Navigating bone health: early life influences & strategies for improvement & injury prevention

1. 0:00 – 1:12

   Intro

   1. PAPeter Attia0:00

      If you look at a group of people who are 65 years old or older who fracture their hip falling, 25% of those people will be dead in six months. By the time you're 75, the risk of death from a fall is enormous. This has a greater mortality than smoking.

   2. SPSpeaker0:20

      What we're gonna talk about today is all things bone health, bone mineral density. What should people be aware of if they're thinking about if they're maybe at risk?

   3. PAPeter Attia0:29

      Family history matters. Genetics accounted for up to 50% of bone health. Having either parent that's had a history of a hip fracture, that's a huge red flag.

   4. SPSpeaker0:37

      Any advice you would have for people who have kids on what they can do so they can really optimize bone health?

   5. PAPeter Attia0:44

      You know, I think the most important thing probably comes down to being adequately nourished and being very active, and in particular, being very active in things that load bones.

   6. SPSpeaker0:55

      I think where we're gonna go next is starting to look at what people can do to improve their bone health. [upbeat music]

   7. PAPeter Attia1:03

      Hey, everyone, welcome to "The Drive" podcast. I'm your host, Peter Attia.

   8. SPSpeaker1:11

      All right,

2. 1:12 – 5:17

   Overview of bone health topics to be discussed

   1. SPSpeaker1:12

      Peter, welcome to another AMA. How you doing?

   2. PAPeter Attia1:15

      Doing well, man. The final, final seven episodes of Ozark drop tonight. We're recording this on, uh, April 29th, so interesting date for two reasons. By the way, the other thing that occurred to me t- this morning, um, [lip smacks] is that the days and dates in this year, 2022, were the same as they were in 1994. So I was like, "Oh my God, today is Friday, April 29th," which is the same as it was in '94. So on Friday, April 29th in 1994 was the practice day at Imola, and that's when Rubens Barrichello had that horrible, horrible accident. Um, [lip smacks] it ... We can link to the accident where he basically hit the chicane and, and launched, um, into a barrier, and amazingly only escaped with a concussion and a broken nose. The following day, which is the same day as tomorrow will be, which was Saturday, April 30th, [lip smacks] was when Roland Ratzenberger was killed, which made it the first fatality in Formula 1 in 12 years, the last one being Gilles Villeneuve in 1982. And then of course, Sunday, May 1st, which will be the same this year, was when Senna died. Uh, so-

   3. SPSpeaker2:34

      All in 1994.

   4. PAPeter Attia2:36

      Yeah, it was at the same race. I mean, you had these three horrible accidents resulting in two fatalities in one weekend. Um, but again, just to think that it, it's the exact same days this year as it was, um, thir- 28 years ago, uh, just ... I don't know why it just sort of ... I didn't, I never, I didn't, uh, I didn't notice that until today.

   5. SPSpeaker2:57

      Well, it's kind of important information, right?

   6. PAPeter Attia2:59

      Yeah.

   7. SPSpeaker2:59

      Like, your brain can only count so much and ... Well, I mean, this is really off topic, but do you still have the skill that you had back in the day where you can, like, remember what day, like, day of the week a date was?

   8. PAPeter Attia3:13

      Uh, only if I can peg it to something, but not, not as profound as it used to be.

   9. SPSpeaker3:18

      Uh, I mean, it, it used to be ... I remember in meetings we used to just throw out random, random dates, and then we would fact check it. I feel like we wasted a lot of time doing that.

   10. PAPeter Attia3:27

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

   11. SPSpeaker3:31

       Yeah. Love it. Love it. [chuckles] Well, on the complete opposite end of that, um, what we're gonna talk about today is, is really a question that, I mean, it's a topic that we get asked about a lot, and we've gotten a lot of questions that have come in, but we've never really dove really deep into it, which is what we're gonna do today, and it's kind of all things bone health, bone mineral density, osteopenia, osteoporosis, kind of all things of that nature. And I know this is something that you work a lot with in your patients, and I know it's something that's of really big interest for people, and so our hope is that we can kind of go through this episode and focus on, you know, why is this important. So why should people care about this? You know, people listening right now, there'll be a subsection of them that are gonna be super interested, and there'll be probably another subsection who are maybe younger, they've never really thought about their bone health, and they might not think it really applies to them. But our hope is, in the beginning at least, we'll kinda walk through why they should care about this and why they should focus on it early on in life. And then from there, we'll talk about, you know, how bone health changes as people age, the differences between sexes, between men and women, and then we'll also focus on things on how people can improve or kind of help their bone health become better from physical activity to nutrition, supplements, drugs, and more. And then if all that goes well and we still have time, which is always 50/50 on how these AMAs go, we'll also focus a little bit on, you know, people dealing with acute injuries and how they need to think about this, which I know is something that you're interested in given your recent shoulder surgery, and now you're kind of not as active in one side of your upper body as you used to be. So

3. 5:17 – 8:43

   Bones 101: bone function, structure, and more

   1. SPSpeaker5:17

      all that said, I think before we start going through those questions, it's gonna be helpful to set the stage a little bit just so everyone is on the same page in the definitions and what we're talking about. So maybe why don't we start with, you know, what are some of the types of bones we'll be referring to? Because at least for myself coming into this, I just kinda think a bone is a bone, and I don't really think much more beyond that. So why don't you dive into that a little bit?

   2. PAPeter Attia5:42

      Yeah, I mean, it ... Bone is, uh ... It's a, it's a living tissue, and, and, I mean, okay, that's obvious, but I think it's also easy for a person to kind of forget that and think of bone as somewhat inert, but in fact, bone is heavily vascularized Uh, bone is an organ that plays a very important role in a lot of things. I'm actually not gonna go super deep into the anatomy and physiology of bones. Um, I'll point out just a couple things, right? So first of all, we kinda think of a couple types of sections of bone. So we think about the cortical or compact bone, and that's what forms, like, the shaft in the exterior of long bones. So if you think of your femur, your humerus, things like that, you know, they have kind of like the, the long shaft and then the nubbins at the end. So the shaft of that is the cortical or compact bone. And then at the end, you have the trabecular, uh, bone, sometimes called the spongy bone. So those are, those are kind of at the end of the bone. And there are some differences amongst those in terms of their vascularization and things like that. Uh, but again, I think for the purpose of this discussion, just, you know, whenever I talk about compact or cortical bone, I'm talking about the shaft. And whenever I speak about the spongy or trabecular part, I'm talking about the end. Um, again, I think marrow, people probably intuitively understand that marrow is important, but again, it's very important, right? Marrow is what's producing our white cells and our red blood cells. So in this era where we're thinking about, you know, a post-COVID world, you know, it's important to understand that the memory B cells and memory T cells that are going to provide lasting immunity against this virus and other viruses reside in the bone marrow. Um, and so the whole purpose of being infected and then having a subsequent infection that's less devastating, purpose of being vaccinated for the same reason, is to have memory B cells and T cells that are sitting there in the bone marrow that can respond immediately and quickly upon, uh, reintroduction of, of the same antigen.

   3. SPSpeaker7:39

      You know, when you mention nubbins, it kind of made me think about your banana nubbins. And you recently posted on Twitter you might be looking for a new profession. Do you wanna let people know kind of what your new interest is in the term o- in the world of longevity?

   4. PAPeter Attia7:55

      Well, yeah, I mean [laughs] as you point out, I mean, I've, I've been very interested in human longevity for, uh, I guess probably about, you know, a little over 10 years. Um, and, and I'm sure I will remain so, but, but I, I, I, I've at least considered moving into banana longevity because I think the opportunity, uh, for impact is huge, right? I mean, it's one thing if you can figure out how to take the average person from being 80 to 90, um, and that, you know, that'll have a huge impact on the world. But if you could take the average banana and go from, like, two days before it turns mushy and brown to 10 days, I mean, I, I think it's revolutionary. And, um, I just noticed I was on the USDA's most wanted list because of how many bananas I waste, so I gotta do something about this.

4. 8:43 – 15:00

   Bone mineral density (BMD), minerals in bone, role of osteoblasts and osteoclasts, and more

   1. SPSpeaker8:43

      Yeah, I mean, if you solve the banana crisis and you move to avocados, they'll probably give you a Nobel Peace Prize as well.

   2. PAPeter Attia8:49

      [laughs]

   3. SPSpeaker8:49

      So I mean, the upside is very high in this new world.

   4. PAPeter Attia8:52

      [laughs] You know, the thing is I, I mean, avocados last so much longer. I mean, you just have a, you just have a window of opportunity to... Like, I can actually buy avoc- I could buy like seven avocados and eat them in a week. I can't buy seven bananas and eat them in a week, like, at one a day. It just doesn't work. So I think, I think that entire fruit space is just a racket. I think the whole banana infrastructure ... I think, I think bananas are a pyramid scheme. Like, I think it's just the whole thing is just total scam.

   5. SPSpeaker9:21

      Yeah, maybe one of our upcoming AMAs we'll just do a conspiracies with Peter Attia, and we'll just go into the world of bananas. So Peter, you mentioned, um, earlier ago B cells and T cells. Can you kinda walk people through what cells make bones?

   6. PAPeter Attia9:36

      Y- yeah. A- and again, this can be made as complicated or as simple as you want. I'm gonna kinda just try to thread the needle a little bit and say just think about osteoblasts and osteoclasts. And I kind of remember from medical school the way I used to remember this. So osteoblasts, B, are responsible for building bone by producing collagen bone matrix and mineralizing it. Osteoclasts remove bone by reabsorbing calcified bone and the matrix. So osteoblasts contribute to increasing bone mineral density, osteoclasts the opposite. It's also important to understand this exists in an equilibrium, right? So we're constantly remodeling bone. Um, so we're, we're sort of adding to and subtracting from this and, and basically turning over calcium. So bone is like 50 to 70% mineral, and obviously, what's the predominant mineral? It's calcium. We'll talk about that in a second. It's about 20 to 40% organic matrix, right? So again, what does organic mean? Organic is carbon, hydrogen, oxygen, sulfur, et cetera. And then the rest of it is, is a bit of water and lipid, and again, you'll see that primarily in the, in the marrow. So in an adult, like, the entire human skeletal system can be remodeled in a really long cycle, right? It might take 10 years to turn over all of the mineral and organic content within the bone over and over again. But at the micro level, calcium balance is, you know, ha- happening quite frequently. Um, I don't remember the exact number. I wanna say it's like 99%, but virtually all of the body's calcium is contained within bone. Um, and therefore, bone plays a very important role in calcium homeostasis, and if anybody's taken a physiology class, they probably remember how important calcium signaling is to everything within a cell. So again, we think of these bones as structural entities, which of course first and foremost they are, but remember, they're also a very important reservoir for calcium, which is another very important ion in, um, in the activity of every cell.

   7. SPSpeaker11:50

      And you talked a lot about calcium. What about vitamin D? What role does vitamin D play in the bones?

   8. PAPeter Attia11:57

      So they're both very important. Um, and again, there's, there's sort of Two forms of vitamin D, vitamin D2 and D3, but really when I talk about vitamin D, I'm gonna mostly talk about D3 which is the active form. So D ... So what's the problem with being deficient in vitamin D? Well, again, people might recall a disease called rickets, and you see this often in developing parts of the world where people are really malnourished and they have really, really soft sort of spongy bones, and it's, it's, it's ... Actually just yesterday I had a friend over who, uh, does a bunch of mission work in, um, Rwanda, and she was showing me a child at their, uh, camp whose legs ... You know, the child was, like, probably five years old. He was sitting down, and they were doing something with his legs that you would think would be impossible to do with a human being. Basically while he was sitting on the ground, they were able to move his foot back and forth, back and forth, and he was in no pain, but it's because he didn't have bones that were anything other than basically rubber bands. So he couldn't stand. And within, I wanna say, six months of correcting his nutrition, totally normal. So, um, you know, amazing opportunity when you think about what's, what happens in that part of the world, uh, and how you can fix that. But what is it about vitamin D? Well, vitamin D increases the gut's absorption of calcium. So if you're woefully deficient in vitamin D, you're going to have trouble absorbing calcium through the gut, and we're gonna talk in this podcast later about the importance of dietary calcium and/or supplementary calcium. And so you can see why that becomes, um, part of the issue.

   9. SPSpeaker13:37

      Yeah.

   10. PAPeter Attia13:38

       So the, the other thing to kinda keep in mind here is the role of another hormone. And again, I'm trying to only introduce concepts now that are going to become relevant later, either through treatments or nutrition or supplementation, so I'm, you know, being a little bit, uh, simplistic. But the other thing that you can't avoid here is understanding the role of calcium and parathyroid hormone. So I think most people are probably familiar with their thyroid gland, sits here in the neck. Um, it's kind of got this shape to it that where it's got, like, kind of two main lobes, and then each lobe has two poles. Well, at each of those poles is a little tiny gland called the parathyroid gland, so you have four of those. And the parathyroid gland is really the master gland for regulating calcium levels. So low levels of calcium in the blood stimulate parathyroid hormone secretion. As parathyroid hormone level goes up, it stimulates the release of calcium from the bone into the blood. Now, it also induces enzymes in the kidney which then convert vitamin D into its active form to then aid and speed up in the process of reabsorbing more calcium from the diet. So all of this stuff, parathyroid hormone, calcium, vitamin D, very important to maintaining bone health. And any time you ha- have things that disrupt that system, you're going to see disruptions

5. 15:00 – 18:55

   The consequences of poor bone health

   1. PAPeter Attia15:00

      potentially in the bones.

   2. SPSpeaker15:01

      Yeah. And I think that was a good and kinda quick overview of what will be important for what we cover next, and I think the natural follow-up to it is, you know, what is the consequence of poor bone health? What is the consequence of low bone density? I think, you know, some people are ... who will be listening to this will have already known issues of bone density, and some people have never thought about this before in their life. And so, you know, what would you say to those people on why they should care about this and why they should think about it?

   3. PAPeter Attia15:31

      This is one of those things that I would say five years ago I was not paying nearly as much attention to as I am today. Um, and I, I think the easiest way to show this is, um, I, I put a, a couple figures together. So can you pull up figure one, Nick? Okay, so this is a figure that we made. It's an internal analysis, but it's, it's a very straightforward analysis. All we've done is taken data from the, uh, CDC database from 2019. The reason we use 2019 is by the time you get to 2020, you start to get some COVID data mixed in there, um, although the accidental stuff only changes in that you see a higher rate of overdose. So you're looking at the absolute number of deaths by decade for people age 25 to 35 all the way up to 85 and up. And we basically break accidental deaths into four categories, so overdoses, transportation accidents, which are mostly car accidents, falls, and everything else. Um, [clears throat] as you can see, those first three, accidental overdose, transport deaths, and falls, represent virtually all accidental deaths, so you can almost ignore everything else. This is the absolute numbers. These are total numbers. And I think kind of two things stand out here, um, really clearly. The first is that for people, you know, younger than 60, uh, overdoses are the predominant cause of accidental death, and for people over 65, falling is. But if you go to the next figure, it tells, I think, a more important story, which is when you adjust for the population ... 'Cause remember, in figure one what I'm showing you is total number of deaths, but what you don't realize is that you, as you move left to right, the denominator, the population, is getting smaller and smaller and smaller. There are fewer and fewer people in each bucket as you go to the right. So to correct for that, we would ask the question which is how many of these deaths per 100,000 people occur in each group? And if you look at that figure, I think the story is readily apparent, which is that by the time you're 75, the risk of death from a fall is enormous. Now, it's not as high as Alzheimer's disease, it's not as high as cancer, and it's not as high as heart disease, but it comes in pretty much just after that. So this is what sets the stage, because on the one hand, I think you can look at these data and say, "Wow, this is really problematic But the other point is you can't wait until you're in that bucket to decide you're going to do something about it. So just as for atherosclerosis, we don't want to wait until we've had our first heart attack to say, "Oh, well, and I really, I really need to worry about my ApoB, and maybe I should stop smoking and make sure my blood pressure's okay." You don't want to wait until you have osteopenia or osteoporosis and you're 60 years old to say, "It's time to do something about this." Now, if you're there, there's lots to do about it. But it's just as important if you're 25 years old, and frankly, it's just as important as a parent if you're thinking about what your 5-year-old and 10-year-old and 15-year-old should be doing to make sure that they're setting themselves up for the best outcomes possible as they age, of course. Okay, so Nick, let's, let's

6. 18:55 – 25:06

   The devastating nature of hip fractures: morbidity and mortality data [18:00];

   1. PAPeter Attia18:55

      look at figure three now, 'cause ... So what you're looking at here is the, uh, excess mortality for women, which is shown on the top, men, which is shown on the bottom, following a hip fracture. And this is going to come up over and over again. We're going to get into some data about what are the fractures that really end lives, and you're going to see it's primarily hip fractures. Uh, a pelvic fracture, I think, is probably second. Um, and again, in part, this results from the immobility that comes after it. Um, but, uh, I think there are some other reasons at play there. But so what we're looking at here in the top graph is women following a hip fracture, men following a hip fracture, and you're looking at mortality as a function of age. Now, th-this is kind of staggering. I mean, when I first saw this, I couldn't believe it. Um, and I apologize for people who are only listening to this podcast. Um, again, this is one of those podcasts where I think it really helps to be able to see the figures. I'll do my best to kind of explain what the figures show. But for those who are looking at it, I don't think you need me to say anything. So you can just plug your ears and go, "La, la, la, la, la, la, la," as I explain this 'cause there's nothing I need to say if you can read this graph. So if you're 90 years old or above, and you're a man, and you have a hip fracture, in this data set, and we're going to talk about other data sets in a moment, 40%, actually more than 40% of you will be dead within a year. Now, that mortality comes down. That's generally the case. The mortality tends to come down because there's kind of a survival benefit or there's fewer people in that group, right? So, you know, what's the mortality of people who are 90 over the next 10 years? That number's going down because most of them have already died. You can see for the younger demographics, the numbers go up. So, you know, the good news is, in this cohort at least, if you're 70 years old and you break your hip, you know, 10% of those people are going to be dead in three years, but that number just keeps going up and up and up. So I think that the, the important thing here from this data set, 'cause we're going to look at another one in a second that I think is more stark, in this data set, what you realize is that for older people, people over the age of 85, people over the age of 80, which I would argue is not really that old. I mean, I think most of us, you know, listening to this podcast, if we're not that age, certainly have aspirations to be that age. Your mortality is, you know, in the neighborhood of a third within a year after a hip fracture. So y- you know, um, Nick, we're going to have Michael Easter on the podcast coming up soon, aren't we? Like, I think we're having, um, we're having Michael ... I mean, I know we do the interview next month, so that'll, that'll, that should come out soon, right?

   2. SPSpeaker21:45

      Yeah, that will come out, uh, midsummer probably.

   3. PAPeter Attia21:49

      Yeah. So, so for those who aren't familiar with Michael's work, he wrote a book called "The Comfort Crisis," which I-I'm going to say is probably, you know, one of the 10 books that I'll sort of force down most people's throats if given the chance. Um, I think it's a really important book. And, um, it'll a- a topic from that book will actually come up later in this episode, Nick, when we start to talk about exercise and what we can do to, um, reduce the loss of bone mineral density as we age. But in the book, he makes some references to a few studies that I went back and looked at that talk about, um, some of the unbelievable high mortalities in other fractions. So, so if you look at another study, study had like about 200 people in it. Um, it looked at the six-month mortality in people who were 65 or older who fractured their hip, and the mortality was 25%. Again, I want to repeat what the implication of that is. So if you look at a group of people who are 65 years old or older who fracture their hip falling, 25% of those people will be dead in six months. Now, obviously, when you include younger people, that mortality goes way down. So if they lowered the threshold in that study to people 50 and older, that mortality came down to just under 14%. Another study, which was a Finnish study that looked at a little over 400 concep- consecutive hip fractures in patients, found that the one-year postoperative mortality was just over 27%. So again, totally different patient population, but identified, and by the way, a different country, very similar trend. And I think perhaps the most rigorous of these studies was a large study that looked at about 122,000 participants who were at least 60 years old from various cohorts. So Europe, the US, et cetera. Followed them for 12 or 13 years on average, and during that time found 4,200, uh, hip fractures This study was able to then compare total mortality and look at the hazard ratio in the first year following the hip fracture. So now this is asking the question: What is the probability or what is the increased risk of death one year following the hip fracture in this patient population? Again, these are people enrolled at the age of 60 or beyond. And the hazard ratio was 2.78. So again, what does that mean? 2.78 means a 178% increase in the risk of mortality within one year following a hip fracture. There are lots of studies like this. I don't think we need to spend the rest of the AMA on it. I think regardless of how you slice and dice these data, a hip fracture is a devastating outcome, and it's something that we really want to avoid, um, at any age, but especially when we're into our seventh decade and beyond.

7. 25:06 – 27:38

   Where fractures tend to occur in the body

   1. SPSpeaker25:07

      Uh, just for reference, what's the hazard ratio for smoking again?

   2. PAPeter Attia25:11

      The hazard ratio for smoking on all-cause mortality is less than 2.78, for sure, because the hazard ratio for end-stage renal disease is about 2.76 for all-cause mortality. Smoking is probably just below two. So great, great point, Nick. This has a greater mortality than smoking.

   3. SPSpeaker25:37

      Yeah. The other really interesting thing when you look at that, those two graphs is I would love to do a study on the people who are over 90 when they fractured their hip and survived at 10 years. You know, who are those people in their hundreds just, like, kicking it around, still going strong?

   4. PAPeter Attia25:55

      Yeah.

   5. SPSpeaker25:55

      It'd be r- be really interesting to see. Do we know where fractures occur in the body?

   6. PAPeter Attia26:01

      Yeah. So the, the... If you pull up this figure, Nick, th- I think this is a, a really elegant way to look at this. So you're, you're looking at all the sites of, um, fractures, and in the first column, it's showing you how many fractures occurred in this study. Um, but it's ranking it by median age. So I've just highlighted the first one, which is proximal femur, which is hip fractures. So not only are those highly frequent, 4,000 fractures, but look at the median age, 81.1. Pelvis, right there, 73.2 behind it. Um, neck of the femur, 70. Distal femur, 70. Acetabulum, which is the, um, uh, cup that holds the femoral head, 68. So, you know, w- a- and, and then down to, say, proximal humerus, so the top of the, uh, humeral bone, 66. So those are the, those are the big fractures for people over the age of 65. And, um, again, you can see the, the, the frequency of proxal-- proximal humerus and proximal femur are very high. Uh, you can go through this list, and it's really telling about how people fall. You know, what's a distal radius fracture, right? That, like, it's a fracture at the end of, uh, your hand. So the radius bone runs right here, just so you can see. Um, and how, how does someone break that, right? Like, you know, they break that by falling, [chuckles] right? Um, so you, you sort of get a sense of how balance, strength, uh, impact a lot of these things.

8. 27:38 – 30:21

   Defining osteopenia and osteoporosis

   1. SPSpeaker27:38

      Yeah. Out of curiosity, what's the talus? What's the-

   2. PAPeter Attia27:42

      Foot

   3. SPSpeaker27:42

      ... the last thing on the list?

   4. PAPeter Attia27:43

      It's the foot.

   5. SPSpeaker27:44

      Foot.

   6. PAPeter Attia27:44

      Yeah.

   7. SPSpeaker27:45

      Got it. So the next kind of terminology that I think would be important for people to know, 'cause we do get a lot of questions on it, we're gonna talk a lot about it, is, you know, the terms osteopenia, osteoporosis. Like, just for people who don't know, myself included, are they the same? Do they mean the same? How do we think about them different? You know, why is it important to differentiate between them?

   8. PAPeter Attia28:07

      Yeah. So just think of this as a continuum, uh, Nick. And in fact, if you pull up figure four, um, this is kind of just a n- not entirely helpful, but at least schematically helpful figure. Osteopenia and osteoporosis just exist on a continuum relative to healthy bone. Now, this is gonna get a little complicated, and I'll explain it in the r- right, you know, the, the, the amount of rigor that's necessary in a moment, but let's just start with the concept. When you go from healthy bone to osteopenia, that represents about a 10% reduction in bone mineral density relative to a young, healthy adult. And then osteoporosis is a further degradation where you hit about 25% reduction. Now, there are two things that I have to add to this to, to make it sort of rigorous. The first is the diagnosis of osteopenia and osteoporosis is based on two locations, technically three, but, uh, two of them are symmetric. The hips and the lumbar spine. So for anybody who's gone and had a DEXA scan before, you may notice that they report the Z-score and T-score, which I'll explain in a second, of the lumbar spine, of the left hip, the right hip, and usually of the entire body. And the reason for that is we use left hip, right hip, lumbar spine, L1 to L5, to make this diagnosis. Those are the areas we look at. I assume the reason for that is that's where the fractures are, right? So we, we, you know, we see people that have atraumatic fractures, compression fractures in the lumbar spine. As you're going to see in a moment, the majority of fractures in older people are in the hip, and as I just shared a moment ago, the mortality for those fractures, uh, is, is very high. So that's where the diagnosis is made. So again, osteopenia, 10% reduction in BMD. Osteoporosis, 25% reduction in BMD. And again, these are made to healthy individuals. Again, healthy bone to osteopenia to osteoporosis, it's just a continuum But osteoporosis and osteopenia are distinct in the degrees to which BMD has been reduced.

9. 30:21 – 38:11

   Measuring BMD with DEXA and how to interpret scores

   1. SPSpeaker30:21

      And Peter, you mentioned DEXA there a little bit ago, and anyone who's listening to this podcast will be familiar with the DEXA scan because we talk about it a lot and looking at, you know, fat and, like, the benefits f- that you can get from that. Is that the best way for listeners to figure out what their BMD is? Is that how you're doing it in patients?

   2. PAPeter Attia30:43

      Yes. Um, so DEXA is a super, super low radiation scan, nothing like a CT scan. Um, it, you know, takes 10 minutes. You lay on a table, a little scanner moves over your body, and it's using two very low-dose X-rays that are absorbed differentially by bones and soft tissues. And so it's able to differentiate between adipose tissue, bone, and lean tissue, or non-adipose tissue. Um, I will say this, not all DEXA scanners are created equal, so if you want to know your bone health, make sure before you go and get the DEXA scan, you confirm with the entity doing this that they are giving you segmental bone analysis for left hip, right hip, lumbar spine. A lot of DEXA places can only give you whole body BMD. So they'll just spit out the Z-score for that one, uh, for that one metric, but they won't give it to you segmentally. So, um, and that's sometimes okay. Like, if a person's BMD is very high, you don't need the segmental analysis. But if you're doing this to screen for BMD, uh, you have to make sure, of course, that the, that the DEXA's capable of doing that.

   3. SPSpeaker32:01

      Yeah. And just a reminder for people, um, we talked about this in another episode, but, uh, we're always surprised at how easy it is to get a DEXA scan, right? You don't need a doctor to do it. So if you just Google the city you're in and then DEXA, you should be able to find different providers that do it for relatively cheap. I think in most cities it's around 100, $150. So it has a lot of benefits. And just maybe remind people again, if they are calling different places, what are the three things they wanna look for?

   4. PAPeter Attia32:31

      Yeah. You wanna make sure when you're doing a DEXA, again, if you care about knowing the full BMD, and you're gonna pay more for that segmental analysis. So when you talk about those scans that are, like, in the 100, 125, even up to 150, a lot of times they aren't showing everything. They're just giving you body composition, um, and usually visceral fat now. Um, you'll say up to $400 typically if you wanna see everything. But again, it's all ... Like, and you're gonna pay more in New York and San Francisco than you're gonna pay in Austin, Texas, for example. Um, I, I, I probably pay, like, 125 for mine, but I'm not getting the full, uh, BMD analysis 'cause I've already had it done and my BMD is high, so I don't need to screen that frequently. Uh, not at the rate that I screen everything. The other things you wanna look at, you obviously wanna make sure you're getting full segmental lean tissue analysis so you can look at appendicular lean mass index that you can calculate for yourself. Obviously fat-free mass index you can calculate for yourself. Fat mass index you can calculate. You need them to be able to give you that. Um, and so those are, those are kind of the things I wanna see along with BMD.

   5. SPSpeaker33:36

      And let's say you have, like you and a friend are going and getting your BMD done through a DEXA scan. Is there gonna be variability that exists in bone density between different people? Like, let's say even if someone didn't have osteopenia or osteoporosis, can there just be natural variability between different types of people?

   6. PAPeter Attia33:57

      Yeah. And, and it's also important to understand the number you're going to get, so they don't, at least to my knowledge, I don't recall seeing them typically report in grams per centimeter cubed your BMD. Because what would you do with that information? Like, it- it's not that helpful. What you really need to know is statistically where do you rank, and this is done via a T-score and a Z-score, and this is done to compare you to a young, healthy adult and to an adult that is your age. So if you go back to Statistics 101, I think many people might recall the idea of a normal distribution, which is a bell curve function, and a Z-score is basically telling you where you lie on that distribution. So a Z-score of zero means you are right in the middle of the distribution, and if you're in the middle of that distribution, it means you are, you have a higher bone mineral density than 50% of people and a lower bone density than 50% of people. If your Z-score is plus one, it means you are one standard deviation above the mean, which means you are, you have a higher bone density than 82.5% of the population and a lower bone density than 17 and a half percent of the population. If your Z-score is plus .2, it means you are two standard deviations above the mean, which means you're at 97.5%. You're, you're higher than 97.5% of the population. Of course, this works in reverse. A Z-score of minus two means you have a lower bone density than 97.5% of the population. So that's what Z-scores do. They're com- I'm sorry. I, I may have misspoke. The Z-score is comparing you to your age when I say the population. The T-score is comparing you to the young, healthy individual. So in other words, for someone who's older, the Z-score is always going to be more favorable than the T-score. Does that make sense?

   7. SPSpeaker36:20

      Yeah. Yeah, 'cause you're comparing to a 30 year... If you're 60, you wanna compare yourself to not only a 30-year-old, but also other 60-year-olds.

   8. PAPeter Attia36:28

      That's correct.

   9. SPSpeaker36:30

      And is it, when you look at for yourself, and even with your patients, their scores, is it kind of like how you do VO2 max, where you always want to be in the elite of the elite categories for, like, you know, VO2 max, you wanna be elite and a decade younger. For, like, BMD, do you, if someone is at that zero, that 50th percentile, does that worry you? Or is it a little different in how you look at this?

   10. PAPeter Attia36:58

       Other things factor into this, Nick. I mean, family history factors into it, history of smoking factors into this, current lifestyle, I hate the word lifestyle, but I think you know what I mean. You know, sort of how active is that person, how much weightbearing activity are they doing? So, uh, being male versus female also factors into it a lot. So if I see a woman prior to menopause, so let's say I'm talking about, you know, I got a 42-year-old female patient who's, you know, I might guess three to five years out from menopause, and she already has a low Z-score, that worries me a lot because of what we'll talk about shortly, uh, vis-a-vis the effect of estrogen here and why women are disproportionately affected by estrodin- estrogen withdrawal. But, you know, you've heard me make this, my glib, stupid joke, right? Never in the history of civilization has a 90-year-old person ever been heard uttering, "I wish I was less strong. I wish I had less muscle. I wish my bone density wasn't so high." Right? Impossible.

10. 38:11 – 41:20

    Variability in BMD between sexes

    1. SPSpeaker38:11

       Yeah. You know how Tim Ferriss always asks people on the podcast, you know, what, uh-

    2. PAPeter Attia38:15

       [laughs]

    3. SPSpeaker38:15

       ... what would they put on a billboard?

    4. PAPeter Attia38:17

       Yeah.

    5. SPSpeaker38:17

       I think we've, we've come to the conclusion of what you would 100% put on your billboard.

    6. PAPeter Attia38:21

       That's right. The Peter Attia billboard would just say, "Find me one example in the history of our species where a 90-year-old said, 'I wish I had less strength. I wish I had less muscle. I wish I had weaker bones.'"

    7. SPSpeaker38:36

       Love it. Love it.

    8. PAPeter Attia38:38

       All right, Nick, so pull up figure five.

    9. SPSpeaker38:41

       All right. Got figure five pulled up.

    10. PAPeter Attia38:43

        Okay, so you can see on this graph we're looking at, uh, males versus females, top to bottom, and then we're looking at Mexican American, non-Hispanic white, non-Hispanic Black. So three races, two sexes, uh, six lines. Um, but I just wanna make one thing [clears throat] to the listener a little bit clear, which is on the Y-axis here, you're seeing units of grams per centimeter squared. Earlier, I said grams per centimeter cubed. Why the difference? Well, the difference is [swallows] even though density [clears throat] in real life is measured in grams per centimeter cubed, because you need mass per unit volume, with bone density, it's actually done as grams per centimeter squared because it's a planar measurement, so the DEXA scan is compressing everything to 2D. Does that make sense? 'Cause the scanner is kind of looking at the area of the bone and imputing the density by what electron beam doesn't go through it. So I've always found this a bit confusing, personally, and I've always thought ... I've always wondered why they just can't do this in grams per centimeter cubed, but I, I'll just point that out for, for the astute observer. Okay. I think there are two observations that one would pretty quickly take away from this. The first is that up until, you know, the 20s, men and women are kind of similar, right? You go through a profound increase in BMD from the time you're eight years old until you're about 20 years old. Difference one is that, uh, while women maintain a reasonable plateau, they tend to fall quite precipitously in midlife, and that's obviously due to menopause. We'll talk about why in a moment. I think the second thing that jumps out here is the racial difference. So non-Hispanic Black has a higher BMD for both men and women than non-Hispanic white, which has a higher BMD than Mexican, or Hispanic, in this case Mexican American. So again, slight differences in race. Truthfully, I don't know why that is. Um, but it is what it is. So, uh, to your earlier question, are there differences? Yeah, there are differences on average. Um, I've never, to be honest with you, factored this into my risk ex- assessment except for the male/female one. Um, so in other words, if I look at a patient who's Black versus white versus His- versus Hispanic, I kind of have never assumed one is at more or less risk. I've just said, "Let's do the kitchen sink on everybody." Um, but I think in females, I'm more worried for the reasons that we are obviously talking about.

11. 41:20 – 44:32

    When should people have their first bone mineral density scan?

    1. SPSpeaker41:21

       Yeah. And in looking at this too, and one of the questions we received is, you know, when, when should people do their first bone mineral density scan? You know, when do you want to know that baseline? 'Cause what's interesting when you look at this, and you talked about it, is, you know, from eight to about 20, 22, you see that huge jump, and then it kind of levels off. So what would your recommendation be for when people should get their first one done?

    2. PAPeter Attia41:49

       Gonna get into a lot of hot water here, Nick. So ... But I'm, I'm used to it, right? I've got very, um, unusual recommendations for a lot of things, and this is no different. So I think in the spirit of fairness, I'm going to communicate the standard recommendations first. So when you look at the American Association of Family Physicians, the American College of Obs- Obstetricians and Gynecologists, the American College of Preventative Medicine, the International Society of Clinical Densiometry, the National Osteoporosis Foundation, and more, the typical recommendation Um, is for high-risk people to be 50, um, but typically 65 is sort of when they want to start screening people. Um, and that's for women, and for men, it's typically 70.

    3. SPSpeaker42:43

       That's a lot of credentials you just laid out there. You sure you want to get in hot water with all of those different people?

    4. PAPeter Attia42:49

       No, I, I, I'm just simply stating what they're recommending, and if I've misrepresented that, uh, feel free to correct us. But, um, you know, it's typically recommended, as I said, women at 65, men at 70, follow-up scans no more than every two years. Um, now, for someone who is at serious risk of osteoporosis, which includes men and women over the age of 50, um, you know, they can-- we can adjust those and c- and come down a little bit. Um, now the WHO, I think, is a little bit more aggressive and recommends screening women by the age of 40, if I'm not mistaken. Um, as you can guess, I tend to be closer, uh, in my thinking, uh, to the WHO, and I certainly believe women in their 30s, where we're doing DEXA scans for many reasons, I'm just as interested in their bone mineral density. In fact, when I'm reporting the DEXA results to patients, we have a template that we've made that I really like that lays all of the DEXA information out, right? So segmental BMD, you know, VAT, um, FFMI, ALMI, FMI, all of these things, body fat for what it's worth. I always tell them out of the gate, like, "The one number you care about is your body fat. That's the one I care least about." Um, and yeah, so when we, you know, when we're looking at a 35-year-old patient and their Z-score is already minus one, I mean, that's just as concerning to me as if their OGTT shows, you know, very elevated postprandial glucose and insulin levels. Um, and I'm really happy that I'm seeing that at the age of 35 and not 65.

12. 44:32 – 49:27

    How BMD changes throughout the life and how it differs between men and women

    1. SPSpeaker44:33

       I think a natural follow-up there is, you know, 'cause one of the questions we got from a subscriber was, you know, how does bone mineral density change throughout the life of a man and woman? And we kinda saw it a little bit there, but is there anything you wanna double-click on or dive deeper on as it relates to that?

    2. PAPeter Attia44:50

       Yeah. This is, this is an area where men and women do differ quite a bit. So [clears throat] let's just kinda go back to the beginning, right? So, so you've got most of the growth in the length of a bone and the size of the bone is happening during childhood and adolescence. Um, and that's also when you're really accumulating the mulk-- the bulk of this, the BMD. So if you remember the graph we showed a moment ago, figure five, we don't have to pull it up again, but remember how I said between about the ages of, like, eight and 20, like, BMD was doubling, right?

    3. SPSpeaker45:20

       Yeah.

    4. PAPeter Attia45:20

       So that doesn't just mean that the size of the bones are increasing, which of course it is. As you go from being eight years old to 20 year-years old, you're getting taller, your bones are getting bigger. But that graph was showing you BMD. So that means the density of those bones is also increasing dramatically. So BMD will actually potentially improve up to about the age of 30, but it, it really peaks in the early 20s. It can stay quite flat, uh, certainly in both sexes, till you're about 40 or 50, and then bone loss effectively sinks in. But for women, it is much more pronounced. So for women, about seven to 10 years around the onset of menopause, bone loss can be, you know, three to 7% annually. And by the time they reach 65, it starts to slow down a bit, so it might be, you know, half a percent to 2% per year. Whereas in men over 65, it's actually a higher rate of bone loss, but they're starting at a much higher point 'cause they didn't suffer that precipitous loss the way women did after menosa- menopause. So for men at the age of 65, it's, it's usually more typically about one to 2% per year. Okay. All right, so, so pull up figure six, 'cause I, when I came across this figure, um, one of our analysts pulled this up, I was really surprised. Um, so this is for women. Um, this is showing bone mass, um, by age. So what, what stands out? So again, two things really stand out to me. We've already discussed one, which is you have this pretty significant rise in, uh, bone density between birth and age 20. It then remains relatively plateaued. In this case, menopause kicks in around 50, and then you really start to see the fall. That's the first thing that stands out, and we've talked about that. But look at the other thing, Nick. Look at the dotted line. The dotted line tells you that there's really a totally separate trajectory for this woman, which is if she didn't reach her full genetic potential by the age of 20, she's missed an enormous opportunity later in life. And remember at the outset I said this is a podcast you should care about even if you're a parent of a 10-year-old child? This is why, right? You wanna make sure that your kid's doing the right things when they're 10 to 20 so that they reach their full genetic potential. Now, the good news is that let's say you're on that dotted line and you're 30 years old, and I see these patients, right? So I see the 30-year-old woman who's got the Z-score of minus two, and she's, you know, 15 years away from menopause. Well, the good news is we can get her closer to that solid line by working really, really hard. Now, I, I don't know if we can get her all the way to that line, but we have this window in time before menopause when we can go through all the stuff we're gonna talk about later on pr-- minus the pharmacology, and try to ratchet up that bone mass so that you get to the highest point when menopause kicks in. And you see that reduction of estrogen. And of course, we'll talk about the opportunities there as far as estrogen withdrawal. Uh, if, if you go to the next, uh, slide, Nick, I wanna just kind of talk about one other thing, and it really shows where the bone loss is occurring. So in slide seven here, you're seeing for both male and female the difference between cortical and trabecular bone. Again, remember cortical is the long shaft part of the bone, the trabeculae are the end. And you're seeing the decline for men and women in both of these segments, and I guess what stands out here is where females are losing this BMD. They're losing it primarily in the trabecular or spongy part of the bone. So, you know, interestingly, women are no different than men when it comes to the cortical section of bone. But obviously a significant reduction at the spongy part

13. 49:27 – 54:35

    How changes in estrogen levels (e.g., menopause) impact bone health

    1. PAPeter Attia49:27

       of the bone.

    2. SPSpeaker49:27

       So yeah, I mean, it's super interesting to look at those graphs, and I think, you know, you pointed it out, but it's another one of those things, yeah, where it's like no matter what age you are why you should think about this because especially with people who have children, I know you and I have kids around that age, where you think about, okay, like that eight to 20 window and what you can do because if you, you know, if you look at that original graph and the full genetic potential where they fell off was still higher than the inadequate line of where they plateaued, which is pretty crazy to see is, you know, for people with kids, it's the biggest thing they can do is in that younger age. And you've mentioned this a few different times, and why don't we double-click on it here, which is -- and we did get a lot of questions about this too, which is, you know, what is it about menopause that creates issues in bone health? Why can it lower bone mineral density? So what do you wanna say about that?

    3. PAPeter Attia50:23

       Yeah, so bone cells are really interesting. Um, they're, they're what we call mechanosensory cells, so they actually can sense forces. So if you think of like what a str-- I got-- I, I was go- I was about to explain what a strain gauge is, but I realized that's like way more complicated than necessary, so forget strain gauges.

    4. SPSpeaker50:40

       [laughs] I was gonna say, I, I think you'd have to also explain-

    5. PAPeter Attia50:44

       What a strain gauge is

    6. SPSpeaker50:44

       ... what that is in a lot of detail.

    7. PAPeter Attia50:47

       Yeah. Okay. So, so I'll, I'll say it more simply, right? So think about how muscles act, right? So a muscle by definition has to have attachments to bones, right? That's how the system works. And a muscle's never attached to the same bone 'cause then it wouldn't do anything. Contracting a muscle on the same bone doesn't do anything. So muscles have to go across joints, right? So your bicep actually crosses a couple of joints, right? So you have a bicep that is attached to the bones of the lower arm and then attached to the bones of the upper arm, and so then when, when it contracts, it actually, uh, closes that angle of the arm. Okay, so muscles are attached via tendons to bones. And think about, like, what we do with our muscles. Think about the load we put on those muscles. Well, the very simple laws of physics tell you that the bones have to feel that load, and we often don't think about that, right? We think about, you know, if you're doing a curl with 40 pounds, obviously your bicep muscle is exposed to that. But guess what? The tendon that is attaching the bicep above and below the joint of the elbow is also feeling that. And the bone cells actually sense that load. So if you're lifting something heavy, when you're climbing stairs, your bone senses that they need to support a greater force, and in response to that, it remodels by depositing more and more bone tissue. So bone mass increases in the presence of stress. So it turns out that that signaling process is regulated very heavily by estrogen. Now, I, I think this is just so fascinating. You know, when you think of, like, es- the importance that estrogen plays in reproduction, it, it's -- I, I don't, I don't have a great answer as to why it's estrogen that is the dominant hormone here as opposed to another hormone, but for what it's worth, that stress signap- si- that signal of stress that is basically being relayed by the strain gauge functionally within the, within the muscle to s- within the bone to say, "Hey, it's time to deposit more bone here," that's modulated by estrogen. And so in the absence of estrogen, that signal gets reduced. And that's effectively why menopause, which is a sudden withdrawal of estrogen, is such a devastating thing for women who don't have their hormones replaced. And that's why BMD loss is significant in the postmenopausal woman. Now, to be clear, men are also losing estrogen as they age because for men, estrogen comes primarily from testosterone con- conversion, right? So testosterone is aromatized into estrogen, and so, you know, a man with a testosterone of 800 nanograms per deciliter, all things equal, is gonna have a higher estrogen level than one with 300 nanograms per deciliter, and that's easily could be explained by an aging phenotype to go from 800 to 300. Now, there are other factors that go into that. Um, adiposity can give you more estrogen, et cetera. Um, this might be one example, by the way, of where adiposity helps because you have the additional weight and load that is a strain signal and you have more estrogen, all things equal. So, um, but men lose estrogen at a far more gradual rate than women, and that's why women experience this loss more significantly, and that's why women are at greater risk for osteop- uh,

14. 54:35 – 57:48

    Why HRT is not considered a standard of care for postmenopausal bone loss

    1. PAPeter Attia54:35

       penia and osteoporosis.

    2. SPSpeaker54:36

       Yeah. And one of the questions we received, which I think is a really good follow-up here, is that, you know, someone asked, "Knowing estrogen's role in bone health for postmenopausal women, should bone health be a factor to consider in women who are thinking about starting HRT?"

    3. PAPeter Attia54:53

       Well, I'm about to get into a whole bunch more trouble, Nick. [lips smack] Um, I'll give you the consensus answer. The consensus answer I believe is still no. I believe the consensus answer is HRT is not considered standard of care for post-menopausal bone loss. Um, and I'll tell you why that's the case. The reason for that is not because HRT was not found to decrease fracture risk, which by the way is the gold standard. Like, that is the single most important metric if you're trying to evaluate if HRT would be beneficial. So the Women's Health Initiative, which was, you know, published over 20 years ago, was a seven-year study or so looking at the administration of hormone replacement therapy on post-menopausal women. Worth noting, these women were far outside of menopause. Look, 100 problems with this study, which we'll be going into in, um... I already went into actually, I think, in the podcast with Avrom Bluming and Carol Tavris. So people who wanna get a better sense of HRT really need to go back to listen to that episode. Um, [lips smack] and I think we have an upcoming episode where we'll go into this in more detail. But in that study, there was no ambiguity that the fracture risk was decreased in the women taking HRT. However, that study came to what I believe is an erroneous conclusion, and I think what many people now believe is an erroneous conclusion, that the risk of breast cancer and cardiovascular disease went up. Um, and those risks seem to outweigh the benefits of the reduced fracture risk. So, um, I think that the increase in the risk of breast cancer was virtually nonexistent. It had an absolute risk increase of 0.1%, and I think there are lots of reasons we discuss in that podcast as to why that's the case and why that -- I, I think today we can say with much more clarity that the risk of breast cancer from hormone replacement therapy is virtually nonexistent. Secondly, the risk of cardiovascular disease has been completely ameliorated by the adoption of topical forms of estradiol as opposed to oral forms of estradiol. So in that trial, they used oral estrogen, which actually does slightly increase the viscosity of blood. And in a susceptible woman, that would indeed increase the risk of cardiovascular disease. But again, we don't use oral estrogen anymore, and so that also becomes a moot point. And I think today we actually know that hormone replacement therapy reduces the risk of cardiovascular disease in women and does not increase it. So again, taken all together, these suggest to me that bone health should in fact be a consideration for women as they consider whether or not HRT makes sense for them.

15. 57:48 – 1:02:20

    Factors determining who may be at higher risk of poor bone health

    1. SPSpeaker57:48

       So Peter, another follow-up is, you know, earlier you mentioned that there might be some risk factors for why someone might get screened for bone health earlier. So kind of what should people be aware of if they're thinking about if they're maybe at risk, and what are some of those red flags they should look out for?

    2. PAPeter Attia58:04

       Uh, so you know, it sounds cliche, but family history matters. Uh, and this is actually not something I appreciated until we were getting ready to do this podcast. I didn't realize genetics accounted for up to 50% of bone health. So having either parent that's had a history of a hip fracture, that's a huge red flag. Um, there are other things we wanna care about, right? So we wanna look at fractures related to mild or moderate trauma. So you look at somebody who's had a fall from standing height or less, that's, you know, someone who's fallen from such a low height and still had a fracture, that's a huge problem. Another thing we look at is in female athletes, and this is really common actually in female endurance athletes, especially runners, um, where weight is such an important part of the sport, right? You know, it's, uh, you're, you're punished a lot, uh, in terms of performance for extra weight. Same is true in cycling, not as true in swimming. So when you look at high-end, uh, female endurance athletes, we care a lot about nu- you know, poor nutritional state, which can lead to a very low BMI, low body fat percent, and eventually estrogen deficiency. So these interrelated conditions of the sort of low bone health, hormone dysfunction, and, and low BMI are kinda collectively known as the female athlete triad. So that's another big risk factor. Low BMI in general, so anything below about 18 or 19. And then the other thing we look at is, uh, is people who have had high exposure to drugs that affect bone metabolism, and I think the most common of these that we see is corticosteroids. Now, that's not always systemic corticosteroids. You know, it's not always people that have had to take lots of steroids for illness. It can also be inhaled corticosteroids, and we see this actually in a number of patients who had significant asthma as children and used a lot of inhaled corticosteroids. So those are-- that's not an exhaustive list, but that's a pretty good list to sort of get you thinking about who is at high risk here.

    3. SPSpeaker1:00:01

       Yeah. And you, you mentioned it a little bit at the end there, and we did receive a lot of questions on it, which are around the various drugs that may impair bone deposition. So, um, anything more you wanna say? I know you mentioned a few of them there, but anything you wanna double-click on?

    4. PAPeter Attia1:00:17

       I, I think the last big risk factor we look for, and I-- we just saw a patient recently who didn't have any other risk factors except for the fact that they have a 20-pack-year smoke history that is more than 15 years old. So you barely think of this person as a former smoker 'cause they've been so long without smoking, but, you know, they did smoke for 20 years prior to quitting. Um, and that is an independent risk factor for low, uh, BMD, which in this case, um, this patient had very low BMD. Uh, we actually had to refer them to an endocrinologist.

    5. SPSpeaker1:00:49

       Do you see anything with patients? 'Cause, you know, we know that BMD, the 8 to 20 is such a big age range, and if you have someone who is smoking kind of in that age range while bone mineral density is really going up, do you see it become kind of even worse?

    6. PAPeter Attia1:01:09

       Yeah. Um, that's a great question, Nick. So, uh, I didn't know this until, again, we got thinking about this study. Uh, but there, there are actually data looking at never smokers, early smokers, and late smokers. Early smokers were defined as people who started smoking before the age of 16, and late smokers... Well, it's hard to believe late is considered after 16. Um, but the early smokers were far more impacted. So when you look at these people later in life, the never smokers, not surprisingly, had the best bone density. The early smokers had the worst, and the late smokers were in the middle. Um, I don't know the stats about teenage smoking today. I, I kind of assumed it was on the decline, but, um, you know, this would certainly be yet another, um, reason to avoid smoking at a young age, even if, you know, that person goes on to stop at the age of 20. Um, and even if their risk of lung cancer becomes relatively moot by the time they're, you know, 50, they may still pay a price for that with bone mineral density throughout their entire life.

    7. SPSpeaker1:02:19

       Yeah.

16. 1:02:20 – 1:06:26

    Common drugs that can negatively impact BMD

    1. SPSpeaker1:02:20

       And on the topic of what you talked about a second ago, we also did receive a lot of questions around various drugs that could impair bone deposition. You mentioned a few of them earlier, but is there anything you wanna double-click on there?

    2. PAPeter Attia1:02:34

       So again, you know, corticosteroids, I, I think have to be considered the first and most important one of these drugs you want to be considered about. And, and, and they... Y- You know, I, I think they, they do a couple of things, right? So they kind of impair the mineralization of bone by favoring bone reabsorption during the early phase, and then they kind of inhibit calcium absorption in the gut. That-- This, this area comes up-- This, this comes up over and over again, right? Anything that impairs calcium absorption is going to be problematic. And it, and it really doesn't need to be mega doses of steroids. Um, people who are familiar with long-term use of steroids might recognize that a, a dose of prednisone of five milligrams a day is not enormous. Um, you know, a prednisone dose of five milligrams a day is... I mean, I think it's actually still a kinda big dose 'cause it's about the physiologic equivalent of how much hydrocor- you know, how much cortisol a person makes. Um, but nevertheless, you know, that amount is associated with significant reductions in bone mineral density and an increased risk fracture within as little as three to six months of initiation. Again, just as we saw in the figure that showed how women are primarily losing trabecular bone, it's, it's the same here with, with, with cortisol. So, um, that doesn't mean you should never take, uh, corticosteroids. There are lots of conditions where corticosteroids are going to save your life. It means you have to be aware of these things, and you're gonna have to work a lot harder to counter their effects, uh, and we'll talk about some of those things. Um, another class of drugs that I get asked about a lot is proton pump inhibitors, PPIs. And, you know, I, I would say the data here are less clear. So there are studies that have assessed the relationship between PPIs, and they do show an increase in osteoporotic fracture. Um, the most likely mechanism suggested is, again, intestinal calcium absorption, so anything that interrupts that, which then goes on to interrupt osteoclast formation and bone remodeling. But I, but I wanna be clear that this is not nearly as well understood as the case is for corticosteroids. So there, there are a number of observational studies that show an increase in the risk of fracture. But, you know, then we look at large meta-analyses that don't find a st- a statistica- a statistically significant, uh, decline in BMD with PPI use. Um, so again, I think you just have to be smart about this, right? Um, there are lots of reasons we're gonna put patients on PPIs. If a patient has significant reflux that is not amenable to other treatments, we're gonna put them on a PPI. If a patient has Barrett's esophagus, we're putting them on a PPI. It's non-negotiable, right? So it just means that we have to be thoughtful about, is the drug really indicated? And if it is, what else can we do to reduce the risk down the line? I think the final class of drugs that, um, tend to have a similar association, although probably from a different mechanism, are some of the anti-epileptic drugs, um, and, and one in particular, which is phenytoin, so a super common, uh, anti-seizure drug. Here, I think the mechanism might have more to do with, um, hepat-- like the liver inducing an enzyme called cytochrome P450 that leads to increased catabolism of vitamin D. And that, of course, you may recall, will lead to decreased, uh, absorption of calcium in the gut. I don't know if anybody's done a study, but it seems to me that a no-brainer study would be taking patients on phenytoin and supplementing them with lots of vitamin D to see if you can overcome that. But again, um, you know, phenytoin is a common drug within the world of anti-seizure meds, but in the big picture, nowhere near as common as corticosteroids and proton pump inhibitors.

    3. SPSpeaker1:06:25

       So

17. 1:06:26 – 1:12:00

    How children can optimize bone health and lay the foundation for the future

    1. SPSpeaker1:06:26

       I think where we're gonna go next is starting to look at what people can do to improve their bone health. I think we laid a lot of the groundwork that we need to do, and, um, this next section will get into kind of everything people can do, um, to improve it individually. But before we get to kind of like how you, the person, can do it, um, we did have some questions from subscribers who said, you know, they have kids and they want to improve their bone health, and we've talked about how important it is. So before we get to the individual, is there anything in particular, any advice you would have for people who have kids on those very important ages, you know, the 8 to 20, on what they can do so they can really optimize the bone health?

    2. PAPeter Attia1:07:10

       Yeah, I think this is very important. You know, I, I... When I Stop to think about all of the things that, you know, a parent's got on their plate to try to help their kids with during this relatively narrow window that your kids are in your house and, and, and therefore somewhat amenable to your influence. Um, you know, I think the most important thing probably comes down to being adequately nourished and being very active, and in particular, being very active in things that load bones. So one of the things that was a bit surprising to me was that running didn't have a greater impact on, uh, BMD. So in a moment, we'll pull up that figure, Nick, that I think is pretty interesting, that shows all of the different sports and how they impact BMD. Now, I'm going to posit that the running one has a confounder in there, because if you think about it, running puts a lot of force on muscles, right? I mean, especially when you think about the hips, which are two of the three bones that are attached to muscles that feel exper- that experience great force during running. So why is it that running, where you're potentially, at, at least at the knees, experiencing eight times your body weight with each impact, why wouldn't that do more? And I've been thinking about this for some time, and maybe somebody knows the answer, but my suspicion is that the confounder here is body weight and BMI, right? And that when you talk about elite runners, and usually these are studied in elite runners, they're very weight conscious, right? Running is ... Running and cycling are the ultimate strength to weight, uh, ratio sports. And I do wonder if we're seeing basically malnourished runners. And what do I mean by that? Basically, people that are ... You know, BMI is too low. It might be perfect for being a runner, but it's too low for optimizing bone mineral density. So I guess this is a long-winded way of saying running might not be enough. Um, so obviously running's a great thing to do, and it ha- comes with a lot of benefit. But you probably want to make sure that your kids, both boys and girls, are doing other sports that involve more power, so probably things that involve jumping and actually lifting heavy things. Um, this is kind of a great plug for rucking. You know, I ta- mentioned Michael Easter briefly at the outset. I mean, one of the things that Michael writes about in his book, The Comfort Crisis, is the importance of just walking with heavy stuff, so either doing a farmer's carry, doing a ruck, which I love. You know, I try to ruck five days a week, so it's, you know, backpack with heavy weight in it and just walking around, and, and always trying to find a hill to walk up and down, kind of loading myself, without the knee joints being susceptible to that. Um, so going back to the kids, I think we just wanna make sure BMI is not too low, hormone dysfunction is not there, um, energy availability is, is there, body fat's not too low, all of those things that tend to occur. Obviously, smoking, you know. You know, uh, we obviously wanna make sure nobody's smoking, but a- as, as, as we just talked about, kids beneath the age of 16 are uniquely susceptible to this. So, um, again, it's pretty straightforward. Lots of nutrition, lots of physical activity, and specifically physical activity that builds muscular strength, and ... Because I think that's gonna apply the m- greatest force to the bone, and the bones, as we talked about, are mechanic- uh, mechanical sensory, uh, entities that are going to remodel in proportion to how much mechanical stress they're under. So again, lifting heavy stuff matters, and that doesn't mean that 12-year-olds need to be deadlifting three times their body weight, but we also don't wanna shy away from kids lifting things.

    3. SPSpeaker1:11:17

       Yeah. When you were talking there about the running, I don't think it came up on the Ryan Hall podcast, but it would've been really fascinating if he ever had a DEXA scan when he was in peak running shape compared to his current body type, just with all the muscle he put on, just to see the difference in his BMD.

    4. PAPeter Attia1:11:37

       You know, that's such a good question. I'm gonna, I'm gonna email Ryan as soon as we're done and ask him, because you gotta think at his level, being one of the best runners in the, in the world, that they had a DEXA scan of him at the time. And yeah, I'd love to know what his, what his BMD was, um, you know, when he was 28 versus what it is today. That's a, that's a great question. Thanks for bringing that up.

    5. SPSpeaker1:11:59

       Yeah.

18. 1:12:00 – 1:21:07

    Types of physical activity that can positively impact bone health

    1. SPSpeaker1:12:00

       So the next set of questions fit perfectly with where we're going, which is, you know, a lot of questions on what does physical activity have to do with bone health? You know, you kinda hinted at it. We got a lot of questions on are there certain types of physical activities that is better for bone health than not? We talked a little bit about it just now with kids, but as people who are adults are also thinking about this, what would you say to them?

    2. PAPeter Attia1:12:26

       Well, again, I just wanna go back to what it is about, um, muscles that have such an impact on bones, and this is, this is not always clear, right? So the more force that a muscle is applying to a bone, which is directly related to how much force you're trying to put on the muscle, you know, picking something up, contracting a muscle under an enormous external load. Um, and by the way, I think that can be isometric. I don't think that has to be isotonic. In other words, I don't even think the muscle has to change in length necessarily for that force to be experienced, so there are lots of safe ways to do this. Um, y- you're applying force to the receptors there. Those receptors are translating that tension into signals that say, "Lay down more bone." Okay, so- You know, we looked through some of the literature on this, and I gotta tell you, this is one of those things where I was kinda surprised. Um, I saw some things that I just didn't expect to see. I already mentioned one of them, right? I kinda thought running was gonna be really great. Um, it turned out that studies looking at resistance training found them to be significantly better at retaining BMD, um, when compared to anything aerobic, you know, running, swimming, cycling, and even impact things like pure jumping. So power lifting turned out to be more effective than just regular strength training in maintaining BMD in post-menopausal women. So think about that for a second. When we talk about power lifting as a sport, we're talking about... And, and I've seen women do this at all ages. We're talking about someone doing a squat, a deadlift, and a bench press. And the squat and the, um, deadlift are, you know, that is lumbar spine, that is hip. I mean, that is really stressing the lower body, um, more than just going into the gym and lifting. Okay? And then we talk about high force impact sports such as football and MMA [chuckles] were associated with the highest BMD values. Uh, now again, I, I know you do MMA, um, at least vis-a-vis jujitsu, so you can probably speak to this more about why it's exhausting. You know, I was having dinner with, um, Joe Rogan the other day, and we actually talked about this 'cause, you know, obviously it's such a big part of his life, and I know nothing about it. 'Cause he, he made a comment that nothing exhausts him more than his jujitsu workouts. Um, and you know, Joe does so many things. I was kinda surprised that he said that that is the single most exhausting thing he does. Uh, but I'm guessing you can relate to this?

    3. SPSpeaker1:15:00

       Yeah, I mean, there's, there is nothing more tiring than that, especially on hard rolls. And I don't, I mean, I don't know the physiology behind it, but it's, you just have to go so hard. Your muscles are pushing, pulling. Like there's some-- Like your mind is also going, so it's not like you can zone out. But there'll be days where you have really, really hard rolls, and you just finish, and you just kinda lay there in a heap of sweat for about five minutes before you can do it. You know, I, I do get questions, people who know you and know me, they're, they're always like, "I'm surprised Peter doesn't do jujitsu 'cause it seems like something you would love." Um, I think if it wasn't for the injury aspect of it, because there is... That is a huge concern. It's not really the most longevity-friendly activity you can do. Um, but I think a, a younger you would've been a killer out there. You would've loved it.

    4. PAPeter Attia1:15:55

       Yeah, it's so funny. I think I, I just can't count the number of friends I have that are so obsessed with jujitsu and have been doing it for years. It's not like... I mean, even in high school, one of my closest friends, who was a really good wrestler when I was a boxer, um, he was like, he was the first person I ever knew who did this. This was back when, like, you were just starting to hear about the Gracies. Uh, you know, we're talking early 90s. That was, at least that was the first time I ever heard of the Gracie brothers from him. And, you know, there's probably like two jujitsu gyms in Toronto, and he used to train in this stuff. Um, but yeah, I've had so many friends that have done this, and I, it, it, it looks incredible, but it doesn't appeal to me in any way, shape, or form. Uh, but that's another story. So, um, on the flip side of that, these low weight-bearing, low impact things like walking, swimming, cycling don't really seem to do a lot to improve, uh, BMD. And again, I, I, I don't know if the studies, you know, it hasn't been done, but my suspicion is that when you make those things a little bit harder, especially with, you know, walking with a rucksack and walking uphill, um, you're gonna apply more strain. Also walking downhill. So again, I, when I'm rucking, I'm always trying to find the maximum elevation change, and I, I actually... You know, the walking uphill is harder cardio, but the walking downhill puts more strain on the muscle. And again, the take home point here is the more this strains your muscles, the better this is for your bones.

    5. SPSpeaker1:17:25

       Yeah. I'm gonna pull up that figure as well that you mentioned, metrics and colors and graph for people to see this too.

    6. PAPeter Attia1:17:33

       Yeah. This is, this is an interesting figure. So on the, on the, on the left here, you're just looking at the absolute BMDs. Um, you may also recall just where these units sit, right? So all of these athletes have very high BMDs compared to, you know, what we were looking at is the average man and the average woman. Um, we don't have to flip back to that, but I just, I'm familiar with the numbers. 1.2 grams per centimeter squared was considered a really good BMD for a middle-aged man or woman. Do you rem- do you remember how we've seen that? That number 1.2 is pretty common, right?

    7. SPSpeaker1:18:08

       Yeah.

    8. PAPeter Attia1:18:09

       Okay. So when you're looking at this, just to put in perspective, even the swimmers or, you know, the resistance training, uh, females, and, and females are tending to be a little bit lower than men, um, they still have excellent BMD. So I, I... You know, we do not wanna be suggesting that some sports are bad for BMD. That's not the take home message here. The take home message here is if you really have to juice it, what do you want to be doing? Again, even the distance runners here, all of them. So, so you're... In, in the brown one, in the black one, you know, you have to look at which ones separate men versus, uh, women, right? So for example, like blue, um, sorry, um, red versus, um, green is showing you the difference between male and female resistance training, whereas all the swimmers, all the distance runners, all the track and field athletes are in the same bucket. Now, again, compare distance to track and field. What's the difference? Track and field, more power, right? A sprinter has more force being applied than a distance runner. Um, what I find amazing is the MMA and the football, like [chuckles] I mean, just staggering, right? Now, I'm gonna say something else that's kind of unpopular. Not really sure playing college football is a great strategy for increasing your BMD when it comes with so many other injuries, um, not to mention all the head trauma. So the purpose of this analysis is not to say you gotta go be a college football player. No, it's to just give you a sense of what types of forces are involved in generating higher BMD. And I think most people who have even watched a football game can appreciate the kind of forces that those athletes are experiencing. And as you talked about with MMA, um, you know, incredibly strong forces applied across muscles transmitted to bones.

    9. SPSpeaker1:20:02

       Yeah. No, yeah, good for the bones, bad for the brain. Um-

    10. PAPeter Attia1:20:05

        Right. So what's the sweet spot here? To me, the sweet spot is resistance training, right? All of these things come with risk if you don't do them correctly. I mean, hell, if you don't swim correctly, you're gonna tear your shoulders apart. So w- we just have to think about this through a risk-reward lens. Um, MMA can pr- I don't know anything about it, but I'm guessing it can be done safely. I'm guessing there are ways to do it and not be, you know, not put yourself at risk to tear your meniscus or tear your shoulder or, you know, have a lumbar spine disc blow up because you get folded into a, you know, half like a pretzel. Um, you can hurt yourself resistance training, but also you can not. So, um, i- if you're gonna take one thing away from this, uh, just notice that walking isn't on here, and gardening is not on here, and golf is not on here. So I just ... I want people to understand that if they're in the business of trying to increase their BMD, they have to get wicked forces on their muscles.

19. 1:21:07 – 1:25:50

    How weight loss can negatively impact bone health and how exercise can counteract those effects

    1. SPSpeaker1:21:08

       I feel like you didn't have to do golf like that. I feel like, uh, I j-

    2. PAPeter Attia1:21:11

       I know. I'm just ... I'm making enemies like none. I'm just, I'm just killing myself today here.

    3. SPSpeaker1:21:16

       I know. I feel like that has the potential to be the most thing that we get feedback for. It's like y- you can insult the different organizations, but once you talk about golf like that, there's no coming back.

    4. PAPeter Attia1:21:26

       Again, I'm not saying don't play golf. Look, race car driving's not on here, okay? Archery's not on here. My favorite things in the world aren't on here. Let's do that. All right? Is that, is that an appropriate, you know, uh, mea culpa? Like, the things I love doing are not on here, so I just don't wanna be deluded into thinking that all that time I'm in a race car, I'm increasing my BMD. It's, it's not enough, you know?

    5. SPSpeaker1:21:50

       Yeah. That's a fair-

    6. PAPeter Attia1:21:51

       Gotta be in the gym. Gotta be hitting it.

    7. SPSpeaker1:21:53

       That's a fair trade-off. Peter, we talked a little bit a- about early on the danger of low BMI or extremely low BMI for bone mineral density, and then everything we just talked about on lifting weights, that's gonna ... You know, the more muscle you put on, you're potentially gonna go up in weight. Um, what about people who are overweight and they lose body weight? Does that have an impact on their BMD?

    8. PAPeter Attia1:22:19

       It does, and this is actually super interesting stuff. So, um, we know, for example, that when people lose significant amounts of weight, they're usually losing lean tissue as well. It's one of the trade-offs, and in some people, it's a totally reasonable trade-off. You know, you see somebody who's already got an appendicular lean mass index at the 90th percentile, and their fat mass index is at the h- you know, 99th percentile, y- y- you'll ... You know, you're gonna have them lift like crazy during weight loss because you wanna keep that lean mass up. Maybe it falls to 70th or 80th percentile while you try to get fat mass index down to 60th or 70th percentile. So what about the impact on BMD? Well, there's no question that the correlation between weight loss and a decrease in BMD, exactly what we don't wanna see, in the obese, and in s- in particular in the elderly, is very strong. But it turns out that there are two different strategies for how you can go about losing weight, and the strategy may impact the outcome. Now, we know that any time you lose weight, there has to be a caloric deficit, right? You can't lose weight without a change in en- stored energy. Losing weight is changing stored energy. Stored energy requires caloric imbalance. But when you look at data for people who have lost weight purely through nutritional manipulations, i.e. purely through manners of reducing caloric intake ... And you can do this a lot of ways, right? You can just directly and generally reduce calories. You can do it through time restricted feeding. You can do it through dietary restriction, meaning restricting various elements within the diet. Those people tend to lose bone mineral density. When you look at people who are doing it in combination with significant exercise, they actually tend to gain bone mineral density. So in other words, you can have people losing the same amount of weight. Some of them are losing BMD. Some of them are slightly gaining it. So what could be going on there? Uh, it's been suggested that the BMD reduction due to weight loss may be caused less by the mechanical loading of bones and more by a change in some of the adipose-derived factors like leptin and adiponectin and other hormones that move around when weight loss changes. So leptin goes down, adiponectin goes down. Uh, obviously we talked about the fact that especially in men when they lose weight, but potentially in women too, we see estrogen going down. So it could be that, you know, when you're loading the muscles, and therefore transmitting that load to bones, you're offsetting some of that. Now again, the, the study that I'm citing is relatively small. Um, and the group that was using exercise as their primary tool to lose weight didn't lose quite as much weight, so even when that's corrected for, it could be a little bit of a confounder. But I would just say intuitively this makes sense, and more importantly it from a longevity standpoint, it makes sense, right? I mean, exercise, you know, you've heard me say this 100 times, it's the single most important tool we have anyway, so why wouldn't we employ it as an important part of a weight loss strategy if this is just one of the other, you know, bonuses that comes with it, which is an ability to minimize the BMD, uh, loss that

20. 1:25:50 – 1:29:16

    Nutrition and supplements for bone health

    1. PAPeter Attia1:25:50

       is almost inevitable with weight loss.

    2. SPSpeaker1:25:53

       Yeah. Super interesting. And kind of on that realm, moving from exercise to nutrition and supplements, we do get a lot of questions on how nutrition supplements can impact BMD. Um, one of the first kind of questions we got was, what are some essential nutrients that are important for optimizing bone deposition that people should think about?

    3. PAPeter Attia1:26:17

       Yeah, so if you don't mind, pull up figure 12, 'cause I think, you know, uh, one of our analysts put this together, and I, I think it's, uh, I think it's just a great way to lay all of this out. I think there are the big three you want to think about. Um, so there, there are other things that matter. Protein matters. Total calories matter. All of those things other matter. But when we think about kind of the micronutrient side, the big three are calcium, vitamin D, and when I say vitamin D, I mean D3, and magnesium. So in the first column here, you can see the required daily amounts. Uh, and I consider this a minimum, right? So, so this is, you know, this would be like a letter grade C, right? So you, you might want to think about having a B or an A. So calcium, about 1,000 to 1,200 milligrams daily, vitamin D, 800 to 1,000 IU daily, and magnesium, 300 to 500 milligrams daily. Now, these can be supplemented. So if you can't get this in food, if you're, if you're not sufficiently getting this, either through sunlight in the case of vitamin D and food, calcium carbonate, calcium citrate are reasonable options. In the magnesium school, um, you know, it really depends on what your gut can tolerate, right? So, uh, magnesium citrate, glycinate, and oxide are fantastic if you're looking for a little speed-up of the bowel. If you aren't, you want magnesium carbonate. It's also worth noting magnesium carbonate more fully absorbed than mag oxide, citrate, or glycinate, which is actually why those three help with bowel regularity. So, uh, personally, I like to mix them up. Um, I'm sort of using three forms of magnesium, so I'm supplementing with mag carbonate in the mornings. I use mag oxide, um, at night, and I also use a bit of mag glycinate with L-threonate as well. So, you know, I'm routinely hitting about a gram of magnesium supplemental. And then the final column here is you can sort of see the foods where these things reside, and you can see why I believe most people are magnesium deficient. Um, you know, it's pretty hard, I think, to get 500 grams predictably of absorbed magnesium every single day, and by the way, I think that's a real minimum, right? I mean, I think a, a gram is really where you want to be. It's ... You gotta, you gotta do a little bit of work to make sure you're getting that from your nutrition. Um, and the same-- I think calcium's a bit easier to get if you consume dairy but, you know, look, a lot of plant-based people aren't gonna eat dairy. They have to sort of look to other things, and some of those other things I don't think you really want to be eating a bunch of. Like, look at how high figs are. Dried figs, a cup of those is 300, uh, milligrams of calcium, so that's, you know, a quarter of your daily minimum amount. But, you know, I don't know that I want to be eating a cup of dried figs every day for other reasons. Um, I love tofu, so, you know, but I'm not eating it every day. So, um, again, I, I, I, I think this is something we need to be paying reasonable attention to, uh, both from a dietary standpoint and then for a number of us also from a supplementary standpoint.

21. 1:29:16 – 1:34:53

    Pharmaceutical drugs prescribed for those with low BMD

    1. SPSpeaker1:29:16

       So, Peter, we kind of talked about supplements there along with nutrition, but what about pharma drugs? We did receive questions on what are the options, what are the benefits, what are the trade-offs, what should people be thinking about there as they explore their options?

    2. PAPeter Attia1:29:31

       Yeah, so drugs are typically last line of defense. And, um, just to give you a sense of how last line of defense that is, we personally in our practice do not prescribe these drugs, and the reason for that is we're just not expert enough to do it. Like, I don't, you know-- I, I like to send people to experts when something is out of our hands. So, you know, for example, we're-- we completely run the gamut of all lipid-lowering drugs 'cause we have great expertise in that. When it comes to this class of drugs, we, we refer patients out who need them to endocrinologists. But, you know, basically, I think there's sort of three big classes. But the lion's share is one class, which are the bisphosphonates. So this is a class of drug that strengthen bones by basically slowing the rate at which the osteoclasts remove bone. Remember osteoblasts, B for build, clasts being the opposite. That's, I don't... They just remove it, right? So these kind of exist in two subtypes, nitrogen-containing versus, uh, non-nitrogen-containing. But, you know, the lion's share of these, um, you know, th- there's kind of three big brands, um, or three, three big versions of these. So the, the nitrogen-containing ones are the much more common one. Um, I, I would say people are probably familiar with some of these. So Boniva, you know, Fosamax, Actonel, those, those are the big ones. And the studies are pretty clear, like these things work, right? They increase BMD by about 4% to 6% in the critical areas that matter, the femoral neck, the hip, the lumbar spine, and they reduce the risk of fractures. So, um, the, the drawback here is, you know, they're typically not used for in, you know, indefinite periods of time. So they're kind of discontinued after about five years. Um, and the evidence suggests that that might not increase the r- risk of fracture, uh, going forward. Um, so, you know, there, there may be some, um... It might be that you, you, you, you, you get the value during that five-year window, you rebuild the bone, and then, then you maintain some of that value. The other two classes of drugs here, personally, I don't have a lot of experience with. I haven't even seen my patients be prescribed these, but one of them are monoclonal antibodies, and then the other is just synthetic, uh, parathyroid hormone. Um, so, um, I don't know a lot about those two, to be honest with you. Uh, but we do have some data, I think, here. We have a pretty good, um- Uh, a meta-analysis that sort of shows the efficacy. I think it's slide nine, Nick.

    3. SPSpeaker1:31:54

       Perfect. Got it.

    4. PAPeter Attia1:31:56

       Yeah. So you're looking at, um, uh, uh, the classes of drugs. Okay, so let me just, you know, help people read this a little bit. Any-- So the first one, the, the, the first drug there on each of the lists, that's synthetic, uh, PTH. Anytime you see an AB on something at the end of it, that's the monoclonal antibody. The other drugs that end in ATE, those are all the bisphosphonates, and then the rest are pretty straightforward. Uh, calcium, vitamin D, et cetera. Um, so if you go over to the right, you're looking at odds ratios. Remember, anything that crosses, that is on or crossing the, the unity line of one means it's not significant, and then anything that's to the left of that line, if the confidence interval doesn't cross the one, is significant. So what you can see here is nothing that's on this list is increasing the risk of fractures. About two-thirds of these things in their various formats are reducing the risk of fracture for either hip fractures, vertebral fractures, or non-vertebral fractures.

    5. SPSpeaker1:33:02

       And for people who are looking at this and aren't familiar with this type of graph, when you say to the left of one, it's not the whole black bar. You're looking at the little white box, right?

    6. PAPeter Attia1:33:13

       N- no. So, so the whole, the whole black line has to be to the left of one for it to be significant. The black line is your confidence interval. So for example, let's look at the very first one. Um, and, uh, y- you'll notice that the little white line is way to the left, right? In fact, it's like-

    7. SPSpeaker1:33:30

       Mm-hmm

    8. PAPeter Attia1:33:30

       ... you know, probably 0.4 or something. In fact, if you go and look, you can see it tells you it's 0.42. So that's, that's huge, right? That's like a 58% risk reduction. So you think, "Well, that's gotta be great." But I can tell you right now it doesn't matter because the confidence interval is so wide that it crosses one. That tells me, without looking at anything, that the P value is greater than 0.05, and the confidence interval crosses unity. So when you look over, sure enough, lower limit 0.1, upper limit 1.82, P value 0.24.

    9. SPSpeaker1:34:04

       Yeah. Got it.

    10. PAPeter Attia1:34:05

        Okay.

    11. SPSpeaker1:34:05

        I mean, that's-

    12. PAPeter Attia1:34:05

        Let's pick, let's pick a winner. Let's go two down from there. Actually, these P values are so small, like they're, they're less than 0.- they're probably less than 0.001. Um, but again, so the one beneath that has a very similar little white dot. It's 0.45, so it's not quite as low, but it's a 55% reduction. But I know it's gonna be significant because the confidence interval doesn't cross one, and sure enough, it doesn't. It's 0.27 to 0.68, and the P value is probably 0.000-- You know, it's less than 0.004. They only just show them to two significant figures here.

    13. SPSpeaker1:34:41

        Yeah. And I mean, again, for people interested in diving deeper into that, that AMA you and Bob did on understanding studies and studying studies dives way more into that. So,

22. 1:34:53 – 1:46:07

    Impact of extreme sedentary periods (e.g., bedrest) and how to minimize their damage to bone

    1. SPSpeaker1:34:53

       Peter, one of the things we haven't really talked about yet is what happens in, like, something like space or low-gravity environments? What happens to your bones if you truly aren't using them?

    2. PAPeter Attia1:35:04

       This is obviously not a subject that is relevant to a lot of people directly, but I think indirectly it's res- it's, it's, it's relevant to a lot of people. So this is... You know, space is just the most extreme version of what we would call disuse osteopenia. So as the name suggests, disuse osteopenia occurs when bones are chronically unloaded, leading to a very unfavorable combination of high bone, uh, resorption and low bone formation. So it's the same thing that's happening with the osteopenia from aging. It's just much more accelerated and much more extreme. So again, the most extreme version of this is astronauts. Um, and I don't know much about what they do in space, but I suspect that they go out of their way to figure out ways to load astronauts in space, um, so that, you know, they don't have to deal with this in its highest form. But I think for most people, where this is relevant is bedrest. So lots of people have to undergo bedrest for all sorts of reasons, right? Pregnant women often are placed on bedrest if they are experiencing fetal retardation. Uh, and I mean that not cognitively, but growth retardation, right? So, um, if in the third trimester the fetus isn't growing at the rate that, um, is expected, uh, not uncommon that the OB will ask the mother to gradually reduce her impact until, um, more and more energy can be reserved for the fetus. Uh, you can also see, um, you know, bedrest being necessary for various types of injuries. Uh, of course, we know today that we don't wanna rest people nearly as much as we used to. I mean, there was a day 50 years ago when if somebody hurt their back, they were put on two weeks of strict bedrest. Today, we know that that's absolutely the last thing you wanna do. So bone loss due to, you know, disuse osteopenia is incremental, and it's progressive with time, and it occurs more rapidly, as you would guess, in the trabecular bone than in the cortical bone. So this is the, this is the, um, the trend we've seen over and over again. Um, and frankly, it can be about 2% per month in microgravity partial paralysis, which I should have mentioned as well, right? So, uh, paralysis-based injuries, uh, or, or immobilization with injury. Um, and in the most extreme setting with complete paralysis, it can be up to 7% per month.

    3. SPSpeaker1:37:21

       So Peter, for people who are experiencing, like, that type of immobility, is there anything in particular they should be thinking about or they can do to kinda help with the BMD concern?

    4. PAPeter Attia1:37:34

       Yeah. The first would be any form of PT that can actively load muscles. Um, so I don't know if there's-- I actually don't know how much data exists on this, but that's one of the things that I think is interesting about cyclic BFR, and that's why The minute I was out of surgery, I got permission from my surgeon to put my, you know, Kaatsu cuffs on my arm and just start cycling the BFR. I wanted to put little bits of stress on that bicep just to have it moving. And again, keep in mind, I was very fortunate. I did not have a bicep tendon repaired. If I did, I would not have been allowed to do that. Um, but, you know, I had to keep my arm completely immobilized, but I was still able to get sort of compression on the bicep. And, um, you know, basically, if you, if ... Let's say you're bedridden with a certain injury, there are still other muscles in your body that don't pertain to that injury that can still be moved and put under load, and even if you're doing these things isometrically, right? So a person is holding you, and you're resisting against them without actually moving in the bed. That's important. Now, there was a super interesting mouse study that we found that, um, used, uh, a bisphosphonate to inhibit the osteoclastic bone resorb- resorption, um, in a mouse model where the mice were given, uh, botulinum toxin to basically prevent them from moving, I think, one part of their leg. So if you ... I think, I think we have this figure here as well. Um, yeah, it's figure 10. Yeah, so what you're looking at here is in the, the first bar on the left is, uh, just sort of the baseline, and then you have control mice in black, and then in white you have what happens to the animal that were just given botulinum toxin. So these were the animals that were basically immobilized, um, because the, you know, botulinum toxin, of course, paralyzes their legs. And then the botulinum toxin plus the bisphosphonate on the right. And I, I think this is a pretty profound result, right? You're looking at this in the femoral neck and in the middle of the, um, the upper part of the femoral bone, uh, below the neck. And you can see that the bisphosphonate plus the immobility really looks no different from the control. And it's a, you know, clear contrast to how the untreated animal looks. So, you know, look, these are 16-week-old female mice. Uh, you know, is this gonna be true in humans? I have no idea, but I, I find this type of research very interesting, and frankly, I hope more people are doing this type of research because I think immobility is a huge problem with everybody. But once you start to deal with an aging population, it becomes more significant. How many times have we talked about that study where, um, you know, a group of 65-year-olds, I believe, were immobilized for two weeks and lost, if I'm not mistaken, something of the neighborhood of about four pounds of lean mass in two weeks? And that, you know, we talked about that through the lens of how much you lose lean mass, but think about what that's doing to, to BMD, and think about how long people are immobilized beyond two weeks, um, especially as they're older.

    5. SPSpeaker1:40:46

       I can't remember offhand, but I know you and Inigo in the second podcast also talked about, um, lactate as it relates to immobility for people on bedrest or in the ICU as well. We'll link to it in the show notes, but you also had a conversation about the importance of, you know, people in the hospital just moving for the lactate levels. So we've seen it over and over across a lot of podcasts.

    6. PAPeter Attia1:41:13

       Well, I mean, that was, that was a pretty exhaustive tour of all things bone, but I don't know. I think this is super important stuff. Uh, I know it's not that sexy. I know that, uh, y- you know, you're not gonna see, you're not gonna see too many Twitter wars about, uh, BMD, although I did probably provide enough substrate for someone to get upset about something I said today, whether it be my position on golf not being the perfect BMD-boosting sport or my, uh, recommendations for earlier screening on BMD. I think there was something else I said that will draw the ire of critics, but ...

    7. SPSpeaker1:41:49

       Yeah, we just better hope that one of those organizations doesn't sponsor an ad in Golf Digest, 'cause then we'll just get it from all fronts. But no, I mean, I think it was good, and I think hopefully it answered a lot of questions. Again, we compiled these questions. We've gotten them a lot, and we've never kind of tackled it at this level and, um, kind of like what we did with muscle and looking at the importance of muscle strength, muscle mass, and kind of what improves there, and then looking on the other side at, uh, the bones too. So hopefully people enjoyed it, and until the next AMA, we'll see.

    8. PAPeter Attia1:42:22

       Sounds good.

    9. SPSpeaker1:42:22

       Ho- hopefully you, uh, don't stay up too late watching Ozark, new season tonight.

    10. PAPeter Attia1:42:27

        I don't get to even start it tonight.

    11. SPSpeaker1:42:29

        How, like, how do you have that self-control?

    12. PAPeter Attia1:42:32

        No, uh, Jill and Olivia are, uh, out of town for a volleyball tournament, so I'm solo with the boys this weekend, and I ... You know, Jill would kill me if I started it without her, so ...

    13. SPSpeaker1:42:43

        Yeah, something tells me you won't have a lot of solo time solo with two boys either, so you'll probably have your hands busy.

    14. PAPeter Attia1:42:49

        I will.

    15. SPSpeaker1:42:50

        All right.

    16. PAPeter Attia1:42:51

        Okay.

    17. SPSpeaker1:42:51

        Well, good luck with that.

    18. PAPeter Attia1:42:52

        Thanks, man.

    19. SPSpeaker1:42:53

        All right. We'll see ya.

    20. PAPeter Attia1:42:55

        Bye. [upbeat music] Thank you for listening to this week's episode of The Drive. It's extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free. So if you wanna take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. Premium membership includes several benefits. First, comprehensive podcast show notes that detail every topic, paper, person, and thing that we discuss in each episode, and the word on the street is nobody's show notes rival ours. Second, monthly Ask Me Anything, or AMA, episodes. These episodes are comprised of detailed responses to subscriber questions, typically focused on a single topic, and are designed to offer a great deal of clarity and detail on topics of special interest to our members. You'll also get access to the show notes for these episodes, of course. Third, delivery of our premium newsletter, which is put together by our dedicated team of research analysts. This newsletter covers a wide range of topics related to longevity and provides much more detail than our free weekly newsletter. Fourth, access to our private podcast feed that provides you with access to every episode, including AMAs, sans the spiel you're listening to now and in your regular podcast feed. Fifth, the Qualies, an additional member only podcast we put together that serves as a highlight reel featuring the best excerpts from previous episodes of The Drive. This is a great way to catch up on previous episodes without having to go back and listen to each one of them. And finally, other benefits that are added along the way. If you want to learn more and access these member only benefits, you can head over to peterattiamd.com/subscribe. You can also find me on YouTube, Instagram, and Twitter, all with the handle PeterAttiaMD. You can also leave us a review on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor-patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take all conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit peterattiamd.com/about, where I keep an up to date and active list of all disclosures. [outro jingle]

Episode duration: 1:46:07