Latest / 'Bone Up' / Cracking the code to prevent breaking our bones

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Cracking the code to prevent breaking our bones · '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
0:15
going to be exploring osteoporosis, bones, what
0:18
we know and what we're yet to discover and we
0:21
hope you will join us on the journey. So for
0:24
anyone keen to learn more about our infrastructure
0:27
of calcified collagen, this is... Bone Up. Hello
0:55
and welcome back to another episode of Bone Up.
0:59
How are you doing, Richie? Not bad, David. Had
1:02
a nice summer holiday. Come back refreshed, ready
1:04
for the new year. How are you doing? I'm doing
1:06
well. Season of mists and mellow fruitfulness
1:08
here in the UK. I had my son's wedding there
1:12
just last week. We were over in Edinburgh and
1:14
not only did we have a great time at the wedding,
1:16
but I got a chance to speak to a number of listeners
1:19
to the podcast, would you believe, who were guests,
1:22
some GPs and some medical students. And some
1:26
people, Richie, would you believe, hadn't heard
1:28
of the podcast, but I was able to point them
1:30
in the right direction and they couldn't wait
1:32
to get away from the reception to download a
1:35
few episodes, or so they told me anyway. We're
1:39
going to have to get some influencers to advertise
1:42
the podcast for us. And I made a speech in which
1:45
I didn't mention osteoclasts for the first time
1:47
in about 20 years as well, so that was a novelty.
1:51
I'm glad you had a good time. Yeah. And I mean,
1:54
my son does some of the graphics for our podcast.
1:56
And indeed, I met the brother of the musician
2:00
who composed our jingle as well, by remarkable
2:02
coincidence. So even though I was getting away
2:05
from Bone and getting away from the podcast,
2:07
it turned out to be interwoven through all aspects
2:10
of my life. We had a really nice time. Yeah,
2:14
it's good to be back. Looking forward to all
2:16
the things between now and Christmas. Listeners,
2:19
this is the last episode in this series of Bone
2:22
Up, but don't worry, we'll be back soon with
2:24
series four. And today we have a really good
2:27
episode to finish the series. We're going to
2:29
touch on a topic that we haven't really discussed
2:31
very much in the past, and that's genetics. David,
2:35
do your patients ever ask about the genetic basis
2:39
of their disease? or whether or not they might
2:42
be able to receive a genetic test for osteoporosis.
2:46
Yeah, it is actually quite a common question.
2:49
I've said to you before, I think the single commonest
2:52
question is often about nutrition or what people
2:55
can eat to influence their bone health. But certainly
2:59
those who I've told have quite significant osteoporosis,
3:02
many of them will ask about genetic testing or
3:06
ask... Even if they're aware that it runs in
3:10
their family, we'll ask if there's anything can
3:13
be done to sort of put a label on that or get
3:16
a clearer idea of how it affects them or how
3:19
it might affect other family members. Of course,
3:23
I have to say to them that there is no one gene
3:25
test for osteoporosis. And you do have to tease
3:29
out a little exactly what people understand.
3:32
By genetic testing, do they mean... Why have
3:35
they got osteoporosis? And sometimes you see
3:38
patients with very low T -scores without any
3:42
very obvious reason for it. And they are very
3:44
interested to know if there's a genetic reason.
3:47
You see others who are worried about their children
3:50
or their grandchildren. when I explain to them
3:56
you know there's no single test for osteoporosis
3:58
that it is caused by dozens if not hundreds of
4:02
different genes all working together that can
4:04
be a bit disappointing for people I would say
4:07
it's a question asked more by younger people
4:10
rather than older people as well although there's
4:15
no doubt that our understanding of how genetics
4:18
influences bone health even when you're older
4:21
is developing as well. It's not just the younger
4:24
people we're interested in. We hear a lot about
4:28
genetic testing in the case of cancer and in
4:31
rare diseases. People would expect there to be
4:34
a test for osteoporosis as well, but I guess
4:37
not everybody knows about the big polymorphisms
4:41
that underlie the disease. That's right. I try
4:45
to explain it to people in terms of, for example,
4:48
you have a journey to work that lasts for an
4:50
hour. And how can you make that journey faster
4:52
or shorter? Well, there's lots of little things
4:55
along the way. You could get held up by a junction.
4:58
There could be roadworks. You could, you know,
5:00
someone might walk out in front and all those
5:02
things just add 10 seconds or you speed up by
5:06
30 seconds. And at the end of the big, long journey
5:08
that determines whether your journey's, you know,
5:10
an hour and a half or an hour, 10 minutes. But
5:13
there's no one big single reason. And with osteoporosis,
5:16
for most people, they then understand that there's
5:19
many, many genes which make a small contribution
5:21
to how strong their bones are, how elastic their
5:24
bones are. And that's when you put all those
5:27
pluses and minuses together that you get an overall
5:30
picture. And to just pick out one or two of those
5:34
genes and to look at them doesn't really help.
5:37
um and in general we're not in a position yet
5:41
to screen hundreds and hundreds of genes and
5:44
put them together for people certainly not in
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a clinical day -to -day nhs setting and i suppose
5:50
the other thing that i sometimes introduce to
5:52
people is the idea that at some point we may
5:55
be able to look and decide which drug is best
5:58
for you in with reference to your to your genes
6:03
um And while genetic testing, to put that in
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inverted commas, for why you have osteoporosis
6:12
might be interesting, more relevantly to your
6:15
treatment and your future might be genes we could
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look at to decide whether you would respond better
6:21
to this anabolic drug or that anabolic drug,
6:24
or perhaps even genes that would suggest how
6:26
long you should be on a bisphosphonate or on
6:29
denosumab for. And I think that's probably something
6:32
that... you know, I would be interested in hearing
6:34
more research about and the patients might be
6:37
interested in as well. Of course, there are gene
6:39
tests for rare bone diseases and, you know, in
6:42
some ways we might want to exclude some of those
6:44
rare bone diseases by gene testing, but that's
6:46
not something we would, you know, we would crop
6:49
up in a lot of conversations. Okay. It's time
6:55
to get our guest on the show. It's our great
7:00
pleasure to introduce our guest today. We have
7:02
Professor Emma Duncan. Emma is Professor of Clinical
7:06
Endocrinology in the Faculty of Life Sciences
7:08
and Medicine at King's College London and an
7:11
Honorary Consultant in Endocrinology at Guy's
7:13
and St Thomas' NHS Foundation Trust. Professor
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Duncan is Joint Director for the KHP Diabetes,
7:20
Endocrinology and Obesity, which is a clinical
7:23
academic partnership at King's College London,
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where Professor Duncan is the co -research lead.
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If that's not enough, Emma's also president -elect
7:32
of the American Society for Bone and Mineral
7:34
Research, the ASBMR. And for those of you who
7:37
don't know, that is the world's leading professional
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society for musculoskeletal disorders. It's based
7:43
in the US, but operates internationally. And
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it's a place where all scientists and all clinicians
7:48
can go to study bone, bone disease and bone medicine.
7:52
Emma, thank you for joining us today. We're really
7:54
delighted you've made time in your busy schedule
7:56
to come and speak to us. We're really looking
7:58
forward to it. chatting to you. It's a great
8:01
pleasure to be here. Thank you for such a warm
8:02
and wonderful welcome. I want to say what an
8:05
honour it is for me and how much I've enjoyed
8:07
listening to you on my walks with the dog in
8:10
the park and at various other times listening
8:12
to the podcast. It's a fantastic program. You
8:15
say all the right things, Emma. We're delighted
8:17
you've made time to speak to us today. Thank
8:20
you. It's really great to hear that you're listening
8:23
to the podcast. I understand this isn't the first
8:26
time you've been on a podcast. No, no, this is
8:29
the second time, but this time I think I've got
8:31
a better idea of what's going to happen. So before
8:36
I left Australia, on the last time that I moved
8:40
between Australia and the UK, I had written an
8:43
article for the ABC conversation called Why Do
8:47
We Have Bones in answer to a question from a
8:50
five -year -old. And in response to this article,
8:53
the ABC said, would I like to come and do a podcast?
8:56
And perhaps I should have thought a little bit
8:58
more about this. But I came in and I went to
9:01
the TARDIS, which is what the recording studios
9:03
are actually called at the ABC in Queensland.
9:07
And it was only when I got there that I realized
9:09
that this was for the under five science program
9:11
called Imagine This. And so, first of all, it
9:14
was a great joy to do that recording. And second
9:16
of all, all the prep that I've done beforehand
9:18
really wasn't necessary because. The things that
9:21
I was being asked about were much more about
9:23
whether the hip bone connected to the knee bone
9:25
and so forth and so on, which was, again, a great
9:28
joy to have a conversation about. But the other
9:31
thing was that the number of parents who'd listened
9:34
to the podcast in the car or when they were putting
9:37
their kids to bed or during bath time amazed
9:39
me. I got a huge amount of feedback from the
9:42
audience. So I'm not expecting the same with
9:46
this, but we'll see. I don't know about the demographics
9:50
of our listeners, Emma, but they say if you can
9:52
explain something to a five -year -old, then
9:54
you really understand it. Well, I'd say the fibroids
9:56
are also very sophisticated. I mean, the sorts
9:59
of things we talked about is, you know, why do
10:01
we have a skeleton? We talked about the armor
10:03
aspect of the, you know, the skull being a helmet
10:06
and being able to have a rib cage to protect
10:08
soft organs like hearts and lungs, but with a
10:11
movable system that allows air to move in and
10:13
out. But we also talked about, in one sense,
10:15
that's the obvious. And we also talked about
10:17
movement and having big bones moved by big muscles
10:20
and little bones moved by little muscles. But
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we also talked about the importance of having
10:24
a silo. for electricity because kids understand
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electricity so talking about the movement of
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electrolytes and that that really you know you
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need to have calcium as a silo from bones to
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be able to keep levels steady they understood
10:35
that and they also understood the concept of
10:37
bone marrow providing white cells to fight infection
10:41
they they knew what germs were and so being able
10:44
to talk about all of these functions of bone
10:47
at really quite a sophisticated level, was, you
10:50
know, I think people often underestimate how
10:53
much science children understand. And certainly
10:56
I find listening to the Imagine This programme,
10:58
which, as I said, is targeting the under fives,
11:01
I learn a great deal of science. It's really
11:06
wonderful. I find that young people always ask
11:09
the most difficult questions, you know, things
11:11
that you haven't really ever thought about before.
11:14
Oh, for sure, for sure. And in fact, the interviewer,
11:17
when I wrote the first article about why do we
11:20
have bones, they actually picked me up because
11:24
I hadn't really answered the question, why do
11:26
we have bones? What I'd actually answered the
11:27
question was, what is the function of a skeleton?
11:30
And it was only when they came back and said,
11:34
well, you know, what is, you know, why do we
11:36
have bones? It's actually a subtly different.
11:39
question to the one that I actually answered
11:41
which people often do on interviews actually
11:44
if you listen to politicians they often give
11:46
you a different answer to the question that you
11:48
actually asked hopefully I won't do that for
11:50
you guys today fingers crossed one of our aims
11:55
for the podcast is to try and bring the most
11:58
recent research to the public and professionals
12:01
and especially if that research is going to be
12:03
helpful for treating and preventing bone disease
12:06
in the future So we'd really like to have you
12:09
on today to talk about the relationship between
12:11
our genome and bone fragility and whether or
12:14
not genetics can cause bone fragility. For the
12:17
audience at home and for many people, we think
12:20
of bone fractures as an accident or a sign of
12:23
ageing. How can genetics play a role in making
12:27
somebody's bone more fragile, even from a young
12:30
age like children? Really, Richie, is what I've
12:36
spent most of my professional scientific life
12:39
answering, which is this question, you know,
12:42
is bone mass genetically determined? So to come
12:46
back to make sure I'm actually answering the
12:47
question that you asked, why are people fracturing
12:50
at an older age and how are genetics actually
12:52
relevant to that? Are genetics really important
12:54
in terms of why somebody might, for example,
12:56
have a fall or a trip? And we can come back to
12:59
that a little bit later on if we want to. But
13:02
really what sets up... Our ability to grow a
13:06
good skeleton is what we inherit from our parents.
13:09
And so we have this term in genetics called heritability,
13:13
and it's how much of the spread of a trait in
13:17
the population is genetically determined. And
13:19
for bone, that's actually quite high. About 60
13:23
to 80 % of what determines the spread of bone
13:26
density in the population is determined by our
13:29
genetics. And it's particularly what helps us
13:33
to grow that's genetically determined. So you
13:35
see heritability, how much is genetically determined,
13:38
highest when you're looking at young adults,
13:41
people at the age of about 20 to 30, which is
13:44
when we think about achieving peak. bone mass
13:46
so as we grow as children then as we go through
13:50
puberty and start sex hormones coming in as our
13:54
bones stop growing in length and start putting
13:56
down as we achieve our peak bone mass for most
13:59
people around the age of 20 to 30 and from then
14:02
on down it's slow attrition all the way life
14:04
gets worse after that point in time at least
14:07
from the point of view of achieving a peak bone
14:09
mass and most people will lose about one percent
14:11
of their bone mass per year from that point on
14:14
with an acceleration for women as they go through
14:18
menopause and experience hypogonadism. And there's
14:21
other insults to the skeleton having an effect
14:23
as well, such as, for example, men who might
14:25
be on androgen ablation therapy for prostate
14:28
cancer or people who smoke. or people who have
14:32
to take steroids for their health for other reasons.
14:34
But leaving aside those issues, it is the determination
14:38
of peak bone mass, which predominantly determines
14:41
what ends up happening in terms of your bone
14:44
at an older age. So somebody who is fracturing
14:48
and having vertebral fractures, say in their
14:51
60s, are achieving that, are having those fractures
14:54
because of how they have grown their skeleton
14:58
as a younger person and then having subsequently
15:01
had gradual losses since with some environmental
15:04
issues put on that. And in terms of what contributes
15:07
to those genetics that actually determine how
15:10
we grow our skeleton, this is true. Sometimes
15:15
we think about genetics in terms of diseases
15:18
as being... disorders where we see big effects
15:23
and certainly from a bone fragility point of
15:27
view there are certain genes where carrying pathological
15:30
variants can have a big effect in terms of skeletal
15:33
fragility. So many people in the audience would
15:35
be familiar with a disease osteogenesis imperfecta
15:39
which is a heterogeneous group of bone disorders
15:41
of really quite severe bone fragility for many
15:45
individuals and people who've got a pathological
15:51
variant or a likely pathological variant in now
15:54
37 known genes for different types of osteogenesis
15:57
imperfecta that's probably 38 and probably by
15:59
the time the podcast goes out 39 these people
16:04
have got a a single variant which explains a
16:09
lot of their bone fragility However, at the general
16:13
population level, that's not the major things
16:15
which determine bone fragility. At a population
16:17
level, it's the cumulative effect of many, many
16:23
variants, each of which have a small effect,
16:26
some of which might increase bone density, some
16:29
of which might decrease bone density. But the
16:31
sum of those, all of these little tiny effects
16:34
sum together to give an individual their particular
16:38
risk of bone fragility. For most of the population,
16:42
that'll be average, almost by definition. But
16:45
you'll still have people at both ends of the
16:48
tail. You'll have some people who've got high
16:50
bone mass because of all of these individual
16:53
variants summing together. And you'll have some
16:55
people who've got low bone mass, again, because
16:57
the variants they have sum together to give the
16:59
lower bone mass. And of course, the people who've
17:04
got pathological variants in rare genes, or in
17:10
genes which cause the rare bone disorders, they
17:13
too have this polygenic background as well. So
17:16
the expression of how those variants with big
17:22
effect, how that plays out in an individual and
17:25
within their family will depend upon their background
17:27
as well. The two are not mutually exclusive.
17:31
Genetic testing is becoming more common. It's
17:34
more accessible. People can go online now and
17:37
buy all sorts of... genetic tests for better
17:39
or worse and people come to my osteoporosis clinic
17:42
sometimes and say can i get can i get a genetic
17:45
test for osteoporosis and you know often i do
17:48
a bit of chatting around that and explain why
17:50
it's not maybe just as simple as they think but
17:52
what sort of genetic tests perhaps could i be
17:56
doing for for standard osteoporosis or perhaps
18:00
in the next five to ten years what sort of genetic
18:03
tests do you think might be useful if we're thinking
18:06
of trying to personalize medicine for for the
18:09
patient in front office i'm going to answer your
18:13
question david by splitting it into into a couple
18:15
of components because there's what can i do now
18:21
in my general bone clinic. There's what can I
18:23
do when I've got somebody who's got a slightly
18:24
unusual presentation. There's what do I think
18:27
is going to come in the very near future in terms
18:29
of genetic technologies playing into normal clinical
18:32
practice. And there's what could those genetic
18:34
technologies actually achieve in terms of personalizing
18:37
things. To come to the first bit in terms of
18:41
what's available now. One of the great strengths
18:44
of practicing in the NHS in England at the moment
18:47
is the excellent access to genetic services,
18:50
which are really quite marked compared to many
18:55
of the rest of the world. We have fantastic resources.
18:58
I know that the other devolved countries of Wales
19:02
and Scotland and Northern Ireland have slightly
19:05
separate access. Nonetheless, this still really
19:09
is amazing at a world -class level to have. these
19:13
genetic resources to help clinical management.
19:16
The capacity to be able to get testing through
19:20
Genomics England's provision of genetic services
19:23
and through the different laboratories that look
19:25
after this is just amazing. We are really blessed
19:28
by being able to do this now. So compared to
19:32
many countries around the world, people in England
19:35
have extraordinary capacity to be able to access
19:39
genetic testing for when people think that they
19:41
might have a rare monogenic disorder. So to come
19:44
to your next question, David, really it's, well,
19:46
how many people in my clinics actually have a
19:48
rare monogenic disorder when they look like they've
19:50
got common or garden osteoporosis? And this is
19:53
a question that we actually answered looking
19:54
at the Anglo -Australasian Osteoporosis Genetics
19:57
Consortium. And here what we did was we sequenced
20:00
500 women who looked like they had otherwise
20:05
unremarkable osteoporosis. Z score, which is
20:09
a measure of where people are relative to the
20:10
average bone density, between minus 1 .5 and
20:13
minus 4. So they were low, but they weren't super
20:15
low compared to the general population. And in
20:18
that cohort, and this were women aged between
20:20
55 to 80, where people might think, well, you
20:23
know, whatever, they've gone through menopause,
20:24
it's not surprising that their bone density might
20:26
be a little bit on the low side. What we actually
20:28
found was that 4 % of these people in this cohort
20:32
had a variant in one of the known dominant osteogenesis
20:37
imperfecta genes where that variant had previously
20:40
been reported for osteogenesis imperfecta or
20:43
where it affected the same base where it had
20:45
been reported previously or it affected the same
20:47
amino acid or where it affected the glycine which
20:50
for various reasons is particularly common for
20:52
people who've got OI. So four percent of the
20:54
people who looks like they had common organ OP
20:57
actually had a form first of osteogenesis imperfecta
21:01
in an otherwise That minus 1 .5 as a Z -score
21:05
is, as I said, it's on the lower side. So to
21:08
come back to where you should be looking, I mean,
21:10
I think that very rapidly, we're going to see
21:14
the evolution of genetic technologies being built
21:18
into our system within the next five to 10 years.
21:21
An awful lot of information is going to become
21:24
available to help clinicians. Some of that will
21:27
be looking for pathogenic variants, and we can
21:30
talk about how that actually might play out.
21:33
Some of it's going to be, and I think this is
21:35
going to be one of the most useful things early
21:37
on for personalising, helping with pharmacogenomics,
21:41
those variants that might alter the dose that
21:44
you need of a medication because you might metabolise
21:47
a drug differently, either more quickly or more
21:49
slowly, or predicting an allergic reaction to
21:52
a drug. So this sorts of pharmacogenomics is
21:55
a really practical application of genetics that's
21:58
got real life consequences to help avoid adverse
22:02
drug reactions and to help maximize the benefit
22:05
from therapeutics that I think we're going to
22:07
see. It's already built in in some health care
22:09
systems already. So I think we're going to see
22:12
that come in as a low hanging fruit relatively
22:15
soon. But I also think we're going to start to
22:19
see genetic testing coming in to help us know
22:22
who would benefit from looking for those rare
22:27
disorders. So if I could perhaps use a slightly
22:31
different example to bone disease and to think
22:34
about diabetes for a minute. I'm an endocrinologist.
22:36
I do diabetes as well as other endocrine disorders
22:39
as well as bone. Both type 1 diabetes and type
22:44
2 diabetes are heritable disorders. They've got
22:47
different genes contributing to developing each
22:49
of those diseases. But when you have a person
22:51
who turns up with hyperglycemia, say it's a young
22:55
person at the age of, say, 25, do you know that
22:59
they've got type 1 diabetes or type 2 diabetes?
23:01
Or could they actually be maturity -onset diabetes
23:04
in the young, a condition called MODY? Now, in
23:08
the immediate care, one immediately needs to
23:11
look after somebody from a life -saving perspective.
23:13
And for many people that will mean insulin, at
23:15
least in the short term. But for some of those
23:18
people, knowing who to test for MODY, you can
23:21
predict that by looking to see whether they've
23:25
got a hypoallergenic risk score for type 1 diabetes
23:28
or a hypoallergenic risk score for type 2 diabetes.
23:31
If they look genetically that they don't have
23:33
type 1 or type 2, then you might go and have
23:36
a look for MODY or some of these other monogenic
23:39
disorders. So you can use things like polygenic
23:42
risk scores to categorise who you would think
23:47
might benefit the most for looking for rare diseases.
23:51
Now, to a certain extent, this conversation may
23:54
well become obsolete within the near future because
23:58
at the moment, genotyping... is a cheaper technology
24:02
than sequencing. That's probably not going to
24:04
be true within about two to three years. It's
24:06
going to become, the price of sequencing has
24:10
dropped so dramatically that although we might
24:13
gain the information about those little individual
24:16
variants that I talked about beforehand, we might
24:18
gain that information from sequencing to make
24:20
a whole data set that we analyze. It's going
24:23
to be done through sequencing. If it's done through
24:24
sequencing, we'll have the information on the
24:26
rare variants as well as having the information
24:28
on the common variants at the same time. Now,
24:31
that's not true today in 2025 in terms of costs
24:35
and how things will work at the moment where
24:37
people are doing this. It's generally in a research
24:40
story and generally for financial reasons, people
24:42
will do the genotyping first and then look for
24:45
the sequencing. But certainly within the very
24:48
near future, that cost differential is going
24:52
to change. And therefore, you'll actually end
24:55
up with both sets of information at the same
24:57
time. You won't have to make a choice. There's
25:02
so much you've said there. You could pick up
25:03
on one thing that stands out for me. You talked
25:05
about the pharmacogenetics and how... you know
25:08
at the moment everyone gets the same dose of
25:10
allandronic acid for the same length of time
25:12
everyone gets 20 micrograms of teriparatide every
25:14
24 hours for 24 months we know people must respond
25:18
differently to those things and the idea that
25:21
in the future we would say let's do a gene test
25:24
and tell you which which drug you're going to
25:27
respond best to and indeed tell you exactly which
25:31
dose and for how long you should be on that drug
25:34
for Would it be too much to ask if considering
25:37
the five or six drugs we use commonly, which
25:40
do you think that a genetic test might be most
25:43
useful for? Would it be one of the osteoanabolic
25:46
agents, do you think? You know, there are people
25:48
probably would benefit from taking, let's say,
25:51
teriparatide for longer than 24 months. There
25:53
may be people who the anabolic window has probably
25:55
closed after 18 months. Is it one of those drugs
25:58
or is it a response, let's say, to bisphosphonate,
26:01
something much more common? So I'm going to come
26:04
back to the question and say it really depends
26:06
whether the drug response to those particular
26:09
drugs is heritable or is not. And of course,
26:12
if something isn't heritable, then if everybody,
26:16
if it's, so I'm going to couch my answer with
26:22
a little bit of taking a few steps back. I would,
26:25
I don't think we know yet. whether allergic reactions
26:29
to bisphosphonates, and some people do get adverse
26:33
reactions to bisphosphonates. I'm not talking
26:36
about first phase reactions, which are extremely
26:38
common. I'm talking about rare reactions like
26:40
the uveitis and iritis and a few of those, you
26:42
know, those more unusual reactions. At this point
26:45
in time, I don't think, I certainly recently
26:48
checked the CPIC, which is the Clinical Pharmaceutical
26:51
Genomics International Consortium. Web page,
26:54
very user -friendly if any of the listeners want
26:57
to go and have a look at it. I recently looked
27:00
at that, and at that point in the story, there
27:02
were no suggestions at this point in time that
27:05
pharmacogenomics was pertinent to bisphosphonates.
27:08
At this point in time. That doesn't mean that
27:10
that would be the case down the track, but certainly
27:12
at this point in time, that's where we are. To
27:14
come to the comment about teraparotide, people
27:16
have done GWAS looking at drug reactions. I can't
27:20
at this particular point in time point you to
27:25
anything that stands out to me from those particularly.
27:28
But I would say, I'm just going to talk about
27:31
pteroparotide in mice because certainly one of
27:34
our colleagues, a lady by the name of Cheryl
27:37
Acker -Bicknell, has looked at exactly this question
27:40
to look at whether genetic differences in all
27:43
the different mouse strains that it's possible
27:46
to consider this in. Do you get differential
27:48
responses to pteroparotide according to the genetic
27:52
background of mouse? And the answer is absolutely
27:54
yes. You can actually, across multiple species
27:58
of mouse who've got all of these different types
28:01
of genetic background, you can see... a graduation
28:04
of responses to teraparotide. So in answer to
28:08
your question, is it likely that some of these
28:10
genetic differences are going to make a difference
28:11
to anabolic patients? Certainly for teraparotide.
28:15
And I believe somebody has actually also done
28:17
a GWAS looking at PTH responses, though again,
28:19
I don't have the results pretty in my head at
28:22
the moment. So I don't want to misquote anybody.
28:26
But if I could say from a mouse perspective,
28:28
if you're a mouse, your ability to respond to
28:31
pteroparatide is determined by your genetic background.
28:34
And if that's true for mice, it's likely to be
28:35
true for humans as well. If you're looking for
28:40
subtle differences, you need to be looking at
28:42
a much bigger data set to be able to see those
28:45
type of subtle differences. If you're looking
28:47
for something which is much more extreme, like
28:49
an allergic reaction, that might be easier for
28:51
us to be able to detect and then predict. than
28:55
something that if you're looking at a difference
28:57
between a 5 % reaction that it's going to take
28:59
a lot more people before you see and you might
29:01
say that 5 % differences isn't going to be worth
29:03
exploiting it that way and I think that's probably
29:05
true but if you see a 50 % difference then that
29:08
would be something that would be easier for us
29:09
to detect if it's a heritable if it's a heritable
29:12
issue I mean of course the biggest and and I
29:14
know that David I know you are a practicing clinician
29:16
as well I think I think the biggest reason that
29:21
people don't respond to drugs is because they
29:23
don't like taking them. And often a lot of our
29:27
drugs, people don't like taking them because
29:29
they don't like fear. A lot of people find that
29:32
they can get reflux symptoms. They don't like
29:34
first phase reactions. They don't like injecting
29:37
anabolics. And I really do understand that taking
29:41
drugs is hard. And I think that's one of the
29:44
things I'd like to think. there is still space
29:48
in osteoporosis genetics to think about new pathways
29:51
to help us develop new drugs that people might
29:53
find easier to take that don't involve infusions
29:57
or injections or don't have the side effects
30:00
that we know that many people experience with
30:02
the bisphosphonates. So I know I'm moving the
30:04
conversation slightly to one side. But I think
30:07
our ability to think about using genetics to
30:10
highlight therapeutic pathways, either for new
30:12
drug development or for repositioning existing
30:16
drugs, is another benefit from continuing doing
30:20
research in common diseases such as osteoporosis,
30:22
but also doing research in rare diseases because
30:27
the pathways that are illustrated... when we
30:32
work with people who've got rare diseases, can
30:34
be very relevant to people who've got common
30:36
diseases as well. And you would know, David and
30:40
Richie, you know, remesozumab, this pathway was
30:44
brought to light by looking at individuals and
30:48
working with families who had sclerosteosis and
30:51
verbucus disease, which is a high bone mass disorder.
30:54
And by understanding that pathway. In these people,
30:57
it became obvious that this was a druggable pathway
31:00
that we could use. And, I mean, this is the pin
31:02
-up story about how genetics has shaped therapeutics.
31:05
Not just, I mean, it's a great story for the
31:07
world, really, for how genetics can help things.
31:09
And it's not, obviously, this is a bone podcast,
31:12
which is why I'm talking about it, but it's not
31:13
the only example by many immune means. It's a
31:17
really wonderful story. We've had some guests
31:19
on before to talk about it from the company that
31:22
made romisozumab, and we heard about. The history
31:25
of development and listeners, if you haven't
31:26
heard that episode already, go back and listen
31:28
to it. It's absolutely fantastic. It's interesting
31:31
to hear about how genetic testing might be useful
31:35
for not only improving existing treatments, but
31:38
also potentially identifying pathways for new
31:42
treatments. One thing we were wondering about
31:45
is gene editing. We hear a lot in the news lately
31:48
about how companies are trying to develop new
31:52
therapies like gene editing. Is it possible that
31:54
we might see gene editing ever replace the more
31:58
traditional medicines like bisphosphonates or
32:00
even the anabolics? I would split that by saying
32:05
I think that we will see the evolution, we are
32:09
already seeing Gene editing technologies and
32:12
RNA technologies coming in to treat particularly
32:16
monogenic disorders and rare disorders. I think
32:20
many people would be aware, for example, that
32:22
I think it was November 2023 that was when the
32:29
trials were first done with respect to some of
32:31
the high cholesterol disorders. And many people
32:35
would be aware that some of the drugs that we
32:37
have, that was a gene editing trial, but many
32:39
people were aware that we already have RNA treatments
32:42
for hypercholesterolemia. I want to move the
32:48
conversation back to bone and to say where I've
32:51
seen the most exciting things. has been have
32:55
been looking at rare bone disorders so there's
32:59
I think over a decade ago there was a paper that
33:02
was looking at the capacity to silence one allele
33:06
so we've got two copies of every of every gene
33:09
and often for osteogenesis imperfecta one of
33:14
the genes for colon alpha one or colon alpha
33:16
two which are the two main genes that code for
33:19
collagen in bone one of these one of the copies
33:22
carries a variant that's damaging. And this was
33:27
a study looking in mice again, and it showed
33:30
that you could selectively take out the allele
33:34
that was damaging and leave the other one, the
33:37
wild type one, to get on with its effects. This
33:39
still would mean that you would only have half
33:42
the coding for collagen because you'd taken the
33:45
other one out. But for many people who've got
33:47
really severe osteogenesis imperfecta, the allele
33:52
that's got the damaging variant doesn't just
33:54
make a bad molecule itself. That molecule interferes
33:58
with the function of the protein that's coming
34:02
from the allele that isn't carrying the mutation.
34:05
And so you end up with this double whammy. One
34:08
has the variant and it makes an abnormal protein,
34:11
but that abnormal protein also interferes with
34:14
what gets coded from the wild type. So for this
34:19
project, which was... which was looking, could
34:22
you selectively take the pathological variant
34:26
out and just allow the wild type to express,
34:29
showed that this was possible in mice. And that
34:32
way you could take somebody who has a really
34:34
severe form of osteogenesis imperfecta and perhaps
34:37
make things milder. It wouldn't cure OI, but
34:41
it would make it mild. That was about 10 years
34:45
ago, and that at this point has not translated
34:48
into humans. But one of the stories that I saw
34:53
at the ASBMR at the back end of 2023 was the
34:59
most extraordinary study. Again, this was done
35:05
in mice. And in this case, it was a study in
35:09
a disease called fibrodysplasia ossificans progressiva,
35:11
or FOP. Now, FOP is a really horrendous disease
35:17
where people have got... a variant in one of
35:20
the signaling, the bone morphogenic protein signaling
35:23
pathways. And this results in any inflammation,
35:27
including things from knocks and bumps and teeth
35:32
coming out. They form bone. And so when the children
35:37
are born, they've just got a slightly knocked,
35:39
their toe is slightly bent. But as they go through
35:42
childhood, they gradually accrue more and more
35:45
bone. And this ultimately leads to problems because
35:51
their jaws fuse and they can't take a deep breath
35:54
because their chest is encased with bone. It's
35:57
a very, very severe disease. While I was on maternity
36:01
leave, the variant that actually caused this
36:05
was identified. My husband was in tears when
36:09
the first drug treatment for FOP was approved
36:13
by the FDA. just such a wonderful story because
36:17
once the gene had been determined the protein
36:20
could be crystallized a pathway people could
36:22
design drugs they could understand what was going
36:25
on they could develop a mouse model they could
36:27
try different drugs and now although there's
36:30
one drug which is licensed there's a lot of other
36:32
drugs which are in trial and this terrible disease
36:36
now has hope for the future So that isn't gene
36:40
editing, but it's just showing the power of doing
36:41
genetic dissection of rare bone diseases. But
36:45
the story that I wanted to tell in answer to
36:48
your question was that I went to this talk at
36:51
the ASBMR in October 2023, and they were talking
36:54
about these things called antisense oligonucleotide
36:57
GAPMAs. I had no idea what a GAPMA was. I had
37:00
to go look it up on ChatGPT. And so what ChatGPT
37:03
told me was that this was a particular type of...
37:07
small interfering RNA and the fact that their
37:10
gapness just has to do with making it more stable
37:12
and being able to bind down. And what they were
37:15
able to do was that they targeted the FOP mutation
37:19
in a mouse and they demonstrated that in their
37:24
mice who had FOP they could use interfering RNA
37:29
to take out this mutation's function. So this
37:32
is an activating mutation, and they took out
37:35
the activating mutation in the mouse. Now, if
37:38
that is true for FOP, that we can use small interfering
37:42
RNA molecules for a gain -of -function mutation,
37:46
then that's likely to be true for many other
37:49
gain -of -function disorders. So it won't work
37:52
for a loss -of -function, because in a loss -of
37:54
-function, by definition, you've got a loss -of
37:55
-function. So taking out it, the gene's not going
37:58
to help you. But for gain of function, a priori,
38:03
there is no particular reason why this should
38:05
be unique to FOP. So there's a long way to go
38:10
between a study that's done in a mouse model
38:15
to getting this safely into clinic for human
38:18
beings. And something has to be both safe and
38:21
effective. it really shows how wonderful the
38:27
opportunities are to use our understanding of
38:31
DNA technologies to start to deliver therapeutics
38:35
in a life -saving sense for individuals. So to
38:38
come back to your question about common or garden
38:40
osteoporosis, I suspect not, because as I said,
38:43
the determination of bone density generally in
38:46
the population is... the cumulative effects of
38:49
multiple variants, each of small effect. So I
38:52
don't think that that's going to be, I don't
38:54
think gene targeting and gene therapies in that
38:57
sense is necessarily going to be effective in
39:00
the way that it would be for a monogenic disorder.
39:03
Would it be possible to change the way the body
39:06
responded to some of the common? treatments that
39:09
we use, even if you can't alter the 20 or 30
39:12
or 40 genes that contribute to osteoporosis,
39:15
could you make a patient more susceptible to
39:18
inhibiting sclerostin or more susceptible to
39:20
the effects of denosumab, for example, which
39:23
may be just editing a single gene? Well, the
39:26
first thing I'm going to say, David, is just
39:28
to contextualize your question, that actually
39:31
the number of variants that we know that determine
39:36
bone density in the population is well over a
39:38
thousand. So just to say that this is, and that's
39:41
at genome -wide significance. So there's lots
39:46
and lots of variants that we'd have to do. In
39:48
terms of how you'd respond to the medication,
39:51
I'd come back to my question about pharmacotherapeutics.
39:55
And I wonder whether there's ways in which that
39:59
we could adjust our dose or our duration of medications
40:03
rather than necessarily changing the way the
40:06
body responds. But so I see in the short term
40:10
that being the easier target to think about how
40:16
we respond to medicines and then change our dosing
40:18
accordingly rather than necessarily changing
40:20
how we respond to the medicines from a physiological
40:23
perspective. But I'm going to give that some
40:26
thought. That's my on -the -fly answer. But I'd
40:30
have to think about it a bit more. Yeah, no,
40:32
I appreciate that. That's a very honest answer.
40:33
I think like many practicing clinicians are always
40:36
conscious that, you know, if you have hypertension,
40:38
you're just the dose of drugs up and down. If
40:40
you have, you know, high cholesterol, you're
40:43
just whereas we just tend to use the same dose,
40:44
same drugs for every patient we see. And, you
40:47
know, imagine we could do better than that. I
40:51
think, you know, with time, we will be able to
40:53
become more sophisticated. And I should say,
40:57
I just want to check myself to say that I said
41:01
well over 1 ,000, and it's probably well and
41:04
truly well over that in terms of the number of
41:08
SNPs that determine bone density. But I can't
41:12
tell you quite how many yet because it's currently
41:14
under embargo. But you can all find out about
41:16
this in due course. I'd get Richie to go back
41:19
and edit in that I said it was over 1 ,000. That
41:25
sounds like a very reasonable decision to make.
41:30
Listeners, you heard it here first. The NHS has
41:33
got very large projects like the Genome Initiative,
41:37
and they're going to sequence over half a million
41:39
people. Will that kind of data allow us to understand
41:43
much more about the number of variants and how
41:46
those variants affect bone density and potentially
41:49
how... gene editing or gene therapy or knowledge
41:53
about some of these genetics might improve our
41:55
bone health in the future? I think the answer
41:58
to that is yes. I think these large data sets
42:01
are incredibly valuable at giving us multiple
42:04
insights for multiple conditions and I would
42:08
reflect on the success of the UK Biobank and
42:13
how astonishingly fruitful that database has
42:18
been for world science for a whole host of disorders
42:22
not just bone and certainly the generosity of
42:29
the UK Biobank and by that I mean also the participants
42:32
and volunteers who so graciously shared their
42:36
data for the benefit of world science. You mentioned
42:41
privacy there. I guess with this large scale
42:44
genetic testing, there could be ethical dilemmas,
42:48
you know, such as family implications or even
42:50
just the privacy risk of having such a huge amount
42:52
of data about people. Are there any things that
42:57
doctors, patients and our community as a whole
43:00
should consider now as we go forward and we think
43:02
about how we can use this genetic data to get
43:04
the best outcomes for people? I think the issue
43:08
that you are speaking about isn't unique just
43:11
to genetic data. So there are some things which
43:15
are unique to genetic data and familial relationships
43:18
and being able to make inferences about relatives
43:23
as a consequence is an example of that. But there's
43:25
many other components of our data which we might
43:28
not want to make public, including your address,
43:30
your hospital number, which strokes you're taking,
43:33
the results of your last HIV test. The fact that
43:36
you're having an HIV test, you know, there's
43:38
a whole host of information that people wish
43:41
to, that medical information that people rightfully
43:45
would not wish to see splashed about on the internet.
43:48
I think that data privacy is a core concern for
43:54
everyone who works with human data, whether that
43:57
data is genetic data or whether it's not. And
44:01
then I think there's additional issues relating
44:03
to genetic information that are on top of that
44:09
general comment about the importance of privacy
44:13
and making sure that we safeguard the information
44:18
with very robust and appropriate due diligence
44:24
to look after it. The first thing I'd say is
44:27
that although I do think there are some unique
44:28
things about genetic data, I think that data
44:31
generally, it's very important that we recognise,
44:35
respect and uphold our integrity of privacy.
44:41
To come back to the question about specifically
44:44
with respect to genetic information, certainly
44:48
from a clinical perspective, one of the things
44:51
that clinical geneticists within secondary care
44:55
work with is with families and thinking about
44:58
you know making sure that they look after those
45:00
many of those ethical concerns and considerations
45:03
that's going to be more pertinent perhaps for
45:07
rare disorders than when we're talking about
45:09
common disorders when we're talking about common
45:13
variants and as we said you know many many hundreds
45:15
and hundreds and hundreds of variants that are
45:17
that are relevant so so i think that the there
45:24
is There are important ethical considerations
45:28
generally about data. There are some which are
45:31
specific to genetics. I think generally speaking,
45:34
the two big issues are monogenic disorders and
45:38
cascade screening and paternity. But well and
45:42
truly, these are not new issues. You know, these
45:47
are not new issues. And people have been working
45:49
with them for decades. Yeah, I feel there's a
45:52
general discourse in the public domain now about
45:56
data protection in all sorts of fields, bank
45:58
details, et cetera. Oh, absolutely. Your telephone
46:00
number. Discovering that you've got a delivery
46:05
coming and being scammed because somehow your
46:09
information has, somebody's accessed the courier
46:13
information and so forth. I think we're all very
46:15
mindful about the importance of data protection.
46:18
yeah even at a clinical level i mean i see a
46:20
number of family groups with osteogenesis and
46:23
perfective for example and people will turn up
46:26
and you know naturally say you're seeing my daughter
46:28
next week or my husband's new drug is causing
46:31
him side effects or things like that and you
46:33
know in theory of course everyone's a completely
46:36
separate individual person but in practice you
46:40
know people do go home and talk about their drugs
46:42
and talk about their appointments and There's
46:45
all sorts of sort of ethical issues around that,
46:48
which we get around in various practical ways,
46:51
you know. I agree with you. And being very, being
46:55
able to say exactly as you said, really, and
46:59
then not being completely deadpan about not talking
47:03
about somebody else in the family. It's a skill
47:07
that you have to learn where you just don't go
47:11
down a pathway of disgusting. another family
47:14
member and saying, I will look forward to talking
47:20
to your husband in due course, but today I'm
47:22
going to focus on you. Or I'll look forward to
47:24
meeting your sister in due course, but today
47:26
we're going to focus on you in a way that very
47:30
politely says, I'm not going to talk about this
47:32
with you because I don't have permission to talk
47:35
about this with you. And being able to very carefully
47:38
bring the conversation to close off. discussion
47:42
about relatives' health. I know that clinical
47:46
geneticists are in a slightly different circumstance,
47:48
but certainly for me as a jobbing endocrinologist,
47:52
and obviously for you too, David, it's being
47:56
able to be very discreet when you're talking
48:00
with families is very important. Hopefully we've
48:07
got time for one more question. Emma. Your career
48:11
is just amazing. You work across the globe in
48:15
different continents, elected president of the
48:18
ASBMR, which, although it's American, is really
48:21
a worldwide institution. You do clinical care
48:24
of your patients and you do research and you
48:28
lead in both of those fields. I've seen you recently
48:32
presented a conference on the scientific end.
48:34
David saw you present at one on the clinical
48:37
end. And in both of those, I saw how you... advocating
48:41
for your patients, advocating for scientists,
48:44
and I know that you have roles mentoring other
48:46
people, both in the clinical and research side.
48:49
That's a lot. How do you sustain that level of
48:53
drive? What keeps you going? So, I mean, the
48:58
first thing, I can give you a very practical
48:59
answer, which is... making sure I eat healthily
49:03
and get enough exercise. But I'm going to...
49:06
It's a doctor's answer now, isn't it? I want
49:10
to give you a slightly higher level answer than
49:13
that. I think we have a responsibility to use
49:17
the gifts that we've been given to help better
49:20
the world. And I feel this very much. I was listening
49:24
to a podcast earlier today. which was talking
49:27
about education of women in Afghanistan and that
49:30
when the Taliban came in, girls were over the
49:33
age of 12 and no longer allowed to go to school.
49:35
Well, I grew up in a country that believed in
49:38
educating women and gave me equal access to go
49:40
to university. And I am... immensely grateful
49:46
to the women who fought the battle for me 100
49:49
years ago to make sure I got the vote and the
49:52
women who fought the battle to make sure that
49:54
degrees at university that women had earned were
49:56
actually given to them 80 or so years ago you
50:00
know it really is shocking to think how recently
50:04
those privileges were extended to me or not to
50:09
me but to women in general so When my mother
50:12
went to work in the 70s, she was in the 60s initially
50:16
and then in the 70s, it was up until the 70s
50:19
where the Equal Pay Act came in, she was paid
50:21
less than her male colleague for doing exactly
50:24
the same job. So, you know, I think I have a
50:28
responsibility to use the opportunities that
50:31
those women who, you know, in some cases died
50:34
for the cause, in thinking about the suffragettes.
50:38
I have a responsibility to use the opportunities
50:42
that I have been given by others struggle to
50:45
help further others. I really feel that and I'm
50:50
blessed in that way. I'm also very mindful that
50:52
I'm having this conversation as a white woman
50:55
and that there are many women who not only have
50:59
to face sexism, but also have to face racism
51:01
as well. I'm also mindful that I come from a
51:04
developed world and there are many people in
51:06
the developing world who haven't had the resources
51:08
that I've been gifted as well. So I feel that
51:12
when we're in a situation where we can do good,
51:16
or I don't know whether it's good or not, but
51:18
where one can, when one's been given resources
51:21
and opportunity, it is my hope that the efforts
51:26
that I make will help others to be able to have
51:30
a slightly easier path. and that this will be
51:33
of benefit to other individuals in 10, 20, 30
51:38
years down the track. That's a very earnest answer,
51:42
but it's what I think. Yeah, no, that's what
51:45
we're hoping for, a sort of earnest answer. I
51:47
appreciate your candor in that answer. I think
51:49
it'll be... inspiring to many people listening
51:52
because we do have listeners believe it or not
51:54
Emma from right around the world in both developing
51:57
world so yeah I think it's an inspirational answer
52:02
Emma thank you so much for joining us today I've
52:07
really enjoyed speaking to you and I've learned
52:08
a lot it's a real pleasure and I really look
52:13
forward to well I really look forward to listening
52:16
to more of your podcasts I just love them oh
52:19
thank you Thank you. You're very kind. And we
52:21
have to say, we didn't pay you to say any of
52:23
those things. You can buy me a drink at the bar
52:28
next time, David. No, we do very much appreciate
52:31
your time and your extremely sort of educated
52:36
and thorough answers to all those things and
52:38
your sort of honesty about it all. It's been
52:40
very interesting and entertaining having you
52:43
on the podcast. So thank you very much. Pleasure.
52:48
Thank you very much. Bye -bye. So, Richie, that
52:51
was a very interesting chat with Emma. So much
52:55
crammed into so little time. You sort of feel
52:59
we could have doubled the length of the podcast
53:01
almost and Emma would still be keeping us entertained.
53:05
What were your big takeaways then? My first takeaway
53:12
is I thought Emma was an excellent guest. We
53:14
managed to cover a lot. as you say, in a short
53:16
amount of time. Emma's got a really interesting
53:20
perspective on genetics. As a working clinician
53:24
and research and geneticist, she was probably
53:27
the best person to talk to about this. I really
53:30
enjoyed her explanations and descriptions. My
53:35
key takeaway is that genetic testing isn't quite
53:40
there yet for osteoporosis. But perhaps in the
53:44
near future, it will be. Emma spoke about how
53:47
there will be some next generation genetic sequencing
53:51
that will arrive in the next two or three years
53:53
that would maybe allow us to genotype people
53:56
properly. And as we were talking right back at
53:59
the beginning of the show, there are hundreds
54:00
of genes that contribute to osteoporosis. Maybe
54:05
it would be possible to start putting all of
54:07
the information about those genes together and
54:09
computing some risk factor for the disease. But
54:12
again, like you said at the beginning of the
54:14
podcast, perhaps the most likely avenue for the
54:19
use of this genetic data could be into predicting
54:22
which patients are going to respond to which
54:26
treatments. Who's going to best respond to an
54:29
anti -resorptive or an anabolic agent or a bone
54:32
forming agent? Maybe it would even be possible
54:36
to think about the sequencing of therapy. What's
54:39
the right sequence of therapy? And also what
54:42
are the right co -treatments? Anything that a
54:45
doctor and a patient can do together to narrow
54:48
down the right treatment and the right treatment
54:51
protocol is going to help doctors to prescribe
54:55
and patients to take with confidence. And hopefully
54:58
that would improve the uptake of treatment. It's
55:02
all about having the data to have the conversation
55:04
better, isn't it? Yeah. And I guess the other
55:07
thing is, is that once... There are very large
55:10
data sets available that people can start to
55:12
mine. Genetic data sets alongside clinical data
55:15
set with clinical outcome measures like bone
55:18
mineral density, fracture risk, response to treatment.
55:21
It will be possible to mine that data and then
55:26
start to come up with predictive tools for people's
55:29
fracture risk and their response to treatment.
55:31
And that would be absolutely phenomenal. What
55:36
were your takeaways, David? Well, I suppose I
55:40
had the novelty of, because as you know, Richie,
55:43
I'm often accused on the podcast and at conferences
55:46
of being told I'm allowed to ask one question
55:48
and I ask two or three or four. So I had the
55:51
novelty this time round of asking one question
55:54
and Emma giving us two or three or four answers.
55:56
So I feel that was some redress for all my behaviour
56:01
in the past. But no, seriously, very, very interesting.
56:06
The things that I think about, for years we have
56:10
talked about, you know, meeting other doctors.
56:12
I wonder how much osteogenesis imperfecta is
56:16
out there that we're not picking up and just
56:19
causing, calling it, you know, bad osteoporosis.
56:22
And Emma mentioned the study that we've covered
56:25
in Australia and the UK, I think, which suggested
56:28
somewhere up to 4 % of patients who were just
56:31
believed to have common or garden osteoporosis
56:35
actually had gene changes associated with osteogenesis
56:40
imperfecta. And that's fascinating because it
56:43
suggests maybe 1 in 25 of my osteoporosis patients
56:46
doesn't really have osteoporosis but has OI.
56:52
And indeed, if it's that common, then there's
56:55
a fair chance that two patients in that scenario
56:58
could be the parents of someone who may have
57:02
very significant osteoporosis. And we do see
57:05
people from time to time with extremely low bone
57:07
mineral density, with fractures, and we do all
57:10
the testing. you know bar the genetic testing
57:13
and there's no obvious reason and it may be that
57:16
you know there's more osteogenesis imperfect
57:19
out there than we think of and that will certainly
57:21
certainly something that i will will sort of
57:24
dwell upon in the future you touched on it as
57:28
well the idea of genetic testing not so much
57:31
to determine why the patient in front of me has
57:34
got osteoporosis but on helping us decide what
57:39
the best treatment might be and that's you know
57:43
that's an interesting area it's an area in which
57:45
there's there's a lot of exciting avenues to
57:48
be explored and indeed i can't remember if it
57:51
was you or i asked the question about sort of
57:54
treatment you know gene editing and that sort
57:56
of thing and how it's very unlikely we could
57:59
edit one or two genes and change the diagnosis
58:04
of osteoporosis suddenly increase someone's bone
58:07
density when they're in their 50s or 60s or 70s
58:09
but the idea that you could maybe alter one or
58:12
two genes or edit one or two genes and dramatically
58:15
change their susceptibility to a drug for example
58:18
that's quite an interesting and exciting area
58:22
because ultimately at the clinic that's what
58:27
it's all about it's about yeah we're interested
58:30
in what's happened up to the last fracture up
58:33
to the last exoscan but it's really the future
58:35
that we're thinking about and it's you know it's
58:38
which drug which exercise regime which form of
58:41
nutrition is best for the patient in front of
58:43
me and in the exciting world of gene editing
58:47
which we hear a little more about all the time
58:49
you know the idea that we could make a drug work
58:53
better by doing that would be quite would be
58:55
quite exciting so Yeah, lots of interesting things
58:58
to think about. And again, as we say with many
59:02
guests, it would be great to hear Emma. It'd
59:05
be great to hear her again in a few years' time
59:07
to follow up on these things. It will be. I'm
59:11
excited to do a follow -up, actually, and find
59:13
out where all this goes. It feels like we could
59:17
be on the cusp of something really big. Yeah,
59:20
it's an exciting time. Well, thank you for joining
59:24
us today, listeners. We hope you enjoyed the
59:27
podcast. Bye bye. Bye now.