... where you
44:02
have loss of tissue turnover, or in the case
44:05
of osteoarthritis, you get loss of bone formation.
44:08
Then we started wondering what is happening with
44:10
the energy that is stored inside of bone marrow
44:12
adipose tissue. Because what you see is that
44:15
the bone marrow adipose tissue is disappearing
44:16
and being gradually replaced by bone. It hasn't
44:20
helped much in the field that people have used
44:22
nomenclature to say this is a fibrovascular invasion
44:26
of bone marrow adipose tissue, which would be
44:28
a process that's completely opposite to what's
44:31
actually happening. It's not an invasion of the
44:33
tissue. It's rather that there's a local expansion
44:35
of the cells that are there in the hematopoietic
44:38
niches, for instance, or the stem cell niches,
44:40
and they need lots of energy basically to fuel
44:43
this process. If you're forming new bone, you're
44:45
producing collagen, you're mineralizing, and
44:47
this in terms of energy requires quite a lot.
44:49
You would say the body will use glucose for that,
44:51
but that's not the case. So elegantly shown in
44:55
animal models, they actually show that lipolysis
44:57
in bone marrow adipocytes energy to the bone
45:02
cells. What's lipolysis? Lipolysis is the process
45:05
by which the energy stored in adipocytes or triglycerides
45:09
get cleaved down to glycerol and free fatty acids
45:13
and these are basically energy substrates that
45:16
can be used by bone tissue. So what we are interested
45:20
in now is basically trying to understand how
45:24
does this tissue remodel in an OA versus a non
45:28
-OA condition. That's the first question. And
45:30
second of all, Can this be a link between obesity
45:35
and OA that we still understand quite poorly?
45:38
Because we have been thinking about this in the
45:40
field for a very long time. And I think for knee
45:43
osteoarthritis, we agree that loading plays a
45:45
big part in it. But we're also still baffled
45:49
by the fact that hand osteoarthritis is also
45:51
associated with BMI. We don't walk on our hands.
45:56
So loading is not the only component of it. People
45:59
in the field then often say, well, then it must
46:01
be systemic low -grade inflammation. And then
46:03
I would question again, but why does anti -inflammatory
46:09
medication then not offer a solution in a way?
46:11
So is this really the case? So that's what my
46:14
research is focused on right now. We're trying
46:16
to investigate it also in different types of
46:18
osteoarthritis. We're investigating base of the
46:21
thumb OA. hip OA and knee OA. We are getting
46:25
clinical samples from patients undergoing knee
46:27
replacement or joint replacement surgery. We
46:30
get them fresh from the surgical theater. We
46:32
isolate the adipocytes. For instance, we do expand
46:35
culture of the whole bone marrow unit just to
46:39
understand if bone formation markers are correlated
46:42
with lipid release, for instance, from these
46:44
adipocytes and try to also modulate this. And
46:47
the modulation is what we're interested in. much
46:50
right now is to use anti -diabetic drugs and
46:52
we're focusing of course a lot on the weight
46:54
loss drugs that are coming on the market now
46:56
because they seem to have in observational studies
46:59
fewer rates of joint replacement in these patients
47:04
and we don't know why but we think that this
47:06
pulmonary adipose tissue that these drugs act
47:08
on that tissue directly They target also the
47:13
pathological bone formation that's ongoing, and
47:15
this might be responsible for less pain and also
47:18
less progression of disease. Wow, what a wonder
47:20
drug. Yes. Yeah, well, it's lovely to see what
47:26
you do as well, outside just being co -chairs
47:28
of ECTS, and we'll watch the research with interest
47:32
then. Thank you very much for joining us. Thank
47:34
you. Thank you, guys. Thank you. Well, we're
47:38
at the airport now, everyone. We're about to
47:40
travel back home. We've had a really wonderful
47:41
trip to the conference. Thank you so much for
47:43
joining us. I hope you enjoyed listening. Au
47:46
revoir tout le monde.