Latest / 'Bone Up' / BoneUP Live 2025 @ECTS - Part 3

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BoneUP Live 2025 @ECTS - Part 3 · 'Bone Up'

0:00
Hello and welcome to Bone Up, the podcast all
0:04
about bones, how we make them, why we break them
0:07
and if we fully understand them. I'm David Armstrong.
0:11
Hi and I'm Richie Abel and over this series we're
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going to be exploring osteoporosis, bones, what
0:18
we know and what we're yet to discover and we
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hope you will join us on the journey. So for
0:24
anyone keen to learn more about our infrastructure
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of calcified collagen, this is Bone up. Welcome
0:54
back to episode three of Bone Up Live at the
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ECTS here in Innsbruck, Austria. We have some
1:01
more interesting interviews lined up for you,
1:03
which I hope you will enjoy. Listeners, we're
1:12
really pleased to introduce our next guest, Dr.
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Morten Svara Hansen. He has two appointments
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at two university hospitals in Denmark, the first
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in the Department of Endocrinology at the University
1:24
Hospital of Southern Denmark, and his second
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is a postdoctoral researcher at the Department
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of Endocrinology at Unze University. We English
1:34
people pronounce it Odense. Well, just when we're
1:37
looking at the football scores, but we've learned
1:39
that it's Unze. And congratulations, Morten.
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You won the prize for the best clinical paper
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at ECTS 2025. That's a really big award. How
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are you feeling? Well, thank you very much. And
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thank you for letting me participate in this
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podcast. So obviously, I feel very good. But
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I mean, I also would like to use the opportunity
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to just announce that while I was the face of
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the paper, that this is... obviously something
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that a lot of other people contributed to in
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a manner that allowed me to be up there and present
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the data. So it's also definitely for my co -authors
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that I just want to state. But on behalf of them
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and also, of course, on behalf of myself, I'm
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extremely proud because this is such a big acknowledgement
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that you put a lot of time and effort into from
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planning a clinical trial, receive the funding,
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recruit the participants. fulfill the trial and
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then write up the data and then i mean it all
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ends out in the paper that's you know not really
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that many pages but but get the acknowledgement
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to to that it was of a certain quality and present
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the basis is really nice you were talking about
2:48
a drug or a family of drugs that's very topical
2:51
at the moment not always associated with bone
2:53
health so tell us a little bit about what you
2:55
were talking about yeah so we talked about semaglutide
2:59
which is a glp -1 receptor so it means that it
3:02
mimics the effects of a natural occurring gut
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hormone known as GLP -1. I actually used a slide
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just to show the timeline for approval of GLP
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-1 receptor agonists because the first one was
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approved in 2005 for type 2 diabetes, but later
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GLP -1 receptor agonists have also been approved
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for type 2 diabetes and obesity. But I used that
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table as a timeline because things have really
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escalated within the last five, six years within
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this area because it's been called a blockbuster
3:34
drug because people who are not even obese or
3:37
severely obese weight can lose weight so i mean
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it's become a very popular drug and and it has
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been so popular that that the demand has overseen
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the the manufacturer's uh availability of the
3:49
drug as well so yeah yeah so so it really is
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a popular drug and and it's also a very good
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drug that that has many beneficial effects so
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it's a weight loss drug but Taloside affects
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the bones then? Yeah. So I just want to state
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first that the dosage that we used was the dosage
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that we normally use in patients with type 2
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diabetes. So that's one milligram, right? So
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the idea of this clinical trial was based on
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a series of mainly animal trials. So it seemed
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like GLP -1 receptor agonist could increase bone
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mass in bone loss models or maybe even protect
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against bone loss from these bone loss models.
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And there was some... studies in cells that indicated
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increases in osteoblast and decrease in osteoblast
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activity and so on. So we hypothesized that treatment
4:36
with this type of drug would have beneficial
4:40
effects on bone formation. And we find that interesting
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because, I mean, when we talk about osteoporosis,
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the thing is that we do not have that many drugs
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to choose between. And some of them, I mean,
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they're in the same group of drugs. So with this,
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I mean, if we had something that was already
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available in the toolbox that had bone formative
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effects, I mean, suddenly the idea was that,
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well, could it be repurposed for treatment of
5:08
low bone mass? It could be another pathway. Exactly.
5:09
Yeah. What happened then? So what happened is
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that we looked, I mean, we used DEXA scans and
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blood samples to look at bone turnover markers,
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and we had bone biopsies to really assess bone
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remodeling at tissue level. But we actually didn't
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see any difference in bone formation in circulating
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markers or in our bone biopsies after 52 weeks
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of treatment. And we compared semaglutide to
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placebo, which in this case was saline. On the
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other hand, we saw a massive increase in CTX,
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which is bone resorption marker, and we also
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observed significant decreases in bone mineral
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density at the lumbar spine and in the total
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hip after one year of treatment. Wow. So you're
5:55
basically in humans and you're finding kind of
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opposite results to what was previously reported
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in mice. Exactly. Actually, the complete opposite.
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Wow. We often talk about mouse and human research
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and how relevant is mouse research to human research.
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What else did you find when you investigated?
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So we also had some extreme CT scans, which is
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mainly made of the distal radius and the distal
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tibial part of the skeleton, and that's to distinguish
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trabecula from cortical bone compartments. And
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we observed that... Cortical thickness and the
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volumetric bone mineral density in the tibia,
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but not in the radius, was decreased with semaclotide.
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So that led us to the assumption or the part
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conclusion that the effects were mainly observed
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on the weight -bearing parts of the skeleton.
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And this corresponded very nicely to the fact
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that we also observed that... the average weight
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loss was 9 % within 52 weeks in the semaglutide
6:58
group compared to placebo group. So just to finish
7:02
that, I mean, we think that it induces this unloading
7:06
effect on the skeleton that we know from the
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mechanostat theory will eventually increase resorption
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and remove bone because the threshold, the strain
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threshold has changed when you lose weight. So
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I suppose the next question then is, for this
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group of patients who took the semi -glutide,
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how was their bone mineral density and their
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bone health at baseline? And how did it change?
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Did it move towards osteoporosis or osteopenia?
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So one of the inclusion criteria were that they
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had to have what we called increased fracture
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risk, which was either a T -score at the lumbar
7:43
spine or total hip or femoral neck below minus
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one. or low energy fracture, so osteoporotic
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fracture within three years of recruitment. But
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we did have 15 participants who had osteoporosis
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either based on their DEXA scan or based on a
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low energy fracture, but some of the participants
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attended the study because they didn't want the
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conventional anti -osteoporosis treatment, right?
8:07
So we did assess at the end of the study all
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of our participants and advised them, depending
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on their... DEXA scan and T -score if they were
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candidates for osteoporosis treatment. I can't
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remember the exact number but I'm pretty sure
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that it was not more than one who might have
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went from the osteopenic T -score into the osteoporotic
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T -score but I mean it's something that we definitely
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should be aware of. So what do we do next then?
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Do we co -prescribe bisphosphonate with the semiglutide?
8:38
Do you tell patients if they're going to take
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the semiglutide they have to do weight -bearing
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exercise? Where are you going next with your
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with your study well i think first of all i mean
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exercise and and focus on nutrient intake when
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you start these type of drugs is is a recommendation
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that you should provide your your patients um
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for the other question i mean it's very important
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to look into risk factors, right? Do they have
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risk factors? So it's an individual assessment,
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but it's definitely something that we as medical
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doctors need to think about. So obviously there's
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a difference if you put a 35 -year -old male
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who is obese on this drug, or if you put maybe
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a fragile old person who has a history of a low
9:24
energy fracture into this drug. So it's an individual
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assessment. Knowing that this type of drug induces
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an almost 10 % weight loss, as a medical doctor,
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you need to expect that they will lose some sort
9:39
of bone. And then it's up to you to kind of assess,
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well, is this something that makes it a higher
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risk for you to, let's say, develop osteoporosis?
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And are you certain that's not something to do
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with the... with the pathway the glp -1 pathway
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it's definitely due well i'm not asking a scientist
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to say anything's definite but your hunch at
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the moment is it's the fact you're just unloading
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the bone there's not as much weight bearing and
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therefore the bone is responding to that you
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don't think there's a bit of the pathway that
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you don't understand that it's maybe contributing
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to bone loss as well i think it's worth looking
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into actually because the thing with this trial
10:15
and that's something that you can look at afterwards
10:17
that when we do see this massive weight loss,
10:20
it really makes it difficult to distinguish potential
10:22
direct from indirect effects, right? So one of
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the things that we talked about was that it would
10:28
have been fantastic to have a third arm in our
10:30
trial in which participants lost the same amount
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of weight but on calorie restrictions only because
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then we would have a chance to do a head -to
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-head comparison between what is the bone loss
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after calorie restriction on diet alone and what
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is the bone loss when you use semaglutide. Or
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a fourth arm using weight -bearing exercise.
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It's a little to lose weight. Positive and negative
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control. Yeah. You mentioned earlier that some
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people are taking the drug even if they're not
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very obese, maybe just overweight, maybe not
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obese. What would this mean for those people?
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Are there any plans to do any research on them
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and how the weight loss might affect their bone
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health? So, I mean, one of the things that, of
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course, makes it difficult now is that now we
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have data that shows a potential negative effect
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of a drug, right? It's harder to do more research.
11:23
Exactly. So, I mean, when we design a study,
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both thinking about how to fulfill the experiment,
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but... also very much because of the ethical
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consideration of what it's like to include participants
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that we know might lose bone, right? So what
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we are thinking about doing next is to actually
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look into patients who are... per se candidates
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to receive this treatment so that we include
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someone who otherwise would actually still be
11:53
candidates to be prescribed this. So that has
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changed our mind of who to include from when
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we designed this trial. And I don't know if this
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is an unfair question. Did you ask the subject,
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the patients, what they thought of the balance
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between losing weight? Because I presume most
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of them were very happy to have lost a lot of
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weight. But if you said to them, look, you've
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lost a little strength in your bone as well,
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what did the patients think of that as a potential
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side effect? It's actually a very good question.
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And actually, once again, I think I need to go
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back to the time and the fact that... you know,
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knowledge has really escalated within this field
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because I can still remember talking to some
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of our participants that at that time we didn't...
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quite have the data on what happens when you
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stop the treatment. And then along came, well,
12:45
these studies that you regain weight when you
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stop. So I told them, please don't change all
12:49
your clothes if you start losing weight. But
12:52
yeah, so this, but obviously we actually invited
12:57
all our participants to discuss the data because
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it showed the opposite of what we found. And
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I mean, it was a... fantastic group of people
13:05
and and they had very nice questions i didn't
13:08
ask that particular questions but i mean they
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were most of them were postmenopausal women so
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they they had some sort of idea of what it's
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like to have osteoporosis and and have focus
13:20
on on bone health so it's actually something
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that i think we need to maybe address a bit more
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when we design our studies to to interview participants
13:29
or at least relatives yeah wonderful This is
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a really interesting story. I hope that you continue
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to research it and hopefully we'll see you at
13:40
future ECTSs so we can get a bit of an update
13:42
on how you're getting on. I think a lot of the
13:44
listeners are going to be excited to hear more.
13:46
Yeah, it's a story I think that has repercussions
13:48
outside just the bone world as well, doesn't
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it? It's an interesting general concept. Well,
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thank you very much for inviting me to this.
13:57
Thank you. Thank you, Morten. Listeners, I'm
14:05
very, very pleased to announce our next guest.
14:08
It's Mr. Jamie Rowe, who is a PhD in the Bone
14:12
Health Research Group at Imperial, which is our
14:15
group. And his primary supervisor is Ulrich Hansen,
14:18
who's my closest collaborator for 10 years. And
14:21
I think this is a really exciting research project.
14:23
Welcome, Jamie. Hello. Lovely to be here. thanks
14:27
for coming to the podcast. Jamie is a relatively
14:29
early career researcher then, as opposed to some
14:33
other people who've been at this for a long time.
14:35
But I mean, one of our aims, I think, in the
14:37
podcast is to give a voice to people who are
14:40
starting off and to encourage them that we're
14:43
all part of the bone community and we can all
14:45
learn from each other. So we will ask you some
14:48
hard questions now about your research. You look
14:51
terrified. It's fiber training. How have you
14:57
found your first ECTS? Yeah, it's been great.
15:00
Really interesting talks. Good to talk to lots
15:03
of different people. And you presented your poster
15:06
here. Did people come and talk to you about it?
15:08
Yeah, I had a few people come over and ask me
15:10
questions and things. Nice. Always good to get
15:12
different opinions. You've been doing some work
15:15
then on, let me call it the quality of bone or
15:18
the strength of bone. Tell us a little about
15:21
just what you've been looking at and why you've
15:24
been looking at it. So at the nanoscale, bone
15:27
is a composite material. Basically, you have
15:29
sort of deformable collagen molecules and brittle
15:33
mineral. And in man -made composite materials,
15:36
we often kind of attribute their good mechanical
15:40
properties to kind of the formation of basically
15:42
residual stresses. These are sort of stresses
15:44
that form during manufacturing generally. Okay,
15:47
and we'll translate that and say that composite
15:49
materials, you make things like concrete. Yeah,
15:52
so something like pre -stressed concrete, basically,
15:54
where you have concrete and then steel bars generally.
16:01
And basically, in pre -stressed concrete, you
16:04
have the steel bars are kind of put under tension,
16:06
the concrete is poured over, and then the tension
16:09
is, like, released, and basically then those
16:11
steel bars kind of compress up and put the concrete
16:14
under compression, basically, and that drastically
16:16
increases the ability of concrete to kind of
16:19
withstand. Yeah, so it's almost like a coil spring
16:22
inside the concrete, which is compressing it
16:24
and making it even stronger than it would be
16:26
by itself. So it turns out human bone might be
16:29
like that, is it? Yeah, exactly. So we believe
16:33
that basically collagen kind of has this... So
16:36
this is work that kind of came from Peter Fratz
16:38
on Potsdam. We believe that collagen kind of
16:41
has a similar role to those steel bars in the
16:43
concrete, where during the process of bone formation...
16:47
the collagen kind of starts to shrink up and
16:50
then that puts the mineral sort of under compression
16:52
and then that will give bone its great mechanical
16:55
properties, basically. So I've been trying to
16:57
understand the molecular origin of this. And
16:59
water's important in that process, is it? How
17:02
wet the bone is? How much water there is in it?
17:05
Yeah, so we can just think about tendons, which,
17:07
you know, is kind of, you can just think of unmineralised
17:10
collagen. And we understand that when tendons
17:13
sort of... dry up or are put under osmotic pressure
17:15
so kind of water is removed from the collagen
17:17
the collagen molecules start to shrink up yeah
17:20
and so the kind of idea is what if a similar
17:22
process is happening when the mineral starts
17:24
forming right so the mineral kind of comes in
17:26
replaces the water yeah and then that replacement
17:30
of the water removes the cause of the collagen
17:32
to kind of shrink up but the thing is we don't
17:35
currently understand why collagen shrinks up
17:37
when it is put under it dries up so that's what
17:41
i've been trying to look at basically Why does
17:43
collagen like to kind of shrink up when water
17:46
is removed? So when the collagen shrinks and
17:49
starts to pre -stress the mineral, how much would
17:53
that increase the strength of bone by? So we
17:56
can estimate from experiments that it is of the
17:58
order of tens of megapascals, which is sort of
18:02
equivalent to kind of the peak stresses that
18:04
you undergo during daily motion. So we can imagine
18:08
this kind of almost doubles the strength of bone,
18:11
basically. You can imagine that during motion
18:14
you're actually just undoing that pre -stressing
18:16
rather than adding extra stress to the bone.
18:19
So it makes a huge difference then if you're
18:21
doubling the strength of bone by tensing it.
18:27
That makes a big difference. Could there be a
18:31
role for this kind of pre -stressing in rare
18:35
bone diseases? We've heard quite a lot at the
18:37
conference about osteogenesis imperfecta where
18:40
mutations in the collagen. cause it to malform
18:42
and lead to malformation of the mineral. Yeah,
18:46
so one of the things we found in my research
18:48
was that these pre -stressing, this pre -stress
18:52
behavior seems to be localized to very specific
18:54
amino acids, basically, in collagen. So we found
18:58
that the collagen has this kind of repeating
19:00
pattern, but the amino acid pattern kind of changes
19:03
as you go along. And we found that most of the
19:06
collagen amino acids... don't actually change
19:09
when they're kind of dehydrated. In fact, actually
19:11
most of them kind of expand slightly. And the
19:14
contraction is actually kind of localized to
19:16
a handful of very important, clearly, amino acids.
19:21
So then we can start to think about rare bone
19:23
disease and think about mutations. So if you,
19:25
for example, mutate some of these regions, do
19:28
you then kind of reduce the ability for the collagen
19:31
to pre -stress the mineral? So we know as you
19:33
get older, your bones become dehydrated in general
19:35
in humans. Bones dry up. So that could be in
19:38
itself contributing to the weakness of the bones,
19:40
just the fact that bones tend to dehydrate as
19:43
you get older. Potentially, could we rehydrate
19:45
older people's bones in some way? That's a hard
19:48
question. It's an interesting one, though, isn't
19:51
it? It would be a very cheap treatment, potentially.
19:56
Look, it's been great to talk to you. Thanks
19:57
for coming and sharing your work. We look forward
20:00
to speaking to you in another 10 years, you know,
20:02
when you're running your own lab and just as
20:04
successful as Richie is. Thanks for having me.
20:08
Jamie's brighter than me. He's going to go further.
20:11
Well, that's great. I hope you've enjoyed your
20:12
first conference and enjoyed your first visit
20:14
to Bone Up. Yeah, it's been great. Thank you.
20:22
Listeners, we have our next guest with us, Friederike
20:25
Schulter from the Institute of Biomechanics at
20:27
ETH Zorich. Welcome. Thank you. Welcome here.
20:30
I'm glad to be here. Thank you for coming back
20:32
to join us. We spoke to you last year. We had
20:34
a really fantastic episode of the podcast where
20:37
we were speaking to you about your animal trials
20:39
where you had potentiated the effect of romasozomab
20:43
using mechanical loading in a mouse model. This
20:46
year you've come back with the next stage of
20:48
the research and you gave a really fantastic
20:50
talk yesterday morning about MPA models. Would
20:53
you tell us a little bit about the work you've
20:55
been doing? Yes, sure. Micro MPA models are another
21:00
approach to learn more about the mechanisms behind.
21:03
and more at the cellular and the molecular level,
21:06
because what we did before is using microcomputed
21:11
tomography scans of the preclinical mouse model
21:16
of osteoporosis, and there we can see how the
21:20
morphometry and the bone remodeling changes over
21:22
time. But we don't have access there to the...
21:27
molecules and which molecule is expressed and
21:30
how are the bone cells communicating with each
21:33
other and that's still the the key question why
21:38
would we see changes in the micro bone microstructure
21:42
of the bone according to osteoporosis according
21:46
to mechanical loading or also to pharmacological
21:50
treatment so we really wanted to understand what
21:54
are the molecular mechanisms and using micro
21:58
multi -physics agent -based modeling so micro
22:01
mba modeling is an approach that goes from bottom
22:05
up actually That is to say, we use mathematical
22:08
rules that we define ahead. And those rules are
22:13
really on the molecular level. How do pre -osteoclasts
22:19
multinucleate into osteoclasts? And which proteins
22:23
do the osteocytes release? which signals do those
22:30
molecules then trigger regarding osteoblasts
22:33
or osteoclasts. So these rules are all defined
22:36
at the beginning, and then you give an input,
22:39
a real experimental in vivo structure of a basal
22:44
scan, actually, of such a bone. And then the
22:48
model is run over iterations and iterations,
22:51
and you hope that the output... the bone microstructure
22:55
that you get in silico as an output that this
22:58
would fit to the experimental microstructure
23:01
that you saw in the experiment. What did you
23:04
find when you compared your MPA model to the
23:07
real mouse data? We tried to calibrate regarding
23:12
the bone volume fraction, this is our primary
23:15
goal, and this worked out in the mice. And we
23:23
defined or we hope that with such micro -MPA
23:26
models, we can then test and validate or also
23:30
reject hypotheses that we set at the cellular
23:33
molecular level. For example, in the study I
23:36
presented yesterday, we tried to simulate postmenopausal
23:41
osteoporosis in an animal model of osteoporosis
23:44
by ovorectomy, which results then in a bone loss.
23:51
in the next five to nine weeks. And we tried
23:57
to define those rules by saying that on the pre
24:03
-osteo class, we reduced the number of bound
24:09
to unbound receptors. And rank L receptors, I
24:14
had to say. And this facilitates the multinucleation
24:18
into the active osteoclast. So osteoclasts are
24:22
more proactive. And this also led to reduction
24:28
in bone mass, as we had expected. So what you're
24:31
saying is instead of doing the experiment on
24:33
a real mouse, to put it like that, you're creating
24:36
a model. And when you say a model, it's a computer
24:38
model? isn't that right exactly yes so and then
24:42
you're sort of doing the experiment on the computer
24:43
model and you can move all the turn the knobs
24:46
up and down and increase this and reduce that
24:48
and then you're checking to make sure that your
24:52
computer model actually reflects the sort of
24:54
work has already been done in mice to make sure
24:56
that it's accurate and then you can do lots of
24:58
new work on the computer model which has never
25:01
been done on the mice that's the That's the sort
25:03
of thinking? That's exactly the way of thinking.
25:05
And because in the computer model, we will then,
25:08
once we have validated the computer model, we
25:11
have access to molecular concentrations, also
25:15
the cytokine dynamics over time, which is very
25:18
hard to get in people. Yeah, in a mouse, yeah.
25:22
Exactly, even in the mouse. Yeah, once it's validated,
25:27
we can then see how, for example, the Larson
25:30
expression changes over time or Rangel expression
25:34
goes up. Yeah, and this is quite interesting.
25:38
And from this, micro -MPA models are used very
25:42
much in order to also generate new hypotheses
25:44
because you have the chance to test various pathways.
25:50
Two or three. And you can do all sorts of crazy
25:52
things in your model that you wouldn't maybe
25:53
want to do on the mice. That as well. Yeah, well,
25:56
you can generate all sorts of hypotheses. Yeah,
25:59
that's right. It's kind of a contribution towards
26:03
the 3R principles to reuse existing experimental
26:07
in vivo data that we have in order to validate
26:10
micro -MPA models, which then hopefully in the
26:13
future can then also give new insights into clinical
26:17
outcomes. And you have to use less for your mice
26:22
then, obviously, as part of your experiments,
26:24
which is a good thing. Because we can pre -test
26:26
certain hypotheses, and when we find in silico
26:30
that this is worth investigating, then only then
26:34
can you go and do experiments. So you can greatly
26:37
reduce the number of animals in the research
26:39
and ask questions in the model that you might
26:42
not be able to answer with the animals at all.
26:45
Exactly. It's an amazing contribution. A cynic
26:49
might listen to this and say, well, that's great,
26:52
you're creating a perfect model of what the bone
26:55
regeneration is like in mice. Why not do that
26:58
in humans? Why bother with the intermediate step
27:01
as you've got a computer that you can just create
27:03
your own model then? Exactly, it's a very good
27:05
question. So the input structure that we give
27:09
is an animal structure, but of course the input
27:12
structure can also be a clinical biopsy or any...
27:18
pqct scan of course a patient scan and the reason
27:21
why we do the pre -clinical um modeling is that
27:27
we as a as an in silico person you always have
27:31
to face the question how how much can i trust
27:35
your model isn't it And this is an attempt to
27:38
first really validate and show that it works
27:41
on the preclinical data, because with the in
27:46
vivo microcomputed tomography data, we do have
27:49
the endpoints and the experimental structure
27:51
at the endpoint, where we can then show whether
27:54
our model is able to reproduce this exact in
27:58
vivo experimental structure, which we sometimes
28:00
don't have in the clinics. And therefore, we
28:05
want to gain more confidence on our model by
28:09
validating it experimentally. And it's easier
28:12
to validate it with mice. Exactly. And then once
28:14
you can show that your model is really working
28:17
well, then you can, with more confidence, probably
28:19
put the human data into it and say, well, with
28:21
confidence, this will work well as a human model
28:23
as well. Yeah, I can see that. microcomputed
28:27
tomography gives you a higher resolution. So
28:29
you can see the individual trabeculae and also
28:33
the modeling and the resorption sites in a higher
28:36
resolution. And this is closer to the rules that
28:40
we apply at the cellular level. So if you're
28:44
confident that the model works on the high -resolution
28:49
images, then we can also apply it in the clinics.
28:53
It's amazing research and you can see, it's lovely
28:56
to see how your research is growing and developing
28:59
and every year you have something new to share
29:01
with us, it's wonderful. Yeah, come back next
29:04
year and you'll have something even more exciting
29:06
to talk about. Yes, of course, I mean there's
29:09
a lot to do so because all the medications are
29:13
there and also we see here in the sessions the
29:18
different... branches or which medication to
29:21
take after which one so there's a lot of potential
29:25
and a lot of questions that's also what i took
29:28
from yesterday the more you talk with people
29:31
about the bone research the more questions arise
29:34
and there's really a lot more to investigate
29:36
i remember making a comment last year that you
29:38
were sending your mice to the gym so now you'll
29:41
be sending your computer model to the gym that's
29:43
the that's the thinking I thought of that picture
29:47
actually. It's a couple of times. And it's true.
29:51
Mechanical loading is kind of sending them to
29:54
the team. It's a funny picture. Thank you very
29:57
much. Thanks. Lovely to speak to you again. Thank
30:00
you for having me here. Bye -bye. And we hope
30:08
you can join us for the fourth and final episode
30:11
recorded here in Innsbruck, which will be released
30:13
very soon. Bye now.