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Your Bones Are Getting Fat: New Science! · HER

0:07
Pam Peeke, MD: Hi, I am Dr.
0:08
Pam Peak, and This is episode number 500.
0:12
52 of the Bold And the Brave, her podcast.
0:18
Yeah.
0:18
This is your podcast.
0:21
Now, today I just can't tell you how excited I am to be joined by
0:27
one of the greats, in the field of endocrinology and all things bone health.
0:32
And that's Dr.
0:33
Clifford.
0:35
Rosen, Dr.
0:36
Rosen.
0:38
Alright.
0:39
He's a bone biologist And in addition, a clinical endocrinologist.
0:44
He's 30 years into the field of continual NIH funding, first at the
0:50
Jackson Laboratory, subsequently at Maine Health Institute of Research.
0:55
And now in the last 15 years, the Rosen Laboratory has been studying.
1:01
All things get this.
1:03
This is what we're talking about today.
1:05
'cause honey, you don't know this.
1:08
And That is the fat bone connection.
1:11
And that also involves the GLP drugs, which we're gonna
1:16
be talking about as well.
1:18
He served as a board member of the Endocrine Society, former
1:22
president of the American Society of Bone and Mineral Research.
1:27
He's been an associate editor at the New England Journal of Medicine for
1:32
11 years and has published more than 640 peer reviewed publications in
1:40
just about every high tier journal.
1:43
Dr.
1:44
Rosen, welcome aboard.
1:46
Clifford Rosen, MD: Thank you.
1:47
Nice to be here, Pam.
1:49
Pam Peeke, MD: Alright, so there you are all bundled up because you're up in Maine.
1:54
Okay.
1:54
And I'm not,
1:57
Clifford Rosen, MD: Right.
1:58
Pam Peeke, MD: down in Florida, you know, so I'm like wearing the
2:01
like the little light stuff and we're gonna have some good weather.
2:04
Clifford Rosen, MD: That's great.
2:05
Pam Peeke, MD: and everyone should also know that, Dr.
2:07
Rosen is a lifelong runner.
2:10
doesn't he look pheno?
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I mean, come on now.
2:13
and I just, I love that because, I'm always collecting doctors who walk
2:20
the talk or run the talk in this case.
2:22
So there you have it.
2:25
Clifford Rosen, MD: That's great.
2:26
Pam Peeke, MD: Alright, now let's get right to it.
2:29
I'm writing my next book, and I'm also working with a group in, bone
2:34
Health, all things bone health.
2:36
And, one of the things I stumbled upon was your brilliant research in looking
2:43
at the relationship between fat and bone.
2:47
Now, when I first.
2:49
read this and I read your pieces and I've been listening to your lectures.
2:53
I, was absolutely astonished because I didn't understand a lot of this.
2:59
I was fully aware of the fact that fat, especially when you're overweight and
3:04
obese, infiltrates organs, And we know about the liver And the heart, et cetera.
3:10
Okay, that's all good.
3:11
However, the bone, what, And then astonishing things that take place,
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we're just gonna say in a woman, you know, an adult, when they.
3:23
Drop weight and when they gain weight And what goes on, especially
3:28
with our wonderful world of yo-yo dieting, and we're up.
3:33
And we're down.
3:33
We're up.
3:34
And what is happening to bone health?
3:38
we all say pop a calcium and make sure your vitamin D is
3:41
okay and get that exercise.
3:44
oh.
3:44
What about the bone fat connection?
3:47
So we're gonna start with basics.
3:50
What is up with bone and fat?
3:54
Clifford Rosen, MD: So Pam, This is an interesting story and it started
3:58
about 20 years ago when we were first doing some mouse experiments at the
4:02
Jackson lab, And we noticed a lot of fat cells in the bone marrow.
4:07
And so it's really interesting because few people described over
4:12
200 years of anatomical pathology.
4:16
Nobody really talked about what these fat cells were doing in the bone.
4:21
And, over time, We began to realize that there's a substantial
4:26
portion of fat in the bone marrow.
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So what's its function?
4:30
And the common explanation was, oh, when you get older, you start to lose
4:36
your ability to make certain cells.
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And so the fat just fills in.
4:42
Where there was no, where there was space and where there were no other
4:46
cells So, it was sort of by default.
4:49
Just a, mechanism to keep the bone marrow space alive basically.
4:55
So we got interested in this And we realized that one of the areas where,
5:01
this bone marrow fat seemed to be more present was in mice that were.
5:08
Restricted in their diet.
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And so we turned to one of my colleagues, Ann Klasky, who's the CEO now of
5:16
Mass General Brigham, and asked her whether that also occurred in humans.
5:22
And she had been studying anorexia for 25 years and had been doing
5:26
a lot of interventional studies to try to prevent bone loss.
5:31
And she said, cliff.
5:32
There's so much marrow fat in women with anorexia, they said, how could that be?
5:38
There's no fat anywhere else.
5:40
some of our patient's have.
5:42
5% fat but yet it's all in the bone marrow.
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So anyways, we started doing our experiments And the conventional thinking
5:51
after we brought this forward was the fat in the bone marrow was causing.
5:57
The bone to be lost.
5:59
So in anorexia, we know that women fracture and they
6:03
have very low bone density.
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And so one of our initial hypotheses was as they accumulate fat, the fat cells make
6:11
things that cause the bone to break down.
6:15
And so that's how we, really started to get the human connection.
6:19
And soon we realized that this was true, not only with, anorexia,
6:24
but with these crash diets.
6:26
So as you start to restrict calories, your bone marrow fat goes up.
6:31
But the ironic thing was that with a high fat diet in the mouse,
6:37
we saw exactly the same thing.
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So we said, how is that possible?
6:42
That's even more likely you gaining fat everywhere you, And so you
6:47
just gain it in the bone marrow.
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And more recently, thanks to, a wealth of great, postdocs and graduate students in
6:54
my laboratory, we've figured out that fat is very dynamic in the bone and sometimes.
7:02
It's bad for bone and sometimes it actually serves as an energy
7:07
reservoir that it actually can help the bone survive stresses.
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So what kind of stresses are we talking about?
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Starvation, for example.
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So Anne Kansky and myself and Puna Elli did a study at the Mass General where
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we took healthy volunteers, brought 'em in, and paid them $7,000 and said.
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You're staying at Mass General for 10 days and we're gonna starve you, but
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we'll give you intravenous fluids.
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But we wanna see what happens.
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And then the good part of the experiment is that you can go home for two weeks
7:43
And then when you come back, we're gonna feed you a high fat diet for two
7:46
weeks and you can eat whatever you want.
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You can have McDonald's, bring in McDonald's, anything you want.
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So we did that.
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And when we did it, we found exactly what we had seen in the mice.
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The fasting caused.
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The bone marrow to expand in fat and with a high fat diet.
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It caused the bone marrow to expand with fat.
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So then we looked at the cellular level And what we realized
8:12
is that with starvation, the bone marrow is so important.
8:18
We put out a billion cells a second for red blood cells to keep our body going.
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And you need probably the bone marrow as much as you need a heart and a brain.
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And so when we looked at the genes that were being regulated and expressed,
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what we found was that these fat cells were actually helping the bone stay
8:43
as good as it can be, which wasn't very good, but it was trying anyways.
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And so these fat cells were actually helpful.
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Pam Peeke, MD: Can I just interrupt you?
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'cause what I'm gonna try to do is, be the little translator here.
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so you have someone who's, really chronically restricting.
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You don't have to be as severe as an anorectic.
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being a woman, basically anyone who owns ovaries has done the
9:08
weird thing, which is almost starve yourself 'cause you're so desperate
9:11
to drop some weight and whatever.
9:13
Okay, now.
9:15
What I'm hearing is that your body is saying Roro, we're in serious caloric
9:21
deficit And we need to protect ourselves.
9:24
'cause the number one prerogative of the human body is survival
9:28
at the end of the day.
9:30
It's survival.
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So the body will do funky things all throughout, to be able to do that.
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So, and just concentrating on bone, the body says, okay, well listen,
9:40
bones are kind of starving here.
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We're not getting calcium.
9:43
The vitamin D thing's looking a little shady.
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we're not at all.
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Supporting the bone, appropriately by nourishment and probably not
9:51
by physical activity either.
9:52
Anyway.
9:53
So now what you're gonna do is you're gonna bring in fat, okay?
9:58
And that fat is going to be a, an energy reservoir to be able to help
10:06
this individual who's already in deep trouble, one way or the other.
10:11
Okay.
10:12
Because I think intuitively people would say, well, I'm not, eating any fat.
10:16
I'm not, overeating and stuff.
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So health, my bone should be empty of fat, but instead, fat migrates
10:23
there as an energy reservoir, right?
10:26
Clifford Rosen, MD: That's right.
10:27
So where does it come from?
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So the stem cells in our bone marrow are the source of those fat cells and
10:33
they, And what we know is those cells can become either fat cells or bone cells.
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So.
10:40
When somebody's starving or calorie restricted, there is a drive in
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those stem cells to make fat cells.
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And those fat cells then ha serve a major purpose.
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Now, they're not perfect and they can't totally protect the skeleton
10:54
because the bone cells need that energy and you can't get enough
10:58
energy, from all those fat cells.
11:01
But it's a way to preserve.
11:03
The skeleton.
11:04
So, we thought we were brilliant about this until I was sitting
11:08
on a, a committee for a PhD for a woman who we I worked with on bears.
11:14
And when bears hibernate, they collect a lot of fat in their bone.
11:18
Okay?
11:18
Even though they're not eating at all.
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So, it turns out that when I said, wow, This is fantastic, And the
11:26
wildlife biologists around the table said, where have you been?
11:30
If you look at roadkill, if you look at animals that are starving.
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They all have tons of fat, and that's why you see the birds eating the, bone marrow.
11:39
So This is a well-preserved technique for all mammals, that as they
11:47
go through a calorie restrictive phase, they really protect, they
11:52
try to protect their skeleton.
11:54
Pam Peeke, MD: can I ask a quick question?
11:56
Forgive any crazy questions.
11:58
Okay.
11:58
so in a woman, let's just say there's an average woman who
12:02
takes great care of herself.
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She's average weighted, Great nutrition, great fitness.
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she's doing just fine.
12:10
Okay.
12:10
She's not an elite athlete.
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She's just really on the money.
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does that woman have bones that have any fat in them?
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in an average, normal person with nothing else going on is does
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fat normally hang out in bone?
12:27
Clifford Rosen, MD: Okay, so the answer is yes.
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And in long bones, in our arms and legs, in humans, about 10% of total
12:38
body fat is located in the bone marrow.
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Pam Peeke, MD: That's crazy,
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Clifford Rosen, MD: is crazy, but with anorexia, that figure goes up to 33%.
12:50
Pam Peeke, MD: get out of
12:50
Clifford Rosen, MD: So, it, it just fills the bone marrow.
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so normally we all have some fat in the marrow, And in fact, what's
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really, really, really cool is when we're young and we're going through
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puberty, there's tons of marrow fat And we never could figure that out.
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How could it be if fat is bad for a bone, how could it be
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that there's lots of marrow fat?
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Before we grow, fully grow and develop.
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And the answer is those bones need that fat to not only survive,
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but to grow and to consolidate.
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So
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more energy, right?
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So.
13:30
So that's, a really essential part of the first half of the story that, that in
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some cases fat is trying to be protective.
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The second half is when you eat a high calorie diet.
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And you put fat in your bone marrow, that fat is actually telling the
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system to start breaking down bone.
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And that where the bad part of fat in bone comes in.
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So if you accumulate a lot of fat And we just have a paper just published
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this week in Bone Research where.
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We showed that as they accumulate these fat cells, they're telling the bone
14:10
cells to break down the bone, and they do
14:15
that by directing traffic in the bone marrow.
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Pam Peeke, MD: So is that because I'm just thinking, alright, so
14:23
you know the bone must NI I'm thinking of what the triggers are.
14:29
Clifford Rosen, MD: right.
14:30
Well, we've been looking at that, Pam.
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That's a great question.
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And we don't know, I mean, this occurs quickly.
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So within five days of calorie restriction.
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You have this tremendous increase in bone marrow fat.
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So there's gotta be a central signal somewhere.
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We don't know what it is.
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And then I heard you start to say, well, the bone must sort of know it's true.
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The marrow stem cell has sensors that somehow say, look, we gotta bring
14:58
in fat cells to help the skeleton.
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so it's very interesting.
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And then.
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When you think about what's happening in the bone marrow, what's happening
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in the periphery as we all gain weight and start to accumulate
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fat, the exact opposite happens And that, the fat accumulation in our.
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bellies And in our arms, in our legs actually are negative to the skeleton.
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So they're sending signals to the skeleton to start to break down bones.
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so we have sort of a complex picture, but I wanted to mention one thing.
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'cause you started to talk about being a woman as you get
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older in through menopause.
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We know that estrogen deficiency leads to a rapid increase
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in fat in the bone marrow.
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And so, yeah, tremendous.
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It's the best signal for generating fat in our mice is
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just by taking out the ovaries.
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And Sandeep cosla in the group at Mayo have shown, repetitively
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that fat in the bone marrow is a very constant accompaniment of.
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Pam Peeke, MD: Have you found that?
16:05
replacing it with
16:07
Clifford Rosen, MD: Yes.
16:07
That suppresses it.
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That totally suppresses it.
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Pam Peeke, MD: But does it, does it reverse it though?
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Clifford Rosen, MD: Yes, yes, yes.
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Totally reverses it.
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And we showed in the fasting study that as soon as you start to eat normally your fat
16:21
goes away in the bone marrow, much of your
16:23
Pam Peeke, MD: Wow.
16:24
see, right now my, her audience is like, whoa, nothing but bad news.
16:29
So, what I'm trying to look at here is, where's the good news here?
16:33
So, And that would be filed under.
16:36
How do we get rid of this fat, that's been hanging out in the bone marrow.
16:41
'cause outside of, just say for instance, someone threw me on an
16:44
island and I gotta survive for a while until the big ship shows up.
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Okay.
16:49
So that's when fat is doing me a favor.
16:52
Right.
16:54
But outside of that,
16:56
right?
16:57
is my job in life as a woman who is striving to have an optimal health span.
17:04
Doing all the right things back and forth is my job in life to,
17:10
maintain a homeostasis, within the bone between fat and bone.
17:18
So you said that even
17:20
Clifford Rosen, MD: you have to.
17:20
That's exactly right, Pam.
17:22
You have to get right in the middle And then that homeostatic.
17:26
Center where you have enough fat to supply the bone, but you don't have
17:31
too much that's causing bone loss.
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So what?
17:34
What can we do?
17:36
So There are things, so for example, if you have osteoporosis, you have a
17:40
lot of marrow fat, parathyroid hormone for tail reverses that bone marrow
17:46
fat because it changes the signal to the stem cell to make more bone
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Pam Peeke, MD: Okay, now wait a minute.
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Hold on now.
17:53
All right, we're gonna back up here for a minute.
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Now, osteopenia right is a loss of bone mineral density, but you haven't reached.
18:04
a score and all of women know that it's a DEXA score, that shows
18:09
that you've passed at minus 2.5.
18:12
Alright?
18:12
Now, if your osteopenic, is your bone recruiting more fat?
18:19
And if so, Why?
18:21
Why
18:22
Why
18:22
Clifford Rosen, MD: no, the signal's there.
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The signal's there.
18:25
It's a
18:25
gradient.
18:26
Yeah, something's wrong.
18:28
So as you age, you lose bone and as you age, you directly
18:32
also increase marrow fat.
18:34
So, so that process is tightly linked.
18:38
And so, for us as physiologists thinking about what does this all mean?
18:43
it reflects the body's attempt to adapt.
18:46
To lower bone density, And that starts very early in the process.
18:52
But Pam, one of the best things you can do is exercise.
18:56
So my friend for fat.
18:58
Fat And the bone marrow.
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So my friend Linda Bone Wall at Indiana University did this beautiful study in
19:04
mice in which he, gave them treadmills, made them exercise, And then did routine.
19:11
Uh.
19:11
Put them on a wheel running wheel in their cage.
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And they did that for eight months.
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And when they got to be two years old, which is very old in the
19:20
mouse, they compared that with those mice who didn't do anything.
19:24
And sure enough, almost no marrow fat in the animals that exercised.
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Pam Peeke, MD: Okay, now just a minute.
19:31
I'm gonna take a deep cleansing breath because once again.
19:36
What I always rave and rant about is physical fitness.
19:41
So you are telling me that what will help establish a healthier
19:46
homeostasis even if you have osteopenia.
19:50
Now, is that true for osteoporosis?
19:53
Clifford Rosen, MD: yes, it's true for both that, exercise does now
19:57
exercise itself, and you alluded to it.
19:59
It doesn't do a lot to the bone mineral density.
20:03
I mean, if it did a lot, we would all just say, okay, we'll just exercise.
20:07
Because some people have such low bone density that the changes are not, but,
20:12
it does a lot to mineral fat And so That is interesting because it would
20:17
suggest that one component of that marrow fat's probably detrimental.
20:22
The rest is probably good.
20:24
And so, as you said, getting in the middle, right in the middle.
20:27
Exercise really, really critical.
20:31
And these are weightbearing exercises,
20:33
Pam Peeke, MD: Oh yeah, definitely.
20:35
swimming.
20:35
Is not, a top of mind here, but it's wonderful.
20:38
I love it.
20:39
I'm a master swimmer.
20:40
So here's, the gig.
20:42
Right.
20:42
So if the bone begins to, decrease in bone mineral density by in a woman, I'm
20:51
just sticking with women right now, right around the age of 30 man, plus or minus,
20:55
okay.
20:56
Alright.
20:57
Does that mean that as the bone mineral density begins to decrease, that fat is
21:06
beginning to accumulate a little bit?
21:08
Okay.
21:08
Now, if I'm someone, which I am, who's been pretty athletic for decades, right?
21:17
And when I was around 30 or so, I mean, I was running and, you know,
21:20
getting ready to marathon, whatever.
21:22
Okay, so.
21:24
I'm mitigating any excessive fat that's going into my bone.
21:32
And so if I continue that for decades, note to self, keep this sucker going
21:37
forever in your life, exercise, always gonna have a small delta.
21:43
I'm not gonna fall off a cliff lose all my bone and all the rest of it.
21:47
But here's the thing I'm struggling with, I'm trying to understand,
21:52
what is normal And what is not.
21:55
you and I are talking about like that middle place and all the rest of it.
21:59
what, if, I break a leg or something, which I have, and I'm out for the count.
22:04
I can't exercise and all the rest of it.
22:08
Now I'm not gonna talk about the broken part of the bone.
22:10
That's a whole different ball game.
22:12
but for the rest of the body, which was used to having physical activity,
22:16
my hips, my spine, whatever, what's going on with that, with those bones
22:21
when I can't do physical activity?
22:24
Clifford Rosen, MD: So it's funny because I have a, a, poet.
22:27
who is also a patient of mine, a very famous poet, and she, just, broke her leg.
22:33
She's 66.
22:34
She broke her foot and.
22:36
As we did the x-rays over time, the bones really looked very demineralized
22:42
and she had low bone density to begin with, so, struggling with that.
22:46
What we know is that as you immobilize and she was in a boot and she and
22:52
no, no gravitated force on that right foot for six weeks that you get this
22:58
tremendous demineralization, the bone just starts to lose its mineral.
23:03
And in the same time, the fat just continues to accumulate.
23:07
And we know this from the astronauts, so we all know that the astronauts go up in
23:12
space and they're there for eight months And then they come back and their bone
23:15
density disease, terrible, they've lost, even with their great physical shape,
23:20
as soon as you get weightless for that period of time, your bones go And what
23:25
they've shown Mary Buck signed at Harvard Brilliant, study in mice in space is
23:31
that they gain all this mi fat and some of it's reversible and some of it isn't.
23:36
And so, what comes first, the chicken or the egg?
23:40
is the fat cells there to destroy the bone or is it there to help the
23:43
bone?
23:44
Pam Peeke, MD: that's what I'm trying to understand.
23:46
Clifford Rosen, MD: Yeah, And we don't know the answer.
23:48
I mean.
23:48
Pam Peeke, MD: Okay, well that's a good answer.
23:50
at the very least, what we can tell people is that for crying out
23:55
loud, to be able to optimize bone health, understanding all of this.
24:01
Right is, physical fitness weightbearing.
24:06
and you know, I've, yelled and screamed about this forever, and
24:09
I've done a number of podcasts about that kind of physical activity.
24:13
Now, when we come back, we're gonna ask Dr.
24:16
Rosen.
24:18
What's going on with those GLP medications?
24:21
'cause there've been some real funky headlines about
24:25
those medications and bone.
25:27
We're back.
25:28
Alright.
25:29
Now this has just been mind blowing and, the thing that I love the
25:33
most is you've made my day Cliff.
25:36
you've said, physical activity is gonna, optimize all this.
25:40
This is great.
25:40
Now, the first thing I wanna do is look at women.
25:45
Right.
25:46
And they're not on any medication, but they're gonna gain some weight.
25:51
Alright?
25:51
Let's say a woman, is anywhere from 30 to 50 pounds overweight
25:56
now, which quite frankly is kind of the average woman right now.
26:01
You know, the stats as well as I do.
26:03
So, there you go.
26:04
And, They're gonna gain the weight and obviously everything we're
26:07
gonna talk about here, we're just gonna say it sort of generically.
26:12
We all know that everything goes straight to hell in menopause And so that's
26:16
only gonna make it 10 times worse.
26:18
But let's just say she's gonna put on 30 to 50 pounds just
26:23
because life got to her, whatever.
26:25
What's going on with fat And the bone?
26:28
Clifford Rosen, MD: Okay, so in general we used to think you put a woman.
26:32
Who's gained weight on a bone density machine and their bone
26:36
density's higher than what it was before they gained the weight.
26:40
And the question is, why is that?
26:43
And so everybody thought obesity was protective against the skeleton, but what
26:47
we now understand is, that estimate from.
26:51
Bone density by the regular machines really just give you an
26:56
estimate of overall size of the bone and, And the rest of the body.
27:02
it's factoring in a couple of different things that as you
27:06
gain that fat mass around the bone itself, you get a distorted
27:11
quantitation of what the bone is.
27:13
But if you look with fine imaging inside the bone using CT imaging.
27:20
the bone is lost.
27:21
There's trabecular bone loss.
27:23
Pam Peeke, MD: that blows my mind because when I was coming through medical school,
27:28
everyone just said, ah, You know, she's obese, she's probably got bones of steel.
27:33
And we just wrote her off.
27:35
We didn't, yeah, like, okay.
27:37
Don't worry about your bone.
27:38
You're good.
27:39
Clifford Rosen, MD: That's right, Pam.
27:40
there is something to having extra weight on your skeleton.
27:44
so we can't discount that, a little bit of that, but truly there's a
27:48
greater risk of fracture in obese individuals that are postmenopausal.
27:53
so that's been fairly well-established.
27:55
And in type two diabetes in which individual, women, You have a fair
27:59
amount of excess weight, their risk of fracture is significantly greater as well.
28:04
Pam Peeke, MD: Is significantly greater.
28:05
I have a, quick sidebar question.
28:07
So, um, African American women don't, they have, heavier bone.
28:12
Clifford Rosen, MD: Yeah, they do.
28:13
They do.
28:14
They do.
28:14
They have much higher bone mass than do, Caucasians.
28:17
And the reason for, that's not totally clear except, there's
28:21
some adaptation, in the calcium parathyroid vitamin D axis that.
28:28
somehow, it has been adjusted for over evolution.
28:31
And we don't know the true mechanism, but generally, if you look at the
28:35
bones of African American, women, their turnover rate, the way they're
28:40
remodeling their skeleton is much slower.
28:43
So they're preserving more the mineral, And we think that's
28:46
probably the reason now what
28:48
Pam Peeke, MD: Okay.
28:48
Clifford Rosen, MD: is, we don't know.
28:50
Pam Peeke, MD: Okay, that's cool.
28:51
I just wanted to ask that as a sidebar.
28:53
So now this woman has gained weight.
28:56
She's, 30 to 50 pounds up and now, she's got much more fat in her bone.
29:03
and is that just because quite frankly, as you get overweight or obese, fat
29:09
infiltrates organs and bone is an organ.
29:12
Clifford Rosen, MD: Yes, it does it and it does that because the body is
29:16
trying to compensate for more fatty acids that are in the circulation.
29:21
So they're depositing them that them into the fat cells.
29:25
so That is the mechanism why that happens.
29:30
so she'll have higher fat mass in the bone marrow.
29:33
She'll have an increase in the cells breaking down bone at the same time.
29:40
And that's key because once you have established obesity and high fat in the
29:48
marrow, you start to break down bone.
29:51
And if you had a GLP one, you actually could stimulate
29:58
more of that bone breakdown.
30:00
Pam Peeke, MD: Okay, now hold that thought.
30:02
Hold on now.
30:03
So, let's just go back to the, we're gonna hit GLP in a second, so now we.
30:08
Have a woman who suddenly, the light bulb goes off.
30:12
Oh my god, I'm, obese and I have all kinds of, problems here.
30:16
Okay, so now I'm going to drop all that weight.
30:19
Now she goes and she does it healthfully.
30:22
Alright, so she's gonna exercise.
30:24
Clifford Rosen, MD: Restriction.
30:25
Pam Peeke, MD: But, and when I say calorie restriction, that's relative because if
30:29
it took her 5,000 calories a day to pack it on, obviously she's not gonna eat that.
30:35
So, restriction is reasonable and appropriate.
30:39
Let's say we bring her down to 2,500, I'm just saying, and
30:43
she's eating appropriately.
30:45
and now she's going to, exercise as well.
30:49
She's not an elite athlete, so she's just gonna do the usual, walking
30:52
and maybe hit the gym, whatever.
30:55
Now she's got 50 pounds off, she's all happy.
30:57
She fits back into her jeans.
30:59
What happened to her bone?
31:01
I.
31:02
Clifford Rosen, MD: Great question.
31:03
So probably not much.
31:05
with that modest calorie restriction, I would suspect that she's fine, that
31:10
there's minimal bone loss and because.
31:13
The bone milieu is the environment is still got a lot of calories around.
31:21
It's not going to induce any kind of, changing the bone marrow fat.
31:26
Pam Peeke, MD: So what I'm saying is that this individual has dropped 50 pounds.
31:31
Right, and she did it appropriately, didn't starve herself.
31:36
obviously ate fewer calories relative to a lot of the calories she was having before.
31:41
The quality of the calories is different, you know, all the rest of it.
31:44
Okay, now my question is she packed on fat inside her bone?
31:51
When she was ob, now what's happening to her bone?
31:55
She's 50 pounds reduced.
31:58
What happened to the fat in the bone?
32:00
What can she be expecting?
32:02
Clifford Rosen, MD: So I think that, hypothetically of course This is
32:05
'cause we don't have a ton of data about it, but I suspect there's
32:09
not much change in bone marrow fat.
32:11
It, in fact, it might go down a little bit because she's not
32:15
packing in the calories anymore, so there's no signal to store fat.
32:20
but she probably is losing a little bit of bone.
32:24
And that's because there is this effect, Pam, that we talked about
32:28
of weight itself on the skeleton.
32:32
So if you lose 50 pounds, you're losing a bit of that gravitate
32:37
force on the skeleton itself.
32:41
And we've looked at this really closely.
32:43
So when we give, when I give presentations and I write articles.
32:47
Everybody says, so it's just the weight That is causing the change in weight
32:52
that's causing the bone loss when, these kind of extreme weight losses occur.
32:58
And the answer is there's probably an element of gravitated force that's
33:02
important for the skeleton, And then it needs to readapt at a lower body weight.
33:08
So the skeleton.
33:10
Actually is remodeling itself to adjust to that lower body weight.
33:18
And when it does that, it's a little less in terms of its overall
33:23
density, but it's remodeled.
33:27
The shape of the bone actually changes a little bit compensate for that.
33:32
Pam Peeke, MD: Okay, now she gains the 50 pounds back.
33:35
Clifford Rosen, MD: Yes.
33:35
Pam Peeke, MD: Welcome to America.
33:37
So now she gains it 50 pounds back.
33:39
What happened to the, bone fat.
33:42
Clifford Rosen, MD: Well, the bone fat will definitely go up
33:44
because the 50 pound weight gain,
33:46
Pam Peeke, MD: But now she has even more bone fat.
33:50
So what she's doing is she's accruing
33:52
Clifford Rosen, MD: right.
33:53
right.
33:54
She's with the weight.
33:55
Yes, she is with the weight.
33:57
The problem is that with that excess fat mass in the bone marrow, it
34:03
is stimulating those bone cells to start to break down bone.
34:07
So that balance between what gravity can do and what's happening in the bone marrow
34:13
is the key element in determining what.
34:16
Pam Peeke, MD: now she's 50 pounds heavy again and she's just had it.
34:20
So she, calls up her doctor and says it is GLP time.
34:24
Alright.
34:25
So we all know the GLP ones.
34:27
these are the drugs, that have become so terribly popular.
34:31
and now they're actually even available not just in the injectable
34:34
form, but in the pill form as well.
34:37
so now I'm not gonna get into, a lot of the mechanism of the G Ps,
34:42
unless it has to do with bone.
34:44
So.
34:44
Now she's doing it.
34:46
What is going to happen to her bone as she's happily
34:50
injecting or popping the pills?
34:52
Clifford Rosen, MD: So that's a great question.
34:53
And unfortunately there aren't a lot of studies.
34:57
they've been done, but they haven't been released by the drug companies.
35:01
Um, You know, it's been a real question mark.
35:03
About why they're holding on to some of this data on bone density.
35:08
But we see very little studies that include bone density
35:12
reporting on bone density.
35:13
But what we can tell you is that the FDA last year signaled that
35:20
there had to be a notification on the labeling for wegovy semaglutide.
35:26
that.
35:27
there's an increased fracture risk and some great work from Novo Nordisk in
35:35
Denmark, where one of their scientists actually, looked at bone density over time
35:42
with both exercise and with, semaglutide.
35:46
And what they showed was Semaglutide causes about 1% bone loss per year
35:53
Pam Peeke, MD: Now that was ozempic for
35:54
Clifford Rosen, MD: Yes, yes, yes.
35:56
And this was due to an increase in bone breakdown.
36:00
So the cells, the osteoclast, that breakdown bone were increased.
36:06
And so.
36:07
What we don't know is what happens long-term, so they lose bone for a year.
36:13
It's about 1% of the skeleton.
36:15
We know there's some evidence there's a fracture risk, but what
36:18
happens long-term for those on it?
36:21
And also what happens if they stop it and they gain back the weight?
36:25
Does do they gain back the skeleton?
36:27
That's another fundamental question that we don't know the answer to
36:32
yet, because just they haven't done the studies and they should.
36:35
Pam Peeke, MD: Why haven't we done the studies?
36:37
Clifford Rosen, MD: great question.
36:39
So we have a study going on in Louisiana And in Maine in which
36:44
we're giving, tirzepatide, um,
36:48
Pam Peeke, MD: That's zep bound for everyone out there.
36:50
Clifford Rosen, MD: to, obese individual individuals with obesity who, are
36:54
otherwise healthy but wanna lose weight.
36:58
And we're looking at their bone density and one group is getting just their
37:02
regular diet And the GLP, And the other one is getting a protein supplement with.
37:09
Some exercise And what we're trying to determine is, is there something that
37:14
we can do to prevent that bone loss?
37:18
So we know with these agents that as you lose weight, you lose lean mass.
37:24
So you lose you.
37:25
You lose muscle mass and you lose bone mass, And that can be five to 10% of your
37:32
lean mass can be lost with these agents.
37:35
And the functional consequences of that are still not clear.
37:40
So we know if you measure muscle, it's lower.
37:45
But what we don't know is, is it functioning better?
37:48
Because maybe, as you said at the beginning, Pam, fat
37:53
infiltrates a lot of tissues.
37:56
In obese individuals, fat infiltrates the muscle.
38:00
So one thought with the GLP is that actually, okay, they lose lean mass,
38:06
but their muscle function, their grip strength is okay, and their muscle
38:11
structure and function is okay.
38:13
They're just losing fat in the muscle itself.
38:17
Pam Peeke, MD: So are you saying then when you do body comp analysis,
38:21
right, let's say we're doing a dexa.
38:23
so when we see that what we call lean body mass, which includes the
38:29
tendons, ligaments, all kinds of goodies in back and forth, right?
38:32
But that also includes the fat
38:34
doesn't.
38:35
Clifford Rosen, MD: right.
38:36
so they're losing fat, and again, This is very controversial because we don't
38:41
have the data, because nobody's really done this study to look at muscle
38:46
biopsies and say, okay, there's less fat mass or MRI, where you can actually see
38:52
the fat in between the muscle fibers.
38:55
So that hasn't been done.
38:56
So we.
38:58
Always talk about loss of lean mass when people go on the GLP one, And
39:03
that includes as you said, tendons and ligaments and muscle, but also bone.
39:08
And we do know from the bone that there is loss.
39:12
There's no question about that.
39:14
but the question is, comes back to that same question you asked
39:18
me about calorie restricted starting to a woman losing weight.
39:22
Is the skeleton just reshaping itself to this lower body weight
39:28
and therefore, May not be harmful and may actually be beneficial.
39:33
And we don't, really know, although there is that greater risk of fracture.
39:37
so we're trying to understand that.
39:39
And goes back to what we talked about at the very beginning with bone marrow fat.
39:44
The body's very smart.
39:46
It's always going to try to compensate.
39:48
The reason we study mice is they have the most rapid way of
39:52
compensating for almost anything.
39:54
You can do anything to a mouse and it'll come back and try to restore
39:58
itself and it'll do it quickly.
40:00
And so quickly.
40:01
You can measure it in the lab.
40:03
Same thing happens in humans.
40:04
There's an adaptation process that goes on.
40:07
We saw it with fasting, 10 days of fasting.
40:10
Wow, you get this, tons of me fat, but then it comes back.
40:14
Pam Peeke, MD: Okay, now I got something wild for you as we're
40:18
bringing all this to together.
40:20
'cause honestly, cliff, you and I could talk about this maybe forever.
40:24
And we will, um, I've just gotten a notice from my team that
40:27
you have now been appointed a repeat offender for our podcast.
40:33
So you're gonna be back now.
40:35
He, here it comes.
40:37
Okay.
40:37
So I had Marian, the famous Marian Nessel.
40:41
my.
40:42
Absolute.
40:43
she and I are both Berkeley grads and, we did our thing and she went the PhD route.
40:48
I went the MD route.
40:49
and I have so much fun with her.
40:51
So she's now 80.
40:53
and she just published her nth book, God knows.
40:56
and she's a riot.
40:57
But she and I both identified with one thing.
41:00
We both identify as cave women.
41:03
Alright, now let's go to it.
41:05
'cause this has to do with bone.
41:07
Now when a cave woman, woke up in the morning, you know, with
41:10
the Tweety birds, 'cause she's, hiding out in a cave or whatever,
41:14
there's no screwing around here.
41:15
She's gotta get out of here and start foraging and, she can't
41:18
just run down to the seven 11 and, pick up a little something.
41:22
So she's rocking.
41:23
From the beginning and all day long and hunting, foraging, I don't know,
41:27
whatever the hell they do, and maybe even migrating the camp or whatever.
41:32
Okay, fine.
41:34
Then right around, sunset time, she's calling it a day because
41:38
if she's out there in the dark, she's somebody's dinner.
41:41
So that being said, there are a lot of hours.
41:47
where she's doing what we now call sort of an intermittent fasting thing.
41:51
I'm actually a huge proponent of Satchin Panda's work and, Longo's work.
41:58
they're both your friends and, so I really like that, trying to get in a little.
42:03
Autophagy, when you're I call it autophagy light.
42:07
when you're doing this, what I love to call non eating, 'cause a lot of people
42:12
break out into hives and have to see a doctor if they hear the word fasting.
42:16
So that being said.
42:18
They also had many periods, like during wintertime, snow's out there,
42:23
whatever, when they didn't eat very much, they may have saved a few nuts
42:28
back in the cave or whatever, and their body absolutely had to adapt to that.
42:35
So going forward, to me, that looks like.
42:39
What Satchin wrote about, and by the way, everyone knows
42:43
that I always talk about Dr.
42:44
Panda's work, out at the Salk Institute, where he really looked at this whole
42:49
issue of what he now calls time restricted feeding, which basically means.
42:53
You eat per the circadian rhythm and you could have a non feeding time.
43:00
The sweet spot appears to be 14 hours, but you know, you could take
43:04
it up to 16 hours, quite healthfully.
43:06
And it really allows you to control your total body fat because for
43:12
the obvious reason, you don't even have that many hours to eat.
43:16
So you know you're going.
43:18
Kind of go into that.
43:19
So what I'm thinking about, you said, well, caloric restriction and
43:23
whatever, not caloric restriction for time restricted feeding.
43:27
You're getting in very healthy calories.
43:29
It's just through a different window with a longer non eating period.
43:35
Now help me understand the effect on bone.
43:38
Clifford Rosen, MD: So I would say that, there aren't a lot of studies,
43:41
but the ones that are out there.
43:43
Don't show any bone loss with time restricted eating.
43:46
Pam Peeke, MD: Thank you, God.
43:48
Just a moment.
43:48
I'm gonna have a drink.
43:49
No, just kidding.
43:52
Clifford Rosen, MD: So, so, yeah.
43:53
And in our mouse models, that's true as well if you restrict
43:57
overly over a given period of time.
43:59
So the parallel for me is going back to bears, because bears, during the time that
44:07
they're hibernating, they're not really asleep or anything, but they're going
44:09
through periods of very little calories.
44:12
But their skeleton is protected, and that's shocking.
44:17
They're not moving around, they're not doing anything.
44:21
and they're very restricted in terms of, eating.
44:24
They're very, very little food.
44:27
And yet their skeleton is protected.
44:28
And I think part of it is this bone marrow infiltration that's, substantial
44:33
enough to protect their skeleton, at least over the short term six month period of
44:39
hibernation.
44:39
Pam Peeke, MD: just wild, you
44:41
Clifford Rosen, MD: It's, but,
44:42
but the other interesting thing is that, and, Panda and other's
44:46
have written about this starving, bears are very insulin sensitive.
44:51
This is, another positive thing about restricting your calories is that these
44:56
individuals have really tremendously,
44:58
Pam Peeke, MD: that means out there is that This is a beautiful way,
45:02
the time restricted feeding, which means that you eat within a window.
45:05
It's superb to be able to control your hemoglobin.
45:08
A1C your blood.
45:10
Glucose and if you have type two diabetes, I mean, you could say goodbye
45:15
to that if you are consistent with really, sticking to this, which I love,
45:21
metabolically, There are just so many benefits to doing it by more by the
45:25
circadian rhythm, instead of making it up as you go along, which is another thing.
45:31
Wow.
45:31
This is just mind blowing.
45:34
I.
45:34
think the takeaway, let's just sort of, cause This is a
45:37
lot of complex science here.
45:39
So one takeaway is that your, bones have their own little triggers to
45:44
be able to protect you as well as get you in, get you into trouble.
45:50
So if you're packing on 50 pounds, you're in trouble.
45:54
Whereas if you are.
45:56
just doing your normal thing and trying to be healthy and
46:00
getting in your physical activity.
46:02
Notice how she sounds like a broken record.
46:04
then you can reach a lovely balance or homeostasis.
46:10
Within the bone between some of the fat, which is great to have on
46:15
board, to have a little fuel and all the rest of it, and back and forth.
46:19
I, I love that.
46:20
I gotta tell you just one thing, cliff, to bring a smile to
46:23
your, face as we close this up.
46:25
So, as many people know, I'm associated with the Senior Olympics
46:30
And we have, a really robust group.
46:32
The average age is 68.
46:34
you can't be a senior Olympian unless you're 50.
46:37
And, I have a researcher, Becca Re who is a PhD, physical therapist,
46:44
from, I believe it's South Dakota.
46:46
And she comes out every two years 'cause the games are every two years
46:50
and she does her little measurements and she's published beautiful work on.
46:55
what happens with their bodies over time, their performance
46:58
measurements by sport 'cause there's quite a few sports, et cetera.
47:03
Alright.
47:03
when I saw her, this past year, at the Olympics.
47:07
and I was helping her out Here's the thing that you're gonna love.
47:11
I said, did you notice something Becca?
47:13
look over here to this woman, she, is the world record holder.
47:18
'cause we have masters world record holders.
47:21
She's a world record holder in the sprint.
47:24
I think she was like the hundred.
47:26
and she's fantastic.
47:27
But then I saw a side picture of her and, What I noticed in so many of these
47:33
Olympians, a little less in track and field 'cause they tend to be kind of
47:36
skinnier, but in the swimmers, whatever, they all have a little something going
47:41
on with a little leak over that, little belt area and it's nothing horrific.
47:46
I mean, they have magnificent bodies, but there's something cooking.
47:49
And she looked at me and she said.
47:51
Listen, Pam, This is the way this works.
47:54
The way it works is as you get older, that's your little safety pack.
47:59
Clifford Rosen, MD: Yeah,
48:00
Pam Peeke, MD: Okay.
48:01
And you wanna have it on board, so you pat it and you love it,
48:06
and you call it a day.
48:07
I just can't even get enough of that Anyway, it just makes
48:10
me think of the bone thing.
48:12
Look, I could talk to you forever.
48:14
I can't, unfortunately.
48:16
Everyone, we have had the absolute delight, honor, and
48:21
pleasure of having on Dr.
48:23
Clifford Rosen.
48:25
And, he is literally one of the world's most renowned experts on
48:30
bone biology, and he's just filled us in on the, fat bone connection.
48:36
So thank you, cliff for being on the her podcast.
48:41
Clifford Rosen, MD: You, Pam.
48:42
It was really fun.
48:43
Pam Peeke, MD: Alright, we're gonna do this a heck of a lot more, and I want to
48:46
thank my sponsor, solar Array Vitamins, minerals and Herbs, rooted in nature
48:50
And the new Her Life Stages product.
48:53
Scope it all out@solararray.com
48:55
and take a moment to leave us a review because we just sit around doing nothing
48:59
all day, waiting to hear from you.
49:01
And this has been a production.
49:03
Podcast Health.
49:05
Remember, your time in this world may be limited.
49:09
Come on la memento Marie, right?
49:12
So your time in this world may be limited, but the things you
49:15
could do with that time are not.
49:17
So get on out there.
49:19
Create a new balance in your bone between fat and bone, and seize the day.
49:25
Hey everyone.
49:26
Thanks for listening.