The Peter Attia Drive - Navigating bone health： early life influences and advanced strategies for improvement and injury prevention (#214 rebroadcast)

00:00:00.000 Hey, everyone. Welcome to the Drive podcast. I'm your host, Peter Atiyah. This podcast,

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00:00:53.200 of a subscription. If you want to learn more about the benefits of our premium membership,

00:00:58.020 head over to peteratiyahmd.com forward slash subscribe. Welcome to a special episode of

00:01:06.360 The Drive. This week, we are rebroadcasting our in-depth AMA, which was AMA 37 on bone health.

00:01:12.860 It was released to subscribers initially, but we're opening this one up to everybody so that

00:01:18.360 those of you who are not subscribers might get a sense of what the AMAs are all about.

00:01:23.200 In this episode, we discuss why fracture-related death rises steeply after the age of 65,

00:01:29.420 especially following hip and pelvic breaks, and why prevention must start decades earlier,

00:01:34.900 what bone mineral density is, and how DEXO scans measure it, and how to read a T-score and Z-score,

00:01:41.320 how bone changes with age in men and women, the outsized effects of menopause and estrogen loss,

00:01:47.260 and the role of vitamin D, calcium, parathyroid hormone, and magnesium in bone turnover.

00:01:53.200 The difference between healthy bone, osteopenia, and osteoporosis, and when each diagnosis is made,

00:01:59.420 major risk factors for low BMD, when to start screening, sooner than most guidelines suggest,

00:02:06.660 and how often to repeat DEXA, which type of exercises best improve or preserve BMD,

00:02:13.020 nutritional priorities for bone, how weight loss without resistance training accelerates bone

00:02:19.280 loss, and why combining diet with heavy load exercise can offset it, pharmacologic options

00:02:25.260 when lifestyle options are not enough, and strategies to minimize bone loss during bed rest

00:02:31.160 or injury. So, without further delay, I hope you enjoy this rebroadcast of the Bone Health AMA.

00:02:43.620 All right, Peter, welcome to another AMA. How are you doing?

00:02:47.720 Doing well, man. The final seven episodes of Ozark drop tonight. We're recording this April 29th.

00:02:55.660 Interesting date for two reasons, by the way. The other thing that occurred to me this morning

00:02:59.040 is that the days and dates in this year, 2022, were the same as they were in 1994. So, I was like,

00:03:06.780 oh my God, today is Friday, April 29th, which is the same as it was in 94. So, on Friday, April 29th in

00:03:15.140 1994 was the practice day at Imola, and that's when Rubens Barrichella had that horrible, horrible

00:03:21.860 accident. We can link to the accident where he basically hit the chicane and launched into a barrier,

00:03:28.280 and amazingly only escaped with a concussion and a broken nose. The following day, which is the same

00:03:34.480 day as tomorrow will be, which was Saturday, April 30th, was when Roland Ratzenberger was killed,

00:03:41.740 which made it the first fatality in Formula One in 12 years, the last one being Gilles Villeneuve in 1982.

00:03:49.580 And then, of course, Sunday, May 1st, which will be the same this year, was when Senna died.

00:03:53.540 All in 1994.

00:03:55.860 Yeah, I was at the same race. You had these three horrible accidents resulting in two fatalities in

00:04:00.960 one weekend. But again, to think it's the exact same days this year as it was 28 years ago. I

00:04:07.260 didn't notice that until today. This is really off topic, but do you still have the skill that you had

00:04:12.440 back in the day where you can remember what day, like day of the week, a date was?

00:04:18.340 Only if I can peg it to something, but not as profound as it used to be.

00:04:22.660 I remember in meetings, we used to just throw out random dates, and then we would fact check it.

00:04:26.880 I feel like we wasted a lot of time doing that.

00:04:29.240 Someone would tell me their birthday, and I would tell them what day of the week they were born on.

00:04:33.060 On the complete opposite end of that, what we're going to talk about today

00:04:36.080 is the topic that we get asked about a lot. And we've gotten a lot of questions that have come in,

00:04:41.000 but we've never really dove really deep into it, which is what we're going to do today.

00:04:45.260 And it's kind of all things, bone health, bone mineral density, osteopenia, osteoporosis,

00:04:51.680 things of that nature. And I know this is something that you work a lot with in your

00:04:56.180 patients, and I know it's something that's of really big interest for people. And so

00:04:59.860 our hope is that we can go through this episode and focus on why is this important? So why should

00:05:07.020 people care about this? People listening right now, there'll be a subsection of them that are going

00:05:11.840 to be super interested. And there'll be probably another subsection who are maybe younger. They've

00:05:16.500 never really thought about their bone health, and they might not think it really applies to them.

00:05:20.340 But our hope is in the beginning, at least, we'll walk through why they should care about this and

00:05:24.040 why they should focus on it early on in life. And then from there, we'll talk about how bone health

00:05:29.880 changes as people age, the differences between sexism and men and women. And then we'll also focus

00:05:34.960 on things on how people can improve or help their bone health become better from physical activity

00:05:41.020 to nutrition, supplements, drugs, and more. And then if all that goes well, and we still have time,

00:05:46.880 which is always 50-50 on how these AMAs go, we'll also focus a little bit on people dealing with acute

00:05:53.740 injuries and how they need to think about this, which I know is something that you're interested in,

00:05:58.620 given your recent shoulder surgery. And now you're not as active in one side of your upper body as you

00:06:04.520 used to be. All that said, I think before we start going through those questions, it's going to be

00:06:09.600 helpful to set the stage a little bit, just so everyone is on the same page and the definitions

00:06:13.920 and what we're talking about. So why don't we start with what are some of the types of bones we'll be

00:06:19.500 referring to? Because at least for myself coming into this, I just kind of think a bone is a bone,

00:06:25.220 and I don't really think much more beyond that. So why don't you dive into that a little bit?

00:06:29.540 So bone is, it's a living tissue. Okay, that's obvious, but I think it's also easy for a person

00:06:35.660 to forget that and think of bone as somewhat inert. But in fact, bone is heavily vascularized.

00:06:42.140 Bone is an organ that plays a very important role in a lot of things. I'm actually not going to go

00:06:46.940 super deep into the anatomy and physiology of bones. I'll point out just a couple of things,

00:06:51.620 right? So first of all, think of a couple types of sections of bones. So we think about the cortical

00:06:56.440 or compact bone, and that's what forms like the shaft in the exterior of long bones. So if you

00:07:00.720 think of your femur, your humerus, things like that, they have the long shaft and then the nubbins at

00:07:06.220 the end. So the shaft of that is the cortical or compact bone. And then at the end, you have the

00:07:12.080 trabecular bone, sometimes called the spongy bone. Those are kind of at the end of the bone. And there

00:07:16.800 are some differences amongst those in terms of their vascularization and things like that. But again,

00:07:22.240 I think for the purpose of this discussion, whenever I talk about compact or cortical bone,

00:07:26.500 I'm talking about the shaft. And whenever I speak about the spongy or trabecular part,

00:07:30.120 I'm talking about the end. Again, I think marrow, people probably intuitively understand that marrow

00:07:35.680 is important. But again, it's very important, right? Marrow is what's producing our white cells and our

00:07:41.040 red blood cells. So in this era where we were thinking about a post-COVID world, it's important to

00:07:46.900 understand that the memory B cells and memory T cells that are going to provide lasting immunity

00:07:53.080 against this virus and other viruses reside in the bone marrow. The whole purpose of being infected

00:07:58.720 and then having a subsequent infection that's less devastating, purpose of being vaccinated for the

00:08:04.480 same reason, is to have memory B cells and T cells that are sitting there in the bone marrow that can

00:08:09.400 respond immediately and quickly upon reintroduction of the same antigen.

00:08:13.460 When you mentioned nubbins, it made me think about your banana nubbins. And you recently posted on

00:08:19.520 Twitter, you might be looking for a new profession. Do you want to let people know what your new

00:08:24.220 interest is in the world of longevity? I've been very interested in human longevity for a little over

00:08:30.860 10 years. And I'm sure I will remain so. But I've at least considered moving into banana longevity

00:08:36.640 because I think the opportunity for impact is huge. It's one thing if you can figure out how to take

00:08:42.220 the average person from being 80 to 90. That'll have a huge impact on the world. But if you could

00:08:47.280 take the average banana and go from like two days before it turns mushy and brown to 10 days,

00:08:53.840 I think it's revolutionary. I just noticed I was on the USDA's most wanted list because of how many

00:08:59.080 bananas I waste. So I got to do something about this. If you solve the banana crisis and you move to

00:09:04.760 avocados, they'll probably give you a Nobel Peace Prize as well. The upside is very high in this new world.

00:09:10.640 Avocados last so much longer. I could buy like seven avocados and eat them in a week.

00:09:16.320 I can't buy seven bananas and eat them in a week at one a day. It just doesn't work.

00:09:20.440 I think that entire fruit space is just a racket. I think bananas are a pyramid scheme.

00:09:25.260 The whole thing is just total scam.

00:09:28.060 Maybe one of our upcoming AMAs, we'll just do a conspiracies with Peter Atiyah and we'll just go

00:09:32.800 into the world of bananas. So Peter, you mentioned earlier ago, B cells and T cells. Can you

00:09:38.320 walk people through what cells make bones?

00:09:41.780 This can be made as complicated or as simple as you want. Just think about osteoblasts and

00:09:47.340 osteoclasts. And I kind of remember from medical school, the way I used to remember this. So

00:09:51.380 osteoblasts B are responsible for building bone by producing collagen bone matrix and mineralizing it.

00:09:59.860 Osteoclasts remove bone by reabsorbing calcified bone and the matrix. So osteoblasts contribute to

00:10:09.420 increasing bone mineral density. Osteoclasts, the opposite. It's also important to understand

00:10:14.720 this exists in an equilibrium. So we're constantly remodeling bone, adding to and subtracting

00:10:22.080 from this and basically turning over calcium. So bone is like 50 to 70% mineral. And obviously,

00:10:31.640 what's the predominant mineral? It's calcium. We'll talk about that in a second.

00:10:35.080 It's about 20 to 40% organic matrix. So again, what does organic mean? Organic is carbon,

00:10:40.200 hydrogen, oxygen, sulfur, etc. And then the rest of it is a bit of water and lipid. And again,

00:10:45.120 you'll see that primarily in marrow. In an adult, like the entire human skeletal system can be remodeled

00:10:51.020 in a really long cycle. It might take 10 years to turn over all of the mineral and organic content

00:10:58.860 within the bone over and over again. But at the micro level, calcium balance is happening quite

00:11:04.540 frequently. I don't remember the exact number. I want to say it's like 99%, but virtually all of the

00:11:10.440 body's calcium is contained within bone. And therefore, bone plays a very important role in

00:11:16.580 calcium homeostasis. And if anybody's taking a physiology class, they probably remember how

00:11:21.920 important calcium signaling is to everything within a cell. Again, we think of these bones as

00:11:28.260 structural entities, which of course, first and foremost, they are. But remember, they're also

00:11:33.300 a very important reservoir for calcium, which is another very important ion in the activity of every

00:11:38.860 cell. You talked a lot about calcium. What about vitamin D? What role does vitamin D play in the bones?

00:11:45.600 They're both very important. And again, there's two forms of vitamin D, vitamin D2 and D3. But really,

00:11:53.000 when I talk about vitamin D, I'm going to mostly talk about D3, which is the active form. So what's

00:11:58.760 the problem with being deficient in vitamin D? Well, again, people might recall a disease called

00:12:03.640 rickets. And you see this often in developing parts of the world where people are really malnourished and

00:12:08.640 they have really, really soft sort of spongy bone. Actually, just yesterday, I had a friend over who

00:12:14.840 does a bunch of mission work in Rwanda. And she was showing me a child at their camp whose legs,

00:12:23.600 the child was like probably five years old. He was sitting down and they were

00:12:26.220 doing something with his legs that you would think would be impossible to do with a human being.

00:12:31.760 Basically, while he was sitting on the ground, they were able to move his foot back and forth,

00:12:36.240 back and forth. And he was in no pain, but it's because he didn't have bones that were anything other

00:12:40.760 than basically rubber bands. So he couldn't stand. And within, I want to say six months of correcting

00:12:47.440 his nutrition, totally normal. Amazing opportunity when you think about what happens in that part of

00:12:52.140 the world and how you can fix that. But what is it about vitamin D? Well, vitamin D increases the

00:12:56.960 gut's absorption of calcium. So if you're woefully deficient in vitamin D, you're going to have

00:13:02.520 trouble absorbing calcium through the gut. And we're going to talk in this podcast later about the

00:13:07.520 importance of dietary calcium and or supplementary calcium. And so you can see why that becomes part

00:13:13.420 of the issue. The other thing to kind of keep in mind here is the role of another hormone. And again,

00:13:17.700 I'm trying to only introduce concepts now that are going to become relevant later, either through

00:13:22.000 treatments or nutrition or supplementation. So I'm being a little bit simplistic. But the other

00:13:27.960 thing that you can't avoid here is understanding the role of calcium and parathyroid hormone.

00:13:32.660 I think most people are probably familiar with their thyroid gland sits here in the neck.

00:13:36.380 It's kind of got this shape to it where it's got like two main lobes and then each lobe has two

00:13:42.720 poles. Well, at each of those poles is a little tiny gland called the parathyroid gland. So you have

00:13:48.040 four of those. And the parathyroid gland is really the master gland for regulating calcium levels. So

00:13:54.680 low levels of calcium in the blood stimulate parathyroid hormone secretion. As parathyroid hormone

00:14:02.160 level goes up, it simulates the release of calcium from the bone into the blood. Now it also induces

00:14:09.100 enzymes in the kidney, which then convert vitamin D into its active form to then aid and speed up in

00:14:15.580 the process of reabsorbing more calcium from the diet. So all of this stuff, parathyroid hormone,

00:14:22.180 calcium, vitamin D, very important to maintaining bone health. And anytime you have things that disrupt

00:14:27.960 that system, you're going to see disruptions potentially in the bones. And I think that was

00:14:32.680 a good quick overview of what will be important for what we cover next. And I think the natural

00:14:37.740 follow-up to it is what is the consequence of poor bone health? What is the consequence of low bone

00:14:44.340 density? Some people who will be listening to this will have already known issues of bone density.

00:14:50.500 And some people have never thought about this before in their life. What would you say to those people

00:14:55.220 on why they should care about this and why they should think about it? This is one of those things

00:14:59.420 that I would say five years ago, I was not paying nearly as much attention to as I am today. I think

00:15:06.360 the easiest way to show this is put a couple of figures together. So can you pull up figure one,

00:15:09.900 Nick? So this is a figure that we made. It's an internal analysis. It's a very straightforward

00:15:15.320 analysis. All we've done is taken data from the CDC database from 2019. The reason we use 2019

00:15:21.360 is by the time you get to 2020, you start to get some COVID data mixed in there. Although the

00:15:26.700 accidental stuff only changes in that you see a higher rate of overdose. So you're looking at the

00:15:31.960 absolute number of deaths by decade for people age 25 to 35, all the way up to 85 and up. We

00:15:40.260 basically break accidental deaths into four categories. So overdoses, transportation accidents,

00:15:45.800 which are mostly car accidents, falls, and everything else. As you can see, those first

00:15:51.580 three, accidental overdose, transport deaths, and falls represent virtually all accidental deaths. So

00:15:56.940 you can almost ignore everything else. This is the absolute numbers. These are total numbers. And

00:16:03.140 two things stand out here really clearly. The first is that for people younger than 60, overdoses are the

00:16:10.460 predominant cause of accidental death. And for people over 65, falling is. But if you go to the

00:16:16.880 next figure, it tells, I think, a more important story, which is when you adjust for the population.

00:16:22.520 Because remember, in figure one, what I'm showing you is total number of deaths. But what you don't

00:16:27.680 realize is that as you move left to right, the denominator, the population is getting smaller and

00:16:33.800 smaller and smaller. There are fewer and fewer people in each bucket as you go to the right. So to

00:16:37.840 correct for that, we would ask the question, which is, how many of these deaths per 100,000 people occur

00:16:43.880 in each group? And if you look at that figure, I think the story is readily apparent, which is that

00:16:51.160 by the time you're 75, the risk of death from a fall is enormous. Now, it's not as high as Alzheimer's

00:16:59.680 disease, it's not as high as cancer, and it's not as high as heart disease. But it comes in pretty much

00:17:06.220 just after that. This is what sets the stage. Because on the one hand, I think you can look

00:17:11.300 at these data and say, wow, this is really problematic. But the other point is, you can't

00:17:16.300 wait until you're in that bucket to decide you're going to do something about it. So just as for

00:17:21.980 atherosclerosis, we don't want to wait until we've had our first heart attack. I really need to worry

00:17:27.280 about my ApoB, and maybe I should stop smoking and make sure my blood pressure is okay. You don't want

00:17:31.560 to wait until you have osteopenia or osteoporosis, and you're 60 years old to say, it's time to do

00:17:38.640 something about this. Now, if you're there, there's lots to do about it. But it's just as important

00:17:43.260 if you're 25 years old. And frankly, it's just as important as a parent, if you're thinking about

00:17:47.620 what your five-year-old and 10-year-old and 15-year-old should be doing to make sure that

00:17:52.280 they're setting themselves up for the best outcomes possible as they age, of course.

00:17:56.500 Let's look at figure three now. So what you're looking at here is the excess mortality for women, 1.00

00:18:03.860 which is shown on the top, men, which is shown on the bottom, following a hip fracture. And this is

00:18:11.160 going to come up over and over again. We're going to get into some data about what are the fractures

00:18:14.720 that really end lives. And you're going to see it's primarily hip fractures. Pelvic fracture, I think,

00:18:20.740 is probably second. In part, this results from the immobility that comes after it. But I think

00:18:26.480 there are some other reasons at play there. So what we're looking at here in the top graph is

00:18:29.960 women following a hip fracture, men following a hip fracture. And you're looking at mortality as a

00:18:36.240 function of age. This is kind of staggering. I mean, when I first saw this, I couldn't believe it.

00:18:42.960 And I apologize for people who are only listening to this podcast. Again, this is one of those podcasts

00:18:48.260 where I think it really helps to be able to see the figures. I'll do my best to kind of explain what

00:18:51.600 the figures show. But for those who are looking at it, I don't think you need me to say anything.

00:18:55.680 So you can just plug your ears and go la la la la la la as I explain this, because there's nothing I

00:19:00.100 need to say if you can read this graph. If you're 90 years old or above, and you're a man, and you

00:19:06.700 have a hip fracture, in this data set, and we're going to talk about other data sets in a moment,

00:19:12.020 more than 40% of you will be dead within a year. Now that mortality comes down. That's generally the

00:19:18.020 case. The mortality tends to come down because there's kind of a survival benefit or there's fewer

00:19:22.760 people in that group. You know, what's the mortality of people who are 90 over the next 10

00:19:29.200 years? That number is going down because most of them have already died. You can see for the younger

00:19:33.940 demographics, the numbers go up. You know, the good news is, in this cohort at least, if you're 70

00:19:40.120 years old and you break your hip, 10% of those people are going to be dead in three years. But that

00:19:45.800 number just keeps going up and up and up. The important thing here from this data set, because we're

00:19:52.760 in this data set, what you realize is that for older people, people over the age of 85,

00:19:59.220 people over the age of 80, I think most of us listening to this podcast, if we're not that age,

00:20:04.220 certainly have aspirations to be that age. Your mortality is in the neighborhood of a third

00:20:08.780 within a year after a hip fracture. Nick, we're going to have Michael Easter on the podcast

00:20:13.980 coming up soon, aren't we? Yeah, that will come out mid-summer probably. For those who aren't

00:20:19.360 familiar with Michael's work, he wrote a book called The Comfort Crisis, which I'm going to say

00:20:25.520 is probably one of the 10 books that I'll sort of force down most people's throats if given the

00:20:33.540 chance. I think it's a really important book. A topic from that book will actually come up later

00:20:38.820 in this episode, Nick, when we start to talk about exercise and what we can do to reduce the loss of

00:20:44.380 bone mineral density as we age. But in the book, he makes some references to a few studies that I

00:20:50.460 went back and looked at that talk about some of the unbelievable high mortalities in other fractions.

00:20:57.320 So if you look at another study, a study had like about 200 people in it. It looked at the

00:21:01.540 six-month mortality in people who were 65 or older who fractured their hip, and the mortality was 25%.

00:21:09.300 Again, I want to repeat what the implication of that is. If you look at a group of people who are

00:21:15.540 65 years old or older who fracture their hip falling, 25% of those people will be dead in six

00:21:22.940 months. Now, obviously, when you include younger people, that mortality goes way down. So if they

00:21:28.720 lowered the threshold in that study to people 50 and older, that mortality came down to just under 14%.

00:21:34.420 Another study, which was a Finnish study that looked at a little over 400 consecutive hip

00:21:40.000 fractures in patients, found that the one-year post-operative mortality was just over 27%.

00:21:47.280 So again, totally different patient population, and by the way, different country, very similar trend.

00:21:53.460 And I think perhaps the most rigorous of these studies was a large study that looked at about

00:21:58.060 122,000 participants who were at least 60 years old from various cohorts, so Europe, the U.S., et cetera,

00:22:07.100 followed them for 12 or 13 years on average, and during that time found 4,200 hip fractures.

00:22:16.560 This study was able to then compare total mortality and look at the hazard ratio

00:22:21.560 in the first year following the hip fracture. So now this is asking the question, what is the

00:22:28.200 probability or what is the increased risk of death one year following the hip fracture in this

00:22:33.180 patient population? Again, these are people enrolled at the age of 60 or beyond. And the hazard ratio is

00:22:38.940 2.78. So again, what does that mean? 2.78 means a 178% increase in the risk of mortality within one year

00:22:49.260 following a hip fracture. There are lots of studies like this. I don't think we need to spend the rest

00:22:54.340 of the AMA on it. I think regardless of how you slice and dice these data, a hip fracture is a

00:23:00.840 devastating outcome. And it's something that we really want to avoid at any age, but especially

00:23:07.120 when we're into our seventh decade and beyond. Just for reference, what's the hazard ratio for smoking

00:23:13.680 again? The hazard ratio for smoking on all cause mortality is less than 2.78 for sure, because

00:23:22.700 the hazard ratio for end stage renal disease is about 2.76 for all cause mortality. Smoking is

00:23:30.700 probably just below two. So great point, Nick. This has a greater mortality than smoking.

00:23:37.760 The other really interesting thing when you look at those two graphs is I would love to do a study on

00:23:42.900 the people who are over 90 when they fractured their hip and survived at 10 years. Who are those

00:23:49.260 people in their hundreds just like kicking it around, still going strong. It'd be really interesting

00:23:55.020 to see. Do we know where fractures occur in the body? If you pull up this figure, Nick, I think this

00:24:01.680 is a really elegant way to look at this. You're looking at all the sites of fractures. And in the first

00:24:07.320 column, it's showing you how many fractures occurred in this study, but it's ranking it by median age.

00:24:15.400 So I've just highlighted the first one, which is proximal femur, which is hip fractures. Not only are

00:24:22.320 those highly frequent, 4,000 fractures, but look at the median age, 81.1. Pelvis right there, 73.2 behind it.

00:24:33.320 So neck of the femur, 70. Distal femur, 70. Acetabulum, which is the cup that holds the femoral

00:24:41.420 head, 68. And then down to say proximal humerus, so the top of the humeral bone, 66. So those are

00:24:48.520 the big fractures for people over the age of 65. Again, you can see that frequency of proximal humerus

00:24:54.100 and proximal femur are very high. You can go through this list and it's really telling about how people

00:24:59.440 fall, you know, what's a distal radius fracture, the fracture at the end of your hand. So the radius

00:25:05.740 bone runs right here, just so you can see. How does someone break that, right? They break that by

00:25:11.200 falling. You sort of get a sense of how balance, strength impact a lot of these things.

00:25:18.520 Yeah. Out of curiosity, what's the talus? What's the last thing on the list?

00:25:23.540 Foot.

00:25:24.020 Foot.

00:25:24.260 It's the foot, yeah.

00:25:24.920 So the next terminology that I think would be important for people to know, because we do get

00:25:29.980 a lot of questions on it, we're going to talk a lot about it, is the terms osteopenia, osteoporosis.

00:25:36.140 Just for people who don't know, myself included, are they the same? Do they mean the same? How do we

00:25:41.660 think about them different? Why is it important to differentiate between them?

00:25:45.480 So just think of this as a continuum, Nick. And in fact, if you pull up figure four, this is not

00:25:50.740 entirely helpful, but at least schematically helpful figure. On the left of this figure,

00:25:54.520 you see you've got kind of like the healthy bone. See how it's got that little inlet beneath it?

00:25:58.440 That's kind of showing you like the density of the calcified mineral that makes up the strong part

00:26:04.920 of the bone. Osteopenia and osteoporosis just exist on a continuum relative to healthy bone.

00:26:10.020 Now this is going to get a little complicated and I'll explain it in the amount of rigor that's

00:26:13.880 necessary in a moment, but let's just start with the concept. When you go from healthy bone to

00:26:18.420 osteopenia, that represents about a 10% reduction in bone mineral density relative to a young,

00:26:25.940 healthy adult. And then osteoporosis is a further degradation where you hit about 25% reduction.

00:26:33.480 Now there are two things that I have to add to this to make it sort of rigorous. The first is

00:26:39.880 the diagnosis of osteopenia and osteoporosis is based on two locations, technically three,

00:26:46.280 but two of them are symmetric. The hips and the lumbar spine. So for anybody who's gone and had

00:26:51.840 a DEXA scan before, you may notice that they report the Z score and T score, which I'll explain

00:26:59.560 in a second, of the lumbar spine, of the left hip, the right hip, and usually of the entire body.

00:27:05.300 And the reason for that is we use left hip, right hip, lumbar spine, L1 to L5 to make this diagnosis.

00:27:12.920 Those are the areas we look at. I assume the reason for that is that's where the fractures are.

00:27:20.660 We see people that have atraumatic fractures, compression fractures in the lumbar spine.

00:27:24.940 As you're going to see in a moment, the majority of fractures in older people are in the hip. And as

00:27:31.300 I just shared a moment ago, the mortality for those fractures is very high. So that's where the diagnosis

00:27:37.760 is made. So again, osteopenia, 10% reduction in BMD, osteoporosis, 25% reduction in BMD.

00:27:45.300 And again, these are made to healthy individuals. Healthy bone to osteopenia to osteoporosis,

00:27:50.900 it's just a continuum. But osteoporosis and osteopenia are distinct in the degrees to which

00:27:56.660 BMD has been reduced.

00:27:58.000 And Peter, you mentioned DEXA there a little bit ago, and anyone who's listening to this podcast

00:28:02.960 will be familiar with the DEXA scan because we talk about it a lot and looking at fat and the

00:28:10.540 benefits that you can get from that. Is that the best way for listeners to figure out what their BMD

00:28:17.840 is? Is that how you're doing it in patients?

00:28:19.380 Yes. So DEXA is a super, super low radiation scan, nothing like a CT scan. It takes 10 minutes,

00:28:28.860 you lay on a table, a little scanner moves over your body, and it's using two very low-dose x-rays

00:28:35.880 that are absorbed differentially by bones and soft tissues. So it's able to differentiate between

00:28:41.200 adipose tissue, bone, and lean tissue or non-adipose tissue. I will say this, not all DEXA scanners are

00:28:49.140 created equal. So if you want to know your bone health, make sure before you go and get the DEXA

00:28:56.560 scan, you confirm with the entity doing this that they are giving you segmental bone analysis

00:29:02.920 for left hip, right hip, lumbar spine. A lot of DEXA places can only give you whole body BMD.

00:29:11.060 So they'll just spit out the Z score for that one metric, but they won't give it to you segmentally.

00:29:15.980 And that's sometimes okay. Like if a person's BMD is very high, you don't need the segmental

00:29:21.140 analysis. But if you're doing this to screen for BMD, you have to make sure, of course, that the

00:29:26.000 DEXA is capable of doing that. And just a reminder for people, we talked about this in another episode,

00:29:31.420 but we were always surprised at how easy it is to get a DEXA scan, right? You don't need a doctor to

00:29:36.220 do it. So if you just Google the city you're in and then DEXA, you should be able to find different

00:29:42.060 providers that do it for relatively cheap. I think in most cities, it's around $100, $150. So

00:29:47.920 it has a lot of benefits and just maybe remind people again, if they are calling different places,

00:29:53.980 what are the three things they want to look for? You want to make sure when you're doing a DEXA,

00:29:57.820 again, if you care about knowing the full BMD, you're going to pay more for that segmental analysis.

00:30:03.500 So when you talk about those scans that are like in the 100, 125, even up to 150, a lot of times

00:30:09.400 they aren't showing everything. They're just giving you body composition and usually visceral fat. Now

00:30:14.940 you'll say up to $400 typically if you want to see everything. But again, you're going to pay more

00:30:20.700 in New York and San Francisco than you're going to pay in Austin, Texas, for example. I probably pay

00:30:24.940 like 125 for mine, but I'm not getting the full BMD analysis because I've already had it done and my

00:30:32.020 BMD is high. So I don't need to screen that frequently, not at the rate that I screen everything.

00:30:36.420 The other things you want to look at, you obviously want to make sure you're getting full

00:30:39.340 segmental lean tissue analysis. So you can look at appendicular lean mass index that you can

00:30:43.680 calculate for yourself. Obviously fat-free mass index, you can calculate for yourself. Fat mass

00:30:47.420 index, you can calculate. You need them to be able to give you that. Those are kind of the things I

00:30:51.400 want to see along with BMD. Let's say you and a friend are going and getting your BMD done

00:30:56.580 through a DEXA scan. Is there going to be variability that exists in bone density between different

00:31:02.680 people? Let's say even if someone didn't have osteopenia or osteoporosis, can there just be

00:31:08.360 natural variability between different types of people? Yeah. And it's also important to understand

00:31:13.200 the number you're going to get. They don't, at least to my knowledge, I don't recall seeing them

00:31:19.760 typically report in grams per centimeter cubed, your BMD, because what would you do with that

00:31:24.960 information? It's not that helpful. What you really need to know is statistically, where do you

00:31:31.640 rank? And this is done via a T score and a Z score. And this is done to compare you to a young,

00:31:41.980 healthy adult and to an adult that is your age. So if you go back to statistics 101, I think many people

00:31:50.300 may recall the idea of a normal distribution, which is a bell curve function. A Z score is basically

00:31:57.920 telling you where you lie on that distribution. So a Z score of zero means you are right in the middle

00:32:06.360 of the distribution. And if you're in the middle of that distribution, it means you have a higher bone

00:32:12.580 mineral density than 50% of people and a lower bone density than 50% of people. If your Z score is

00:32:20.160 plus one, it means you are one standard deviation above the mean, which means you have a higher

00:32:28.120 bone density than 82.5% of the population and a lower bone density than 17 and a half percent of

00:32:37.280 the population. If your Z score is plus 0.2, it means you are two standard deviations above the mean.

00:32:45.200 You're higher than 97.5% of the population. Of course, this works in reverse. A Z score,

00:32:50.160 of minus two means you have a lower bone density than 97.5% of the population. So that's what Z 0.90

00:33:01.400 scores do. I'm sorry, I may have misspoke. The Z score is comparing you to your age when I say the

00:33:06.660 population. The T score is comparing you to the young, healthy individual. So in other words, for

00:33:13.820 someone who's older, the Z score is always going to be more favorable than the T score. Does that make

00:33:18.960 sense? If you're 60, you want to compare yourself to not only a 30 year old, but also other 60 year

00:33:24.860 olds. That's correct. When you look at for yourself and even with your patients, their scores,

00:33:29.980 is it kind of like how you do VO2 max, where you always want to be in the elite of the elite

00:33:36.820 categories? You know, VO2 max, you want to be elite and a decade younger. For BMD, if someone is at that

00:33:43.920 zero, that 50th percentile, does that worry you or is it a little different in how you look at this?

00:33:49.480 Other things factor into this, Nick. Family history factors into it. History of smoking factors into

00:33:55.420 this. Current lifestyle, I hate the word lifestyle, but I think you know what I mean. How active is that

00:33:59.920 person? How much weight bearing activity are they doing? Being male versus female also factors into it a 0.99

00:34:06.320 lot. If I see a woman prior to menopause, let's say I got a 42 year old female patient who's, I might 1.00

00:34:14.860 guess, three to five years out from menopause and she already has a low Z score, that worries me a lot

00:34:21.520 because of what we'll talk about shortly vis-a-vis the effect of estrogen here and why women are 1.00

00:34:27.220 disproportionately affected by estrogen withdrawal. You've heard me make this glib, stupid joke, 0.99

00:34:33.240 right? Never in the history of civilization has a 90-year-old person ever been heard uttering, 1.00

00:34:41.540 I wish I was less strong. I wish I had less muscle. I wish my bone density wasn't so high,

00:34:48.240 right? Impossible. You know how Tim Ferriss always asks people on the podcast,

00:34:52.580 what would they put on a billboard? We've come to the conclusion of what you would 100% put on your

00:34:57.160 billboard. That's right. The Peter Atiyah billboard would just say, find me one example in the history of

00:35:03.000 our species where a 90 year old said, I wish I had less strength. I wish I had less muscle.

00:35:09.420 I wish I had weaker bones. So Nick, before we leave this point, let's just pull up figure five

00:35:15.140 and show some of the sex differences and race differences. Yep. Got it pulled up. Okay. So you

00:35:22.200 can see on this graph, we're looking at males versus females top to bottom. And then we're looking at

00:35:27.260 Mexican-American, non-Hispanic white, non-Hispanic black. So three races, two sexes, six lines. 0.91

00:35:35.320 But I just want to make one thing to the listener a little bit clear, which is on the y-axis here,

00:35:40.600 you're seeing units of grams per centimeter squared. Earlier, I said grams per centimeter cubed. Why

00:35:45.480 the difference? Well, the difference is even though density in real life is measured in grams per

00:35:50.780 centimeter cubed, because you need mass per unit volume, with bone density, it's actually done

00:35:55.880 as grams per centimeter squared, because it's a planar measurement. So the DEXA scan is compressing

00:36:01.920 everything to 2D. Does it make sense? Because the scanner is kind of looking at the area of the bone

00:36:08.560 and imputing the density by what electron beam doesn't go through it. I've always found this a

00:36:14.520 bit confusing, personally. I've always wondered why they just can't do this in grams per centimeter

00:36:18.300 cube, but I'll just point that out for the astute observer. Okay. There are two observations that

00:36:23.580 one would pretty quickly take away from this. The first is that up until the 20s, men and women are

00:36:32.820 kind of similar. You go through a profound increase in BMD from the time you're eight years old until

00:36:38.520 you're about 20 years old. Difference one is that while women maintain a reasonable plateau, 1.00

00:36:44.700 they tend to fall quite precipitously in midlife. And that's obviously due to menopause. We'll talk

00:36:51.320 about why in a moment. I think the second thing that jumps out here is the racial difference.

00:36:56.920 So non-Hispanic black has a higher BMD for both men and women than non-Hispanic white, which has a 0.63

00:37:04.260 higher BMD than Mexican or Hispanic, in this case, Mexican American. So again, slight differences in

00:37:10.780 race. Truthfully, I don't know why that is, but it is what it is. So to your earlier question,

00:37:18.000 are there differences? Yeah, there are differences on average. I've never, to be honest with you,

00:37:24.960 factored this into my risk assessment, except for the male female one. So in other words,

00:37:29.720 if I look at a patient who's black versus white versus Hispanic, I kind of have never assumed one

00:37:35.340 is at more or less risk. I've just said, let's do the kitchen sink on everybody. But I think in females, 1.00

00:37:40.660 I'm more worried for the reasons that we're obviously talking about.

00:37:43.880 And in looking at this too, and one of the questions we received is when should people do

00:37:49.680 their first bone mineral density scan? You know, when do you want to know that baseline? Because

00:37:54.900 what's interesting when you look at this and you talked about it is, you know, from eight to about

00:37:59.220 20, 22, you see that huge jump and then it kind of levels off. So what was your recommendation be

00:38:07.100 for when people should get their first one done?

00:38:09.560 Going to get into a lot of hot water here, Nick, but I'm used to it, right? I've got very

00:38:13.720 unusual recommendations for a lot of things, and this is no different. So I think in the spirit of

00:38:19.100 fairness, I'm going to communicate the standard recommendations first. When you look at the

00:38:24.300 American Association of Family Physicians, the American College of Obstetricians and Gynecologists,

00:38:29.700 the American College of Preventative Medicine, the International Society of Clinical Densiometry,

00:38:34.560 the National Osteoporosis Foundation, and more, the typical recommendation is for high-risk people

00:38:42.940 to be 50, but typically 65 is when they want to start screening people. And that's for women. 0.98

00:38:51.300 And for men, it's typically 70.

00:38:53.160 It's a lot of credentials you just laid out there. Are you sure you want to get in hot water with

00:38:56.920 all of those different people?

00:38:58.440 No, I'm just simply stating what they're recommending. And if I've misrepresented that,

00:39:02.500 feel free to correct us. But it's typically recommended, as I said, women at 65, men at 70,

00:39:08.200 follow-up scans no more than every two years. Now, for someone who is at serious risk of osteoporosis,

00:39:15.260 which includes men and women over the age of 50, we can adjust those and come down a little bit.

00:39:21.180 Now, the WHO, I think, is a little bit more aggressive and recommends screening women by the

00:39:27.540 age of 40, if I'm not mistaken. As you can guess, I tend to be closer in my thinking to the WHO.

00:39:34.960 And I certainly believe women in their 30s, where we're doing DEXA scans for many reasons,

00:39:41.500 I'm just as interested in their bone mineral density. In fact, when I'm reporting the DEXA results

00:39:45.920 to patients, we have a template that we've made that I really like that lays all of the DEXA information

00:39:52.040 out. Segmental BMD, VAT, FFMI, ALMI, FMI, all of these things, body fat for what it's worth. I

00:40:00.200 always tell them out of the gate, like, the one number you care about is your body fat. That's

00:40:04.320 the one I care least about. When we're looking at a 35-year-old patient and their Z-score is already

00:40:11.020 minus one, that's just as concerning to me as if their OGTT shows very elevated postprandial

00:40:18.620 glucose and insulin levels. And I'm really happy that I'm seeing that at the age of 35 and not 65.

00:40:24.720 I think a natural follow-up there is, because one of the questions we got from a subscriber was,

00:40:29.340 how does bone mineral density change throughout the life of men and women? And we kind of saw it

00:40:35.240 a little bit there, but is there anything you want to double-click on or dive deeper on as it relates

00:40:39.560 to that? This is an area where men and women do differ quite a bit. So you've got most of the

00:40:44.820 growth in the length of a bone and the size of the bone is happening during childhood and

00:40:49.100 adolescence. And that's also when you're really accumulating the bulk of this, the BMD. So if you

00:40:53.780 remember the graph we showed a moment ago, figure five, we don't have to pull it up again, but

00:40:57.820 remember how I said between about the ages of like eight and 20, BMD was doubling. So that doesn't

00:41:03.800 just mean that the size of the bones are increasing, which of course it is. As you go from being eight

00:41:07.920 years old to 20-year-old, you're getting taller, your bones are getting bigger. But that graph was

00:41:11.620 showing you BMD. So that means the density of those bones is also increasing dramatically. So BMD will

00:41:19.200 actually potentially improve up to about the age of 30, but it really peaks in the early 20s. It can

00:41:25.900 stay quite flat, certainly in both sexes, till you're about 40 or 50. And then bone loss effectively

00:41:33.560 sinks in. But for women, it is much more pronounced. So for women, about seven to 10 years

00:41:41.040 around the onset of menopause, bone loss can be three to 7% annually. By the time they reach 65,

00:41:48.760 it starts to slow down a bit. So it might be, you know, half a percent to 2% per year. Whereas in

00:41:53.440 men over 65, it's actually a higher rate of bone loss, but they're starting at a much higher point

00:41:58.500 because they didn't suffer that precipitous loss the way women did after menopause. So for men at the 0.72

00:42:03.340 age of 65, it's usually more typically about one to 2% per year. So pull up figure six. When I came across

00:42:09.980 this figure, one of our analysts pulled this up, I was really surprised. So this is for women. 1.00

00:42:17.260 This is showing bone mass by age. Again, two things really stand out to me. We've already discussed one,

00:42:22.980 which is you have this pretty significant rise in bone density between birth and age 20. It then

00:42:30.660 remains relatively plateaued. In this case, menopause kicks in around 50, and then you really start to see

00:42:36.780 the fall. That's the first thing that stands out. And we've talked about that. But look at the other

00:42:41.560 thing, Nick. Look at the dotted line. The dotted line tells you that there's really a totally separate

00:42:48.540 trajectory for this woman, which is if she didn't reach her full genetic potential by the age of 20, 0.99

00:42:56.220 she's missed an enormous opportunity later in life. Remember at the outset, I said,

00:43:01.740 this is a podcast you should care about. Even if you're a parent of a 10-year-old child, this is why

00:43:09.580 you want to make sure that your kid's doing the right things when they're 10 to 20 so that they

00:43:14.840 reach their full genetic potential. Now, the good news is that let's say you're on that dotted line

00:43:21.580 and you're 30 years old. And I see these patients, right? So I see the 30-year-old woman who's got the 1.00

00:43:26.820 Z-score of minus 2, and she's 15 years away from menopause. Well, the good news is we can get her

00:43:34.220 closer to that solid line by working really, really hard. Now, I don't know if we can get her all the

00:43:39.780 way to that line. But we have this window in time before menopause when we can go through all the

00:43:46.180 stuff we're going to talk about later on, minus the pharmacology, and try to ratchet up that bone mass

00:43:51.800 so that you get to the highest point when menopause kicks in. And you see that reduction

00:43:57.780 of estrogen. And of course, we'll talk about the opportunities there as far as estrogen withdrawal.

00:44:01.920 If you go to the next slide, Nick, I want to just talk about one other thing. And it really shows

00:44:06.680 where the bone loss is occurring. So in slide 7 here, you're seeing for both male and female the

00:44:14.480 difference between cortical and trabecular bone. Again, remember, cortical is the long shaft part of

00:44:19.400 the bone, the trabeculi or the end. And you're seeing the decline for men and women in both of

00:44:26.800 these segments. And I guess what stands out here is where females are losing this BMD. They're losing 1.00

00:44:33.880 it primarily in the trabecular or spongy part of the bone. So interestingly, women are no different 1.00

00:44:39.960 than men when it comes to the cortical section of bone, but obviously a significant reduction at the

00:44:45.600 spongy part of the bone. Yeah. I mean, it's super interesting to look at those graphs. And I think

00:44:50.540 you pointed out, no matter what age you are, why you should think about this, because especially

00:44:55.140 with people who have children, I know you and I have kids around that age where you think about,

00:44:59.840 okay, that eight to 20 window and what you can do. Because if you look at that original graph and

00:45:06.100 the full genetic potential where they fell off was still higher than the inadequate line of where

00:45:12.200 they plateaued, which is pretty crazy to see is for people with kids, it's the biggest thing they can

00:45:18.000 do is in that younger age. And you've mentioned this a few different times. And why don't we double

00:45:23.160 click on it here, which is what is it about menopause that creates issues in bone health? Why can it lower

00:45:30.720 bone mineral density? So what do you want to say about that? Yeah. So bone cells are really

00:45:36.180 interesting. They're what we call mechanosensory cells. So they actually can sense forces. So if

00:45:42.560 you think about how muscles act, a muscle by definition has to have attachments to bones,

00:45:49.920 right? That's how the system works. And a muscle's never attached to the same bone because then it

00:45:55.820 wouldn't do anything. Contracting the muscle on the same bone doesn't do anything. So muscles have to

00:46:00.260 go across joints. So your bicep actually crosses a couple of joints. So you have a bicep that is

00:46:07.920 attached to the bones of the lower arm and then attached to the bones of the upper arm. And so

00:46:13.160 then when it contracts, it actually closes that angle of the arm. Okay. So muscles are attached

00:46:20.440 via tendons to bones. And think about like what we do with our muscles. Think about the load we put

00:46:27.500 on those muscles. Well, the very simple laws of physics tell you that the bones have to feel that

00:46:35.040 load. And we often don't think about that. We think about you're doing a curl with 40 pounds. Obviously

00:46:41.400 your bicep muscle is exposed to that. But guess what? The tendon that is attaching the bicep above and

00:46:49.760 below the joint of the elbow is also feeling that. And the bone cells actually sense that load. So if

00:46:58.660 you're lifting something heavy, when you're climbing stairs, your bone senses that they need to support a

00:47:04.380 greater force. And in response to that, it remodels by depositing more and more bone tissue. So bone mass

00:47:13.160 increases in the presence of stress. It turns out that that signaling process is regulated very heavily

00:47:24.660 by estrogen. I think this is just so fascinating. You know, when you think of the importance that

00:47:29.400 estrogen plays in reproduction, I don't have a great answer as to why it's estrogen that is the

00:47:34.320 dominant hormone here, as opposed to another hormone. But for what it's worth, that signal of

00:47:39.840 stress that is basically being relayed by the strain gauge within the bone to say, hey, it's time to

00:47:45.920 deposit more bone here, that's modulated by estrogen. And so in the absence of estrogen, that signal gets

00:47:54.380 reduced. And that's effectively why menopause, which is a sudden withdrawal of estrogen, is such a

00:48:02.320 devastating thing for women who don't have their hormones replaced. And that's why BMD loss is 1.00

00:48:08.780 significant in the postmenopausal woman. Now, to be clear, men are also losing estrogen as they age

00:48:15.560 because for men, estrogen comes primarily from testosterone conversion, right? So testosterone

00:48:21.440 is aromatized into estrogen. A man with a testosterone of 800 nanograms per deciliter, all things equal,

00:48:28.640 is going to have a higher estrogen level than one with 300 nanograms per deciliter. And that's easily

00:48:35.000 could be explained by an aging phenotype to go from 800 to 300. Now, there are other factors that go

00:48:40.140 into that. Adiposity can give you more estrogen, etc. This might be one example, by the way, of where

00:48:46.000 adiposity helps because you have the additional weight and load that is a strain signal and you

00:48:51.160 have more estrogen, all things equal. But men lose estrogen at a far more gradual rate than women.

00:48:56.740 And that's why women experience this loss more significantly. And that's why women are at 0.91

00:49:02.040 greater risk for osteopenia and osteoporosis. One of the questions we received, which I think

00:49:06.780 is a really good follow-up here, is that someone asked, knowing estrogen's role in bone health for

00:49:12.160 postmenopausal women, should bone health be a factor to consider in women who are thinking about 1.00

00:49:18.240 starting HRT? Well, I'm about to get into a whole bunch more trouble. I'll give you the consensus answer.

00:49:24.660 The consensus answer, I believe, is still no. I believe the consensus answer is HRT is not considered

00:49:35.000 standard of care for postmenopausal bone loss. And I'll tell you why that's the case. The reason for

00:49:41.660 that is not because HRT was not found to decrease fracture risk, which, by the way, is the gold standard.

00:49:49.280 That is the single most important metric if you're trying to evaluate if HRT would be beneficial.

00:49:56.440 So the Women's Health Initiative, which was published over 20 years ago, was a seven-year study or so

00:50:02.300 looking at the administration of hormone replacement therapy on postmenopausal women. Worth noting, these

00:50:07.940 women were far outside of menopause. A hundred problems with this study, which we'll be going into, 0.95

00:50:12.560 I already went into, actually, I think, in the podcast with Avram Blooming and Carol Tavaris. So people who

00:50:17.360 want to get a better sense of HRT really need to go back to listen to that episode. I think we have

00:50:22.680 an upcoming episode where we'll go into this in more detail. But in that study, there was no

00:50:27.000 ambiguity that the fracture risk was decreased in the women taking HRT. However, that study came to

00:50:35.440 what I believe is an erroneous conclusion, and I think what many people now believe is an erroneous

00:50:39.160 conclusion, that the risk of breast cancer and cardiovascular disease went up. And those risks

00:50:44.580 seem to outweigh the benefits of the reduced fracture risk. I think that the increase in the

00:50:49.720 risk of breast cancer was virtually non-existent. It had an absolute risk increase of 0.1%.

00:50:55.720 I think there are lots of reasons we discuss in that podcast as to why that's the case and why that

00:51:00.780 today we can say with much more clarity that the risk of breast cancer from hormone replacement therapy

00:51:06.320 is virtually non-existent. Secondly, the risk of cardiovascular disease has been completely

00:51:12.320 ameliorated by the adoption of topical forms of estradiol as opposed to oral forms of estradiol.

00:51:19.480 So in that trial, they used oral estrogen, which actually does slightly increase the viscosity of

00:51:25.220 blood. In a susceptible woman, that would indeed increase the risk of cardiovascular disease. 1.00

00:51:29.740 But again, we don't use oral estrogen anymore. And so that also becomes a moot point. And I think

00:51:35.680 today we actually know that hormone replacement therapy reduces the risk of cardiovascular disease

00:51:40.780 in women and does not increase it. So again, taken all together, these suggest to me that bone

00:51:48.320 health should in fact be a consideration for women as they consider whether or not HRT makes sense for 0.97

00:51:56.460 them. So Peter, another follow-up is earlier you mentioned that there might be some risk factors

00:52:01.660 for why someone might get screened for bone health earlier. What should people be aware of if they're

00:52:07.260 thinking about if they're maybe at risk and what are some of those red flags they should look out for?

00:52:12.640 You know, it sounds cliche, but family history matters. Actually not something I appreciated

00:52:16.580 until we were getting ready to do this podcast. I didn't realize genetics accounted for up to 50%

00:52:21.220 of bone health. Having either parent that's had a history of a hip fracture, that's a huge red flag.

00:52:27.120 There are other things we want to care about, right? So we want to look at fractures related to

00:52:31.280 mild or moderate trauma. So you look at somebody who's had a fall from standing height or less,

00:52:36.280 someone who's fallen from such a low height and still had a fracture, that's a huge problem.

00:52:41.940 Another thing we look at is in female athletes. And this is really common actually in female 1.00

00:52:46.840 endurance athletes, especially runners, where weight is such an important part of the sport.

00:52:52.720 You're punished a lot in terms of performance for extra weight. Same is true in cycling, not as true

00:52:58.660 in swimming. So when you look at high-end female endurance athletes, we care a lot about poor 1.00

00:53:05.300 nutritional state, which can lead to a very low BMI, low body fat percent, and eventually estrogen

00:53:10.520 deficiency. So these interrelated conditions of the low bone health, hormone dysfunction,

00:53:17.020 and low BMI are collectively known as the female athlete triad. So that's another big risk factor. 0.98

00:53:22.180 Low BMI in general, so anything below about 18 or 19. The other thing we look at is people who have had

00:53:28.680 high exposure to drugs that affect bone metabolism. And I think the most common of these that we see

00:53:33.900 is corticosteroids. Now, that's not always systemic corticosteroids, not always people that have had

00:53:39.740 to take lots of steroids for an illness. It can also be inhaled corticosteroids. And we see this

00:53:43.760 actually in a number of patients who had significant asthma as children and used a lot of inhaled

00:53:49.300 corticosteroids. That's not an exhaustive list, but that's a pretty good list to get you thinking

00:53:54.460 about who is at high risk here. You mentioned it a little bit at the end there, and we did receive a lot

00:53:58.880 of questions on it, which are around the various drugs that may impair bone deposition. So anything

00:54:05.820 more you want to say? I know you mentioned a few of them there, but anything you want to double click on?

00:54:09.980 I think the last big risk factor we look for, and we just saw a patient recently who didn't have any

00:54:15.940 other risk factors except for the fact that they have a 20-pack year smoke history that is more than 15

00:54:22.060 years old. So you barely think of this person as a former smoker because they've been so long

00:54:26.220 without smoking, but they did smoke for 20 years prior to quitting. And that is an independent

00:54:31.980 risk factor for low BMD, which in this case, this patient had very low BMD. We had to refer them to

00:54:37.940 an endocrinologist. We know that BMD, the 8 to 20 is such a big age range. And if you have someone

00:54:46.460 who is smoking in that age range while bone mineral density is really going up, do you see it become

00:54:51.460 even worse? That's a great question, Nick. I didn't know this until, again, we got thinking

00:54:56.300 about this study. There are actually data looking at never smokers, early smokers, and late smokers.

00:55:02.800 Early smokers were defined as people who started smoking before the age of 16. And late smokers,

00:55:09.240 well, it's hard to believe late is considered after 16, but the early smokers were far more impacted.

00:55:15.740 So when you look at these people later in life, the never smokers, not surprisingly, had the best

00:55:21.180 bone density. The early smokers had the worst and the late smokers were in the middle. I don't know

00:55:27.700 the stats about teenage smoking today. I kind of assumed it was on the decline, but this would

00:55:33.980 certainly be yet another reason to avoid smoking at a young age, even if that person goes on to stop at

00:55:41.340 the age of 20. And even if their risk of lung cancer becomes relatively moot by the time they're

00:55:47.680 50, they may still pay a price for that with bone mineral density throughout their entire life.

00:55:53.240 We also did receive a lot of questions around various drugs that could impair bone deposition.

00:55:58.200 You mentioned a few of them earlier, but is there anything you want to double click on there?

00:56:02.080 So again, corticosteroids, I think, have to be considered the first and most important one of

00:56:06.460 these drugs you want to be considered about. They do a couple of things. They impair the

00:56:10.440 mineralization of bone by favoring bone reabsorption during the early phase, and then they kind of

00:56:15.880 inhibit calcium absorption in the gut. This area comes up over and over again. Anything that impairs

00:56:22.180 calcium absorption is going to be problematic, and it really doesn't need to be mega doses of

00:56:27.700 steroids. People who are familiar with long-term use of steroids might recognize that a dose of

00:56:32.140 prednisone of five milligrams a day is not enormous. Prednisone dose of five milligrams a day is,

00:56:37.380 I think, I think it's actually still a big dose because it's about the physiologic equivalent of

00:56:41.280 how much hydrocortisol a person makes. But nevertheless, that amount is associated with

00:56:46.660 significant reductions in bone mineral density and an increased wrist fracture within as little as

00:56:51.520 three to six months of initiation. Again, just as we saw in the figure that showed how women are 0.99

00:56:58.840 primarily losing trabecular bone, it's the same here with cortisol. That doesn't mean you should never

00:57:05.700 take corticosteroids. There are lots of conditions where corticosteroids are going to save your life.

00:57:10.500 It means you have to be aware of these things, and you're going to have to work a lot harder to

00:57:14.420 counter their effects. And we'll talk about some of those things. Another class of drugs that I get

00:57:18.900 asked about a lot is proton pump inhibitors, PPIs. And I would say the data here are less clear. So there

00:57:27.080 are studies that have assessed the relationship between PPIs, and they do show an increase in osteoporotic

00:57:33.660 fracture. The most likely mechanism suggested is, again, intestinal calcium absorption. So anything

00:57:41.340 that interrupts that, which then goes on to interrupt osteoclast formation and bone remodeling.

00:57:47.400 But I want to be clear that this is not nearly as well understood as the case is for corticosteroids.

00:57:53.680 There are a number of observational studies that show an increase in the risk of fracture. Then we look

00:57:58.520 at large meta-analyses that don't find a statistically significant decline in BMD with PPI use. I think you

00:58:05.500 just have to be smart about this. There are lots of reasons we're going to put patients on PPIs. If a

00:58:11.200 patient has significant reflux that is not amenable to other treatments, we're going to put them on a

00:58:16.980 PPI. If a patient has Barrett's esophagus, we're putting them on a PPI. It's non-negotiable. So it just

00:58:22.540 means that we have to be thoughtful about, is the drug really indicated? And if it is, what else can

00:58:28.480 we do to reduce the risk down the line? I think the final class of drugs that tend to have a similar

00:58:34.600 association, although probably from a different mechanism, are some of the anti-epileptic drugs,

00:58:40.020 and one in particular, which is phenytoin, so a super common anti-seizure drug. Here, I think the

00:58:46.080 mechanism might have more to do with liver-inducing an enzyme called cytochrome P450 that leads to

00:58:54.500 increased catabolism of vitamin D. And that, of course, you may recall, will lead to decreased

00:59:01.520 absorption of calcium in the gut. I don't know if anybody's done a study, but it seems to me that a

00:59:06.840 no-brainer study would be taking patients on phenytoin and supplementing them with lots of vitamin D

00:59:11.900 to see if you can overcome that. But again, phenytoin is a common drug within the world of

00:59:17.300 anti-seizure meds, but in the big picture, nowhere near as common as corticosteroids and proton pump

00:59:22.040 inhibitors. I think where we're going to go next is starting to look at what people can do to improve

00:59:28.380 their bone health. I think we made a lot of the groundwork that we need to do, and this next section

00:59:32.820 we'll get into everything people can do to improve it individually. But before we get to how you,

00:59:39.080 the person can do it, we did have some questions from subscribers who said they have kids and they

00:59:43.960 want to improve their bone health, and we've talked about how important it is. So before we

00:59:48.600 get to the individual, is there anything in particular, any advice you would have for people

00:59:53.680 who have kids on those very important ages, you know, the 8 to 20, on what they can do so they can

01:00:00.020 really optimize the bone health? I think this is very important. When I stop to think about all of the

01:00:05.480 things that parents got on their plate to try to help their kids with during this relatively narrow

01:00:11.280 window that your kids are in your house and therefore somewhat amenable to your influence,

01:00:16.640 the most important thing probably comes down to being adequately nourished and being very active,

01:00:23.400 and in particular, being very active in things that load bones. One of the things that was a bit

01:00:29.640 surprising to me was that running didn't have a greater impact on BMD. So in a moment, we'll pull

01:00:39.040 up that figure, Nick, that I think is pretty interesting that shows all of the different

01:00:42.440 sports and how they impact BMD. Now, I'm going to posit that the running one has a confounder in

01:00:51.280 there. Because if you think about it, running puts a lot of force on muscles, especially when you think

01:00:56.580 about the hips, which are two of the three bones that are attached to muscles that experience great

01:01:03.200 force during running. So why is it that running, where you're potentially, at least at the knees,

01:01:08.740 experiencing eight times your body weight with each impact, why wouldn't that do more? And I've been

01:01:14.600 thinking about this for some time, and maybe somebody knows the answer, but my suspicion is that the

01:01:19.780 confounder here is body weight and BMI. And that when you talk about elite runners, and usually these are

01:01:26.540 studied in elite runners, they're very weight conscious. Running and cycling are the ultimate

01:01:31.820 strength to weight ratio sports. And I do wonder if we're seeing basically malnourished runners.

01:01:40.820 And what do I mean by that? Basically, people that are, BMI is too low, might be perfect for being a 0.96

01:01:46.640 runner, but it's too low for optimizing bone mineral density. I guess this is a long-winded way of

01:01:52.540 saying running might not be enough. Obviously, running is a great thing to do, and it comes with

01:01:57.540 a lot of benefit, but you probably want to make sure that your kids, both boys and girls, are doing

01:02:04.440 other sports that involve more power. So probably things that involve jumping and actually lifting

01:02:11.860 heavy things. That's kind of a great plug for rucking. I mentioned Michael Easter briefly at the

01:02:18.060 outset. I mean, one of the things that Michael writes about in his book, The Comfort Crisis,

01:02:21.540 is the importance of just walking with heavy stuff. Either doing a farmer's carry, doing a

01:02:27.980 ruck, which I love. I try to ruck five days a week, backpack with heavy weight in it, and just walking

01:02:33.400 around and always trying to find a hill to walk up and down, kind of loading myself without the knee

01:02:39.460 joints being susceptible to that. Going back to the kids, I think we just want to make sure BMI is not 0.99

01:02:45.640 too low. Hormone dysfunction is not there. Energy availability is there. Body fat's not too low.

01:02:51.980 All of those things that tend to occur. Obviously, smoking. We obviously want to make sure nobody's

01:02:57.320 smoking, but as we just talked about, kids beneath the age of 16 are uniquely susceptible to this.

01:03:03.740 So again, it's pretty straightforward. Lots of nutrition, lots of physical activity,

01:03:07.840 and specifically physical activity that builds muscular strength, because I think that's going

01:03:12.800 to apply the greatest force to the bone. And the bones, as we talked about, are mechanical sensory

01:03:19.560 entities that are going to remodel in proportion to how much mechanical stress they're under.

01:03:26.540 So lifting heavy stuff matters. And that doesn't mean that 12-year-olds need to be deadlifting three

01:03:32.180 times their body weight. But we also don't want to shy away from kids lifting things.

01:03:36.200 When you were talking there about the running, I don't think it came up on the Ryan Hall podcast,

01:03:41.460 but it would have been really fascinating if he ever had a DEXA scan when he was in peak running

01:03:46.220 shape compared to his current body type, just with all the muscle he put on, just to see the difference

01:03:52.400 in his BMD. You know, that's such a good question. I'm going to email Ryan as soon as we're done and ask

01:03:57.780 him, because you got to think at his level, being one of the best runners in the world, that they had

01:04:03.280 a DEXA scan of him at the time. And yeah, I'd love to know what his BMD was when he was 28 versus

01:04:09.820 what it is today.

01:04:11.340 The next set of questions fit perfectly with where we're going, which is a lot of questions on what

01:04:16.580 does physical activity have to do with bone health? You kind of hinted at it. We got a lot

01:04:20.280 of questions on, are there certain types of physical activities that is better for bone health than not?

01:04:25.960 We talked a little bit about it just now with kids, but as people who are adults are also

01:04:30.360 thinking about this, what would you say to them? Well, again, I just want to go back to what it is

01:04:35.480 about muscles that have such an impact on bones. This is not always clear. The more force that a

01:04:44.200 muscle is applying to a bone, which is directly related to how much force you're trying to put

01:04:50.900 on the muscle, picking something up, contracting a muscle under an enormous external load. And by the

01:04:57.500 way, I think that can be isometric. I don't think that has to be isotonic. In other words,

01:05:00.340 I don't even think the muscle has to change in length necessarily for that force to be experienced.

01:05:05.060 So there are lots of safe ways to do this. You're applying force to the receptors there. Those

01:05:09.700 receptors are translating that tension into signals that say lay down more bone. Okay. So we look

01:05:17.140 through some of the literature on this and I got to tell you, this is one of those things where I

01:05:20.340 was kind of surprised. I saw some things that I just didn't expect to see. I already mentioned one

01:05:24.740 of them, right? I kind of thought running was going to be really great. It turned out that studies

01:05:29.100 looking at resistance training found them to be significantly better at retaining BMD when

01:05:34.660 compared to anything aerobic, running, swimming, cycling, and even impact things like pure jumping.

01:05:40.860 So power lifting turned out to be more effective than just regular strength training in maintaining

01:05:46.520 BMD in post-menopausal women. So think about that for a second. When we talk about power lifting as a 0.89

01:05:52.080 sport, we're talking about, and I've seen women do this at all ages, we're talking about someone doing a 0.99

01:05:57.000 squat, a deadlift, and a bench press. And the squat and the deadlift, that is lumbar spine,

01:06:03.140 that is hip. I mean, that is really stressing the lower body more than just going into the gym and

01:06:07.720 lifting. And then we talk about high force impact sports such as football and MMA were associated with

01:06:12.820 the highest BMD values. I know you do MMA, at least vis-a-vis jiu-jitsu. So you can probably speak

01:06:19.060 to this more about why it's exhausting. You know, I was having dinner with Joe Rogan the other day,

01:06:24.180 and we actually talked about this. It's such a big part of his life and I know nothing about it.

01:06:27.660 He made a comment that nothing exhausts him more than his jiu-jitsu workouts. Joe does so many things.

01:06:33.800 I was kind of surprised that he said that that is the single most exhausting thing he does. But I'm

01:06:39.520 guessing you can relate to this? There is nothing more tiring than that, especially on hard rolls.

01:06:44.960 I mean, I don't know the physiology behind it, but you just have to go so hard. Your muscles are

01:06:51.040 pushing, pulling, like your mind is also going, so it's not like you can zone out. But there'll be

01:06:57.080 days where you have really, really hard rolls and you just finish and you just lay there in a heap

01:07:01.600 of sweat for about five minutes before you can do it. I do get questions, people who know you and know

01:07:06.960 me, they're always like, I'm surprised Peter doesn't do jiu-jitsu because it seems like something

01:07:11.460 you would love. I think if it wasn't for the injury aspect of it, because that was a huge concern,

01:07:17.020 it's not really the most longevity friendly activity you can do. A younger you would have 0.96

01:07:22.940 been a killer out there. You would have loved it. I just can't count the number of friends I have 0.99

01:07:27.460 that are so obsessed with jiu-jitsu. Even in high school, one of my closest friends who was a really

01:07:33.560 good wrestler when I was a boxer, he was the first person I ever knew who did this. This was back when

01:07:38.660 you were just starting to hear about the Gracie's. Now we're talking early nineties. That was at least

01:07:44.020 that was the first time I ever heard of the Gracie brothers from him. You know, there's probably

01:07:47.180 like two jiu-jitsu gyms in Toronto and he used to train in this stuff. But yeah, I've had so many

01:07:52.660 friends that have done this and it looks incredible, but it doesn't appeal to me in any way, shape or

01:07:56.500 form. On the flip side of that, these low weight bearing, low impact things like walking, swimming,

01:08:01.940 cycling don't really seem to do a lot to improve BMD. And again, I don't know if the study hasn't been

01:08:09.840 done, but my suspicion is that when you make those things a little bit harder, especially with

01:08:15.260 walking with a rucksack and walking uphill, you're going to apply more strain. Also walking downhill.

01:08:21.480 So again, when I'm rucking, I'm always trying to find the maximum elevation change. Walking uphill

01:08:26.800 is harder cardio, but the walking downhill puts more strain on the muscle. And again, the take-home

01:08:32.620 point here is the more this strains your muscles, the better this is for your bones.

01:08:36.740 I'm going to pull up that figure as well that you mentioned earlier, which puts metrics and colors

01:08:43.100 and graphs for people to see this too. Yeah, this is an interesting figure. On the left here,

01:08:48.080 you're just looking at the absolute BMDs. You may also recall just where these units sit.

01:08:54.340 All of these athletes have very high BMDs compared to what we were looking at as the average man and

01:09:01.740 the average woman. We don't have to flip back to that, but I just, I'm familiar with the numbers. 0.60

01:09:04.720 1.2 grams per centimeter squared was considered a really good BMD for a middle-aged man or woman.

01:09:13.420 Do you remember how we've seen that number 1.2 is pretty common? Okay. So when you're looking at

01:09:18.000 this, just to put in perspective, even the swimmers or the resistance training females,

01:09:25.120 and females are tend to going to be a little bit lower than men, they still have excellent BMD. 0.53

01:09:29.560 So I do not want to be suggesting that some sports are bad for BMD. That's not the take-home

01:09:35.360 message here. The take-home message here is if you really have to juice it, what do you want to be

01:09:40.620 doing? Again, even the distance runners here, look at which ones separate men versus women, right? So 0.97

01:09:46.380 for example, red versus green is showing you the difference between male and female resistance

01:09:51.720 training. Whereas all the swimmers, all the distance runners, all the track and field athletes are in the

01:09:56.540 same bucket. Now, again, compare distance to track and field. What's the difference? Track and field,

01:10:00.940 more power. A sprinter has more force being applied than a distance runner. What I find amazing is the

01:10:06.580 MMA and the football. I mean, just staggering. Now, I'm going to say something else that's kind of

01:10:11.480 unpopular. Not really sure playing college football is a great strategy for increasing your BMD when it

01:10:17.580 comes with so many other injuries, not to mention all the head trauma. So the purpose of this analysis

01:10:23.700 is not to say, you got to go be a college football player. No, it's to just give you a

01:10:28.160 sense of what types of forces are involved in generating higher BMD. And I think most people

01:10:36.240 who have even watched a football game can appreciate the kind of forces that those athletes are

01:10:41.220 experiencing. And as you talked about with MMA, incredibly strong forces applied across muscles

01:10:47.080 transmitted to bones. Good for the bones, bad for the brain.

01:10:50.760 Right. So what's the sweet spot here? To me, the sweet spot is resistance training. All of these

01:10:57.040 things come with risk if you don't do them correctly. I mean, hell, if you don't swim correctly, you're

01:11:00.520 going to tear your shoulders apart. So we just have to think about this through a risk reward lens.

01:11:05.840 MMA, I don't know anything about it, but I'm guessing it can be done safely. I'm guessing there

01:11:09.440 are ways to do it and not be, you know, not put yourself at risk to tear your meniscus or tear your

01:11:15.260 shoulder or have a lumbar spine disc blow up because you get folded in half like a pretzel.

01:11:20.140 You can hurt yourself resistance training, but also you can not. If you're going to take one

01:11:24.340 thing away from this, just notice that walking isn't on here and gardening is not on here and

01:11:29.940 golf is not on here. I want people to understand that if they're in the business of trying to

01:11:35.280 increase their BMD, they have to get wicked forces on their muscles.

01:11:40.180 I feel like you didn't have to do golf like that. I feel like out of every...

01:11:43.220 I know. I just, I'm making enemies like I'm just killing myself today here.

01:11:46.940 I know. I feel like that has a potential to be the most thing that we get feedback for.

01:11:51.440 You can insult the different organizations, but once you talk about golf like that,

01:11:55.500 there's no coming back.

01:11:56.520 And I'm not saying don't play golf. Look, race car driving is not on here. Okay. Archery is not on

01:12:01.260 here. My favorite things in the world aren't on here. Is that an appropriate mea culpa? The things

01:12:07.620 I love doing are not on here. I just don't want to be deluded into thinking that all that time I'm in a

01:12:12.160 race car, I'm increasing my BMD. It's not enough. I got to be in the gym. I got to be hitting it.

01:12:17.560 So Peter, we talked a little bit about early on the danger of low BMI or extremely low BMI for

01:12:24.220 bone mineral density. And then everything we just talked about on lifting weights,

01:12:28.220 the more muscle you put on, you're potentially going to go up in weight.

01:12:31.440 What about people who are overweight and they lose body weight? Does that have an impact on their BMD?

01:12:39.040 It does. And this is actually super interesting stuff. We know, for example, that when people

01:12:44.920 lose significant amounts of weight, they're usually losing lean tissue as well. It's one of the trade

01:12:49.940 offs. And in some people, it's totally reasonable trade off. You see somebody who's already got an

01:12:55.500 appendicular lean mass index at the 90th percentile and their fat mass index is at the 99th percentile.

01:13:03.180 You're going to have them lift like crazy during weight loss because you want to keep that lean

01:13:08.180 mass up. Maybe it falls to 70th or 80th percentile while you try to get fat mass index down to 60th

01:13:13.400 or 70th percentile. So what about the impact on BMD? Well, there's no question that the correlation

01:13:19.920 between weight loss and a decrease in BMD, exactly what we don't want to see in the obese, in particular

01:13:25.760 in the elderly, is very strong. But it turns out that there are two different strategies for how

01:13:31.620 you can go about losing weight. And the strategy may impact the outcome. We know that anytime you

01:13:39.560 lose weight, there has to be a caloric deficit. You can't lose weight without a change in stored

01:13:45.980 energy. Losing weight is changing stored energy. Stored energy requires caloric imbalance.

01:13:51.140 But when you look at data for people who have lost weight purely through nutritional manipulations,

01:13:59.800 i.e. purely through manners of reducing caloric intake, and you can do this a lot of ways, right?

01:14:05.920 You can just directly and generally reduce calories. You can do it through time-restricted

01:14:09.700 feeding. You can do it through dietary restriction, meaning restricting various elements within the

01:14:13.200 diet. Those people tend to lose bone mineral density. When you look at people who are doing it

01:14:19.800 in combination with significant exercise, they actually tend to gain bone mineral density.

01:14:27.020 In other words, you can have people losing the same amount of weight. Some of them are losing BMD.

01:14:31.600 Some of them are slightly gaining it. What could be going on there? It's been suggested that the BMD

01:14:38.580 reduction due to weight loss may be caused less by the mechanical loading of bones and more by a change

01:14:47.900 in some of the adipose-derived factors like leptin and adiponectin and other hormones that move around

01:14:53.620 when weight loss changes. So leptin goes down, adiponectin goes down. Obviously, we talked about

01:15:00.320 the fact that especially in men when they lose weight, but potentially in women too, we see estrogen

01:15:04.300 going down. So it could be that when you're loading the muscles and therefore transmitting that load to

01:15:11.260 bones, you're offsetting some of that. Now again, the study that I'm citing is relatively small

01:15:16.900 and the group that was using exercise as their primary tool to lose weight didn't lose quite as

01:15:23.000 much weight. So even when that's corrected for, it could be a little bit of a confounder.

01:15:27.880 But I would just say intuitively this makes sense. And more importantly, from a longevity standpoint,

01:15:33.480 it makes sense. I mean, exercise, you know, you've heard me say this a hundred times,

01:15:36.740 it's the single most important tool we have anyway. So why wouldn't we employ it as an important

01:15:43.020 part of a weight loss strategy if this is just one of the other bonuses that comes with it,

01:15:47.540 which is an ability to minimize the BMD loss that is almost inevitable with weight loss.

01:15:54.720 Moving from exercise to nutrition and supplements, we do get a lot of questions on how nutrition

01:16:01.060 supplements can impact BMD. One of the first questions we got was what are some essential

01:16:07.260 nutrients that are important for optimizing bone deposition that people should think about?

01:16:12.820 If you don't mind, pull up figure 12. One of our analysts put this together and I think it's a

01:16:17.520 great way to lay all of this out. I think there were the big three you want to think about.

01:16:21.380 There are other things that matter. Protein matters, total calories matter, all of those things

01:16:25.560 other matter. But when we think about the micronutrient side, the big three are calcium,

01:16:30.540 vitamin D, and when I say vitamin D, I mean D3, and magnesium. In the first column here,

01:16:35.960 you can see the required daily amounts. And I consider this a minimum. This would be like

01:16:40.980 a letter grade C. You might want to think about having a B or an A. So calcium, about 1,000 to 1,200

01:16:47.000 milligrams daily, vitamin D, 800 to 1,000 IU daily, and magnesium, 300 to 500 milligrams daily.

01:16:54.680 Now these can be supplemented. So if you can't get this in food, if you're not sufficiently getting this,

01:16:59.820 either through sunlight, in the case of vitamin D in food, calcium carbonate, calcium citrate

01:17:04.600 are reasonable options. In the magnesium school, it really depends on what your gut can tolerate.

01:17:10.840 Magnesium citrate, glycinate, and oxide are fantastic if you're looking for a little speed

01:17:18.360 up of the bowel. If you aren't, you want magnesium carbonate. It's also worth noting magnesium carbonate

01:17:25.160 more fully absorbed than magoxide citrate or glycinate, which is actually why those three

01:17:30.100 help with bowel regularity. Personally, I like to mix them up. I'm sort of using three forms of

01:17:36.440 magnesium. So I'm supplementing with magcarbonate in the mornings. I use magoxide at night, and I also

01:17:42.840 use a bit of magglucinate with L3 and 8 as well. You know, I'm routinely hitting about a gram of

01:17:49.040 magnesium supplemental. And then the final column here is you can sort of see the foods where these

01:17:54.340 things reside. And you can see why I believe most people are magnesium deficient. It's pretty hard,

01:18:00.940 I think, to get 500 grams predictably of absorbed magnesium every single day. And by the way,

01:18:08.100 I think that's a real minimum. I think a gram is really where you want to be. You got to do a little

01:18:12.380 bit of work to make sure you're getting that from your nutrition. Calcium is a bit easier to get if you

01:18:16.640 consume dairy, but you know, look, a lot of plant-based people aren't going to eat dairy. They have to sort of

01:18:21.560 look to other things. And some of those other things, I don't think you really want to be eating

01:18:24.380 a bunch of. Like, look at how high figs are. Dried figs, a cup of those is 300 milligrams of

01:18:30.020 calcium. So that's a quarter of your daily minimum amount. But I don't know that I want to be eating a

01:18:34.200 cup of dried figs every day for other reasons. I love tofu, but I'm not eating it every day. So

01:18:39.820 I think this is something we need to be paying reasonable attention to, both from a dietary

01:18:44.060 standpoint and then for a number of us also from a supplementary standpoint.

01:18:47.340 What about pharma drugs? We did receive questions on what are the options? What are the benefits? What

01:18:54.720 are the trade-offs? What should people be thinking about there as they explore their options?

01:18:58.800 Yeah. So drugs are typically last line of defense. Just to give you a sense of how last line of

01:19:03.940 defense that is, we personally in our practice do not prescribe these drugs. And the reason for that

01:19:08.180 is we're just not expert enough to do it. I like to send people to experts when something is out of

01:19:12.420 our hands. For example, we completely run the gamut of all lipid-lowering drugs because

01:19:17.100 we have great expertise in that. When it comes to this class of drugs, we refer patients out who need

01:19:22.880 them to endocrinologists. But basically, I think there's sort of three big classes. But the lion's

01:19:28.100 share is one class, which are the bisphosphonates. So this is a class of drug that strengthen bones by

01:19:33.060 basically slowing the rate at which the osteoclasts remove bone. Remember, osteoblast,

01:19:38.500 B for build, clasps being the opposite. They just remove it. These kind of exist in two subtypes,

01:19:45.320 nitrogen-containing versus non-nitrogen-containing. But the lion's share of these, there's kind of

01:19:53.260 three big versions of these. So the nitrogen-containing ones are the much more common one.

01:19:57.500 I would say people are probably familiar with some of these. So Boniva, Fosamax, Actanel,

01:20:01.820 those are the big ones. And the studies are pretty clear. These things work. They increase BMD

01:20:05.920 by about 4% to 6% in the critical areas that matter, the femoral neck, the hip, the lumbar

01:20:11.740 spine. And they reduce the risk of fractures. The drawback here is they're typically not used

01:20:17.340 for indefinite periods of time. So they're discontinued after about five years. And the

01:20:22.160 evidence suggests that that might not increase the risk of fracture going forward. It might be that

01:20:28.020 you get the value during that five-year window, you rebuild the bone, and you maintain some of that

01:20:32.620 value. The other two classes of drugs here, personally, I don't have a lot of experience

01:20:37.020 with. I haven't even seen my patients be prescribed these, but one of them are monoclonal antibodies,

01:20:43.240 and then the other is just synthetic parathyroid hormone. I don't know a lot about those two,

01:20:47.620 to be honest with you. We do have some data, I think, here. We have a pretty good meta-analysis

01:20:52.620 that shows the efficacy. I think it's slide nine, Nick.

01:20:57.560 Perfect. Got it.

01:20:58.520 You're looking at the classes of drugs. Okay, so let me just help people read this a little bit.

01:21:04.340 The first drug there on each list, that's synthetic PTH. Anytime you see an AB on something,

01:21:10.320 at the end of it, that's the monoclonal antibody. The other drugs that end in ATE,

01:21:15.300 those are all the bisphosphonates, and then the rest are pretty straightforward. Calcium, vitamin D,

01:21:20.300 et cetera. If you go over to the right, you're looking at odds ratios. Remember, anything that is on or

01:21:26.080 crossing the unity line of one means it's not significant. And then anything that's to the

01:21:32.540 left of that line, if the confidence interval doesn't cross, the one is significant. So what

01:21:38.380 you can see here is nothing that's on this list is increasing the risk of fractures. About two-thirds

01:21:44.560 of these things in their various formats are reducing the risk of fracture for either hip fractures,

01:21:50.380 vertebral fractures, or non-vertebral fractures. And for people who are looking at this and aren't

01:21:56.200 familiar with this type of graph, when you say to the left of one, it's not the whole black bar,

01:22:02.060 you're looking at the little white box, right? No. So the whole black line has to be to the left

01:22:08.300 of one for it to be significant. The black line is your confidence interval. So for example, let's look

01:22:12.940 at the very first one. You'll notice that the little white line is way to the left. In fact,

01:22:18.300 it's probably 0.4 or something. In fact, if you go and look, you can see it tells you it's 0.42.

01:22:23.860 That's huge, right? That's like a 58% risk reduction. So you think, well, that's got to be

01:22:27.980 great. But I can tell you right now, it doesn't matter because the confidence interval is so wide

01:22:33.000 that it crosses one. That tells me without looking at anything that the p-value is greater than 0.05

01:22:40.000 and the confidence interval crosses unity. So when you look over, sure enough, lower limit 0.1,

01:22:46.280 upper limit 1.82, p-value 0.24. Okay, let's pick a winner. Let's go two down from there. Actually,

01:22:53.360 these p-values are so small. They're probably less than 0.001. But again, so the one beneath that

01:22:59.300 has a very similar little white dot. It's 0.45. So it's not quite as low, but it's a 55% reduction.

01:23:06.900 But I know it's going to be significant because the confidence interval doesn't cross one. And sure

01:23:12.180 enough, it doesn't. It's 0.27 to 0.68. And the p-value is probably 0.000. You know, it's less

01:23:17.320 than 0.004. They only just show them to two significant figures here.

01:23:22.000 For people interested in diving deeper into that, that AMA, you and Bob did on understanding

01:23:27.060 studies and studying studies dives way more into that. Peter, one of the things we haven't really

01:23:32.560 talked about yet is what happens in like something like space or low gravity environments? What happens

01:23:37.820 to your bones if you truly aren't using them? This is obviously not a subject that is relevant

01:23:43.200 to a lot of people directly. Indirectly, it's relevant to a lot of people. Space is just the

01:23:49.820 most extreme version of what we would call disuse osteopenia. As the name suggests, disuse osteopenia

01:23:55.900 occurs when bones are chronically unloaded, leaving to a very unfavorable combination of high bone

01:24:02.460 resorption and low bone formation. It's the same thing that's happening with the osteopenia from aging.

01:24:07.560 It's just much more accelerated and much more extreme. So again, the most extreme version of

01:24:13.000 this is astronauts. And I don't know much about what they do in space, but I suspect that they

01:24:17.360 go out of their way to figure out ways to load astronauts in space so that they don't have to

01:24:23.060 deal with this in its highest form. But I think for most people where this is relevant is bed rest.

01:24:28.680 So lots of people have to undergo bed rest for all sorts of reasons. Pregnant women often are placed

01:24:34.440 on bed rest if they are experiencing fetal retardation. And I mean that not cognitively, 0.92

01:24:40.300 but growth retardation. If in the third trimester, the fetus isn't growing at the rate that is expected, 0.98

01:24:47.000 not uncommon that the OB will ask the mother to gradually reduce her impact until more and more

01:24:53.460 energy can be reserved for the fetus. You can also see bed rest being necessary for various types of

01:25:00.720 injuries. Of course, we know today that we don't want to rest people nearly as much as we used to.

01:25:06.040 I mean, there was a day 50 years ago when if somebody hurt their back, they were put on two

01:25:09.520 weeks of strict bed rest. Today, we know that that's absolutely the last thing you want to do.

01:25:13.900 Bone loss due to disuse osteopenia is incremental and it's progressive with time. And it occurs more

01:25:18.360 rapidly, as you would guess, in the trabecular bone than in the cortical bone. So this is the

01:25:22.460 trend we've seen over and over again. And frankly, it can be about 2% per month

01:25:27.760 in microgravity, partial paralysis, which I should have mentioned as well,

01:25:31.920 paralysis-based injuries or immobilization with injury. And in the most extreme setting with

01:25:36.920 complete paralysis, it can be up to 7% per month. So Peter, for people who are experiencing

01:25:41.680 that type of immobility, is there anything in particular they should be thinking about or they

01:25:46.520 can do to kind of help with the BMD concern? The first would be any form of PT that can actively

01:25:52.860 load muscles. I actually don't know how much data exists on this, but that's one of the things that I

01:25:57.660 is interesting about cyclic BFR. And that's why the minute I was out of surgery, I got permission

01:26:04.520 from my surgeon to put my katsu cuffs on my arm and just start cycling the BFR. I wanted to put

01:26:11.960 little bits of stress on that bicep just to have it moving. And again, keep in mind, I was very

01:26:16.940 fortunate I did not have a bicep tendon repaired. If I did, I would not have been allowed to do that.

01:26:22.160 I had to keep my arm completely immobilized, but I was still able to get compression on the bicep.

01:26:29.600 Let's say you're bedridden with a certain injury. There are still other muscles in your body that

01:26:33.900 don't pertain to that injury that can still be moved and put under load. And even if you're doing

01:26:38.320 these things isometrically, right? So a person is holding you and you're resisting against them

01:26:42.540 without actually moving in the bed, that's important. Now, there was a super interesting mouse

01:26:46.420 study that we found that used a bisphosphonate to inhibit the osteoclastic bone reabsorption

01:26:54.020 in a mouse model where the mice were given botulotoxin to basically prevent them from moving,

01:27:01.220 I think, one part of their leg. I think we have this figure here as well. Yeah, it's figure 10.

01:27:07.660 Perfect. I got that pulled up.

01:27:08.800 So what you're looking at here is in the first bar on the left is the baseline. And then you have

01:27:15.420 control mice in black. And then in white, you have what happens to the animal that we're just

01:27:20.200 given botulotoxin. So these were the animals that were basically immobilized because botulotoxin,

01:27:25.500 of course, paralyzes their legs. And then the botulotoxin plus the bisphosphonate on the right,

01:27:33.360 I think there's a pretty profound result. You're looking at this in the femoral neck

01:27:38.100 and in the middle of the upper part of the femoral bone below the neck. And you can see that the

01:27:43.820 bisphosphonate plus the immobility really looks no different from the control. And it's a clear

01:27:51.180 contrast to how the untreated animal looks. You know, look, these are 16-week-old female mice. 0.92

01:27:57.540 Is this going to be true in humans? I have no idea. But I find this type of research very interesting.

01:28:02.120 And frankly, I hope more people are doing this type of research because I think immobility

01:28:06.500 is a huge problem with everybody. But once you start to deal with an aging population, 0.96

01:28:12.300 it becomes more significant. How many times have we talked about that study where a group of 65-year

01:28:17.320 olds, I believe, were immobilized for two weeks and lost, if I'm not mistaken, something in the

01:28:22.660 neighborhood of about four pounds of lean mass in two weeks? We talked about that through the lens of

01:28:27.960 how much you lose lean mass. But think about what that's doing to BMD. And think about how long

01:28:33.900 people are immobilized beyond two weeks, especially as they're older.

01:28:38.700 I can't remember offhand, but I know you and Inigo in the second podcast also talked about

01:28:44.660 lactate as it relates to immobility for people on bed rest or in the ICU as well. We'll link to it

01:28:50.660 in the show notes. But you also had a conversation about the importance of people in the hospital just

01:28:57.000 moving for the lactate level. So we've seen it over and over across a lot of podcasts.

01:29:03.540 That was a pretty exhaustive tour of all things bone, but I think this is super important stuff.

01:29:09.680 I know it's not that sexy. You're not going to see too many Twitter wars about BMD. Although I did

01:29:15.360 probably provide enough substrate for someone to get upset about something I said today, whether it be my

01:29:19.860 position on golf not being the perfect BMD boosting sport or my recommendations for earlier screening

01:29:27.580 on BMD. I think there was something else I said that will draw the ire of critics.

01:29:32.380 Yeah. We just better hope that one of those organizations doesn't sponsor an ad in Golf

01:29:36.220 Digest because then we'll just get it from all fronts. But hopefully it answered a lot of questions.

01:29:41.900 Again, we compiled these questions. We've gotten them a lot and we've never tackled it at this level.

01:29:46.660 And like what we did with muscle and looking at the importance of muscle strength, muscle mass,

01:29:50.780 what improves there, and then looking on the other side out of the bones too. So

01:29:55.020 hopefully people enjoyed it. And until the next AMA, we'll see you. Don't stay up too late watching

01:30:01.780 Ozark, the new season tonight. I don't get to even start it tonight. How do you have that self-control?

01:30:06.360 Jill and Olivia are out of town for a volleyball tournament. So I'm solo with the boys this

01:30:11.860 weekend and Jill would kill me if I started it without her. Yeah. Something tells me you won't have a lot of

01:30:16.320 solo time, solo with two boys either. So you'll probably have your hands busy.

01:30:20.380 I will. Well, good luck with that. Thanks, man. We'll see you. Bye.

01:30:24.220 Thank you for listening to this week's episode of The Drive. Head over to peteratiamd.com

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The Peter Attia Drive - July 07, 2025

Navigating bone health： early life influences and advanced strategies for improvement and injury prevention (#214 rebroadcast)

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