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Nothing about us without us · 'Bone Up'

0:00
Hello and welcome to Bone Up, the podcast all
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about bones, how we make them, why we break them
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and if we fully understand them. I'm David Armstrong.
0:11
Hi and I'm Richie Abel and over this series we're
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going to be exploring osteoporosis, bones, what
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we know and what we're yet to discover and we
0:21
hope you will join us on the journey. So for
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anyone keen to learn more about our infrastructure
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of calcified collagen, this is Bone up. Welcome
0:54
listeners to a new episode of Bone Up. How are
0:58
you doing, David? I'm doing well, thanks, Richie.
1:01
We're here in high summer in the Northern Hemisphere,
1:04
although it's another cloudy day today. Things
1:08
used to be a bit quieter in the hospitals over
1:10
the summer, but I think those days are gone.
1:12
We seem to be just as busy as we ever were. And
1:15
how about you? The same. It used to be that summers
1:21
were a bit more relaxing, but nowadays we just
1:24
seem to be busy the whole year through. trying
1:26
to keep the research going and writing up the
1:29
work that's been done over the previous year.
1:31
It's an exciting time but I'm quite tired and
1:34
I need a holiday. What plans have you got for
1:41
the new year? Well for the sort of the new term
1:46
coming up I suppose one of the things apart from
1:49
doing my normal NHS job is is we've got a face
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-to -face osteoporosis conference coming up in
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September, which is one of the things that you
1:57
and I have both been involved with the planning
1:59
with the Royal Osteoporosis Society. So that's
2:03
exciting. It's exciting to be working on a program,
2:06
to be inviting experts from all around the world,
2:09
and to be seeing all our friends again from the
2:12
world of bone research. And it's a great chance,
2:14
again, to get clinicians and researchers together
2:17
to talk about how we can do better for patients.
2:20
I'm really excited about the conference in Manchester.
2:24
I think the title is Equity in Bone Health, which
2:27
is a very pertinent title at the minute. The
2:30
Royal Osteoporosis Society who are organizing
2:32
the conference have been very active lately.
2:35
They seem to be doing a lot of good work and
2:37
it's going to be great to hear an update. And
2:40
there's loads of wonderful speakers at the conference
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and I've heard a lot of them before, but it's
2:43
always nice to hear what they've got to say.
2:46
It's always a really good learning experience
2:48
and it's... Honestly, I think first and foremost,
2:51
it's nice to catch up with friends and I'm looking
2:53
forward to seeing you there. Yeah, that'll be
2:56
good. As you say, we're focusing on sort of equity
2:59
of access at the conference. And I think that's
3:02
important. We talk about all these exciting drugs
3:05
and so on, but it's really important that everyone
3:08
who needs them has access to them, no matter
3:10
where you live in the country, no matter whether
3:13
you're male or female or whether, you know, whatever
3:15
ethnic group you come from or lots of different.
3:18
people that we see, we need to make sure that
3:20
everyone has the same access to the services
3:23
we provide and sort of look at how we do that.
3:26
So yeah, that'll be an interesting part of what's
3:30
coming up. Speaking of equity, I've been trying
3:33
to write some papers and grants in the last few
3:35
months, and I always have to begin with an explanation
3:37
of osteoporosis. And I always try and think of
3:41
sort of insightful off -the -cuff ways to try
3:43
and explain it to get people interested. I feel
3:46
that a lot of people tend to think about osteoporosis
3:50
as a condition that really affects old people,
3:53
and in particular, older women. But looking at
3:57
the literature, it seems actually a lot of young
4:00
people are affected by osteoporosis. Have you
4:03
got any experiences in your clinic? Yeah, I think
4:08
particularly working in the hospital as a sort
4:12
of secondary or even tertiary referral center.
4:15
I probably get a disproportionate number of young
4:18
people at the clinic. It's one of those difficulties,
4:22
I think, Richie, you're quite right, to get the
4:24
attention of those who would give grants for
4:26
funding, to get the attention of the media, to
4:29
get the attention of politicians. You sometimes
4:32
have to try to provide an interesting story,
4:35
and often that involves young people. Whereas,
4:39
of course, the majority of patients with osteoporosis
4:41
are still postmenopausal women. But yeah, I do
4:46
see a fair number of young people at the clinic.
4:49
I suppose I would divide them into a number of
4:53
groups. Certainly the first group would be those
4:55
who have taken steroids for some condition, glucocorticoids,
4:58
often things like asthma or types of arthritis
5:03
or inflammatory bowel disease. And as we know,
5:06
and as we've discussed before, taking steroids
5:09
in the long term can be very bad for your bone
5:11
health and significantly increase your risk of
5:14
osteoporosis. So they've always been a group
5:17
of people in their maybe sort of 30s or 40s who
5:20
have quite low bone mineral density related to
5:24
steroids. There's another group of people we've
5:26
been seeing more of, I think, in the last few
5:30
years, and those are people with... eating disorders
5:33
and other conditions related to that who are
5:37
a very interesting group of people to treat sometimes
5:40
more complex because eating disorders and particularly
5:45
anorexia nervosa often results in poor bone health
5:49
the reasons for that are complex it's sometimes
5:52
perceived that the weight in itself It contributes
5:56
to low bone density and it does, but often it's
5:58
linked to the menstrual cycle and of course to
6:01
nutritional needs in general. So I think there's
6:04
an increasing awareness of that. And I certainly
6:06
see an increasing number of young people with
6:09
eating disorders at the clinic. And then again,
6:13
there's probably a third group of people coming
6:15
through. And those are people who have serious
6:20
long term conditions. who are being better treated
6:25
as children and as adolescents and as a result
6:29
are surviving into adulthood. There are sadly
6:33
a range of conditions which in the past caused
6:36
people to die young, caused them to die as children
6:38
but as those people do better now, there are
6:42
new drugs, there are better ways of looking after
6:44
them and as they survive into adulthood often
6:47
they carry various chronic problems with them
6:50
and one of them is quite often low bone mineral
6:52
density with the risk of fracture sometimes that's
6:56
inherent in the condition and sometimes it's
6:58
because they have again taken a lot of steroids
7:00
as children and that's challenging um and challenging
7:05
in a good way at the adult clinic because we're
7:07
having to sometimes learn about conditions which
7:10
we just didn't see in adult medicine before and
7:12
we're having to learn how to think and how to
7:16
involve and talk to and try to get into the headspace
7:19
of someone who has now turned to be 18 or 19
7:22
and is living with a chronic condition they've
7:25
had sometime since birth. So, yeah, lots of young
7:28
people at the clinic, lots of challenges. But
7:30
again, positive challenges, I think, because
7:33
it helps us think about, you know, how we do
7:36
medicine and how we communicate with patients.
7:41
conditions do you see in your clinic david where
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the treatments might cause osteoporosis i mean
7:51
i i suppose the commonest by some distance at
7:54
a day -to -day clinic would be patients with
7:56
cancer particularly patients whose cancer is
8:00
considered not curable but treatable and often
8:05
those patients will have steroids or they will
8:08
have had other sort of hormone blocking drugs,
8:11
which can cause quite significant osteoporosis
8:13
and fracture. And in those cases, then there's
8:18
always that playoff between the benefits of getting
8:21
the osteoporosis drugs, but just how quickly
8:24
those drugs work and the potential side effects
8:27
of those drugs, because quality of life is, of
8:30
course, important. There are some of those other
8:34
conditions that I was talking about that patients
8:37
are now surviving longer without of childhood
8:40
cystic fibrosis certainly in certain parts of
8:44
the world used to be very common which is a serious
8:46
lung condition and a condition that affects absorption
8:50
and in the gut and used to reduce the length
8:53
of people's lives very considerably and would
8:55
cause osteoporosis but people are now doing much
8:57
better from that but are living into adulthood
9:00
and presenting with with very low bone density
9:03
and fracture risk And of course, then there's
9:06
always those conditions that require a lot of
9:10
steroid and particularly people who've been on
9:12
high doses of steroid in childhood, which will
9:15
lengthen lives, which is really good, but will
9:17
cause severe osteoporosis. And probably the one
9:20
that most obviously springs to mind for that
9:23
is Duchenne muscular dystrophy, which is one
9:27
of the muscular disorders. It's a condition which
9:32
affects young boys almost always. It's what's
9:36
called an X -linked condition. In other words,
9:39
the gene passes from the mother to the son. Occasionally
9:44
mothers can be affected, they can have muscle
9:46
weakness in later life, but it's the boys that
9:49
are quite severely affected. They have weakness
9:51
of their muscles in early childhood and without
9:54
treatment, usually by the age of maybe eight
9:57
or nine, they're unable to walk unaided any longer
10:00
and would need to use a wheelchair. There has
10:04
been extensive use of steroids in the last number
10:08
of years. which can extend the period of time
10:12
during which these boys are able to walk and
10:14
don't need a wheelchair. But it also can cause
10:17
significant problems with puberty and with the
10:20
development of normal bone density. And these
10:25
patients, therefore, are at high risk of fracture
10:27
and indeed do often go on to fracture, particularly
10:31
vertebral fractures, which, as we know from other
10:33
episodes, are painful and debilitating. And even
10:39
though the great news is that these boys are
10:41
now surviving to transfer to adult clinics, which
10:44
is great, so I get to see them, but they're coming
10:47
to me already on lifelong steroids and already
10:50
with low bone density and often with fractures.
10:56
And therefore, it's another complex and challenging
11:00
and interesting group of people to see at the
11:03
adult clinic. Listeners, this brings us neatly
11:06
on to our guest for today. who's going to talk
11:09
to us about management of osteoporosis with Duchenne
11:13
muscular dystrophy. Today we're very excited
11:17
to announce our guest Dr Gerard Wong on the podcast.
11:19
Hi Gerard, how are you? Hi Richie, how are you?
11:23
And hi to you David. Hi Gerard, it's a real pleasure
11:26
to have you on the podcast today. Gerard, you're
11:30
a clinical senior lecturer and consultant paediatric
11:33
endocrinologist with a special interest in bone.
11:37
working at the University of Glasgow, where you
11:40
do your clinical work in the Royal Hospital for
11:42
Children. I was wondering if you could just begin
11:45
by telling us about your clinical practice and
11:48
the patients that you work with. So thanks, Vichy.
11:51
So you're right. So I'm a consultant paediatric
11:54
endocrinologist, but with an academic appointment,
11:57
meaning I also do research and teaching within
12:01
the University of Glasgow. A consultant pediatric
12:04
endocrinologist looks after children and adolescents
12:08
with problems with their hormones, their different
12:12
glands in the body. And within pediatric endocrinology,
12:16
a large proportion of my case loads and patient
12:19
load also involves children with various different
12:22
issues with growth and puberty. My special interest
12:26
also is in bone metabolism, so children with
12:30
rare bone disorders. but also children with bone
12:35
disorders or osteoporosis as a result of chronic
12:38
ill health, which is something that we are increasingly
12:41
seeing more of as management and treatment of
12:45
various different childhood chronic disease has
12:47
improved over the last 10 to 20 years or more.
12:52
And Gerard, we caught up with you at the BRS
12:54
in 2022, where we had a discussion about childhood
12:57
diseases, and we spoke very briefly about Duchenne
13:01
muscular dystrophy. Would you just remind the
13:03
listeners what the condition is? So, yes, that's
13:07
right, Richie. So certainly in paediatric practice
13:10
or those of us who see paediatric bone disorders,
13:13
there are numerous chronic disorders which leads
13:16
to osteoporosis. And one of the chronic disorders
13:22
which lead to significant bone issues is a rare
13:27
condition, a rare muscle condition called Duchenne
13:30
muscular dystrophy. and it is an X -linked disorder,
13:34
meaning it predominantly only affects boys, and
13:38
it causes muscle wasting or muscle disorders.
13:42
These children are effectively born with that
13:45
condition, but issues are usually present within
13:48
the first few years of life, and diagnosis usually
13:51
happens four to five years of life, and it causes
13:54
progressive muscle wasting, where these boys
13:57
will eventually lose... the ability to walk and
14:01
without any management and therapy will lead
14:04
to unfortunately early mortality. But this is
14:08
a condition which obviously with the muscle weakness
14:12
itself and those other factors can lead to devastating
14:14
osteoporosis and bone weakness. Some of the people
14:20
listening to us will probably know about Duchenne
14:22
muscular dystrophy and others won't. Just in
14:25
terms of the disease course, what age do the
14:28
boys get to normally where they have difficulty
14:30
walking? Because most people end up as wheelchair
14:33
users. What age does that sort of occur at? So
14:36
that's right, David. Without any treatment, the
14:40
majority will actually end up using a wheelchair
14:42
fully by late childhood. between 9 to 11 years
14:49
of age, and with death expected around late adolescence
14:54
without any treatment. But the trajectory of
14:57
this condition has improved over the last 20
15:01
years, and that's with the introduction of better
15:04
healthcare, multidisciplinary care, better protection
15:09
of the heart and the lungs, but also the use
15:11
of a medicine that alters the trajectory of the
15:15
disease, cause steroids, which perhaps a lot
15:17
of the listener will know of in different contexts.
15:20
And in that case, in steroid -treated boys with
15:23
Duchenne, the average age of losing the ability
15:28
to walk and needing to use a wheelchair fully
15:30
is in adolescence, approximately sort of the
15:34
13 to 15 years of age, with mortality extending
15:38
to about the 30s instead of in adolescence. So
15:42
this isn't a primary bone condition, but you
15:45
and I might see patients as bone experts because
15:47
they develop osteoporosis and they develop fractures,
15:51
well, because of the treatment or because of
15:54
the condition or because of other things. And
15:57
we're extending that ability to be mobile by
16:00
what you're saying, maybe three, four, five years
16:03
by using steroids, which... is good, but then
16:08
it has long -term consequences, doesn't it? So
16:10
what's the story with osteoporosis in patients
16:13
with this condition? So I think it's multifactorial.
16:15
So meaning there are lots of reasons why bones
16:17
are fragile or weak in boys with Duchenne. So
16:20
we know in the listenership. perhaps will understand
16:23
that weak muscles or lack of physical activity
16:27
and stimulus during childhood will lead to weaker
16:30
bones somewhat and there are some animal studies
16:32
which suggest that animal models or animal studies
16:36
of models of Duchenne muscular dystrophy do have
16:39
some bone weakness and certainly the user's steroid
16:44
compounds or worsens the bone weakness bone fragility
16:48
to a lot of extent by a direct impact weakening
16:52
the bones themselves and the cells that lead
16:55
to the formation and the breakdown of bones the
16:59
structure of the bones themselves the density
17:02
of the bones themselves as steroids which is
17:05
used over a long term period is a tablet daily
17:09
steroids which is taken from early childhood
17:11
all the way to to adulthood also causes poor
17:15
growth almost no growth at all it hampers the
17:18
onset of puberty and growth in puberty in childhood
17:21
is very very important to make bones stronger
17:23
and thicker there are also other factors some
17:27
some young people with muscle weakness for instance
17:30
may not spend as much time in the sun and Vitamin
17:34
D deficiency and nutritional deficiencies like
17:37
calcium deficiency certainly can contribute a
17:39
part to that. And some of these boys, because
17:42
of the use of long -term steroid, need to take
17:45
medicines to protect their stomach. There's something
17:47
called proton pump inhibitor, which certainly
17:51
has also been shown to contribute in part to
17:54
bone weakness. So you can see that it just does
17:56
seem that there is a multitude of... factors
18:00
which leads to bones being weak as a result of
18:03
the condition itself and also the use of steroids
18:06
which is beneficial in part in slowing down the
18:09
muscle weakness. And these boys also fracture
18:13
bones much more commonly because of the osteoporosis.
18:16
Is there a particular pattern to the fracture
18:19
of bones? That's right. So certainly, I guess,
18:22
if you look at almost practically any chronic
18:24
disease and if you look in detail into experimental
18:27
studies or high resolution imaging, you will
18:31
probably find some bone deficits. But these boys
18:34
not only have got horrendous osteoporosis in
18:39
terms of the imaging you see of the bones, but
18:41
they do fracture. The fracture rate is very high.
18:45
So even without steroids, boys with Duchenne.
18:48
do fracture and that speaks to the abnormal bones
18:52
themselves particularly the small thin bones
18:55
and the commonest long bones that these boys
18:59
fracture are actually fracture of the femur or
19:02
the hip bones the long bones of the thigh and
19:05
they fracture with little injury at all the majority
19:09
of the time just either from falling from a standing
19:12
or at a walking pace and this is without any
19:15
injury With the introduction of steroids, we
19:19
find that we're seeing more and more of spine
19:23
fractures or vertebral fractures. There has been
19:27
some suggestion that very rarely you can see
19:31
vertebral or spine fractures in boys with Duchenne
19:34
who are not treated with steroids. I certainly
19:37
haven't seen somebody like that. um the the use
19:43
of steroids much more um regularly as routine
19:47
standards of care over the last 10 15 years and
19:50
especially on a daily basis we are seeing now
19:53
osteoporosis of the spine with lots of boys with
19:58
vertebral fractures or spine fractures at the
20:01
back jarrod you were recently awarded a grant
20:05
congratulations to develop guidelines for managing
20:08
vertebral fractures in boys living with Duchenne
20:12
and I understand that you're applying a mixed
20:14
methods approach so I guess you're trying to
20:17
combine some measurements of the patient's health
20:19
but also some survey of their opinions. How is
20:23
a mixed methods approach going to help you design
20:26
the new guidelines? So in 2018, an international
20:32
care consideration or standards of care managing
20:35
all aspects of care of boys with Duchenne Muscular
20:38
Dystrophy was published and there are much more
20:43
detailed guidance on surveillance and management
20:46
of osteoporosis. It is much more focused towards
20:51
growing children, I must say, and this is something
20:54
that we probably can expand on later. And for
20:58
the first time, it actually recognizes that spine
21:01
fractures are very common in this condition and
21:04
in steroid -treated children, and also the fact
21:07
that spine fracture itself, regardless of bone
21:10
density, is a sign of osteoporosis, and therefore...
21:16
that necessitate introduction of osteoporosis
21:19
medicine. Now, this guidance suggests that we
21:24
should start medicines to protect the bones using
21:27
medicines called bisphosphonate or medicines
21:29
that slows down bone breakdown. Once we find
21:33
fractures in the spine, even without any back
21:36
pain, if it's in the moderate category, but not
21:39
in the mild category. Some of us have actually
21:45
realized that actually applying these standards
21:47
of care where we do not treat mild fractures,
21:50
in fact, actually will almost invariably lead
21:53
to these fractures progressing and this boy's
21:55
getting back pain. So the clinical aspect of
21:59
the study is actually a retrospective study from
22:02
several centers where we want to report that
22:04
experience to see what happens with mild fractures.
22:08
without any bisphosphonate therapy. Certainly
22:10
the experience from my center in Glasgow is that
22:13
invariably almost as short as a year time they
22:16
will present with more mal fractures or the mal
22:20
fractures will become either moderate or severe.
22:24
And this is because we believe that this is a
22:26
condition where fractures are so common about
22:29
up to 75 % of these boys will develop fractures.
22:34
if you follow them up long enough, that maybe
22:36
there is a case to think of giving osteoporosis
22:40
medicine to prevent fractures rather than a secondary
22:44
approach, meaning treating once there is a problem
22:48
and in this case fracture. But to do that, we
22:51
want to ask the opinion of parents and carers
22:56
and also the young people themselves of whether
23:00
this is something that... they think is useful,
23:03
and also the right timing to do that, and also
23:07
how we do that. And the reason being, tablet
23:11
bisphosphonates are not particularly very effective
23:13
in growing children because not much of it is
23:17
actually absorbed. And the studies, not necessarily
23:21
in Duchenne, but a whole range of other conditions,
23:23
shows that it may not be very helpful in helping
23:28
spine osteoporosis. And therefore... In growing
23:32
children, we tend to use intravenous bisphosphonates.
23:36
So bisphosphonate that's given into the drip,
23:38
which obviously has got issues where these young
23:41
people have to come to the hospital and have
23:43
to have pokes in the veins. And also for the
23:48
first infusion usually, but sometimes in subsequent
23:50
infusions, you actually get reactions where these
23:53
boys don't feel so well. And for that, we thought
23:57
that actually developing guidance or guidelines.
24:00
in collaboration with the patients or asserting
24:03
the patient's voice is very important and this
24:06
is this piece of research we which we hope will
24:08
actually be brought to the next revision of the
24:11
international standards of care where we can
24:13
actually marry in the patient's voice as well
24:16
which i think is more and more important in rare
24:18
conditions that sounds like such a wonderful
24:22
research project i see that mixed methods are
24:26
becoming increasingly important in medicine now
24:29
And the voices of patients are being considered
24:33
more carefully. It's really interesting that
24:36
your approach is even extending to the families
24:38
of the patients as well. And I suppose because
24:41
these are young people, it's even more important
24:44
to make the effort to try and get their opinions.
24:47
That's right. So certainly I'm no expert in qualitative
24:51
research. I've been very... fortunate to be able
24:54
to collaborate with a professor of nursing whose
24:57
expertise specifically is in qualitative research,
25:00
somebody called Professor Lucy Bray in Edge Hill
25:04
University in Liverpool, whose expertise also
25:07
extends to interviewing children and adolescents,
25:10
which I think is actually very important because
25:12
we find that we might be quite good, we think,
25:16
in asking the opinion of parents and carers,
25:19
but I think... perhaps may not be very good or
25:22
maybe not good at all, up to much more recently
25:25
in actually asking the opinion of the young person.
25:27
And ultimately, it is their life, it is their
25:29
health. And I think their voice is also very
25:31
important. Yeah, isn't it so important? And as
25:35
Richie says, I think we're slowly waking up to
25:37
this idea that we have to, you know, nothing
25:39
about us without us, as they say, we have to
25:41
listen to what patients say. The evidence, for
25:44
example, I was going to ask, is there evidence
25:46
bisphosphonate works? Because as you know, we
25:48
have evidence bisphosphonate is helpful in postmenopausal
25:51
women. But as far as I know, there's no huge
25:54
long -term studies looking at bisphosphonate
25:56
in Duchenne muscular dystrophy. And I suppose,
26:00
isn't it important as well not to just attribute
26:03
effectiveness in one group to another? And one
26:07
presumes even the attitude of a postmenopausal
26:10
woman who has maybe 20 or 30 years left to live,
26:12
even to having fractures and to taking preventative
26:14
treatment, may be very different to the attitude
26:17
of a young man of 18 or 20 who perhaps only has
26:21
a few years to live. That's right. So that's
26:25
right, David. I think, you know, and what I've
26:28
learned over time is that I think never make
26:30
assumptions. Ask the patients, right? You know,
26:32
you might think that something is acceptable
26:34
to them, but maybe it's not. In terms of the
26:37
original question of the evidence, certainly
26:40
the evidence in pediatric conditions or pediatric
26:42
rare conditions is much limited compared to a
26:47
much more commoner condition like postmenopausal
26:50
osteoporosis. But there is building evidence
26:52
to suggest that bisphosphonate certain improves
26:55
bone density. in boys with Duchenne muscular
26:59
dystrophy treated with steroids. While there
27:02
are no comparative studies, the increase in bone
27:05
density probably is. greater in the intravenous
27:09
studies and perhaps makes sense and talks to
27:12
that whole issue of the reduce in absorption.
27:16
And there's certainly one randomized control
27:20
trial specifically in boys with Duchenne muscular
27:22
dystrophy who have been treated with intravenous
27:27
bisphosphonate in the form of zoledronic acid
27:29
compared to no treatment, which gave a suggestion
27:32
that in fact, spine fractures may be lower in
27:35
the... treated groups. So for sure, we don't
27:39
have a lot of very large scale studies in the
27:42
thousands, and we don't have studies for, you
27:46
know, five, 10 years. That trial that I mentioned,
27:49
which was led by Margaret Zachary and Craig Munns
27:52
in Australia, included something like a total
27:56
of just over 60 patients, so about 30 over patients
28:00
in each arm. So do you have a conversation with
28:04
patients then when they reach that age group,
28:06
let's say, when you're going to start steroids?
28:09
Because being on steroids may keep you mobile
28:11
for a few more years, but it may increase your
28:14
risk of painful debilitating fractures substantially.
28:17
Now that decision, I presume, is made when these
28:19
people are still children. And that's a discussion
28:23
with parents, with children. How do you have
28:25
that discussion with pre -pubertal children?
28:29
So thankfully, I don't have to have that discussion
28:31
because it's the neuromuscular clinicians or
28:35
neurologists who have that discussion. And maybe
28:38
up to much more recently, and I'm speaking in
28:44
general terms, there is... perhaps less of a
28:48
discussion. And part of it is not the issue with
28:50
the clinicians, but we're actually learning a
28:52
lot more about the risk benefit of medicine.
28:55
The other thing to say is that there are also
28:57
different ways and types of steroids that's given
29:00
in Duchenne muscular dystrophy. There is a steroid
29:02
that a lot more... of us are familiar with, called
29:05
prednisolone. But there's also a steroid that's
29:07
used in Duchenne called the Flasacode, which
29:10
does not seem to be used very much at all other
29:12
than Duchenne. And the other commonest way of
29:15
giving it is either giving it on a daily regimen
29:17
or an intermittent regimen. They give it 10 days
29:20
on, 10 days off. And we've learned a lot more
29:22
about that whole... benefit and also side effect
29:25
profile and much more recent conversations raised
29:29
by the patient group but also the clinician community
29:32
is how do we navigate that discussion of risk
29:35
benefit of well one the risk benefit of taking
29:38
steroids versus not taking steroids but also
29:41
the relative risk benefit depending on the types
29:45
of steroids you choose and i'm not sure that
29:49
we've got that right but i think that's something
29:52
that we need to consider further and perhaps
29:54
that's another piece of work which needs to be
29:57
done in asking these families how they actually
29:59
want to be to be involved in these discussions
30:04
because you could overwhelm the family with a
30:06
whole lot of discussion of a whole lot of research
30:08
at the time of diagnosis but similarly you don't
30:12
want to not give them information Gerald, given
30:20
that you're a pediatrician taking care of children,
30:24
from what I understand, the doctors who take
30:26
care of adults with bone disease are a different
30:29
speciality. How long do you support patients
30:33
for? And do you have to do a handover? So that's
30:39
that million dollar question. I don't think there's
30:42
an absolute right answer. And it may have to
30:45
be different depending on the... situation somebody
30:49
practices in, and in some ways, maybe also the
30:52
actual patient itself. So I guess you're talking
30:54
about the concept of transition from pediatric
30:58
to adult care, and I guess the whole transfer
31:02
to adult care. I think this is something that
31:07
I think needs to be thought out. I tend to see
31:13
this boy's toe a little bit older because one...
31:16
probably till their 20s, simply because one of
31:19
the other side effects, which I've mentioned
31:22
already, of the use of long -term steroids is
31:25
that puberty is delayed and needs managing. And
31:32
quite often, these boys are probably still developing.
31:36
through puberty and maturation and growing until
31:39
their late teens to 20s. And I think that it's
31:43
important that I manage that aspect of it, make
31:46
sure that they've progressed through puberty,
31:49
they've developed into an adult before I move
31:52
them on to an adult specialist. The handover
31:56
happens and they obviously... different models
31:59
of how you do it. Some centers, I suspect, do
32:02
joint clinics or joint discussions. And maybe
32:07
the ideal situation is when you've got the pediatric
32:11
and adult specialists looking after these patients
32:14
for an overlap period. But I suspect these are
32:17
things that still needs to be ironed out and
32:20
is quite challenging. I can imagine that doctor
32:25
and patient can build quite a strong bond over
32:27
such a long period. And you mentioned it's challenging.
32:30
Is it difficult for doctor and patient when there's
32:33
a transition? I think it's always difficult because
32:38
I would imagine that, you know, the transition
32:41
to adult care for any. chronic long -term illness,
32:44
particularly if you've been looked after in a
32:46
particular setting. It's not just a doctor, but
32:49
also an environment, particularly hospital, the
32:52
way things work. And it's quite different in
32:56
a different setting. I think it certainly can
33:00
be very challenging. A concept that actually
33:03
is very helpful in rare conditions is actually
33:07
having a transitioned nurse specialist, for instance,
33:11
or a patient navigator. that helps them navigate
33:14
that whole process of... I suppose, transitioning
33:16
from paediatrics to adult care. We're quite fortunate
33:20
because we exist in a hospital complex where
33:24
the paediatric hospital is literally just next
33:26
to the adult hospital. In fact, there's a corridor
33:30
that links us together. So at least they are
33:32
in principle familiar with the hospital building,
33:35
parking and surrounding. But there are some patients
33:38
who have to navigate moving to a completely different
33:40
hospital building. It's amazing how the design
33:44
of a building and the organisation of hospitals
33:48
can impact a patient and their experiences. I
33:54
mean, this is good news here, isn't it, in some
33:56
ways? Because when you and I were medical students,
33:58
Jared, you know, we were taught we'd never need
34:00
to transition Duchenne patients to adult care
34:03
because we knew that people didn't survive that
34:05
long. This is great news now that as an adult
34:09
bone expert, I'm seeing these patients and having
34:12
to think about that. If I ask, I mean, you said
34:15
earlier on in this, the high rate of osteoporosis,
34:19
the high rate of fractures, it could be the steroid
34:21
use. It could be the fact that these patients
34:24
are usually wheelchair users from an early age
34:27
and therefore don't have weight bearing. It could
34:30
be the lack of vitamin D exposure. It could be
34:32
something inherent in the condition itself. If
34:35
I ask you to sort of get, maybe this is unfair,
34:38
but if I ask you to guess. Which of these, or
34:41
let me put that another way, actually. If we
34:43
discovered a new drug which completely negated
34:47
the use of steroids, do you think we'd be having
34:50
this conversation? Do you think this is primarily
34:53
long -term high -dose steroids? Or do you think
34:56
it's primarily something inherent in the condition
34:58
itself? So I think steroids is the main culprit,
35:02
so to speak. in regards to spine osteoporosis
35:05
or spine fractures. So I think if there's actually
35:08
a medication that works just as well as steroids
35:11
in terms of delaying the muscle decline, but
35:16
has none of the steroid side effects on bone,
35:21
spine fractures will be reduced, perhaps eliminated.
35:26
But unless we've got a medicine that actually
35:29
completely rescued dystrophine, which is in fact
35:33
the abnormality to deficiency as part of the
35:36
genetic mutation, i .e. you completely rescue
35:40
that and rescue that really early and these boys
35:42
have normal muscle function, we will still see
35:47
osteoporosis because of the muscle bone connection
35:50
and long bone fractures. already are reported
35:55
in patients previously who are not treated with
35:58
steroids just because when you've got profound
36:01
and declining muscle weakness bone density is
36:05
impaired to some degree but the thing that we
36:07
are we effectively see is that they've got small
36:10
thin bones so in fact i would say that you will
36:14
still see long bone fractures but in the context
36:17
that you're describing spine fractures will if
36:21
not eliminated the minimized to a very low frequency
36:25
because i have at least one patient who is a
36:29
female carrier is a sort of a mother who herself
36:33
has quite severe osteoporosis and who does have
36:36
some symptoms of muscle weakness who is still
36:38
mobile who doesn't take steroids but has quite
36:41
severe osteoporosis and that has made me wonder
36:44
how much actually it is inherent in the condition
36:46
itself is there any screening of Mothers for
36:51
osteoporosis, do you know? So, no. So, again,
36:55
the whole sort of, I suppose, carriers or in
36:58
the literature among patient groups, sometimes
37:01
they talk of the female Duchenne, although we
37:04
say, and that's why I say it's predominantly
37:07
a condition of males, but female carriers are
37:12
called female Duchenne. There's still very little
37:16
understanding of the whole natural history of
37:20
the condition. We do know that some do get symptoms
37:26
usually much later on in life. There are a very,
37:29
very, very small number. who are so severe where
37:33
they behave almost like a boy with Duchenne in
37:36
the pediatric age group. And certainly there
37:39
are, but the majority do seem to have some muscle
37:43
weakness in adulthood. And there's no standard
37:48
of care on screening for osteoporosis in carriers.
37:51
There's a lot more management and also monitoring
37:56
of other health outcomes like these women are
37:59
supposed to have. echocardiogram of the heart
38:02
because the heart weakness can happen in the
38:04
carriers. But I do wonder whether some of these
38:07
women may have either more severe osteoporosis
38:10
or perhaps a little bit more early onset or when
38:14
you compare with a healthy group of women in
38:17
their 40s or 50s, more of female carriers have
38:21
osteoporosis in the manner that you know or the
38:24
adult clinicians know. Are there any new treatments
38:29
on the horizon? There are various different...
38:32
There's a whole lot of strategies that have been
38:35
investigated. David talks about a medicine which
38:41
perhaps has less of the steroid side effects,
38:43
and there's certainly a new steroid -related
38:47
compound called bamorolone, which looks like
38:51
steroid, but one of the side chain is different
38:53
from steroids, which... in principle should have
38:58
the same efficacy as steroid medicines like prednisolone
39:03
that we know, but potentially very little or
39:07
none of the steroid side effects. And this has
39:09
been investigated in clinical trials. Results
39:11
have been published. And it's shown that it works
39:14
just as well in the muscle compared with prednisolone
39:17
given every day. There are some good news in
39:21
the initial results that we've seen so far. is
39:24
that the blood test which tells us how active
39:27
these bones are so the bone formation and bone
39:30
breakdown markers in this new drug is normal
39:34
as opposed to it being very suppressed with prednisolone
39:37
and the growth is normal in these in these boys
39:41
treated with this new medicine we don't have
39:44
very much data on fracture yet some of the other
39:47
side effects of steroids with this new compound
39:49
is still present including weight gain and also
39:53
adrenal suppression, which is a side effect of
39:57
steroids. So it's still to be seen whether this
40:00
drug will have less of an impact on bone, and
40:04
it is being reviewed by the regulators and currently
40:07
not available for clinical use. but in the UK
40:12
we certainly have got a cohort of boys who have
40:15
been on compassionate use following participation
40:17
in the clinical trials. The Duchenne field has
40:20
also been very rich in all the genetic -based
40:25
medical therapies including exon skipping and
40:28
gene therapies. These are being investigated.
40:32
But it's not been as easy because dystrophin
40:36
is the largest gene and there are a whole lot
40:38
of issues that is beyond my expertise. But in
40:41
summary, it's not been as easy to deliver gene
40:46
therapy to boys with Duchenne. But this hopefully
40:50
will be overcome and we may have some positive
40:55
results in time. But even if we have gene therapy
40:58
that works, bear in mind that we can't reverse
41:01
the muscle weakness that's already present. So
41:05
for gene therapy to finally work, these boys
41:09
will need to have gene therapy delivered pretty
41:11
much almost at birth, which obviously doesn't
41:16
quite happen because often the symptoms don't
41:19
present until at least the earliest, around the
41:21
two years of age. Does that mean that in the
41:25
future, if there is, A very effective treatment,
41:28
especially a gene treatment that maybe everybody
41:31
would have to be screened to identify the mutation.
41:35
So there certainly is a screening program for
41:39
Duchenne and there are some programs in different
41:41
parts of the world, different states in the US
41:44
that's being piloted or studied as a research
41:46
program. It certainly doesn't exist in the UK,
41:49
but potentially I can see how, if that works,
41:53
that will be very beneficial and perhaps that's
41:55
where... things are headed. It sounds like a
41:59
very well connected and smooth running community.
42:04
How many clinicians and researchers do you think
42:07
around the world are involved in the field? Oh,
42:10
it's hard for me to answer that question. Certainly,
42:14
I would say that it's a very well connected community
42:17
in the UK, if I'm speaking in the UK. care of
42:23
the primary carers of boys with Duchenne muscular
42:26
dystrophy are delivered by neuromuscular clinicians
42:29
in the context of the UK North Star Clinical
42:33
Network. And there are approximately 27 centres
42:37
that deliver care to these boys. And they have
42:40
regular meetings and, you know, a lot of discussion
42:44
on clinical pathways. It is also bound by a sort
42:49
of almost a UK national database or registry
42:52
where regular clinic information is collected.
42:57
And as part of this community are the patient
43:02
groups, which are amazing and well connected.
43:05
There is a organization called World Duchenne
43:07
Organization with numerous organizations from
43:10
all over the world. And within the UK, the patient
43:14
groups work well together with clinicians and
43:16
one of the patient groups called Duchenne. UK
43:18
have in fact delivered a project called DMD Care
43:23
UK which is a collaborative project between the
43:26
patient group Duchenne UK and Newcastle University
43:28
and all the clinicians in the North Star Network
43:32
to develop UK -based standards of care for patients
43:37
with Duchenne muscular dystrophy and try to overcome
43:41
some of the barriers of actually delivering care
43:44
in the center. It's very nice for us to write
43:47
guidance for five, 10, 20 of us to write guidance.
43:51
But the important thing is how we actually mix
43:53
it to the clinic and sometimes that's lacking.
43:56
And the patient groups have actually been instrumental
43:58
in getting us all together, the neuromuscular
44:02
clinicians, but also the other specialty, like
44:05
the bone endocrinologists and the cardiologists,
44:07
the physiotherapists and the gastroenterologists
44:09
and the nutritionists in this project. So I definitely
44:12
agree with you, Richie. I think it's a brilliant
44:16
and excellent and well -connected community.
44:19
It's a model almost for other conditions, isn't
44:21
it? How in Duchenne it's the patients who are
44:24
sitting really in the driving seat of all this
44:27
and the clinicians and scientists are sort of
44:28
responding to the sort of lead from the patient,
44:32
which is great. I suppose that brings us neatly
44:36
onto our last question. Jarrod, I was wondering,
44:40
how did you find your calling in life? Because
44:43
it's almost as though you're a specialty within
44:45
a specialty within a specialty. A paediatrician
44:48
with an interest in bone, working in rare condition.
44:52
And even above and beyond that, you've become
44:54
a specialist in scientific and public communication,
44:57
like a voice for your community. That's a tough
45:03
question, Richie. I think things happen as they
45:08
happen. So other than Duchenne muscular dystrophy,
45:13
my work has always been around the area of growth,
45:17
puberty, body composition, and bone development
45:19
in chronic ill health. I started looking into
45:22
pediatric inflammatory bowel disease and childhood
45:25
arthritis. So there's lots of common themes,
45:28
inflammation, steroids. But I think I tend to
45:33
stumble upon things. and if i find that something
45:37
moves me i stay with it and importantly i've
45:42
also got a few criteria of myself i need to i'll
45:45
do things if i enjoy the people i work with i
45:49
think that's critically important and if i think
45:53
i can if it moves me and i think that it actually
45:56
makes a difference to the people i .e the patients
46:00
i it wakes me up at night i think over time those
46:04
are probably the things that um leads me to where
46:08
i am but a lot of it is by chance i would say
46:11
i stumble upon it but i then decide whether i
46:14
stay where i stumble upon that's a very interesting
46:20
answer thank you very much Okay, we better draw
46:24
it to a close there. Gerard, thank you so much
46:27
for coming to speak to us today. That was really
46:29
interesting. Thank you very much for having me,
46:31
Richie and David. It's been a real pleasure,
46:34
Gerard, and I hope to speak to you again soon.
46:38
So, Richie, that was very interesting to talk
46:41
to Gerard. What are your takeaway points from
46:46
that then, once it's sort of settled down? It
46:51
was a really interesting interview. I felt that
46:54
Jarrod explained everything around the condition
46:57
and the treatment of the condition really well.
47:00
And we also got a very good insight into the
47:03
clinician's perspective. I would say overall,
47:07
my biggest takeaway is that I'm impressed by
47:10
the ambition of the project. Jarrod is aiming
47:13
to produce and develop international standards
47:17
of care. And I think it's a really wonderful
47:20
approach that in writing those guidelines, he's
47:22
really focusing on not just the patients, but
47:24
also their families to try and find out what
47:28
they would like to see in the guidelines so that
47:30
people can get the best management of their condition.
47:33
And that's a really wonderful and interesting
47:35
approach. And increasingly, medical research
47:39
is using qualitative research, research of people's
47:43
perceptions, thoughts and feelings to help guide.
47:46
clinical research and clinical care but i think
47:50
this is a really exemplar case of how qualitative
47:53
research is being used in order to improve patient
47:57
care that's absolutely wonderful and i hope that
48:01
lots of people are going to listen to this podcast
48:03
and maybe think about how they should also be
48:05
using qualitative research to direct medical
48:09
research to where it's most needed And to improve
48:14
the care in the way that's going to benefit patients
48:17
the most. And it was quite, I felt this was quite
48:24
a hard, a hard episode to record. Ever since
48:27
we first spoke to Jarrod and Nicola way back
48:30
at the BRS conference, I was quite taken aback
48:33
by Duchenne and what a serious condition it was
48:35
and how many people are affected by it. And I
48:38
have a young son and it's a, you know, it's a
48:40
difficult topic. And it must be really, really
48:45
hard for clinicians, and I include you in this,
48:47
when you're working with people who are young
48:51
and maybe they don't have very long to live and
48:54
you have to do whatever you can in order to be
48:57
able to improve their quality of life. And there
49:00
must be some really difficult discussions there.
49:05
Yeah, there certainly are. You know, it's one
49:08
of the other things. I suppose I learn as an
49:11
adult clinician and someone who's trained as
49:13
an adult clinician is involving families in that
49:17
sense, because most of these patients transfer
49:20
over to my clinic, you know, round about the
49:24
age of 18. And up to that age, obviously their
49:27
parents and their families have been very involved
49:30
in their care. And, you know, they've always
49:33
come with their parent. And for Duchenne patients,
49:36
it's very often their mother they've come with
49:38
them. And then when they turn 18, you know, they
49:41
do have autonomy. So you're in that situation
49:44
where you have to say to the patient, do you
49:47
want your mother to be in the room with us any
49:49
longer? Because you're my patient and everything
49:51
you and I talk about is entirely confidential.
49:53
And if you wanted to be as confidential from
49:56
your parents and your carers and everyone else
49:59
as well. So quite apart from the underlying condition,
50:02
there's that little sort of bit of management
50:04
of now treating people as... um you know autonomous
50:09
adults who possibly in the health care system
50:13
up to now have been treated as children whose
50:16
parents were there to sort of make the decisions
50:17
for them so you know that's that's separate from
50:21
everything else we're talking about about osteoporosis
50:23
that's another learning experience you know for
50:26
adult clinicians i mean i've learned i've learned
50:30
a bit about duchenne muscular dystrophy certainly
50:33
from seeing patients um it emphasizes for me
50:36
again and we've talked about this before the
50:39
link between muscles and bones and you know we
50:42
talked to gustavo duque last year about all the
50:45
interesting research about how bones and muscles
50:47
talk to each other and it just emphasizes again
50:51
how muscle diseases affect bones how bone diseases
50:54
affect muscles and how we often think of these
50:56
things together jared mentioned how there's still
51:02
a dearth of research in this area, particularly
51:04
treating osteoporosis in young men with Duchenne's.
51:10
And so much of the research that we use comes
51:16
really from older people. And we're just presuming
51:20
that the body behaves in the same way. And so
51:23
there's a big need for specific focused research
51:26
in young people with osteoporosis. Because to
51:28
be honest, a lot of the stuff we do is really
51:31
not based in research in this group. And I suppose
51:35
the other thing just in general, it has always,
51:38
it cuts through all the sort of woolly thinking
51:41
and woolly talking we do to people. You can say
51:45
to an older person. Take this drug. It'll make
51:48
your bones a bit stronger. It'll reduce your
51:49
risk of fracture. Do you remember you broke your
51:51
hip last year? And they'll say, yes, doctor.
51:54
And, you know, you don't have to be... Older
51:57
people sometimes don't ask the difficult questions.
52:00
My experience is in seeing patients who are maybe
52:03
18 or 19 years old and they know they have a
52:06
very life -limited condition and they just cut
52:09
straight through to the questions. They know...
52:11
They say, how effective is this drug? What are
52:14
the side effects? How likely is it to actually
52:16
reduce my risk of a fracture? How long does it
52:20
take to work? I only have a few years maybe left
52:23
to live. How long does this take to work? And
52:25
even questions, the presumption is, for example,
52:29
that people will do anything to avoid a fracture.
52:31
That's generally what my clinic is based on.
52:34
People come to see me because they want to avoid
52:35
fractures. I can see a young person who said
52:38
to me, you know, I've had a dozen fractures in
52:40
my life right the way through childhood and adolescence.
52:43
And you're telling me to take this drug that
52:44
I don't know much about because it'll reduce
52:46
my risk of further fractures. They may say to
52:48
me, well, you know, what what difference to my
52:51
quality of life is having another fracture going
52:53
to have? And questions like that are really challenging
52:56
for someone who has more dealt with adults and
52:59
dealt with older people. And as I say, it really
53:02
it really makes you focus in on. how the drugs
53:06
work and what we're actually trying to achieve
53:08
for patients. And as we've talked in other areas,
53:12
sometimes looking at what you might call extreme
53:15
cases or very unusual cases does make you think
53:19
about how you do your job in general and how
53:22
we look after patients in general. And certainly
53:25
in this group of patients, I find myself very
53:28
much, and I think I largely should be in this
53:30
role, as someone who provides data. provides
53:34
support, provides the information, but is to
53:37
a very strong degree led by the young person
53:40
and led by the patient as to what's important
53:43
to them. And in fact, you could get two very
53:46
similar patients and they could have a very different
53:49
outlook on whether they want to take the medication,
53:53
whether they don't, and what their values and
53:57
hopes and fears are for the rest of their lives.
53:59
So it can be quite a humbling experience. Your
54:03
role as a doctor, I think, is quite different
54:05
here than it is in some other groups. And that's
54:09
always, you know, that's always good. So it was
54:11
good to think about things differently and then
54:13
to see how you can maybe even apply those lessons
54:15
to other patients. A while back, we did what
54:20
I felt was one of our best episodes on pregnancy
54:23
associated osteoporosis. When we spoke to Kirsty,
54:27
I wonder if maybe we need to talk to somebody
54:30
living with Duchenne. to try and get some more
54:34
insights into this condition, try and get a handle
54:38
on how they see the doctor -patient interactions
54:40
from their perspective. I think that would be
54:42
very interesting. Absolutely. And, you know,
54:46
it's the patient's voice that ultimately is the
54:48
very important one here because that's at the
54:51
basis of everything that we do. Yeah, you had
54:55
a very nice phrase in the interview. I think
54:56
you said, nothing about us without us. I'm going
55:02
to try and remember that. I can't claim to have
55:05
invented that now. I got that from another patient,
55:10
actually, who also does a lot of work about people
55:13
with disabilities and making sure they have access
55:15
to services. But yeah, it's a good one to remember.
55:18
I think it summarizes what our attitude should
55:21
be. While we're being honest with each other,
55:25
I gave a talk the other day and I... I wholeheartedly
55:28
stole your analogy for osteoporosis being a bathtub
55:31
slowly emptying with water. Oh, there's plenty
55:35
more of those come from Richie. Good, good. Okay.
55:40
We better wrap it up there. Listeners, thank
55:42
you for joining us. Thanks again to Gerard for
55:44
coming and talking to us. See you again soon,
55:47
David. Bye -bye. Bye now.