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Personalised osteoporosis care · 'Bone Up'

0:00
Hello and welcome to Bone Up, the podcast all
0:04
about bones, how we make them, why we break them
0:07
and if we fully understand them. I'm David Armstrong.
0:11
Hi and I'm Richie Abel and over this series we're
0:15
going to be exploring osteoporosis, bones, what
0:18
we know and what we're yet to discover and we
0:21
hope you will join us on the journey. So for
0:24
anyone keen to learn more about our infrastructure
0:27
of calcified collagen, this is bone up hello
0:45
and welcome to another episode of I was going
1:00
to describe this as the high summer episode,
1:02
Richie, but I don't know if we really have high
1:04
summer any longer in the UK. We sort of have
1:08
rain that's a bit warmer for a few weeks. I think
1:12
we're into autumn, but welcome to the high summer
1:15
episode anyway. You've been away anywhere nice?
1:19
Yes, I managed to go on a short holiday with
1:21
the family to Spain to escape the tragic summer
1:25
in Britain right now. um i think everybody could
1:28
do with some sun just to cheer everybody up a
1:31
bit it's about time yeah what have you been up
1:34
to this summer yeah my wife and i were in harlem
1:37
actually that's the netherlands harlem and uh
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we've been to the netherlands before but never
1:41
to harlem and it was a lovely place and actually
1:43
we got really good weather so it's nice to get
1:46
a break and get get away from work although i
1:49
must admit i did bring a paper on macrophage
1:52
contribution to osteoporosis development with
1:55
me to read because i've been meaning to read
1:57
it for months and i read it on the plane and
2:00
i was the only person on the plane reading about
2:02
macrophage functioning osteoporosis i think um
2:06
but after that yeah it was good to get a break
2:09
and uh back refreshed and ready for ready for
2:13
more bone health There you go, listeners. Medicine
2:16
is a way of life, not a job. So it might come
2:20
in handy that you've read that paper, given today's
2:23
topic. So listeners, on the show, we've talked
2:25
a lot about bisphosphonate and romisosomab treatments,
2:29
but a few of you have got in touch to say that
2:31
we haven't really spoken much about another important
2:34
treatment, which is denusamab. I was wondering,
2:37
David, if you'd be able to explain to us your
2:41
clinical uses for denusamab. Yeah, well, adenosumab
2:46
or Prolia, as it's probably still widely called,
2:49
is at its simplest, is simply another drug for
2:52
osteoporosis. It's a six -monthly injection,
2:55
which generally in the UK is administered by
2:59
the nurse and administered in primary care, although
3:02
oversight is from secondary care, from your consultant.
3:07
It works on the side off the fence, you might
3:11
say, preventing bone loss. So you remember the
3:14
very first episode we did of the podcast, Richie,
3:18
I used the metaphor of the bath, and we're trying
3:21
to fill the bath up with water. You can either
3:23
turn the tap on faster to get more water into
3:26
the bath, or you can put a plug into the plug
3:29
hole to stop losing water. So denosumab is on
3:33
the plug hole side, if you'd want to say. It
3:36
reduces bone loss, but it works differently from
3:41
bisphosphonate. it has advantages over bisphosphonate
3:45
in that the mode of onset or the action speed
3:49
of onset is quicker you can use it in patients
3:52
who have renal impairment and in fact even end
3:56
stage renal failure and it's not it's not orally
4:01
administered so it's very useful in patients
4:03
who have gi side effects with with bisphosphonates
4:09
It's been available now for over 10 years and
4:12
I think it's probably fair to say like many drugs
4:16
when it came out at first we sort of rushed to
4:20
use it for lots and lots of patients and then
4:23
we discovered lots of good things about it and
4:25
then there were sort of issues around where we
4:28
had to think more carefully and its use has probably
4:31
reduced a little I would say in the last few
4:34
years. But we're sort of getting more of a handle
4:38
now on exactly when it should be used and where
4:41
it should be used and how long it should be used
4:43
for as well, which is important. So you're saying
4:48
then that it's a drug that's been in use for
4:50
a long time, seems to work more quickly than
4:54
bisphosphonates, at least at the beginning, and
4:56
it seems to be better in terms of side effects.
4:59
So why don't you just give it to everyone all
5:01
the time? Yeah, that's a good question. One of
5:07
the issues with bisphosphonates, as I think most
5:10
people who have any insight into osteoporosis
5:13
will know, that you cannot use them indefinitely.
5:18
You have to have what's called a drug holiday.
5:21
And that's because reducing the action of osteoclasts,
5:25
reducing bone loss, is good for the bone in the
5:28
short term. But if you do that in the very long
5:31
term, then you run into problems with almost
5:33
switching bone turnover off completely and you're
5:37
on the risk of these very rare side effects like
5:39
atypical femoral fracture. And those exist with
5:44
denosumab as well. Whereas with bisphosphonate,
5:48
you can simply have a drug holiday and the levels
5:51
of bisphosphonate in the bone will go down very
5:54
slowly and you may have what you call a soft
5:57
landing. In other words, bone turnover will quite
6:01
slowly start to rise again and you can control
6:04
that. With denosumab, when you consider a drug
6:08
holiday, bone turnover rises very rapidly and
6:12
the patient can lose bone again very rapidly
6:15
and can run into risks of increased risk of fracture
6:19
during that period. So one of the things I think
6:23
we've discovered in the last 10 years or so of
6:25
using denosumab is that you need to plan carefully
6:28
at the start of the treatment how you're going
6:32
to get the patient off the drug again and that
6:35
may be after five years, it may be after 10 years.
6:38
Of course there will be patients you may decide
6:41
to stay on the drug indefinitely but then that
6:43
involves a careful discussion of the risks and
6:47
balances with the patient. And trying to give
6:50
the patient, you know, the sort of the scientific
6:53
background to how that works and the evidence
6:56
about how it works. But also explaining to the
6:59
patient, I think, that there are gaps in the
7:01
evidence and that there are areas in the long
7:04
term use of denosumab where we simply have to
7:07
say the research hasn't been done yet. So it's
7:11
a very useful drug, but there are challenges
7:14
with its use. And certainly once you start the
7:17
drug. You can't just stop it again without using
7:21
something else. So you need to think in the long
7:24
term. And again, that involves, you know, just
7:26
building up a relationship with the patient and
7:28
trust with the patient and explaining and trying
7:31
to interpret data and interpret these difficult
7:35
issues about risk and so on, you know, to the
7:39
patient. And that's something we've obviously
7:41
covered before. The exciting thing about donosumab
7:46
is it can be used in a much greater range of
7:49
patients than bisphosphonate which is good and
7:52
it works in a different way. It works on what's
7:57
called the rank and rank ligand sort of pathway.
8:02
I'm always encouraged at how interested patients
8:07
are at how their drug works and always surprised
8:10
sometimes how deep discussions I end up getting
8:15
into with patients even at the clinic about exactly
8:19
how their bones work how the cells respond to
8:21
medication i think the more information patients
8:24
have the more likely they are to take a drug
8:26
and comply or at least the more likely they are
8:29
to make a decision that they are happy with in
8:32
the long term so i mean one of the things i'm
8:36
always interested to hear how you explain these
8:39
quite complex scientific issues because i think
8:44
it's something you're very good at so tell me
8:46
about rank and rank ligand then richie and how
8:49
i can explain that to patients in terms of of
8:53
how their cells work that is a good question
8:56
and it's a topic i've covered quite a bit in
8:59
teaching so denusamab then is a medicine that
9:03
acts on the bone cells which maintain our bone
9:06
mass many listeners will know we're talking about
9:09
the osteoclasts which resorb old bone and the
9:12
osteoblasts, which form new healthy bone. And
9:15
basically, denosumab works by preventing the
9:18
osteoclasts from resorbing bone. Denosumab exerts
9:23
its effects on osteoclasts via this physiological
9:26
pathway, the rankel pathway. And it's a very
9:30
interesting pathway in boneless and very fundamental.
9:33
And essentially what happens is the osteoblasts
9:36
release a protein, which we call rank. And RANK
9:40
travels to the osteoclasts and binds to receptors
9:44
on the osteoclast cell surfaces. And this triggers
9:48
a reaction in the osteoclasts. Primarily what
9:51
it does is it encourages immature osteoclasts
9:55
to mature into mature osteoclasts and begin to
10:00
start resolving bone. So think about the baby
10:02
osteoclasts turning into adult osteoclasts and
10:05
beginning their work. And denosumab works by
10:10
blocking this pathway. It acts as a decoy for
10:13
this rank protein. Denosumab binds to the rank
10:16
protein and inactivates it. And therefore the
10:20
osteoblasts cannot upregulate the osteoclastic
10:23
activity and that slows and stops the resorption
10:27
of bone. And denusamab is a very interesting
10:30
drug. It actually works by mimicking naturally
10:33
occurring proteins in our body called osteoprotegerin,
10:37
which would normally carry out this decoy job.
10:41
It's really good that scientists have been able
10:44
to study this rankle rank pathway and the regulation
10:48
by osteoprotegerin and then create a drug which
10:51
mimics its action. It's really good. a really
10:54
great example of how basic science is translated
10:57
into clinical science and not just within osteoporosis,
11:01
but across many chronic diseases. Yeah, that's
11:05
an excellent explanation. And as you say, it's
11:08
a very good example of how understanding how
11:12
the body works has enabled us to design very
11:15
specific drugs. One of the big differences probably
11:21
from the bisphosphonates and from denosumab is,
11:23
of course, that bisphosphonates stick to the
11:26
surface of the bone and stay there for a long
11:29
time, whereas denosumab really doesn't adhere
11:32
to the bone in any way. It has its effect and
11:36
then it sort of disappears from the system. And
11:39
there are many ways in which that's advantageous.
11:42
And there are other ways in which that's sort
11:44
of disadvantageous for people. But, you know,
11:47
like many things, there's still lots to discover
11:49
and lots to learn here. Isn't that right? Yeah.
11:53
Yeah. And it makes me wonder, actually, the last
11:56
two episodes that we did from the ECTS conference.
12:01
What guests we interviewed who are studying a
12:05
physiological pathway, which will result in new
12:09
treatments in the future. It'll be a long time
12:11
before we find out. But listeners, we can tell
12:14
you that we brought it to you first. One of the
12:17
big areas that we want to know more about, I
12:20
think, in the use of denosumab is what we do
12:23
in the longer term. What do we do when you have
12:25
been on this drug? And while we don't have all
12:28
the answers for that, we were able to speak to
12:32
someone who was attending the ECTS conference,
12:35
but who kindly agreed to join us for a full -length
12:39
episode of the podcast, who is doing research
12:43
specifically in this area, very exciting and
12:45
interesting clinical research and something that's
12:48
very relevant to day -to -day practice. We're
12:51
delighted to have with us now a longtime friend
12:55
of the podcast, I think, enthusiastic supporter,
12:58
Eleanor Sordy. Thank you for taking time to speak
13:02
to us. We're very excited to hear what you have
13:04
to say. We're here actually in Marseille at the
13:07
Congress at the moment. So are you enjoying yourself?
13:09
I'm enjoying it very much. Thank you, David.
13:11
Thank you, Richie, for inviting me. And I'm really
13:14
looking forward to talking to you about osteoporosis
13:17
and all. You gave a talk yesterday at ECTS about
13:24
treatment targets for osteoporosis medications.
13:27
Yes. What did you tell the learned audience?
13:31
First of all, I enjoyed very much that it was
13:33
very interactive. I tried to do it so. I tried
13:37
to give some food for thought and also people
13:40
bringing their own cases. So the particular subject
13:43
was what targets to reach in order to discontinue
13:48
osteoporosis treatment. And of course, it is
13:51
a subject that has been very widely discussed
13:54
the last years, I would say. I base it more on
13:59
bisphosphonates, but of course... Of course,
14:00
as you know, it's also a very big issue regarding
14:04
the denosumab and its discontinuation. Of course,
14:09
given the different particularities of bisphosphonates
14:15
with their long -lasting use and the fact that
14:18
after you discontinue them, you don't have this
14:20
massive overshoot of bone turnover and the loss
14:25
of bone mass that you have with denosumab, strategies
14:30
of going about it so especially pertaining bisphosphonates
14:36
I think. It's very difficult to pinpoint it to
14:42
a specific T -score or BMD target. It should
14:47
be rather individualized. You should take into
14:50
account a lot of aspects. Some are mostly inherent
14:55
to bisphosphonates, because not all bisphosphonates,
14:58
of course, are created equal. You have others
15:01
with greater affinity to hydroxyapatite, for
15:06
example, Zol. others with less so. So this is
15:10
one aspect to consider. And of course, patient
15:14
adherence, because especially this is notoriously
15:17
very low when it comes to oral bisphosphonates.
15:21
So you cannot be sure where you say, okay, this
15:23
person has been on oral bisphosphonates for three
15:26
to five years. You cannot be absolutely sure
15:29
that they have been taking them also. There are
15:33
ways of taking it, like with doing bone turnover
15:35
markers. bone suppression markers in order to
15:38
get an idea if they are compliant. And then again,
15:43
there are also aspects which are inherent to
15:47
these patients per se. So other risk factors,
15:51
other diseases, other concomitant medication
15:54
that they might have. So it's quite complex,
15:58
and it was also what came out of the discussion
16:01
that it's very, very difficult to pinpoint it
16:03
to a specific BMD or T -score target. What I
16:08
see in clinical practice maybe a few years ago,
16:11
Lots of patients were going on to bisphosphonate
16:14
and staying on it for a long, long time. And
16:16
we were running into problems with atypical fractures
16:19
with some people. And the message, I think, got
16:22
out there very strongly, both to general practice
16:26
and to patients that we should be considering
16:29
holidays or treatment pauses. I sometimes think
16:33
now the pendulum has almost swung the other way,
16:36
where I see patients taking bisphosphonates maybe
16:38
only for three or four years and then stopping.
16:42
And I think that patient should really have stayed
16:45
on for longer. And I also find there's a message
16:48
we need to get out there that it's okay to restart
16:51
the bisphosphonate because lots of people are
16:54
stopping it and never going back on to it. Where
16:57
do you feel all that fits in? Where do you think
16:59
the message is at in your clinical experience?
17:02
Are you worried about too many people stopping,
17:04
too many people staying on for too long? What's
17:07
your... Yeah, I agree with what you're saying.
17:09
And I think it has provoked also an overreaction
17:13
about stopping bisphosphonates too soon, or as
17:17
you say, being very reluctant to start them again.
17:20
And I think there's very little evidence also
17:23
on how long this drug holiday should be. or how
17:27
exactly you monitor this. Should you monitor
17:30
it with consequential DEXA measurements? Probably
17:36
you should monitor it with also the clinical
17:39
aspects of the patients and if the risk for fracture
17:42
increases during that time. And what about bone
17:47
turnover markers? Bone turnover markers, yes.
17:50
Is that useful, do you think, during a drug holiday?
17:53
They're certainly useful during a drug holiday,
17:57
not a drug holiday, but in the concept of denosumab
18:02
and its discontinuation. I think for your bisphosphonates,
18:06
it's a bit more difficult because there's not
18:09
really a cut -off as there has been issued for
18:12
denosumab. So which cut -off is then the one
18:16
that when you go above that, you would restart
18:20
them again? Most osteoporosis. is managed by
18:23
GPs in primary care and I find you know when
18:27
I'm advising that there's a drug holiday I will
18:30
often say to the GP would you repeat the DEXA
18:32
scan in two to three years to see what's happening
18:35
if the patient has a fracture during the drug
18:37
holiday they'll certainly let me know the bone
18:39
turnover markers might be a quicker and easier
18:42
thing to do but they're not available in primary
18:44
care they can only be done in the hospital so
18:47
we end up using DEXA scanning which is a radiological
18:50
investigation but the gp can arrange that and
18:53
probably knows how to interpret that whereas
18:55
the bone marker which is a simple blood test
18:57
yeah it's harder to interpret and it's only done
18:59
in the hospital so we don't use that interestingly
19:02
we do a more complicated test yeah yeah i agree
19:06
there's also like aspects of pre -analytic and
19:09
also analytic aspects of bone turnover markers
19:13
and also other limitations for example patients
19:17
with renal disease or where they would not be
19:21
so helpful. And as you say, of course, the one
19:26
thing is to order them, the other thing is knowing
19:28
to interpret them. Yes, yes, I agree, yeah. You
19:35
mentioned earlier on that potentially the best
19:37
way to approach this was to provide some kind
19:39
of individualised care for the patients. Yes.
19:44
In practice how does that work when you're a
19:46
busy doctor and you've got lots of patients?
19:48
Are there hints and tips that you gave people
19:50
for achieving it? So I think I'm quite fortunate
19:54
to also work in a specialized center and treat
19:58
primarily patients with osteoporosis or secondary
20:01
osteoporosis or rare bone diseases. So for me,
20:06
I think it's really part of what I do and in
20:10
my everyday life. I think talking to the patient
20:14
and also this patient informed consent is very,
20:19
very important nowadays. where you have all these
20:22
media and also patient fora where they really
20:27
get sometimes information which is incorrect
20:30
or people really pinpoint the rare adverse effects
20:36
or side effects and there's a lot of misinformation
20:40
I think regarding bisphosphonates but also other
20:46
osteoporosis drugs so I think this is very very
20:50
important. I make sure to take a long time also
20:54
to relativize. It's something we have been talking
20:55
about recently. People go straight to the internet
20:58
and don't always get the most reliable information
21:01
or get a lot of pseudoscience that sounds quite
21:04
convincing. But actually, if you peel back, a
21:07
lot of it is nonsense, particularly with bisphosphonates.
21:11
It's one of the reasons why we started the podcast,
21:13
to try and give you, the clinicians, a direct
21:16
line to the patients and back again. so that
21:20
we can build a bit of trust and try and make
21:22
sure that there's quality information available
21:24
to everyone. Yes, and I think it's a great endeavor
21:27
and also to cover so many facets of bone disease.
21:30
It's nice of you to pay us a compliment. I'm
21:32
just going to ask you the hard question now about
21:34
denosumab. Yes. And we have many listeners in
21:38
all sorts of different backgrounds. So just to
21:41
say denosumab, it's a great drug for osteoporosis.
21:45
You build a lot of bone, but when you stop the
21:48
drug, then you lose the bone quite rapidly. And
21:50
the concern is actually that you get a rebound
21:53
increased fracture risk, unlike bisphosphonates,
21:56
where when you stop the drug, you get a very
21:57
gradual letting down. Yes. And there's a lot
22:01
of debate at the moment as to if you stop denosumab,
22:04
when you stop denosumab, and what you do when
22:07
you stop denosumab. um so i might just throw
22:11
that up in the air i'll throw that ball up in
22:13
the air and let you let you serve it because
22:15
we know we've got a great interest indeed i do
22:19
yes so yeah and an awesome discontinuation it
22:24
is of course uh the subject of the days as you
22:27
said um yeah It is again an individual approach
22:33
to each patient and if you would consider, of
22:39
course, to discontinue it. In order to come into
22:46
this discussion in the first place, also we have
22:50
to consider when to start it. It was something
22:53
that we also discussed before. So I think there
22:58
has been a... maybe a trend shift of starting
23:02
adenosumab in patients which have more severe
23:06
osteoporosis or vertebral fractures or high -risk
23:12
patients for vertebral fractures or other fragility
23:17
fractures. This is one thing to consider. And
23:19
also, of course, if they're very young patients,
23:22
because then you could come into this conundrum
23:27
of having to treat them for... 30 -40 years which
23:30
of course there is no data at all what happens
23:34
and then you would indeed worry about adenamic
23:39
bone disease and low bone turnover so for patients
23:43
that have been on it for the if I may say so
23:47
for the correct reasons yeah one option would
23:52
be of course to to continue it, and we have a
23:57
lot of patients where we continue it even over
24:00
the 10 years. So another thing is that there
24:03
is no magical number of 10 years. And let me
24:07
just say you continued over 10 years, and that's
24:10
because... the disadvantages of stopping it are
24:13
greater than the advantages of continuing it.
24:15
And that comes back to personalised care, doesn't
24:18
it? So it's not just one size fits all. You're
24:20
saying for my individual patient here, if we
24:22
stop it for good reasons, the risk of you having
24:24
a fracture is going to be so high, you're better
24:26
to stay on it. Yes, yes. And indeed, this is
24:29
also what you were saying beforehand about information
24:32
and misinformation. I have a lot of patients
24:34
who come and say, oh no, you cannot give it after
24:37
10 years, but this is just like... because the
24:41
longest series of published data pertain 10 years,
24:46
not that there is one magical number of 10 years
24:48
and something awful happens afterwards. So one
24:53
option would be that. Another option, and this
24:56
was also something which we issued in the ECTS
25:01
position papers, which I was very fortunate to
25:04
lead, was that if the patient is really low risk,
25:09
if he has... attained t -score there are some
25:12
data that a hip t -score of above minus 1 .5
25:18
could be a target to aim for that you could then
25:24
not discontinue it without any kind of follow
25:27
-up of course but you could use bisphosphonates
25:32
especially iv um to uh kind of mitigate this
25:38
uh overshoot gently letting them die yes yes
25:41
so of course there's a lot of discussion and
25:45
also studies going on which is the optimal regimen
25:48
of this uh add -on bisphosphonates and of course
25:53
there are also challenges with that because some
25:56
patients have had like a negative experience
25:59
with iv bisphosphonates or there are some other
26:02
characteristics like renal kidney insufficiency
26:06
where you cannot do it anyway. So it is a really,
26:09
really individual. I remember we chatted about
26:12
this briefly with Qasim Javed last year, and
26:15
I think we got around to saying there's almost
26:18
an illogical concept that you give denosumab
26:22
for a long time and the bone turnover is really
26:24
low, and then you stop it because you're worried
26:27
about the bone turnover being so low. So what
26:30
do you do? do instead you give a bisphosphonate
26:31
with the intention to keep it low but it's not
26:35
just as good at keeping it low yes you think
26:37
well where's the logic in that yes which brings
26:40
me around to saying why don't you just half the
26:42
dose of the denosumab or why don't you just give
26:44
it a little less frequently would that be just
26:46
as effective do you think yeah well there are
26:49
some preliminary studies looking into this they're
26:52
a case series so that they have tried as you
26:56
say to then half it on their main maybe use one
27:00
fourth. Of course, these are mostly BMD and BDM
27:05
case series. We have no fracture. It seems to
27:10
be one possible way, what you're saying. I have
27:13
often wondered if in the future we will end up
27:15
giving sort of higher dose denosumab for five,
27:19
eight years and then giving a lower dose for
27:21
a year or two and then going back up to the high
27:23
dose. And if perhaps that is the way that we
27:25
will end up. treating these things rather than
27:28
using zoledronate. Yes, yes. And, you know, there's
27:31
a structure in bringing people into maybe hospital
27:33
or clinics to give them the drip, and there's
27:36
problems, as you say, patients with renal failure.
27:38
So maybe we will end up moving away from the
27:41
bisphosphonate and just altering the dose of
27:43
the denosumab? Yeah, there are ideas and studies
27:47
beginning along those lines, yes. I think some
27:51
of our listeners would be keen to know a bit
27:53
more about the discussions that you have with
27:55
your patients around the medications and when
27:59
you stop them. I guess it might be useful for
28:02
people who are going to have similar conversations
28:03
with their own doctors. What kind of questions
28:06
do the patients have for you and what kind of
28:09
messages do you give them? I think first of all
28:13
it's important to explain maybe this notion of
28:18
osteoporosis to the patients per se because of
28:22
course if patients have not experienced fractures
28:27
and it is an opportunistic finding let's say
28:31
so in a DEXA they don't really understand these
28:35
T -scores and what's like the relation to a risk
28:38
for fracture and why would they be willing to
28:42
start on a prophylactic treatment. So I think
28:45
this is one major issue which you have to talk
28:49
to really at the first patient's visit to make
28:56
them understand this. then what they want of
29:00
course to ask i have a lot of patients now which
29:03
are more informed also through the internet and
29:07
they do even know this differentiation and classification
29:11
between bone resorptives and also osteoanabolics
29:15
so they of course if they are very eager to do
29:21
the best for themselves they ask right from the
29:25
beginning can I get an osteoanabolic this is
29:27
also a question that I have so you also have
29:33
to explain the indications also the differentiation
29:37
and then of course a lot goes into side effects
29:42
and rare side effects to try to relativize things
29:49
because you also have the extra pedantic if i
29:53
might say so or acribic patients that go through
29:56
all the information that you can find in the
30:00
the drug sheets and everything that has been
30:03
described once and you have also of course explained
30:07
to them that there is no causal or no plausible
30:10
causal relationship between this side effect
30:13
and And so I think usually my first patient visit
30:20
with a patient that I don't know takes about
30:23
an hour because I try to be, yes, I try to be
30:27
really thorough. I think it's so important to
30:29
get the information in right at the start. Yes.
30:32
We've all seen patients who have been. prescribed
30:35
a bisphosphonate for eight years and when you
30:38
talk to them you realize they haven't been taking
30:40
it correctly they've been taking it with their
30:41
evening meal and they really may as well not
30:43
have been taking it and if someone spent 10 minutes
30:45
eight years ago explaining the thing properly
30:48
not even an hour even 10 minutes then would have
30:51
made such a difference in the long in the long
30:53
term i agree i agree do you feel as well everyone
30:56
needs to be on message because You and I, maybe
30:59
as osteoporosis specialists, understand this
31:02
and try to explain it to the patient in the clinic.
31:04
And we're all on message. And then maybe the
31:06
patient goes to a dentist who maybe isn't just
31:09
as up to date. The dentist says, oh, bisphosphonate,
31:12
that's terrible. Your teeth will rot. Yes, yes.
31:14
And it undoes all the... So we need everyone.
31:16
We need the pharmacist and the dentist and the
31:18
GP and everyone to be... giving the most up -to
31:22
-date advice at the same time definitely definitely
31:24
and especially with the dentists and anti -resorptives
31:28
it's a really big issue so what we have implemented
31:31
it is so that we write we write patient letters
31:34
for the gps and we also have a special paragraph
31:39
which is addressed to the dentist and it has
31:41
to do with future dental procedures what should
31:46
be taken into account what about the interval
31:52
between for example the denosumab and the dental
31:56
procedure if you should do of course um antibiotics
32:00
during the time that you should also have regular
32:03
checks so what are you what are you advising
32:06
with denosumab for dental work at the moment
32:08
because lots of people will want to hear this
32:10
yeah so um of course If it is possible, and it
32:15
is an elective dental procedure, and it is something
32:18
that you can do before, that you can perform
32:22
before starting on denosumab, it is advisable
32:26
to do so. If it is something which also is not
32:29
an emergency and during treatment with denosumab,
32:33
it would be, of course, better to, if you can
32:36
plan it, to do it at around, say, month five
32:39
or month four and a half after. the last injection
32:45
of denosumab in order to have the most duration
32:50
since the last shot. But of course, you should
32:55
also let them know that if they have a dental
32:58
abscess, it's not like that they should postpone
33:01
having treatment of an emergent dental procedure
33:05
because of denosumab. This would not make any
33:08
sense at all. I think if you have quite high
33:10
-risk patients, the risks of delaying denosumab
33:12
are much higher probably than the risks of having
33:16
treatment -related osteonecrosis. And of course
33:19
it is also the risk profile that they bring with
33:21
themselves independently of denosumab if they
33:24
take corticoids, if they're immune -suppressed,
33:27
if they smoke, if they have diabetes. So there
33:29
are a lot of risk factors also to consider. It
33:34
sounds like hard conversations in many ways,
33:38
a lot of information. a lot of explanation and
33:43
maybe having to challenge some preconceived ideas
33:46
that people come with. How do you feel having
33:50
that conversation again and again and again with
33:52
every patient? I think it's our, if I might say
33:58
so, our duty as MDs and also it helps very much
34:05
to have a relationship where the patient thinks
34:09
that they can trust you because it's not a good
34:13
thing, I think, if you try not to mention subjects
34:17
which, as I said, are in everyday social media,
34:20
like osteonecrosis of the jaw or, I don't know,
34:24
smoke discontinuation and rebound phenomenon.
34:26
I practice in Germany and I have, like, the patients
34:30
which know the word rebound and say it in English
34:34
because, yes, yes, yes. So it's definitely something
34:41
that it is on people's mind, and I think it's
34:44
very important to address it right from the beginning.
34:47
Do you think we have all these very effective
34:49
drugs now, which sometimes, I don't just mean
34:52
for osteoporosis, across medicine in general,
34:54
which means the doctor -patient relationship,
34:57
the caring attitude, doesn't almost have to be...
35:00
as important it should be important but you know
35:04
we were talking before we started about ancient
35:06
greece so if you go thousands of years ago to
35:08
the first doctors they had no drugs that worked
35:11
all they had was their caring attitude the patient
35:14
relationship and then we develop these drugs
35:16
that worked and you know penicillin will kill
35:19
infection whether you're nice to the patient
35:21
or not yes and we therefore lose some of that
35:23
patient relationship because we're so focused
35:26
on how well the drugs work. But actually then
35:29
we overlook the fact that unless you explain
35:31
the drugs and build up trust and have that caring
35:35
attitude, which goes way back thousands of years
35:37
into what a doctor is all about, then you do
35:39
lose some of the effectiveness of the drugs because
35:42
the drugs are only good enough if they actually
35:43
get into the patient's body. I agree. It's very,
35:46
very important. And also another aspect, of course,
35:49
is also the non -medicinal, non -drug treatment
35:53
for osteoporosis. It has to do with... dietary
36:00
or with exercise or with a healthy lifestyle.
36:04
So this is also a very important aspect, which
36:07
I also try. I try also to convey the message
36:11
that it's not like that we're giving you now
36:13
the super drug and now just be a coach potato
36:17
and don't do anything. It's not just what Richie
36:19
teaches us from the lab. It's what Apocrates
36:21
taught us for thousands of years ago. You mentioned
36:25
other things other than just drugs and other
36:28
lifestyle methods. We've got to ask you a little,
36:30
if you had to recommend a sport for patients,
36:32
which would you recommend? I have a strong suspicion
36:35
what you're going to say here. You know about
36:38
tennis. You can play tennis. every age I think
36:44
of your life like starting from a very maybe
36:49
young age where you're more competitive you play
36:52
singles and then as you move along maybe into
36:55
life you can switch into doubles and where I
36:58
play of course in my tennis club I also get the
37:05
opportunity to see this and another aspect which
37:08
really makes me happy that we have this is that
37:12
we have a program for wheelchair tennis. So this
37:15
is also very beautiful to see young children,
37:18
how they get introduced to this wonderful sport
37:22
and they have fun playing it. I've played a lot
37:25
of tennis. You're preaching to the converted
37:27
here. What is it about tennis then? Is it jumping
37:29
about, is it? What is it that makes tennis good
37:31
for osteoporosis? Well, I think there's a lot
37:36
to do also with balance, which is also very important.
37:41
and there is of course a lot of running if you
37:44
do it like in a high energetically right yeah
37:49
so it has to do also with the particular osteoporosis
37:53
patient I wouldn't like recommend it to a very
37:56
frail patient which I think that they are at
37:59
a very high risk for fractures but yeah I think
38:04
it's something like it keeps you it's outdoors
38:07
normally it keeps you going and in and in movement
38:12
and it has also a lot of coordination with also,
38:17
which is for maybe preventing falls. So it's
38:22
not just the resistance training aspect of it,
38:24
it's the coordination and the stability and the
38:28
balance of it. And it's good fun as well. But
38:31
I have to say about tennis, I'm not objective
38:33
at all. Who's your favourite tennis player? Oh,
38:37
it's between two. It's Roger Federer and Sir
38:40
Andy Murray. And Sir Andy Murray. Well, Rog and
38:47
Andy. If you're listening, get in touch. We can
38:49
switch emails. Maybe you won't get osteoporosis
38:54
later in life. And for the listeners, it sounds
38:56
like tennis is the holistic approach to avoiding
39:00
fractures. Indeed. Thank you very much for joining
39:04
us today, Elena. Thank you so much, David and
39:06
Richie. I really enjoyed it. Thank you. Listeners,
39:11
it was a lot of fun talking to Elena. We had
39:15
a good laugh. David, what were your takeaways?
39:19
Apart from Elena's enthusiasm about tennis and
39:24
about the health benefits of tennis, with which
39:28
I agreed. You know, we often say the takeaway
39:32
is we need more research, but I think probably
39:35
my single takeaway from this is the need for
39:38
a large, carefully designed study that I can
39:44
give people. proper scientifically backed advice
39:48
on what to do when they've been on osteoporosis
39:51
drugs for a long time but very specifically denosumab
39:55
for a long time you know you get up to maybe
39:58
eight ten years on the drug the options are you
40:02
can simply stop the drug and we know that that's
40:04
not a good idea that there are you will lose
40:07
bone and there'll be an increased risk of fracture
40:09
you could switch to intravenous bisphosphonates
40:14
you could reduce the dose of the drug you could
40:17
reduce the frequency of the drug or you could
40:20
simply stay on the drug you could switch to an
40:23
alternative you know the study almost sort of
40:25
designs itself and um you know i like to be able
40:31
to give patients proper scientifically backed
40:34
evidence and at the moment we really don't have
40:36
convincing evidence of what to do um and i think
40:41
elena very carefully sort of set out almost the
40:44
almost the protocol of how what that sort of
40:47
study would look like and i do think it's one
40:50
you know each individual center could do a study
40:54
with 100 patients i do think it's one that really
40:56
a large international study you know would be
41:00
would be the best option here we could all take
41:02
part in and we could then give patients really
41:06
good, solid advice on what's best to do. And
41:11
from a more maybe basic science point of view,
41:15
I know you love talking about mechanisms of osteoclast
41:19
activation and so on. What did you take out of
41:22
our chat? I think my first takeaway is that patients
41:28
are really good researchers, both Elena and yourself.
41:32
talked about the questions that you get from
41:33
patients and the detail that they want to go
41:36
into, what great knowledge they can come to the
41:39
consultations with. And I think that's really,
41:43
really wonderful. My other takeaway really is
41:46
about the role that education of patients plays
41:50
in building trusts, supporting patients to take
41:54
the treatments that they're offered and then
41:56
stick with those treatments. When we were doing
42:00
the interview and Elena was talking about how
42:03
long she spends talking to the patients, explaining
42:05
to them what osteoporosis is, what the treatments
42:07
are, what the side effects are, and answering
42:10
a lot of detailed questions, my first thought
42:13
as an educationalist is, well, is there a way
42:17
that you could package that information for people
42:19
to take away so that you don't have to keep having
42:22
that conversation all of the time? I hadn't really
42:27
appreciated, and I got this from Elena's really
42:30
eloquent and enthusiastic and heartwarming answers,
42:34
that actually having those conversations, actually
42:39
having those conversations is as much about building
42:41
trust with the patient as about actually informing
42:44
the patient. And I hadn't realized that. I guess
42:47
it's really important that those conversations
42:49
get had again and again and again. And I suppose...
42:55
A third takeaway is that we talked to Elena quite
42:59
a bit about individualized medicine. Elena was
43:02
explaining how when she treats patients, especially
43:04
with the Nusimab, that she tries to take an individualized
43:08
approach to the patients. But actually, the clinical
43:11
trials that collected the data, the evidence
43:15
that support the use of the medicine, were done
43:18
at a population level on large numbers of people.
43:21
And it makes me wonder about... how it is that
43:24
we can go from large scale clinical trial data
43:29
on a medicine through to individualized patient
43:34
care. And I think maybe in the future, we need
43:38
to get a guest on who can talk to us about that
43:41
and how the clinical trials we have around osteoporosis
43:44
and the medicines for osteoporosis can actually
43:46
help inform clinicians. about how to go about
43:51
individualized care for patients i think that
43:53
would be really interesting yeah i think that's
43:56
an interesting point um when when a new drug
44:00
comes along there are lots of studies looking
44:04
at the drug many of those sponsored or organized
44:07
even by the pharma company that's developing
44:09
the drug and that's quite understandable because
44:11
you have to prove that the drug works and prove
44:13
that it's effective Where there are fewer studies
44:18
are down the line, and that is how to get off
44:21
the drug again further down the line. There's
44:25
probably less incentive for the pharma company
44:28
to sponsor that drug, or to sponsor that trial,
44:31
I should say. The drug is often off -license
44:33
at that stage, so there's really very little
44:35
incentive. And I think that's where it falls
44:38
more to the osteoporosis community, to the science
44:41
community, and to the medical community to organize
44:44
those trials. and to make sure that those trials
44:48
are relevant to the individual patient. And yes,
44:52
I know it sounded as if we were getting quite
44:54
sort of philosophical and talking about, you
44:56
know, doctors over thousands of years, but I
44:59
do think that's very true. It's always amazed
45:03
me in some ways how medicine became a profession
45:05
and a reasonably respected profession over thousands
45:09
of years when really there were very few effective
45:12
medicines. And that must have been, it was based
45:14
largely on the fact that doctors were, I presume,
45:17
caring people and honest people and trustworthy
45:19
people. And it's really important now that we're
45:23
in the age of exciting, scientifically designed
45:27
biological medicines, that we retain that traditional
45:33
professional approach, that caring approach,
45:36
that honesty and integrity, because it's still
45:39
absolutely vital to what we do. to get the patient
45:43
to take the medicine. And then actually, if you've
45:47
been taking a medicine for years and it's been
45:49
working well, to trust the doctor when the doctor
45:52
says to you, you may actually need to stop that
45:54
medicine again. And that's not something can
45:58
be done by just saying to someone, watch a video
46:00
or read this handout. It still, I think, is based
46:04
largely on a lot of face -to -face interaction
46:06
and getting to know the patient and getting to...
46:10
remember the name of their of their spouse or
46:14
their their pets and just little things like
46:16
that that you know make a difference um and as
46:19
long as that's part of medicine then it's something
46:22
i will still enjoy doing oh i think that's a
46:26
nice place to leave it today thank you for joining
46:29
us listeners bye