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Vertebral fractures, never events & Martha's rule · '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 Listeners, welcome
0:55
to the last Bone Up episode of 2024. It's been
0:59
quite a year. How are you doing, David? I'm doing
1:02
well, thanks. Looking forward to getting a few
1:04
days off over Christmas. And yeah, just looking
1:07
back at all the things we have crammed into the
1:10
year, both professionally and actually on our
1:12
bone -up recordings as well. Yeah, it has been
1:15
a busy year. It was nice that, what, about a
1:18
month ago, you visited London and we got to see
1:21
each other face -to -face to plan what we're
1:23
going to do for the podcast next year. That was
1:25
really a lot of fun. I like that a lot. We visited
1:28
ECTS this year. I think we got some really great
1:31
episodes live from the conference. And we got
1:34
the interviews with Eleanor Tesordi and Roland
1:37
Barron. It was a really fantastic event. Yeah,
1:41
it was great. The weather in Marseille was fantastic.
1:43
We got to speak to a whole range of people from
1:46
some of the most senior bone research people
1:48
in the world, right through to people doing undergraduate
1:52
and doing doctorates from right across Europe
1:55
and, in fact, across the world. at large so yeah
1:58
it was a really really good time um at a personal
2:02
level i was actually over in london as well as
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meeting you richie to attend the the adult rare
2:06
bone disease clinical network uh meeting which
2:09
was good and uh and my trust in northern ireland
2:12
is now part of that which is which is excellent
2:15
the ects meeting was a big highlight for me this
2:18
year but i also had my visiting professorship
2:21
renewed by my colleagues at ulster university
2:23
so that was nice as well but clearly they expect
2:27
more work out of me so there's no such thing
2:31
as a free lunch there's not this year seems to
2:35
have been a very busy year for you clinically
2:37
as well david yeah every year seems to get clinically
2:41
clinically more busy i suppose and um i mean
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i was speaking earlier to one of my senior nurse
2:48
colleagues and she was just saying to me that
2:50
she seems to do nothing but treat people with
2:53
vertebral fractures now you know within the fracture
2:55
liaison service and and that's certainly a big
2:58
change something we see at conferences we hear
3:00
a lot more with vertebral fractures but even
3:02
in day -to -day practice you know the vertebral
3:05
fracture is now front and center of sort of driving
3:08
what we do and the patients we now see as as
3:12
the highest risk patients and the patients we
3:14
prioritize largely in seeing um and that As years
3:18
go on, I think that the vertebral fracture becomes
3:21
more and more important, which is, of course,
3:26
very topical because of our guest today, Professor
3:29
Ken Poole, who has agreed to talk to us. I'm
3:32
sure he will talk to us about a range of things.
3:33
Ken is a man of many talents, but we're hoping
3:37
he will focus on vertebral fractures and on his
3:39
insights and research work in that area. Listeners,
3:44
we're very excited to announce our guest today.
3:46
We've been trying to get him on the podcast for
3:48
a while. He's incredibly busy. We have Professor
3:51
of Metabolic Bone Disease, Ken Paul, from the
3:53
University of Cambridge. Professor Paul applies
3:56
novel imaging techniques to investigate bone
3:59
diseases in his research practice, and he also
4:02
runs the NHS Clinical Services for Metabolic
4:05
Bone Disease. Ken, hi, great to have you today.
4:08
Hello, thank you for having me. It's lovely Ken
4:11
that we've been able to get a window to catch
4:14
up so we're really looking forward to speaking
4:15
to you. To kick us off with the questions then
4:18
Ken we'd like to get an idea about what your
4:21
day job is like. We know that you combine clinical
4:24
work and research work with your special interests.
4:28
How do you bring that all together? Well I think
4:31
I've probably got four jobs. One of them is being
4:34
a clinical doctor for patients with osteoporosis
4:37
and particularly vertebral fractures and people
4:40
who've got complex osteoporosis and then people
4:45
with rare diseases of which we look after about
4:47
550 people in Cambridge with rare diseases. The
4:51
particular interest in osteogenesis imperfecta,
4:54
so brittle bone disease and all that goes through
4:55
families so there's a lot of them. The other
4:58
hats are I'm an academic at the University of
5:01
Cambridge and I do a lot of clinical trial work.
5:03
imaging work and studies to try and work out
5:06
why people fracture and how we can better treat
5:09
them and third job I'm a capacity lead so trying
5:12
to bring on tomorrow's researchers with the NIHR
5:15
Cambridge Biomedical Research Centre so that
5:18
and we've got a current focus on trying to get
5:19
nurses midwifery and allied health professionals
5:22
into research and support them here and my fourth
5:26
job is well because my wife is a consultant obstetric
5:28
anesthetist I'm a I'm a sort of very busy dad
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so lots of drop -offs to school and back it's
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nice to hear you including that as part of a
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proper job ken oh it's the best so um we were
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going to talk today about many things but but
5:48
significantly about vertebral fractures We were
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talking earlier, I was thinking maybe 15, 20
5:54
years ago, we didn't hear as much about vertebral
5:56
fractures in terms of conferences and research
5:59
and practice. Why do you think we're hearing
6:01
so much about vertebral fractures now as compared
6:05
to in the past? Well, I think you're talking
6:10
about whether we hear them about them at conferences.
6:13
I think you and I in our clinics. We've never
6:18
stopped seeing patients with vertebral fractures.
6:20
When someone loses height from a vertebral fracture
6:24
or has a curved back, that's really the archetypal
6:28
osteoporotic patient or person with osteoporosis.
6:31
And once seen, especially when someone's had
6:35
multiple vertebral fractures and they've lost
6:37
a lot of height or it's really changed them,
6:39
never forgotten. And I think the difference between...
6:45
You know, I've been doing this 27 years. The
6:47
difference between then and now is that there
6:51
are treatments that really mean that it should
6:54
be a never event for someone to have multiple
6:57
vertebral fractures. And the reason it should
6:59
be a never event is because we've got medicines
7:02
that prevent the fractures. And there's always
7:07
been a real problem trying to identify people
7:10
with vertebral fractures. And part of the...
7:14
Part of the research question is trying to find
7:16
who those people are and get them targeted to
7:19
the right treatments at the right time. I remember
7:22
years ago, it was this incredible, the first
7:25
ever real epidemiology in osteoporosis from Professor
7:28
Cyrus Cooper. And it had this exponential increase
7:32
in hip fractures with time. And everybody was
7:35
amazed by this exponential curve as you got older,
7:38
as age increased, the hip fractures got more
7:40
common. There was also a steady increase in forearm
7:44
fractures. And then another part of the curve
7:46
that less looked at was the vertebral fractures.
7:49
And they started to go up very rapidly after
7:51
50. But that was only if you look for them with
7:55
x -rays, if you did radiographs. They're all
7:58
out there. It's just that they come to us late.
8:03
Do you think it's been driven, like I suppose
8:06
like many diseases, you finally get a drug that
8:08
works well for it and there's naturally more
8:11
interest in the disease or in the sub -disease,
8:16
whatever. Do you think this, and this is sort
8:18
of interesting probably for researchers, is this
8:21
somewhere where research and new drugs have really
8:23
pushed clinicians to search harder for patients
8:26
who will benefit from these treatments and to
8:28
do better for these patients? Jonathan Reeve,
8:34
who was my PhD supervisor, he gave the first
8:37
teriparatide, as is now, or parathyroid hormone
8:40
treatments in 1972 at Northwick Park, or at least
8:45
the publication was in 1972, in The Lancet. And
8:50
that's possibly one of the most effective treatments
8:53
for vertebral fracture. It took until 2004 for
8:57
that to become a drug, but it's been a drug that's
9:00
been able to... de -risk someone within about
9:04
six months such as there's a 90 % reduction in
9:08
severe vertebral fractures with that medication
9:11
and I don't think it's I mean obviously there
9:15
was a lot of problems with its price to begin
9:17
with it being a you know an expensive hormone
9:21
drug but nowadays there are biosimilar drugs
9:23
to teriparatide that we use here I think the
9:28
problem is that there's always been a One of
9:32
the first problems came because radiologists
9:34
and doctors got together and said back pain should
9:37
not be x -rayed. I never could understand that,
9:41
but it came along. And so you have people like
9:45
Emma Clark and Stephen Kaptogi in the research
9:48
world who've done great studies to show these
9:52
are the types of back pain that require you as
9:54
a doctor or a nurse to request an x -ray or radiograph.
9:58
And you should be finding them in that way because
10:01
the ultimate problem is that some of the back
10:04
pain you feel with a vertebral fracture seems
10:06
similar to other types of pain with back pain.
10:10
And since back pain is so common, there was a
10:13
thought, well, it's going to be chronic musculoskeletal,
10:16
the word that covers everything. And actually
10:18
there you miss the person who's just collapsed
10:21
a vertebrae and who could be helped enormously
10:23
by treatments. And you asked me about the medication.
10:28
I think that it's fair to say that with newer
10:30
medications that come along, like bromisosumab,
10:34
abalaparatide has come, and hopefully there'll
10:37
be more anabolic treatments like this. Yeah,
10:40
I think that because they work so rapidly and
10:43
with such an enormous effect, then of course
10:46
it focuses the doctors' and nurses' attention
10:49
on trying to get the patients the treatment quicker,
10:52
especially if they're at very high risk. And
10:54
we all know that if you've had one vertebral
10:56
fracture... The second is, you know, what is
10:59
it, nine times more likely, and the third is
11:01
27 times more likely. Once you're going up through
11:04
the vertebral fractures, they're like dominoes.
11:06
So, yeah, there's some truth to what you say,
11:08
but I think that we've all seen the patients
11:12
who could benefit, and they've always been there.
11:16
How similar are the vertebrae to other bones
11:18
in the body, like the hip? Do they fracture in
11:22
the same way? That's a great question. You've
11:27
got these 24 out of your 33 spine bones, the
11:32
24 of your cervical, thoracic and lumbar vertebrae.
11:36
And they make that lovely double S shape that
11:39
we have because we're bipedal and we have to
11:41
stand upright and support our heads right at
11:43
the top, which is quite unusual for apes. And
11:48
so they are formed the same way as the hip. The
11:51
endochondral ossification, they're formed from
11:53
a cartilage template, which is then... made mineralized
11:58
and ossified but there the similarities probably
12:01
end you could probably say they've both got a
12:04
cortical shell so a hard compact bone shell like
12:08
scaffolding tube and they've both got an inner
12:12
honeycomb or trabecular bone which is like the
12:15
inside of a crunchy bar but in the vertebrae
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it's very much more the honeycomb working with
12:22
the shell that's giving it the strength That's
12:25
the front of it, the vertebral body. And then
12:28
at the back of all your individual vertebrae,
12:29
you've got these spinous processes and articular
12:35
processes. They're the bits you can feel if you
12:37
lean forward and press on the lower part of your
12:40
back. You'll often feel that that's the spinous
12:42
process. That's giving you the bony support and
12:46
protection for your spinal cord and all your
12:49
nerves. Whereas your hip is this lovely cantilevered
12:52
arch. transferring the body weight in a ball
12:58
and socket joint down to your leg, your thigh
13:00
bone, and really given to compression and tensile
13:06
forces and lots of torsional forces as well,
13:09
whereas your spine has a very different loading
13:11
pattern. And then how they fracture couldn't
13:16
be more different, really. I mean, if you fall
13:18
to the ground hard enough on your bottom, you
13:20
could fracture a vertebrae. And if you fall to
13:23
the side, landing on your hip, you can fracture
13:26
a hip or proximal femur. But actually, that's
13:29
not how we often see people with a spine fracture
13:33
break it. It's more often that they're lifting
13:36
something or they've bent in flexion. And that
13:39
comes back to your background, Richie, about
13:42
material properties. And the material properties
13:46
of the hip and spine are very different. The
13:49
vertebrae can only withstand a certain amount
13:51
of flexion loading or the compressional loading
13:57
before it gives way. And it gives way in that
14:01
sort of non -elastic way for a bit and then is
14:04
a complete failure point. So that sometimes if
14:09
someone hasn't got any honeycombs, as happens
14:11
in severe osteoporosis, the whole vertebrae can
14:14
collapse. And that's one of the things that,
14:17
you know. We want to know the bone density because
14:21
we want to know whether any of the other vertebrae
14:23
are going to be collapsing in that way. And whereas
14:26
your hip has got a complex way of fracturing
14:28
because of its design and shape, it's got some
14:33
regions which are very, very thin and porous
14:36
and liable to give way at the slightest, you
14:40
know, reversal of forces. So when you fall on
14:43
the side, you reverse the normal forces the hip
14:45
feels and therefore... That's how you often break
14:47
a hip. Is the mechanism of fracture important
14:51
in terms of a vertebra, or is it something do
14:56
you think, you know, we measure, we do a DEXA
14:58
scan and we measure bone mineral density at the
15:01
spine, but it strikes me sometimes the actual
15:04
mechanism is something that we should... that
15:08
I wish I knew more about why people fracture
15:11
certain vertebrae at certain times. We've all
15:14
seen patients with T -scores of minus five who
15:17
remarkably have never broken anything. And yet
15:20
again, we've all had, I think, the clinical conundrum,
15:22
Ken, of seeing someone with two or three vertebral
15:24
fractures, but a T -score of minus 1 .5. And
15:27
it strikes me sometimes at the clinic, we're
15:29
way far behind in terms of the mechanism of understanding
15:33
how the vertebrae actually fracture. We are.
15:38
And I mean, I should probably say you've already
15:43
done in your podcast T -scores and DEXA, but
15:46
it's worth sort of, it's worth restating that
15:50
in someone who's a younger postmenopausal woman
15:53
or a man of the same age, a spinal DEXA is a
15:57
really good readout of the strength of someone's
16:01
vertebrae. It's only when you get into the older
16:04
range where all those bits i mentioned before
16:07
like the pedicles and the spinous processes and
16:10
all the other bits of the vertebrae get worn
16:12
and and hardened and you can't then measure the
16:16
the the honeycomb parts of the vertebrae with
16:18
the dexa and you know some people get very upset
16:21
locally when they can't have a spinal dexa over
16:24
a certain age but actually the reason we say
16:26
you can't have it is because it doesn't give
16:28
you the information we need on the honeycomb
16:30
so So bearing that in mind, we don't measure
16:34
directly the strength, whereas Richie and colleagues
16:38
at Imperial and around the world, there are techniques
16:42
which measure the actual performance of a tissue
16:47
or a structure, or in this case a bone, under
16:51
loading conditions. So there even exist at the
16:54
moment ways of taking... images. They have to
16:57
be 3D images in order to, so a CT scan or a tunnel
17:03
scanner that goes all the way around the body
17:04
to give you a 3D picture. And then doing a finite
17:09
element analysis, which breaks down the structure
17:13
into little focal elements, and then can subject,
17:20
if in the case of a spine or a vertebrae or a
17:23
hip, subject it to the sort of forces that take
17:27
place when you do give extra force to the body.
17:34
So when you do bend down and lift up the really
17:37
heavy end of the sofa or fall sideways onto the
17:41
floor, you can recreate those conditions in the
17:43
laboratory using finite element tools. And when
17:47
you do that, you get amazing results because
17:48
you can take someone's... bones and virtually
17:53
break them in the lab and also see which bits
17:57
are giving way first. So in the case of what
18:01
turns out to be really useful in humans to work
18:05
out how their bones might break is spinal finite
18:10
element imaging. The great proponent of this
18:14
has been Tony Keaveney. And his software can
18:19
take an L3 vertebrae and get internal tissue
18:23
failure by virtually loading it and virtually
18:27
compressing it. And you actually see, because
18:30
of a little color map, you can see the individual
18:33
elements of the trabecular part giving way at
18:37
the stress. And you can work out, you can say
18:39
this vertebrae in this person, you know, its
18:42
baseline strength was three and a half thousand
18:44
newtons. And obviously the really beautiful thing
18:48
about that is then you can say a year or two
18:51
later with some treatment, look, its strength
18:54
now is 5 ,500 newtons, and that's the difference.
19:01
I was thinking about the clinic. Will we ever
19:04
see that at the clinic, do you think? Well...
19:10
And is it useful to have it at the clinic? Will
19:12
it ever guide us to say, well, you know, I've
19:15
done your finite element analysis. And I think
19:17
in your case, teriparatide might be better than
19:20
romo or proli. Do you think it has a clinical
19:22
or is it just something that makes Richie's eyes
19:24
light up because it's such an exciting way of
19:27
looking at bone? Well, I think. what you have
19:33
when someone comes in particularly if they've
19:35
had a vertebral fracture is they don't they've
19:37
got no confidence in their own bones ability
19:40
to withstand simple acts of daily living and
19:43
they feel you know when's the next one going
19:45
to happen and it is in my experience with the
19:48
patients coming to me really an awful event in
19:50
their life so you know is everyone going to get
19:54
this no but but there are some things that are
19:57
just a quite a long way along the towards finite
20:01
element modeling like 3d um qct which is a method
20:06
method that's gaining a lot of traction of measuring
20:08
the the trabecular the honeycomb bone density
20:11
which gives you it's not miles away from the
20:14
from the finite element readouts for how strong
20:16
the bones are and you can start to look at that
20:18
and say yeah yeah actually you had a okay let
20:21
go to go back to your question david you had
20:22
an okay t score but let look inside your honeycomb
20:25
and actually what's going on here is that the
20:27
the trabecular the honeycomb bone is not as strong
20:30
as we thought And therefore, you know, where
20:34
we were sitting on the fence and wondering whether
20:35
you should have a bone building therapy first.
20:38
Now we're sure. And we're actually doing that
20:40
right now. I mean, because we're very blessed
20:42
in Cambridge. I think we've calibrated with Dan
20:45
Chappell in the team and Judith have calibrated
20:47
every CT scan that we can reach within miles
20:51
and miles of Cambridgeshire and the fens. If
20:53
we find a CT scanner, we go out and we calibrate
20:56
it. And so if someone says to us in Kingsland
20:58
or, you know, Norwich. I've got a CT already
21:02
done on this patient. Because we calibrated it,
21:05
we can get the image exchange portal to send
21:07
us the pictures and say, right, yeah, we'll do
21:10
the QCT, which is not quite a finite element,
21:14
but it's along the way. Once it's working in
21:19
a number of people and it's shown to be useful,
21:21
then industry, commercial companies can get behind
21:24
it and then work to develop better scanners that
21:27
can then go into hospitals to fill the need.
21:30
Yeah, I mean, and it's worth saying that the
21:33
great majority of our current research in this
21:37
area is just done on ordinary scans done for
21:40
other reasons. And we've got like a buy one,
21:42
get one free project going on where if someone's
21:46
coming in, we've got sort of six scanners in
21:49
Addenbrookes. And if anyone picks up a leaflet
21:53
as they go through, it's going to ask them safety
21:54
questions about having a CT scan. And then it's
21:58
going to ask on the second page is going to be
22:00
what you've covered in another podcast, which
22:02
is the FRAX questions. And then, you know, big
22:05
capital letters at the top. Would you like to
22:08
know your bone health? Because we can do this
22:10
for free using the CT scan you're about to have,
22:13
whether it's to look at your gallstones or your
22:15
kidneys or whatever else or your bowel. We can
22:18
use that. And because we've captured the questions
22:20
beforehand, we can then add that all together
22:23
and then. plumb the results of the qct into frax
22:27
and give someone a personal 10 -year fracture
22:29
risk and also some treatment advice about you
22:32
know we picked up lots of people with spine fractures
22:35
and lots of people with osteoporosis in that
22:37
way so um that's really i think where it's going
22:42
to come from and in china they recently they
22:45
recently published in 70 000 people a reference
22:49
range of qct um so When you overlay the results
22:55
from the QCT as well, it looks exactly the same
22:58
as it does in the big huge Indian reference range.
23:00
It looks exactly the same as it does in the US
23:04
reference range. They just overlay one another.
23:08
There are very few differences in how people's
23:11
honeycomb bone, the trabecular bone with QCT
23:14
changes with age. And that comes to you, Richie,
23:19
because the... The actual three -dimensional
23:24
density maps so well to the Newton strength of
23:27
the vertebrae. It's really nice to get that readout
23:31
and be able to know where someone is in terms
23:35
of the strength of their vertebrae. It's fantastic.
23:38
And the vertebral structure, as you described
23:40
earlier on, is relatively simple in comparison
23:42
to other bones. So it's quite suited to the modelling.
23:45
CT scans are fantastic for capturing the distribution
23:48
of the bone, the thickness of the shell. the
23:50
amount of trabecular bone, etc. I think we should
23:54
probably say that we wouldn't ask for a CT scan
23:57
over a DEXA scan because of the radiation involved
24:01
in taking the CT scan. It's why it's sort of
24:03
a nice little add -on or, as I say, a buy one
24:05
get one free rather than the first line thing
24:08
that we should all be asking for. It's a really
24:11
wonderful way of getting more data from the patients
24:14
and, I guess, opportunistically screen them for
24:17
a disease. What kind of uptake do you get when
24:20
people read the forms? Do people overwhelmingly
24:22
want to know what their bone health is? We had
24:26
a lovely result from our, we had this sort of
24:29
free text entry part of the form where people
24:32
were just given their form and they're sitting
24:35
there with their pen and they were writing and
24:38
we said, what do you think of this? And overwhelmingly
24:39
people thought it was a great idea. They've explained
24:43
it in multiple ways, which we're analysing, which
24:45
is really nice to do. So you got that. And then,
24:48
and then at the end of a year, if they'd had
24:50
our Phoenix pathway, then they were, you know,
24:54
five times more likely to have been found to
24:57
have osteoporosis and three times more likely
25:00
to be on medicines. And we were really pleased
25:02
with that, but we want to do better. So we've
25:05
run the whole thing again for another year where
25:08
this time, instead of asking GPs, would you start,
25:10
would you take this bone information and go through
25:14
it with the patient? one of our peer reviewers
25:17
said why aren't you doing it yourselves you lazy
25:18
people so we actually just fed the people who
25:21
were the high risk into our ordinary and very
25:24
stretched clinical service and to see whether
25:26
by the end of a year we can actually bring that
25:29
up to the to more like the five or six times
25:31
and because if if nothing's done then nothing's
25:34
found and that's that's the that's the sad bit
25:36
but yeah the uptake's great and people this was
25:40
running during covid i was the only person from
25:42
my team still in the hospital on the covid ward
25:45
But I was running down to still put the little
25:47
invites in the CT scanner because that was still
25:53
running the whole time. And even during COVID,
25:56
people were really happily just filling in that
25:58
bit and posting it through our little box. And
26:02
they were happy to have that extra information.
26:06
That's an episode by itself almost, isn't it?
26:09
Why we kept osteoporosis services running during
26:11
COVID when they seemed... less important to the
26:14
rest of the world but we were the uh the voices
26:17
crying in the wilderness that you still have
26:19
to pay attention to people's bones that's right
26:21
and they'd managed to keep going with denosumab
26:23
and treatments like that people were busily injecting
26:26
themselves at home it was but yeah we learned
26:29
a lot and you coped with the clinical service
26:31
because i think that's the thing that that always
26:34
worries me a little and worries the team i work
26:36
with when i think of new ways of finding even
26:39
more vertebral fractures that we didn't know
26:41
about that it will overwhelm the service that
26:44
we have? That is the million -dollar question.
26:48
And the simple answer is it does completely overwhelm
26:53
the services. And I don't know if you've ever
26:57
covered this in the podcast series about machine
27:01
learning and approach to finding vertebral fractures,
27:04
but nowadays you can point... a neural network
27:09
or a server, you could just get every CT scan
27:12
ever done. Now, say we've got 50 ,000 of them
27:14
a year in our hospital. And you can point the
27:18
machine learning algorithm at that and say, could
27:21
you find me every single person with a vertebral
27:23
fracture anywhere in their spine, please, and
27:25
give them to me in a list. And Cas Javed has
27:29
been testing a huge commercial system with this.
27:34
Now, You turn it on for three months and you
27:37
have an absolutely overwhelming number of calls
27:41
of virtual fractures. And it's in a way purely,
27:46
you know, the pure software engineering part
27:48
of it. It's great. Well, well done. You found
27:51
those. But in terms of what you do with that,
27:54
because you have to go and look at them, you
27:56
have to go and verify them. You have to see whether
27:58
there was anything else going on with you. There's
28:01
no screening there. There's no saying, oh, I'm
28:03
already on. zaledronate or i'm already taking
28:06
the alendronate tablets or do you know what i
28:09
mean it's a huge issue and we're all in it together
28:12
to try and try and work out who we see and how
28:18
we see them i think it's going to involve some
28:20
patient centers patients themselves or hospital
28:25
attenders saying yeah i'd like to know this and
28:29
i'm going to go to this portal and i'm going
28:31
to enter my clinical information and simple information
28:35
about whether I'm on a medicine so that down
28:37
the far end when it hooks up with the machine
28:40
learning outputs it's not going to just be as
28:45
it was in with Optasia in Nottingham 850 I never
28:51
forget it 850 patients in three months when they
28:55
were we were going and using the Optasia which
28:58
is another way of looking for vertebral fractures
29:00
with a with a um you know machine learning technique
29:05
with that active shape modeling technique from
29:08
tim coote it's just incredible and it is there's
29:10
nothing wrong with it there's literally nothing
29:12
wrong with it that was perfect but you imagine
29:14
trying to tell your fls team you've got another
29:17
850 patients to follow up in three months yeah
29:21
exactly that's it's the it's the big challenge
29:23
isn't it some people say you need to break a
29:26
service to get to get more funding and then to
29:29
you know And others say you need to sort of build
29:31
it organically and it's never easy. What's the
29:36
real barrier to you and your clinics providing
29:39
better healthcare? Because it feels like there's
29:42
a really good understanding of the biology behind
29:45
fractures. There's technologies that are available
29:48
that can get really good data. Then AI and computer
29:52
and software technologies that can use that data
29:54
to identify people who've already fractured.
29:57
maybe even predict who's going to fracture next
29:59
and where they're going to fracture and how they're
30:01
going to fracture. What's stopping this taking
30:05
off? I think, so in relevant to that, we audited
30:10
the time taken to get just a patient from the
30:13
general practice onto one of these therapies,
30:16
which is supposed to be maximum of 16 weeks by
30:19
national guidelines. And our average was 35 weeks.
30:24
If you were unlucky enough to come into the hospital
30:27
with an agonizing vertebral fracture, which is,
30:31
I think there's 30 ,000 a year in England and
30:34
Wales now, you got onto the treatments within
30:37
20 weeks. But no, not the 16 weeks that's required.
30:42
And the problem is, if you, and this is the problem
30:45
across the NHS, is that specialties in the NHS
30:49
are either silo specialties, which are... got
30:54
a nice fence around them or they're down the
30:57
bottom on the ground specialties where there
30:59
are no fences and bone health and bone care osteology
31:05
as David calls it is a down on the ground specialty
31:08
and it can be and to get onto one of these medicines
31:12
one of these de -risking medicines that turns
31:16
your risk away very very fast requires a specialist
31:19
so It has to be a specialist initiation of the
31:22
medicine. So there's only a limited number of
31:24
us now. But because we are not fenced, there's
31:29
not a fence around what we do. We see everybody
31:32
with everything. And in a hospital like mine,
31:34
it can be everything to do with the musculoskeletal
31:36
system. If there's a new transplant being done
31:39
in Papworth, or there's a new leukemia induction
31:45
that causes avascular necrosis in young people.
31:48
then all those patients come towards, ah, there's
31:50
something wrong with the bones, let's send them
31:52
to the bone people. And in a system where you
31:56
were able to expand to meet demand, you would
32:01
increase the supply. But actually, in our specialty,
32:04
there is no expansion to meet the demand. And
32:09
so we are ending up, I suppose we're having the
32:11
same conversation across the UK, and it was the
32:14
case at the rare bone disease meeting. Emma Duncan
32:18
was mentioning that you have to make these really
32:23
difficult decisions. I'm going to look after
32:25
the patients who are really sick with the rare
32:27
bone disease and I'm going to have to look after
32:29
the patients who are really sick with the multiple
32:30
vertebral fractures. And some of the other things
32:34
that are coming through, even though people are
32:38
shouting louder and louder, particularly post
32:40
-COVID in ways that I never would have imagined
32:43
pre -COVID. If we're going to keep it free at
32:47
the point of delivery, then we're going to have
32:48
to try and put a fence around what we can do.
32:52
Otherwise, everyone's just going to get upset
32:54
and the times are going to get much longer before
32:56
people are seen. When you talked, maybe to change
33:01
the topic slightly, you talked about patient
33:04
-centered care and what this means to the patient.
33:08
I think the two things in terms of vertebral
33:10
fractures that patients say to me over and over
33:12
at the clinic. One is their loss of height and
33:15
how that changes their body shape. But the other
33:17
is pain they get from vertebral fractures. And
33:20
pain stands out to me with vertebral fractures
33:22
more than wrist, more than hip, more than anywhere
33:25
else. Is that because we just don't do well with
33:29
pain? Or is there something different about vertebral
33:33
fractures and the nature of the fracture that
33:35
is intrinsically more painful? That's a great
33:39
question. I'm going to bring it back to my son.
33:44
three weeks ago, four weeks ago, was pushed off
33:50
a box in a drama class and broke his wrist. Had
33:55
a buckle fracture of his wrist and I could watch
33:57
just how he couldn't move it and I could see
34:01
the image, the radiograph of the fracture. And
34:05
what your natural thing to do there is to not
34:08
move it at all. until it's cast or he didn't
34:11
need an operation thank goodness but you would
34:14
sometimes fix those bone fragments surgically
34:17
or you'd put them in a cast and stop that moving
34:21
until the process of healing is and i think what
34:24
i see and you're describing with a vertebral
34:26
fracture is that you have a an actual fracture
34:30
in your spine and you cannot keep it still and
34:35
the worst thing that can be done is is completely
34:37
lying flat and not moving in this situation but
34:41
that way it takes an enormous amount of pain
34:44
relief and and and mental fortitude when somebody's
34:48
vertebrae is is painful and fractured to actually
34:50
to actually be able to keep still enough for
34:54
it to to start healing and it will heal in the
34:57
end but anything I mean I can never believe how
35:01
poor the data quality is for what to do in this
35:04
situation When you get a set of national experts
35:08
reading out what to do, all they do is say, well,
35:11
that doesn't work and that doesn't work and that
35:13
one doesn't work. And we've looked really carefully
35:15
at that one and that one doesn't work. And as
35:17
physicians and even the surgeons who do procedures,
35:21
they sort of say, well, we've got to do something.
35:23
These people are in agony. So that's why I think
35:26
you cannot stabilize these spine fractures. And
35:29
I think those of us who've looked after patients
35:33
with. with with vertebral fractures would love
35:36
and welcome the um the best msk symptomatic vertebral
35:43
fracture pathway it's one sheet or one pdf and
35:48
it takes the person from fracture right through
35:52
to how they're managed and um best msk sort of
35:55
taken up by get it right first time it's an nhs
35:57
thing today in the news is martha's rule it's
36:02
just very personally important to me has just
36:05
come out for for people able to get that call
36:09
off and and and say to people my child or my
36:13
um my relative is is much sicker than you think
36:16
and I don't think you're taking it seriously
36:17
and you make that call to a to Martha's line
36:22
and that's helped people get a second opinion
36:24
and often treatment for sepsis. But in the same
36:27
way, if someone's out there and they're struggling
36:29
with a vertebral fracture and they're being told,
36:31
have some paracetamol. To me, it's a never event
36:35
that someone should have that vertebral spine
36:38
pain and not be able to access the things that
36:40
are needed to try and improve it. Yeah, so the
36:43
best MSK symptomatic spine fracture pathway takes
36:46
every part of that care through to how it should
36:49
be. And my managers tell me it's an aspirational
36:52
document, but... I think aspirational documents
36:55
are great for starting out and to improve things
36:59
like that. Yeah, I find myself sometimes because
37:03
people will ask, you know, will this injection
37:05
improve my pain? And you have to be honest and
37:09
say to them, this is not a pain killing. One
37:11
of the bone building injections, you know, you
37:13
say this is not a pain killing injection. And
37:16
obviously, you have to be clear about that. And
37:18
then sometimes, you know, patients will take
37:20
that on board. Occasionally, their face will
37:22
fall. And, you know, you think, I wish I could
37:25
promise you an injection. And even though we
37:31
talked about time pressures on clinics. Yeah.
37:34
You know, we were focusing very much on the bone.
37:36
But I do find myself then spending time and prescribing
37:39
for pain as well and trying to manage the pain
37:42
as well. at my osteoporosis clinic and at my
37:45
flf service and i'm sure you do as well you know
37:48
but i i feel i have less tools and less ability
37:53
and less data behind me to do that can i can
37:56
i bring up one of my little eccentricities here
37:58
we'd be delighted world friends here so another
38:01
thing that happened in lockdown was i've had
38:04
a i the the colleagues dr adrian crisp and Juliet
38:09
Compton and Jonathan Reeve, I was lucky to train
38:12
with three greats here in Cambridge. And Tim
38:14
Cox as well, the enzyme, the Gauches expert who
38:20
works in lysosomal storage disease, they all
38:22
use permidronate. And Adrian in particular used
38:26
it as an analgesic in acute vertebral fracture.
38:30
And one really good randomized controlled trial
38:34
was done by Armingia. And it was given as a single
38:39
dose after a vertebral fracture compared to placebo
38:41
with the pain scales done at regular intervals
38:45
to see. And it was quite clear from this one
38:47
RCT that it worked. And I've always been using
38:50
a single dose of permidronate before I start
38:54
other things in acute fracture pain. And I also,
38:58
I only have one RCT to go in, but it's my eccentricity
39:01
here that I have a special patient information
39:03
sheet written about that drug. It's 90 milligrams.
39:08
And I was so cross with how it was treated, that
39:13
RCT, because it was a sole piece of evidence.
39:17
And it doesn't stand up to get through all of
39:20
the national guidelines. And I found Dr. Armingiat.
39:24
He was working in New Zealand during lockdown.
39:27
And I managed to get a one -to -one with him
39:30
on a video call. And he's great. And I just said
39:33
to him, right, I went through the whole procedure.
39:36
You know, what were the patients like? How did
39:38
you do it? How did you infuse? Do you trust that
39:41
this drug was genuinely reducing people's pain?
39:44
And the answer was yes. So in a placebo -controlled
39:47
trial, I do think we have something that can
39:49
help them. And with enough time in the world,
39:52
I would love to redo that study because I love
39:55
single studies like that. When I was doing my
39:57
PhD in 2000, I gave a single dose of zoledronate,
40:01
a zometer, four milligrams to people after a
40:04
stroke. And it was only me and Liz Warburton.
40:07
We did the whole thing together at a trial versus
40:10
placebo, measured the bone density at six and
40:12
12 months. And we could show that a single dose
40:15
of zoledronate stopped them losing their bone
40:17
after a stroke. And 20 years later, the great
40:21
Dr. Katya from Cornwall has put together an NIHR
40:26
proposal to try and do the definitive study.
40:29
It wasn't for our want of trying, by the way.
40:30
We had five rejected grant applications to try
40:33
and turn that into a proper study. But yeah,
40:35
so there's my eccentricity. I like pomidronate,
40:38
as did my illustrious and brilliant forebear,
40:41
Dr. Adrian Crisp. And that's following on then
40:44
with a bone building drug, presumably? Yeah,
40:46
absolutely. In appropriate circumstances. Absolutely,
40:49
yeah. Yeah, it is. Dr. Aminjad, if you're listening
40:51
to the podcast, get in touch and we'd love to
40:54
speak to you. I will have to say that the background
40:57
of Dr. Armingiat's current GP clinic in New Zealand
41:02
looked absolutely gorgeous. So, yeah, watch this
41:07
space. I guess the listeners at home are going
41:11
to be clamouring now for this research to be
41:14
done. All right. Crowdfunding, yeah. So, yeah,
41:19
it's... I hope that the... So what we did...
41:23
I remember the zoledronate study so well was
41:27
we went to Dr. Cummings, Steve Cummings, who'd
41:31
done all of the great alendronate and raloxifene
41:37
studies with Dennis Black in UCSF San Francisco.
41:40
And we got together with his team and worked
41:44
out how many people would have to give a single
41:45
dose of zoledronate to in order to prevent fractures
41:50
and work that out. And it wasn't. terribly expensive
41:53
but sometimes as you both know as researchers
41:55
sometimes it's just either not the right time
41:59
or i didn't write it correctly or we didn't we
42:01
just none of us could get the funding for it
42:03
so the fact that it's phoenix is the name of
42:05
my study because it was from the flames of not
42:09
four rejections for the opportunistic bone density
42:12
analysis with ct but that that title's already
42:15
been used but we should phoenix permedronate
42:17
and phoenix zoledronate after stroke so yes I've
42:23
got one last question for you. I've seen you
42:26
speak many times at conferences and I've been
42:29
to visit you in Cambridge. A thing that really
42:32
comes across is how much you care. You care so
42:36
much for your patients and also for the people
42:39
that work in your lab and also you have this
42:41
role in the BRC developing young academics. You
42:44
give so much of yourself to other people. while
42:48
simultaneously managing complex research tasks
42:51
and complex clinical tasks and making time for
42:55
a podcast. What is your secret? Because you always
42:59
seem so calm and practical in the way that you
43:02
approach everything. The single secret, well...
43:07
Easy answer. I'm a Christian, so that's the easy
43:10
answer for that part. But if any of those people
43:15
who work with me know anything about me, it's
43:17
the utter chaos of all those tasks overlapping
43:23
one another and never being able to complete
43:28
any one of them and always being way behind on
43:32
just about anything you can think of. Other secrets
43:35
are... I just work with great people here, clinically
43:38
and in research. And one little gem of being
43:44
in Cambridge is if you end up in, there's this
43:50
thing where we've been finding people who've
43:52
lost their intervertebral discs due to a weird
43:55
and new genetic condition. And then you look
43:58
up all around the world, who's the expert on
44:00
intervertebral discs? And this particular gene.
44:05
And then you look it up and it's a neurosurgeon
44:09
for dogs who works in Cambridge in the Cambridge
44:12
University Veterinary School. And when you look
44:15
at we did another one with rare condition hyperphosphatasia.
44:19
And, you know, we needed to look at the mineral
44:21
structure of the bone. You know, and we look
44:27
around, who is the one person who can do. nuclear
44:29
magnetic resonance imaging of bone and understands
44:32
its complete complex molecular structure it's
44:34
melinda doer up the road in university of chemistry
44:37
in cambridge so one of the things you get is
44:40
you just get great and lovely people around you
44:42
and i think we get a real a really large amount
44:45
of them here and and to say that my clinical
44:49
colleagues and nurses i work with here say this
44:51
to david a wee bit because everyone knows what
44:53
it's like in the nhs at the moment i think you
44:56
just couldn't come in every day if it wasn't
44:58
for your nursing secretary or you know the the
45:02
clinic team down there you you know you're sort
45:05
of holding on together aren't you at this sort
45:07
of stage absolutely yeah it's it's all about
45:10
the team working together and working for the
45:12
benefit of patients i know that sounds like a
45:14
corny thing to say almost but it's true you know
45:17
it's absolutely true It's really easy to do this
45:23
kind of research because, you know, you just
45:26
know how good things can be. It's like someone
45:31
hearing that someone who could hear that music
45:33
and know that it was I could be I could be better.
45:37
It could be more. It could always be better.
45:38
And that's what drives you, I think, to try and
45:40
make the clinical services better. And they get
45:43
a bit annoyed with my passion here in Cambridge,
45:45
but it won't stop. yeah i think that's very important
45:49
if people realize you're passionate about what
45:51
you do it actually can carry a lot of things
45:54
even with managers sometimes you see a glint
45:58
in your eye and they know you really care about
46:00
it and yeah it's it's i think if you lose that
46:04
then you've really lost something so continue
46:06
to inspire people can do my best I also know
46:10
where you keep your secret stash of chocolate
46:12
biscuits in your clinic as well. So that didn't
46:15
come up, but I know that's important. Yeah, I'm
46:18
going to, a whole separate podcast is how to
46:20
run a clinic, where to store your coffee. flask
46:23
where to store your snack how to go to the toilet
46:26
without people glowering at you because you're
46:28
taking a break you know the corrigan secret door
46:32
many years ago in dublin who had two doors to
46:37
the clinic so he could go out without patients
46:39
seeing him leave As a young scientist working
46:45
in the Faculty of Medicine, I very quickly realised
46:48
that if you want a meeting with a clinician,
46:49
take food and you'll get their undivided attention.
46:54
Yeah, but dairy food with lots of calcium in
46:59
it. Ken, it's been lovely, lovely talking to
47:07
you today. We're going to have to get you back
47:09
on the podcast again. I'm sure the listeners
47:11
are really going to enjoy this episode. Patients
47:14
and professionals alike. Thank you so much. Guys,
47:17
pleasure. Thanks for having me on. Thanks, Ken.
47:19
It's really good to talk to you and we really,
47:21
really enjoyed that. Thank you. David, I really
47:25
enjoyed the interview today. I learned a lot.
47:29
What were your takeaways? Yeah, goodness, Kent
47:31
covered so much. It's hard to even even begin
47:34
to summarise the things that he said. Just now
47:38
fresh from it, thinking about it. The history
47:41
is always important in these things. You know,
47:43
he mentioned the first time PTH was given to
47:45
a patient was back in the early 70s. And yet
47:48
it took more than 30 years before that became
47:50
a drug which we use every day. And how important
47:53
it is to learn. Not just, you know, in the lab
47:57
about new drugs, but learn about the process
47:59
of how we translate science into medicine, how
48:02
we move drugs from the planning stage into getting
48:05
them to the clinic. And just look back 5, 10,
48:08
15 years, even how vertebral fractures have become
48:11
more centre stage and see how we could do things
48:15
better. You know, because there's no doubt if
48:17
we look back 20 years, I'm sure we would have
48:20
wanted to promote the use of osteoanabolic drugs
48:22
more than we've done. And, you know, Ken a couple
48:26
of times mentioned just, you know, just of the
48:28
history and his training back 15, 20, 25 years
48:32
and the people he trained with and the things
48:34
they brought to medicine. So just how that's,
48:36
you know, it's important to be reflective on
48:39
where we've come from as well as where we're
48:41
going. The other thing I suppose as a clinician
48:44
that sort of blew my mind a little bit is that
48:46
idea where you can sort of virtually recreate
48:50
a patient's actual. bone structure and then virtually
48:55
apply pressure apply load to that bone and watch
48:59
the bone breaking or watch the bone resisting
49:02
fracture and put different pressures at different
49:05
angles to my mind the day that i can sit in a
49:10
clinic and say to the patient you've just had
49:12
a scan next door now let's look at a real model
49:15
of your bone and let's stress it and let's see
49:18
if it's going to break or how it's going to break
49:21
That strikes me as amazing. And I know we're
49:24
nowhere near that yet, but these are the first
49:26
few beams of light coming over the horizon. And
49:30
you know yourself how quickly things move on
49:32
in science and medicine. And, you know, perhaps
49:35
before I retire, there'll be something at the
49:38
clinic that I can use for patients, maybe not
49:41
for every patient, but certainly for some patients
49:44
where I'll be able to virtually stress patients.
49:47
bones or virtually stress real models of real
49:50
patients' bones and share that with the patient
49:53
and be able to use that to sort of to feed into
49:57
treatment. That's real translational medicine,
50:00
which is really, really exciting for me. And
50:04
I suppose the other little thing Ken mentioned
50:06
about just giving IV pomidronate to patients
50:09
immediately after a vertebral fracture, the benefits
50:12
you get from pain relief. and also obviously
50:17
some anti -resorptive effect there we talked
50:20
a little bit more research needed in that area
50:22
but it's interesting that you know that's a throwback
50:25
to maybe 10 15 20 30 years ago when iv bisphosphonate
50:29
was used in that setting um and it's interesting
50:33
not to forget about those little things that
50:35
they may still have a place in the future so
50:37
Yeah, lots and lots of really exciting and interesting
50:40
things to take away and think about and just
50:43
be inspired by Ken's enthusiasm and calmness
50:47
for all this. What about you? What did you take
50:52
away primarily? My big takeaway is that the field
50:57
of osteoporosis research is very advanced, even
51:01
at the clinical level. Here we've got Ken Poole,
51:04
who is a clinician and an excellent researcher
51:06
combining those jobs together, working at the
51:09
very cutting edge to try and develop better diagnostics
51:12
and better treatments for patients. I think maybe
51:15
a lot of people don't appreciate how forward
51:18
thinking and how cutting edge osteoporosis research
51:22
is. The software programs that you use to take
51:26
a CT scan of a bone and model it in 3D and load
51:30
it and simulate the fractures. It's the same
51:33
software that they used to design aeroplanes
51:36
and racing cars. This is really advanced technology
51:39
being applied to osteoporosis and, importantly,
51:44
in a clinical setting. There are lots of researchers
51:48
using these modelling tools, they're called finite
51:51
element models, in engineering research around
51:54
bone science and orthopaedics. But there are
51:57
not many people actually doing it in clinical
52:00
practice. It's like the edge of the edge, if
52:03
you like. I always go back, Richie, and we talk
52:07
about this a lot. The first time we met, you
52:09
said, you know, I'm not sure if I believe in
52:11
osteoporosis or if it exists. And, you know,
52:14
when we do that sort of we had that sort of discussion
52:17
today and we were talking both during the interview
52:19
and after the interview as well. But how vertebrae
52:22
develop differently, how they fracture differently,
52:25
how drugs work differently in vertebrae than
52:28
they do on hips, for example. And even though
52:31
we like to draw a big circle around all of this
52:33
and call it all osteoporosis, in many ways, the
52:37
cause of vertebral fractures, the detection of
52:40
vertebral fractures. The technology we would
52:43
use to detect and improve and predict vertebral
52:46
fractures, the drugs for vertebral fractures
52:48
are actually really quite different from all
52:52
of those variables for, let's say, hip fractures
52:54
or for that matter, ankle fractures or shoulder
52:58
fractures, you know, all very different. As Ken
53:03
said today, the bone that you're treating is
53:05
very different. When he described the vertebrae
53:08
and basically you've got lots of trabecular bone.
53:11
the honeycomb and a very thin shell whereas in
53:14
the hip you've got a very thick shell as well
53:18
as the trabecular bone and often in the people
53:20
who fracture the trabecular bone has been lost
53:24
or almost lost already so fundamentally it's
53:27
different types of bone that are fracturing and
53:30
you're going to need different types of treatments
53:32
because the metabolism in those bone types is
53:35
quite different Absolutely. And while it's very
53:37
useful to have a big circle to draw around everything
53:40
and call this osteoporosis, within that circle,
53:43
there's lots and lots of different areas and
53:47
different treatments. And certainly from the
53:49
clinician's point of view, and this seems to
53:50
come up with more and more of our interviews,
53:52
there's more and more need for bone specialists.
53:56
in medicine you know because a lot of osteoporosis
53:58
is still done by people who don't really specialize
54:01
very much in it and the more we read about this
54:03
the more we research the more complex this becomes
54:05
um and of course specialist bone researchers
54:10
as well we definitely need more of those well
54:16
listeners we hope you enjoyed this episode we
54:19
really did see you next year bye -bye very happy
54:24
new year to all Bye now.