Hi, everyone. This is Lucas Voss with the
Becker's healthcare. Thanks so much for tuning in
to the Becker's healthcare podcast series.
Today, we're talking about innovations in bone healing,
how science
is shaping
the future of regeneration.
I'm so excited
to welcome doctor James Riebe. He's the principal
scientific advisor at Orthofix and brings more than
thirty years of experience in pharmaceutical and medical
device development.
He's a member of the American Academy of
Orthopedic Surgeons and is widely recognized for his
expertise in bone healing and bone growth therapies.
Doctor Ibe, welcome to the podcast. It's so
great to have you.
Well, thank you for the invitation, Lucas.
I'm excited to be here today.
It's great to have you. We have so
much to talk about. So much has happened
in your field
over the last couple of decades, I'd argue.
Again, you've been at the forefront of all
of this, including a lot of the innovations
that we've seen.
Looking back to the early days of bone
growth stimulation,
what first sparked interest in exploring
elect the electrical and mechanical signals as therapeutic
tools here?
Well, I think the the most interesting thing
really went back to the early discoveries
about when you bent bone,
you actually
generated
a electrical signal. So
Mhmm. Obviously,
this started in Japan with
piezoelectric
signals, but then followed up here in The
US by
the group at University of Pennsylvania
in Philly
showing that these electric potentials were really
streaming potentials. And, of course,
this open this whole
area
up of
do cells
really
respond to these electrical
signals.
And then
years later, the same thing happened with mechanical,
signals,
and that led to really development of ultrasound.
So I think
to really
summarize,
it was the ability
to talk to cells and tissues
without
having to provide
a drug or a protein
to
basically
activate
the healing process.
And so
that was really, really
exciting. And I can remember some of the
first
presentations
we made, for example, at the,
academy meeting, the AAOS
meeting
on this and really the audiences
that we were able
to draw to see this new data
and really
get excited about it.
Yeah. So when you're describing it, it sounds
really futuristic. It was it's really a step
forward for and, again, less less invasive. It
gives people a chance to to have better
therapy. And I wanna touch on the the
technology piece of this a little bit more
in detail, specifically pulsed electromagnetic
field technology or PEMF as we might refer
to it. It's become an important approach
in bone healing itself.
From your perspective, what were some of those
key scientific or clinical milestones that help
validate PMF as a credible
evidence based therapy?
Well, I think,
scientifically,
it was really when
several
labs showed
that you could with
post electromagnetic
fields, you could
actually
stimulate
cells and tissue culture
to make growth factors like
insulin like growth factor, TGF
beta,
bone morphogenetic
protein. And some of this work was
done by Roy Aaron, for example, at Brown
University
and Barbara Boyan at the time
at Georgia Tech.
So these were really key scientific things, but
I think the most important
clinical evidence
was really in spine fusion,
and that was
the use of post electromagnetic
fields for both
lumbar fusion and the cervical fusion
based on
multicenter
placebo.
So these were double blind placebo
controlled
clinical trials that really showed very strongly
the positive benefit of
pemph stimulation
for spine fusion.
And that's something that it actually, the first
placebo
the first double blind placebo
controlled
prospective
multicenter
study,
ever in the spine fusion was on pulsed
electromagnetic
fields.
The other thing I wanna bring up and
not to host
any particular company,
but
what the FDA
particularly
liked was that
there was independent
blinded
radiographic
review,
and this was done by
a group of surgeons and radiologists
that
had no
knowledge of who was randomized
to the
active PEMF device
or the control PEMF device.
And I think
that those studies
really set the stage
for the growth of PEMF technology
really across the country.
You you've touched on the ultrasound aspect of
this as well, again, in the in the
early days and and that this was essentially
what was focused on in the ultrasound based
therapy, such as low intensity pulse ultrasound, introduced
a a different mechanism of action compared to
PEMF.
How did the growing understanding of cellular signaling
and bone biology influence the development
of ultrasound based bone healing technologies then?
Well well, when you go back to some
of my earliest
comments, you know,
the
mechanosensing
effects of bone
have been known for over a hundred years.
You know,
originally, wolf's law, but
there there has always been this tremendous
interest
in direct mechanical
effects on bone.
The work of Alan Goodship and John Kenwright
in The UK
really showed
how important this was, and this was followed
by
people, you know, Lutz Klyse and Ulm, Germany.
So
so we knew
forty plus years ago that
mechanosensitivity
of bone
was a real thing,
and it was really that
that allowed
ultrasound
as a micro mechanical
stimulus.
And then
all the work that labs were doing around
the world on cellular
signaling with
micromechanical
loads
really drove that. You know, a lot of
this is based
on integrins, and integrins
were
a class of
protein
receptors that really,
you know, allowed the ultrasound
field to grow
very well. And then again,
there were
randomized
placebo controlled
clinical trials conducted
of the pulse ultrasound
technology.
And at that point, it was sort of
accepted
from an FDA standpoint that the right way
to do the research, the clinical research,
was in fact to do these
randomized
placebo controlled trials,
which as you know
had been the standard in pharmaceutical
development
for many, many years.
I loved your description earlier of the conference
that you had mentioned, where this was first
described and first presented and and sort of
the some of the reactions that you've saw.
And and non invasive bone growth stimulation devices
have really moved from early skepticism to to
broader clinical adoption now.
What were some of the biggest challenges in
in gaining physician acceptance there? And and for
us, physicians
evaluating whether to do this, whether to incorporate
technologies
like this today,
what factors should they be considering?
Well, the biggest challenges
really had to do with
getting
thought leader surgeons
to speak
about their use of these technologies.
And that took
some time because
the reality is
the clinicians
who
originally
were approached about these technologies
are all surgeons.
And I think
just to say in a very
gentle way,
most surgeons
believe that their surgery
is gonna be successful.
You know, they trained
for years and years. You know, most of
them were,
you know, five years of residency,
then spine fellowships or trauma
fellowships,
and they worked with
great institutions.
So
to say to a surgeon that
you might need this adjunctive
bones
growth stimulation
technology
on top of your excellent surgery,
that was clearly a challenge
in the early days.
And so
today,
if I'm out giving a lecture,
I really focus on comorbidities.
So
if you have a, for example, a two
level
lumbar spine fusion patient or
a adult deformity
spine fusion patient
that maybe
is being treated for diabetes,
maybe they were a former smoke smoker,
maybe they have peripheral vascular disease,
osteopenia,
or osteoporosis.
All of these risk factors,
clearly, there's publication
showing that these risk factors
are a negative
influence
on successful,
for example, spine fusion
or fracture healing. And I think
that's where we
really emphasize. It's not for the healthy
45 year old who might need a one
level
lumbar fusion due to
maybe work injuries
or
or sporting injuries.
These devices
really
are
for those patients that have
a lot of risk factors that negatively
affect their ability to heal.
Earlier on our conversation, we've talked a little
bit about the evolution of this and the
evolution of these technologies
and the development of them as well.
As we look to the future now
and looking back at the technologies themselves,
for you personally, what lessons stand out about
translating
the some of the venture research that we've
talked about into real world clinical solutions right
now?
Well, it you know, very good question, Lucas.
So
translating
bench research
is always
tricky,
but
I think our approach
with pulse electromagnetic
fields was really
to do the bench research
with
some of the most highly respected labs in
the country. So
when we
were investigating
pulse electromagnetic
fields as an adjunct
stimulation
to rotator
cuff repair,
we worked with Lou Zyslowski's
group, which included
Andy Coombs at University of Pennsylvania.
And they're widely
considered one of the best shoulder
research labs in the world
with tens and maybe hundreds of publications
over the last
twenty years.
And the the reason why we did that
is then when we went to a
clinical site
and we were able to show them all
of the
basic research that went into this potential new
clinical application,
we never had
a shoulder surgeon say to us,
I don't wanna be in this clinical trial.
They were when they saw the
the
basic research data,
which included animal studies,
they were so enthusiastic
to sign up to participate
in the clinical trial.
Doctor Ravey, thank you so much for joining
us. It's been so great to have you.
Well and I I appreciate the opportunity, Lucas,
and
wish you always the best at Becker's
because, it's
something that I read every morning when I
open up my Outlook.
So great to hear that, and we're certainly
grateful that you do. And we also want
to thank our podcast sponsor Orthofix.
You could tune in to more podcasts from
Becker's Healthcare by visiting our podcast page at
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