Navigating bone health: early life influences and advanced strategies for improvement and injury prevention (#214 rebroadcast)

27:14But I assume the reason for that is that's where the fractures are. We see people that have atromatic 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 is very high. So that's where the diagnosis is made. So again, osteophenia, 10 % reduction in BMD, osteoporosis, 25 % reduction in BMD. And again, these are made to healthy individuals. Healthy bone to osteophenia to osteoporosis, it's just a continuum. But osteoporosis and osteophenia are distinct in the degrees to which BMD has been reduced.

27:58And 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 fat and the benefits 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? Yes. So DexA is a super, super low radiation scan. Nothing like a CT scan 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 differently by bones and soft tissues. So it's able to differentiate between adipose tissue, bone, and lean tissue or non -adipose tissue.

28:46I will say this, not all dexascanners are created equal. So if you want to know your bone health, make sure before you go and get the dexascane, 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 metric, but they won't give it to you segmentally. 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, you have to make sure, of course, that the dexas capable of doing that.

29:27But just to remind you for people, we talked about this in another episode, but we were always surprised at how easy it is to get a Dexascane, 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 $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 want to look for? You want to make sure when you're doing a Dexa again, if you care about knowing the full BMD, you're going to pay more for that segmental analysis.

30:03So when you talk about those scans that are like in the 125, even up to 150, a lot of times they aren't showing everything. They're just giving you body composition and usually visceral fat now. You'll say up to $400 typically if you want to see everything. But again, you're going to pay more in New York and San Francisco than you're going to pay in Austin, Texas. For example, I pay like 125 for mine, but I'm not getting the full BMD analysis because I've already had it done and my BMD is high, so I don't need to screen that frequently. Not at the right that I screen everything. The other things you want to look at, you obviously want to 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.

30:44Obviously, 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. Those are kind of the things I want to see along with BMD. Let's say you and a friend are going and getting your BMD done through a Dexascan, is there going to be variability that exists in bone density between different people? Let's say even if someone didn't have osteopheny or osteoporosis, can there just be natural variability between different types of people? Yeah, and it's also important to understand the number you're going to get. 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?

31:26It'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 may recall the idea of a normal distribution, which is a bell curve function. A z -score is basically telling you where you lie on that distribution. So as 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 have a higher bone mineral density than 50 % of people and a lower bone density than 50 % of people.

32:18If your z score is plus one, it means you are one standard deviation above the mean, which means you have a higher bone density than 82 .5 % of the population and a lower bone density than 17 .5 % of the population. If your z -score is plus 0 .2, it means you are two standard deviations above the mean. 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. I'm sorry I may have missed but the Z score is comparing you to your age when I say the population.

33:08The 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? If If you're 60, you want to compare yourself to not only a 30 -year -old, but also other 60 -year -olds. That's correct. 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? You know, VO2 max you want to be elite in a decade younger for BMD. 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?

33:48other things factor into this Nick 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? How active is that person? How much weight -bearing activity are they doing? Being male versus female also factors into it a lot. So if I see a woman prior to menopause, let's say I got a 42 -year -old female patient who's 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. vis -a -vis the effect of estrogen here and why women are disproportionately affected by estrogen withdrawal.

34:30You've heard me make this 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. You know how Tim Ferriss always asked people on the podcast, well, but they put on a billboard. We've come to the conclusion of what you would 100 % put on your billboard. That's right. The Peter Tia 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.

35:11So Nick, before we leave this point, Let's just pull up figure five and show some of the sex differences and race differences. Yep. Got to pull that. Okay, so you can see on this graph, we're looking at 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, six lines. But I just want to make one thing 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 even though density 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 plane or measurement.

36:00So the dexascane is compressing everything to 2D. Does it make sense? Because 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. I've always found this a bit confusing personally. I've always wondered why they just can't do this in grams per centimeter cube, but I'll just point that out for the astute observer. Okay, there are two observations that one would pretty quickly take away from this. The first is that up until the 20s, men and women are kind of similar. You go through a profound increase in BMD from the time you're eight years old until you're about 20 years old.

36:40Difference one is that 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. 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, but it is what it is. So, to your earlier question, are there differences? Yeah, there are differences on average.

37:22I've never, to be honest with you, factored this into my risk assessment, except for the male female one. So in other words, if I look at a patient who's black versus white 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. But I think in females, I'm more worried for the reasons that we are obviously talking about. And then looking at this too, and one of the questions we received is, when should people do their first bone mineral density scan? You know, when do you want to know that baseline? Because 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.

38:04So what was your recommendation be for when people should get their first one done? I'm going to get into a lot of hot water here, Nick, but I'm used to it, right? I've got very 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. When you You look at the American Association of Family Physicians, the American College of Obstetricians and Gynecologists, the American College of Preventative Medicine, the International Society of Clinical Denseometry, the National Osteoporosis Foundation, and more.

38:38The typical recommendation is for high -risk people to be 50, but typically 65 is when they want to start screening people. That's for women and for men, it's typically 70. It's a lot of credentials. You just light out there. Are you sure you want to get in hot water with all of those different people? No, I'm just simply stating what they're recommending. And if I've misrepresented that, I feel free to correct us. But it's typically recommended, as I said, women at 65, men at 70, follow -up scans, no more than every two years. Now, for someone who is at serious risk, a osteoporosis, which includes men and women over the age of 50, we can adjust those and come down a little bit.

39:20Now, the WHO, I think, is a little bit more aggressive and recommends screening women by the age of 40, if I'm not mistaken. As you can guess, I tend to be closer in my thinking to the WHO. And I certainly believe women in their 30s, where we're doing dexas cans for many reasons. I'm just as interested in their bone mineral density. In fact, when I'm reporting the dexar results to patients, we have a template that we've made that I really like that lays all of the DexA information out. Segmental BMD, VAT, 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.

40:04That's the one I care least about. When we're looking at a 35 year old patient and their Z score is already minus one, that's just as concerning to me as if their OGTT shows very elevated post -prandial glucose and insulin levels. And I'm really happy that I'm seeing that at the age of 35 and not 65. I think a natural follow up there is, because one of the questions we got from the subscriber was, how does bone mineral density change throughout the life of a man and woman? And we kind of sought a little bit there, but is there anything you want to double click on or dive deeper on as it relates to that?

40:40This is an area where men and women do differ quite a bit. 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. That's also when you're really accumulating 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 twenty BMD was doubling. 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 old, you're getting taller, your bones are getting bigger.

41:10But 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 really peaks in the early 20s. It can stay quite flat, 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 3 to 7 % annually. 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 because they didn't suffer that precipitous loss the way women did after menopause.

42:02So for men at the age of 65, it's usually more typically about 1 to 2 % per year. So pull up figure 6. When I came across this figure, one of our analysts pulled this up, I was really surprised. So this is for women, this is showing bone mass by age. Again, two things really stand out to me. We've already discussed one, which is you have this pretty significant rise in bone density between birth and age 20. it then remains relatively plateaued, in this case, Manipaz 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.

42:41But 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. You want to make sure that your kids 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?

43:24So I see the 30 -year -old woman who's got the Z -score of minus two and she's 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 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 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 and draw.

44:02If you're the next slide, Nick, I want to just 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 trebecular bone. Again, remember, cortical is the long, shaft part of the bone, the trebeculae 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 trebecular or spongy part of the bone. So interestingly, women are no different than men when it comes to the cortical section of bone.

44:42But obviously a significant reduction at the spongy part of the bone. Yeah, I mean, it's super interesting to look at those graphs and I think you pointed out 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, that 8 to 20 window and what you can do because 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 for people with kids. It's the biggest thing they can do is in that younger age.

45:20And you've mentioned this a few different times and why don't we double click on it here, which is what is it about menopause that creates issues in bone health, why can it lower bone mineral density? So what do you want to say about that? Yeah, so bone cells are really interesting. They're what we call mechanosensory cells. So they actually can sense forces. So if you think about how muscles act, a muscle by definition has to have attachments to bones, right? That's how the system works. And a muscle is never attached to the same bone because then it wouldn't do anything. Contracting a muscle on the same bone doesn't do anything.

45:59So muscles have to go across joints. So your bicep actually crosses a couple of joints. 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 that when it contracts, it actually closes that angle of the arm. Okay, so muscles are attached, the attendance to bones. And think about 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. We think about you're doing a curl with 40 pounds. Obviously, your bicep muscle is exposed to that.

46:44But 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. It turns out that that signaling process is regulated very heavily by estrogen. I think this is just so fascinating. You know, when you think of the importance that estrogen plays in reproduction, I don't have a great answer as to why it's estrogen that is the dominant hormone here, as opposed to another hormone.

47:37But for what it's worth, that's signal of stress that is basically being relayed by the strain gauge 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 conversion.

48:20right? So testosterone is aromatized into estrogen, a man with a testosterone of 800 nanograms per desoleter, all things equal is going to have a higher estrogen level than one with 300 nanograms per desoleter. 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. Adiposity can give you more estrogen, et cetera. 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. 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 osteophenia and osteoporosis.

49:04One of the questions we received, which I think is a really good follow -up here, is that someone asked knowing estrogen's role in bone health for postmenopausal women, and should bone health be a factor to consider in women who are thinking about starting HRT? Well, I'm about to get into a whole bunch more trouble. 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 postmenopausal bone loss. 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.

49:49That 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 published over 20 years ago, was a seven -year study or so looking at the administration of hormone replacement therapy on postmenopausal women, worth noting these women were far outside of menopost. A hundred problems with this study, which we'll be going into. I already went into actually, I think, in the podcast with A from Blooming and Carol Tavris. So people who want to get a better sense of HRT really need to go back to listen to that episode. I think we have an upcoming episode where we'll go into this in more detail.

50:25But 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. And those risks seemed to outweigh the benefits of the reduced fracture risk. I think that the increase in the risk of breast cancer was virtually nonexistent. It had an absolute risk increase of 0 .1%. I think there are lots of reasons we discuss in that podcast as to why that's the case and why that today we can say with much more clarity that the risk of breast cancer from hormone replacement therapy is virtually nonexistent.

51:09Secondly, 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 in a susceptible woman that would indeed increase the risk of cardiovascular But again, we don't use oral estrogen anymore. And so that also becomes a moot point. And I think today we actually know at hormone replacement therapy reduces the risk of cardiovascular disease in women and does not increase it. So again, taking 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.

51:56So, Peter, another follow -up is earlier you mentioned that there might be some risk factors for why someone might get screened for bone health earlier. 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? You know, it sounds cliché, but family history matters. 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. having either parent that's had a history of a hip fracture, that's a huge red flag. There are other things we want to care about, right?

52:28So we want to look at fractures related to mild or moderate trauma. So you look at somebody who's had a fall from standing height or less, 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, where weight is such an important part of the sport. You're punished a lot in terms of performance for extra weight, the same as true in cycling, not as true in swimming. So when you look at high -end female endurance athletes, we care a lot about poor nutritional state, which can lead to a very low BMI, low body fat percent, and eventually estrogen deficiency.

53:11So these interrelated conditions of the low bone health, hormone dysfunction, and low BMI are collectively known is the female athlete triad. So that's another big risk factor. Low BMI in general. So anything below about 18 or 19. The other thing we look at 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. Not always people that have had to take lots of steroids for no reason. 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.

53:50That's not an exhaustive list, but that's a pretty good list to get you thinking about who is at high risk here. 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 anything more you wanna say, I know you mentioned a few of them there, but anything you wanna double -click on. I think the last big risk factor we look for, we just saw a patient recently who didn't have any other risk factors, except for the fact that they have a 20 -pack your smoke history that is more than 15 years old.

54:22So, you barely think of this person as a former smoker because they've been so long without smoking, but they did smoke for 20 years prior to quitting, and that is an independent risk factor for low EMD, which in this case, this patient had very low EMD. We had to actually refer them to an smoking in that angriage while bone mineral density is really going up. Do you see it become even worse? That's a great question. Nick, I didn't know this until again, we got thinking about this study. 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.

55:08Well, it's hard to believe late is considered after 16, but the early smokers were far more impact it. 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. I don't know the stats about teenage smoking today. I kind of assumed it was on the decline, but this would certainly be yet another reason to avoid smoking at a young age, even if that person goes on to stop at the age of 20. And even if their risk of lung cancer becomes relatively moot by the time they're 50, they may still pay a price for that with bone mineral density throughout their entire life.

55:52We also did receive a lot of questions around various drugs that could impair bone deposition. You mentioned a few of them earlier, but is anything you want to double click on there? So again, corticosteroids, I think, have to be considered the first and most important one of these drugs you want to be considered about. They do a couple of things. They the mineralization of bone by favoring bone reabsorption during the early phase, and then they kind of inhibit calcium absorption in the gut. This area comes up over and over again. Anything that impairs calcium absorption is going to be problematic.

56:25And it really doesn't need to be mega doses of steroids. People who are familiar with long -term use of steroids might recognize that a dose of prednisone of five milligrams a day is not enormous. Prednisone dose of five milligrams a day is, I think it's actually still a big dose because it's about the aphysiologic equivalent of how much hydrochordisol a person makes. But nevertheless, 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 the same here with cortisol.

57:03That doesn't mean you should never take 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. And we'll talk about some of those things. Another class of drugs that I get asked about a lot is proton pump inhibitors, PPI's. And I would say the data here are less clear. So there are studies that have assessed the relationship between PPI's, and they do show an increase in osteoporotic fracture. The most likely mechanism suggested is again, an intestinal calcium absorption.

57:40So anything that interrupts that, which then goes on to interrupt osteoclast formation and bone remodeling. But I want to be clear that this is not nearly as well understood as the case is for corticosteroids. There are a number of observational studies that show an increase in the risk of fracture. Then we look at large meta -analyses that don't find a statistically significant decline in BMD with PPI use. I think you just have to be smart about this. There are lots of reasons we're going to put patients on PPI's. If a patient has significant reflux that is not amenable to other treatments, we're going to put them on a PPI.

58:17If a patient has Barrett's esophagus, we're putting them on a PPI. It's non -negotiable. 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 tend to have a similar association, although probably from a different mechanism are some of the anti -epileptic drugs, and one in particular, which is phenetone, so a super common anti -seizure drug. Here I think the mechanism might have more to do with liver inducing an enzyme called cytokrome P450 that leads to increased catabolism of vitamin D, and that, of course, you may recall, will lead to decreased absorption of calcium in the gut.

59:03I don't know if anybody's done a study, but it seems to me that a no -brainer study would be taking patients on fennitoin and supplementing them with lots of vitamin D to see if you can overcome that. But again, fennitoin 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. I think what we're going to go next is starting to look at what people can do to improve their bone health. I think we made a lot of the groundwork that we need to do and And this next section will get into everything people can do to improve it individually.

59:36But before we get to how you, the person can do it, we did have some questions from subscribers who said 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 eight to 20 on what they can do so they can really optimize the bone health. I think this is very important when I stop to think about all of the things that parents got on their plate to try to help their kids with during this relatively narrow window that your kids are in your house and therefore somewhat amenable to your influence.

1:00:17The 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. One of the things that was a bit surprising to me was that running didn't have a greater impact on 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, especially when you think about the hips, which are two of the three bones that are attached to muscles that experience great force during running.

1:01:04So why is it that running where you're potentially, 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. and that when you talk about elite runners, and usually these are studied in elite runners, they're very weight conscious. Running and cycling are the ultimate strength to weight ratio sports. And I do wonder if we're seeing basically malnourished runners. And what do I mean by that?

1:01:41Basically people that are, BMI is too low. Might be perfect for being a runner, but it's too low for optimizing bone mineral density. I guess this is a long and good way of saying, running might not be enough. Obviously running is a great thing to do and it 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. This is kind of a great plug for rocking. I 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.

1:02:25Either doing a farmer's carry, doing a ruck, which I love. You know, I try to ruck five days a week, backpack with heavy weight in it, and just walking around. And always trying to find a hill to walk up and down, kind of loading myself without the knee joints being susceptible to that. But going back to the kids, I think we just want to make sure BMI is not too low. Chormone dysfunction is not there. Energy availability is there. Body fat is not too low. All of those things that tend to occur. Obviously, smoking, we obviously want to make sure nobody's smoking. But as we just talked about, kids beneath the age of 16 are uniquely susceptible to this.

1:03:03So again, it's pretty straightforward. Lots of nutrition, lots of physical activity, and specifically physical activity that builds muscular strength because I think that's going to apply the greatest force to the bone and the bones as we talked about our mechanical sensory entities that are going to remodel in proportion to how much mechanical stress they're under. So 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 want to shy away from kids lifting things. when you were talking there about the running, I don't think it came up on the Ryan Hall podcast, but it would have been really fascinating if he ever had a Dexascan 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.

1:03:54You know, that's such a good question. I'm going to email Ryan as soon as we're done and ask him because you got to think at his level being one of the best runners in the world that they had a Dexascan of him at the time. And yeah, I'd love to know what his BMD was when he was 28 versus what it is today. The next set of questions fit perfectly with where we're going, which is a lot of questions on what is physical activity have to do with bone health. You kind of 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.

1:04:31What would you say to him? Well, again, I just want to go back to what it is about muscles that have such an impact on bones. This is not always clear. 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, picking something up, contracting a muscle under an enormous external load. And by the way, I think 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.

1:05:07You're applying force to the receptors there. Those receptors are translating that tension into signals that say lay down more bone. Okay. So we looked through some of the literature on this and I got to tell you, this is one of those things where I was kind of surprised. I saw some things that I just didn't expect to see. I already mentioned one of them, right? I kind of thought running was going to be really great. It turned out that studies looking at resistance training found them to be significantly better at retaining BMD when compared to anything aerobic running, swimming, cycling, and even impact things like pure jumping.

1:05:40So powerlifting turned out to be more effective than just regular strength training in maintaining BMD in postmenopausal women. So think about that for a second. When we talk about powerlifting as a sport, we're talking about, 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 deadlift, that is lumbar spine, that is hip, I mean, that is really stressing the lower body, more than just going into the gym and lifting. And then we talk about high -force impact sports such as football and MMA were associated with the highest BMD values.

1:06:14I know you do MMA, at least vis -a -vis jiu -jitsu, so you can probably speak to this more about why it's exhausting. You know, I was having dinner with Joe Rogan the other day and we actually talked about this. It's such a big part of his life and I know nothing about it. He made a comment that Nothing exhausts him more than his jiu -jitsu workouts. Joe does so many things. I was kind of surprised that He said that that is the single most exhausting thing he does, but I'm guessing you can relate to this There is nothing more tiring than that especially on hard rolls I mean, I don't know the physiology behind it but you just have to go so hard, your muscles are pushing, pulling, 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 lay there and heep a sweat for about five minutes before you can do it.

1:07:04I do get questions, people who know you and know me there, but always like, I'm surprised Peter doesn't do a jiu -jitsu because it seems like something you would love. I think if it wasn't for the injury aspect of it because that's a huge concern, It's not really the most longevity friendly activity you can do a younger you would have been a killer out there You would have loved it. I just can't count the number of friends I have that are so obsessed with Jiu -Jitsu Even in high school one of my closest friends who was a really good wrestler when I was a boxer He was the first person I ever knew who did this this was back when he were just starting to hear about the Gracies now we're talking early 90s.

1:07:43That was the least that was the first time I ever heard of the Gracie brothers from him There's probably two Jiu Jitsu gyms in Toronto and he used to train in this stuff. But yeah, I've had so many friends that have done this and it looks incredible, but it doesn't appeal to me on any way, shape or form. 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 the MD. And again, I don't know if the study hasn't been done, but my suspicion is that when you make those things a little bit harder, especially with walking with a Rucksack and walking up Hill.

1:08:17You're going to apply more strain also walking downhill. So again, when I'm rucking, I'm always trying to find the maximum elevation change. 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. I'm going to pull up that figure as well that you mentioned earlier, which puts metrics and colors and graphs for people to see this too. Yeah, this is an interesting figure. On the left here, you're just looking at the absolute BMDs. You may also recall just where these units sit.

1:08:54All of these athletes have very high BMDs compared to what we were looking at as the average man and the average woman. We don't have to flip back to that, but I just am 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 remember how we've seen that number 1 .2 is pretty common? Okay, so when you're looking at this, just to put in perspective, even the swimmers or the resistance training females, then females tend to be a little bit lower than men, they still have excellent BMD. So I do not want to be suggesting that some sports are bad for BMD.

1:09:34That'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. Look at which one's separate men versus women, right? So for example, red versus 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. A sprinter has more force being applied than a distance runner.

1:10:05What I find amazing is the MMA and the football. I mean, just staggering. Now, I'm going to 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, not to mention all the head trauma. So the purpose of this analysis is not to say, you've got to 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 Incredibly strong forces applied across muscles transmitted to bones good for the bones bad for the brain Right, so what's the sweet spot here to me the sweet spot is Resistance training 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 going to tear your shoulders apart.

1:11:02So we just have to think about this through a risk -reward lens. MMA, I don't know anything about it, but I'm guessing it can be done safely. I'm guessing there were ways to do it and not be, you know, not put yourself at risk to tear your miniscus or tear your shoulder or have a lumbar spine disc blow up because you get folded in half like a pretzel. You can hurt yourself resistance training, but also you can not. If you're going to take one thing away from this, just notice that walking isn't on here and gardening is not on here. and golf is not on here. 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.

1:11:40Feel like you didn't have to do golf like that. I feel like out of every... I know, I just, I make an enemies like, I'm just killing myself today here. I know, I feel like that has a potential to be the most thing that we get feedback for it. You can insult the different organizations, but once you talk about golf like that, there's no coming back. And I'm not saying don't play golf. Look, race car driving is not on here, okay? Arturie's not on here. My favorite things in the world aren't on here. Is that an appropriate mea culpa? The things I love doing are not on here. I just don't want to be diluted into thinking that all that time I'm in a race car, I'm increasing my BMD.

1:12:14It's not enough. I gotta be in the gym, I gotta be hitting it. So Peter, we talked a little bit about early on, the danger of low BMI, extremely low BMI, for bone mineral density. And then everything we just talked about on lifting weights, It's the more muscle you put on, you're potentially gonna go up and wait. What about people who are overweight and they lose body weight? Does that have an impact on their BMD? It does, and this is actually super interesting stuff. 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.

1:12:50And in some people, it's totally reasonable trade -off. You see somebody who's already got an app -indicular lean mass index at the 90th percentile and their fat mass index is at the 99th percentile, you're going to have them lift like crazy during weight loss because you want to 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 want to see in the obese, and particularly in the elderly, is very strong.

1:13:27But it turns out that there are two different strategies for how you can go about losing weight, and the strategy may impact the outcome. We know that anytime you lose weight, there has to be a chloric deficit. You can't lose weight without a change in stored energy. Losing weight is changing stored energy. Stored energy requires chloric 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 that you can do this a lot of ways, right? You can just directly and generally reduce calories.

1:14:08You 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. 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. What could be going on there? 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 adipanectin and other hormones that move around when weight loss changes.

1:14:55So leptin goes down, adipanectin goes down. 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 when you're loading the muscles and therefore transmitting that load to bones, you're offsetting some of that. Now again, the study that I'm citing is relatively small. 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.

1:15:30And more importantly, from a longevity standpoint, it makes sense. I mean, exercise, you know, you've heard me say this a hundred 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 bonuses that comes with it, which is an ability to minimize the BMD loss that is almost inevitable with weight loss. Moving from exercise to nutrition and supplements, we do get a lot of questions on how nutrition supplements can impact BMD. One of the first questions we got was, what are some essential nutrients that are important for optimizing bone deposition that people should think about?

1:16:12If you don't mind, pull up figure 12. One of our analysts put this together and I think it's a great way to lay all of this out. I think they're the big three you want to think about. There are other things that matter, protein matters, total calories matter, all of those things other matter. But when we think about the micronutrient side, the big three are calcium, vitamin D, and when I say vitamin D, I mean D3 and magnesium. In the first column here, you can see the required daily amounts. And I consider this a minimum. This would be like a letter grade C. You might want to think about having a B or an A.

1:16:44So 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 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, it really depends on what your gut can tolerate. 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 knowing magnesium carbonate more fully absorbed than mag oxide citrate Glucinate, which is actually why those three help with bowel regularity.

1:17:32Personally, I like to mix them up. I'm sort of using three forms of magnesium, so I'm supplementing with mag carbonate. In the mornings, I use mag oxide at night, and I also use a bit of mag Glucinate with L3 and 8 as well. 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. 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. I think that gram is really where you want to be.

1:18:11You got to do a little bit of work to make sure you're getting that from your nutrition. Calcium is a bit easier to get if you consume dairy, but look, a lot of plant -based people aren't going to 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 milligrams of calcium. So that's quarter of your daily minimum amount. But I don't know that I want to be in a cup of dried figs every day for other reasons. I love tofu, but I'm not eating it every day.

1:18:39So I think this is something we need to be paying reasonable attention to, both from a dietary standpoint and then for a number of us also from a supplementary standpoint. What about farmer drugs? We did receive questions on one of the options, one of the benefits, one of the trade -offs, what should people be thinking about there as they explore their options? Yeah, so drugs are typically last line of defense. 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.

1:19:09I like to send people to experts when something is out of our hands. For example, we completely run the gamut of all lipid lowering drugs, because we have great expertise in that. When it comes to this class of drugs, we refer patients out who need them to endocrinologist. But basically, I think just 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 strengthened bones by basically slowing the rate at which the osteoclasts remove bone. Remember osteoblast B for build, clasps being the opposite, they just remove it. These kind of exist in two subtypes, nitrogen containing versus non -nitrogen containing.

1:19:48but the lions share of these. There's kind of three big versions of these. So the nitrogen containing ones are the much more common one. I would say people are probably familiar with some of these. So, Boniva, Phosamax, Actonell, those are the big ones. And the studies are pretty clear, like these things work. They increase BMD by about four to six percent in the critical areas that matter. The femoral neck, the hip, the lumbar spine, and they reduce the risk of fractures. The drawback here is they're typically not used for indefinite periods of time. So they're discontinued after about five years.

1:20:21And the evidence suggests that that might not increase the risk of fracture going forward. It might be that you get the value during that five -year window, you rebuild the bone, and 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 parathyroid hormone. I don't know a lot about those two to be honest with you. We do have some data, I think here. We have a pretty good meta -analysis that shows the efficacy.

1:20:54I think it's slide nine, Nick. Perfect. Got it. You're looking at the classes of drugs. Okay. So let me just help people read this a little bit. The first drug there on each list, that's synthetic 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 best phosphonates and then the rest are pretty straightforward. Calcium, vitamin D, etc. If you go over to the right, you're looking at odds, ratios. Remember, anything that is on or crossing 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.

1:21:37So 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. 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? No, so 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.

1:22:14You'll notice that the little white line is way to the left. In fact, it's probably 0 .4 or something. In fact, if you go and look, you can see it tells you it's 0 .42. That's huge, right? That's like a 58 % risk reduction. So you think, well, that's got to 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. Okay, let's pick a winner.

1:22:51Let's go two down from there. Actually these p values are so small, they're probably less than 0 .001. But again, so 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 going to 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 .00. You know, it's less than 0 .004. They only just show them to two significant figures here. For people interested in diving deeper into that, that AMA you and Bob did on understanding studying studies and studying studies, dives way more into that.

1:23:31Peter, one of the things we haven't really talked about yet is what happens in something like space or low gravity environments? What happens to your bones if you truly aren't using them? This is obviously not a subject that is relevant to a lot of people directly, indirectly, it's relevant to a lot of people. Space is just the most extreme version of what we would call disuse osteopenia. As the name suggests, dysusostopenia occurs when bones are chronically unloaded, leaving to a very unfavorable combination of high bone, resorption, and low bone formation. It's the same thing that's happening with the osteopenia from aging.

1:24:07It's just much more accelerated and much more extreme. So again, the most extreme version of this is astronauts. 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 so that 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. Pregnant women often are placed on bedrest if they are experiencing fetal retardation. And I mean that not cognitively, but growth retardation. If in the third trimester, the fetus isn't growing at the rate that is expected, not uncommon that the OB will ask the mother to gradually reduce her impact until So more and more energy can be reserved for the fetus.

1:24:56You can also see bedrest being necessary for various types of injuries. Of course, we know today that we don't want to 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 want to do. Bone loss due to dysususopenia 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 trend we've seen over and over again. And frankly, it can be about 2 % per month in microgravity, partial paralysis, which I should have mentioned as well, paralysis -based injuries, or immobilization with injury.

1:25:35And in the most extreme setting with complete paralysis, it can be up to 7 % per month. So Peter, for people who are experiencing that type of immobility, is there anything in particular they should be thinking about or they can do to kind of help with the BMD concern? The first would be any form of PT that can actively load muscles. 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 katsu cuffs on my arm and just start cycling the BFR.

1:26:11I 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 repair. And if I did, I would not have been allowed to do that. I had to keep my arm completely immobilized, but I was still able to get compression on the bicep. 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.

1:26:44That's Now, there was a super interesting mouse study that we found that used a bisfossinate to inhibit the osteoclastic bone resorption in a mouse model where the mice were given botulotoxin to basically prevent them from moving, I think, one part of their leg. I think we have this figure here as well. Yeah, it's figure 10. Perfect. Got that pulled up. So what you're looking at here is in the first bar on the left is the baseline and then you have control mice in Black and then in white you have what happens to the animal that we're just given botulotoxin So these were the animals that were basically immobilized because botulotoxin of course paralyzes their legs and then the botulotoxin plus the Bisfosfinate on the right.

1:27:33I think this is a pretty profound result. You're looking at this in the femoral neck and in the middle of the upper part of the femoral bone, below the neck. And you can see that the gusphosphonate plus the immobility really looks no different from the control. And it's a clear contrast to how the untreated animal looks. You know, look, these are 16 -week -old female mice. Is that going to be true in humans? I have no idea. But 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.

1:28:13How many times have we talked about that study where a group of 65 -year -olds, I believe, were immobilized for two weeks and lost, if I'm not mistaken, something that neighborhood of about four pounds of lean mass in two weeks? We talked about that through the lens of how much you lose lean mass, but think about what that's doing to BMD and think about how long people are immobilized beyond two weeks, especially as the older. I can't remember offhand, but I know UN, in you go, in the second podcast, also talked about lactate as it relates to immobility for people on bedraster and the ICU as well.

1:28:50We'll link to it in the show notes, but you also had a conversation about the importance of people in the hospital just moving for the lactate level. So we've seen it over and over across a lot of podcasts. That was a pretty exhaustive tour of all things bone, but I think this is super important stuff. I know it's not that sexy. You're not gonna see too many Twitter wars about 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 recommendations for earlier screening on BMD.

1:29:29I think there was something else I said that will draw the eye of critics. Yeah, we just better hope that one of those organizations doesn't sponsor an ad in golf digest because then we'll just get it from all fronts. But hopefully I'd answered a lot of questions again. We compiled these questions, we've gotten them a lot and we've never tackled it at this level. And like what we did with muscle and looking at the importance of muscle strength, muscle mass, us what improves there and then looking on the other side of the bones too. So hopefully people enjoyed it and until the next AMA, we'll see you.

1:30:00Don't stay up too late watching Ozark, the new season tonight. I don't get to even start it tonight. How do you have that self control? Jill and Olivia are out of town for a volleyball tournament. So I'm solo with the boys this weekend and Jill would kill me if I started it without her. 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. Well, well, good luck with that. Thanks, man. We'll see you. Bye. Thank you for listening to this week's episode of The Drive. Head over to peteratia -md .com forward slash show notes if you want to dig deeper into this episode.

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