The future of bone health
Endocrinologist Joy Wu says that osteoporosis can affect more than half of women and a quarter of men over 50 – often without symptoms until a fracture changes everything, leading to a loss of mobility and independence.
Wu explains why bones weaken with age and how to strengthen them through exercise and smart medicine. Her lab is exploring innovative drugs and turning skin cells into new bone-forming osteoblasts. We’re delving into the great mystery of building new bone and making old bones stronger, Wu tells host Russ Altman on this episode of Stanford Engineering’s The Future of Everything podcast.
Transcript
[00:00:00] Russ Altman: This is Stanford Engineering's The Future of Everything, and I'm your host, Russ Altman. I thought it would be good to revisit the original intent of this show. In 2017 when we started, we wanted to create a forum to dive into and discuss the motivations and the research that my colleagues do across the campus in science, technology, engineering, medicine, and other topics. Stanford University and all universities, for the most part have a long history of doing important work that impacts the world, and it's a joy to share with you how this work is motivated by humans who are working hard to create a better future for everybody. In that spirit, I hope you will walk away from every episode with a deeper understanding of the work that's in progress here, and that you'll share it with your friends, family, neighbors, coworkers as well.
[00:00:48] Joy Wu: We can make bone, we can make osteoblast in the lab. It takes a really long time and, uh, it's a very low yield, so not super-efficient. Something that we're a little bit more excited about more recently is, uh, direct reprogramming. So that's, um, an approach where we can actually take skin cells, uh, right now we can do it in mice, uh, and we can basically, uh, convert them directly into bone forming osteoblasts, uh, much more quickly, um, and more efficiently.
[00:01:21] Russ Altman: This is Stanford Engineering's The Future of Everything, and I'm your host Russ Altman. If you're enjoying the show or if it's helped you in any way, please consider rating and reviewing it on whatever app you listen to. We'd love to get a 5.0 if we deserve it, but just tell us what we deserve. Your ratings help spread the word about the podcast, so everyone is clued in to The Future of Everything. Today, Joy Wu will tell us that weak bones or osteoporosis is an affliction that affects both women and men. She's working hard to create new treatments to build strong bones. It's the future of bone health. Before we get started, another reminder, I always say it, please rate and review the show.
[00:02:02] Bones are a miracle. We have 206 of them, we humans, and they do support of our stature, they protect our organs, they make blood products in the bone marrow. They make hormones and they store minerals. They also heal when we break them, so they're kind of amazing. But you know what? Sometimes a large number of us, both men and women, can get weak bones through osteoporosis, weakening, and thinning of the bones. This is a problem because it can lead to fractures, fractures in your spine, which can cause pain and disability and fractures of your hip, which can be very disabling and often associated with lots of other sickness and morbidity. Well, Joy Wu is a professor of endocrinology at Stanford University and she's looking hard with her colleagues on ways to build that bone back up with medications. The key piece there is understanding the basic biology of how bones are built and how they are broken down, and make sure that we can modulate that balance so we're doing more building up then breaking down. Joy, to start out with, why have you decided to devote your work to bone health?
[00:03:12] Joy Wu: Bones are really fascinating. Uh, you know, I think they're sort of underappreciated. Uh, they, you know, we're used to the idea that they provide mechanical support, and they protect our organs. But, um, while I was doing my clinical training in endocrinology, I became aware of all the other things they do, like producing hormones. Um, and then for the sake of my lab, maybe the most interesting thing is that they support the blood cell production in the bone marrow. So ever since I think high school biology, uh, I've known that hematopoiesis takes care, takes place in the bone marrow cavity, but never really thought about it, um, until I was doing my research in bone biology and realized, you know, the bone forming osteoblasts on the inside surface of bone are actually very closely opposed to hematopoietic stem cells and the other lineages of hematopoietic cells. I mean, it turns out those interactions are really critical for, uh, both bone health and normal hematopoiesis. And I've always f found the intersection of two very, uh, fields to be very fascinating.
[00:04:10] Russ Altman: Great. Great. Thanks very much. And so, um, when we think about bones, I think just thinking from a non-professional perspective, we think of calcium. So, I guess one place to start is calcium, uh, and its role in bone health. Uh, I, I guess we have to eat it. We have to absorb it, we have to make sure it gets into the bones. I know we're gonna get in a few minutes to some of the disorders, uh, of bone biology. But tell me about the role of calcium.
[00:04:36] Joy Wu: Sure. So, calcium is, um, part of the mineral in the bone. That's what makes bones so strong. So, calcium and phosphate, um, are stored within the bone, and so it is important to have enough calcium both through, uh, dietary either, um, calcium based, uh, dairy products or, um, calcium supplements. Um, it's enough to have, it's important to have enough so that our bones can be strong and uh, and resist fractures.
[00:04:59] Russ Altman: Yes. And, and vitamin D plays in there somehow too, doesn't it?
[00:05:03] Joy Wu: Right. Yeah. So, vitamin D is important 'cause that's what helps, um, us absorb the calcium from our diet. Um, so it acts on the intestine and increases the absorption efficiency.
[00:05:13] Russ Altman: So, so one thing I wanted to ask, and I think we all know this, but many injuries, um, you know, you have scars and, you know, and sometimes the, the tissue doesn't grow back, but many of us have broken a bone and one of the kind of remarkable things is that we, uh, as long as things are working okay, we often get like almost a hundred percent of our bone back, uh, in the, it's in the right shape. It's, it's still providing strength. Uh, do we understand what's, why this amazing property of bone, where does it come from? Uh, because it seems like it sure would be nice if like our brain or our lungs could do similar things.
[00:05:49] Joy Wu: Yeah, I think the, um, the ability of bone to regenerate is really interesting. And, um, and also the developmental biology. Most adults have 206 bones and, uh, almost every single one is differently shaped, that they fit together perfectly. So, it's really a beautiful example of, uh, development. Um, but you're right. So, when you have a fracture, for the most part, you know, our bones are able to heal themselves. So, we have both cells that break down the bone called osteoclasts and cells that make bone, the ones that are referred to earlier called osteoblasts, and somehow, they're able to work together along with the, all the other, um, cells in the microenvironment and repair that bone pretty much back to normal.
[00:06:26] Russ Altman: It's just, it's just amazing. And I, I've benefited, benefited from it once or twice and um, you know, sometimes you get these little aches, like when it's humid out, hot and humid, or cool and humid, you get little bone aches that remind you that you used to have a fracture. Do we know anything about why that happens? 'Cause I think it's a pretty common experience that people say, oh yeah, my old fracture aches when it's cold and damp outside.
[00:06:50] Joy Wu: Yeah. You know, it's interesting. One of the reasons we have to screen for, um, osteoporosis is because for the most part, we don't think that we can feel, uh, bones, but clearly when you listen to patients, uh, they can sense, you know, that's quite a common report is that if they've had a previous fracture or sometimes at their joints, um, there's certainly nerves that, uh, innervate the bone and bone marrow cavity. So that makes sense that they must be transmitting some kind of signals back. Um, and, you know, maybe that repair process didn't, um, didn't happen completely and, and something changed a little bit about those nerve signals that are sending back.
[00:07:23] Russ Altman: Or, or may, or I've always thought, it's your body reminding you that there's been this accident and let's not, let's not try to do it again. Um, okay, so you said the magic word, or at least one of the magic words for your work is osteoporosis. And I think this is something that's on a lot of people's minds. Uh, I, I don't know if we would call it an epidemic, but it's certainly on a, we're seeing a lot of it. And so maybe, uh, give us a, a landscape of osteoporosis, what kind of health burden it creates for, uh, for the nation or for the world and, and where we are in understanding it.
[00:07:53] Joy Wu: Sure. So, um, osteoporosis, uh, quite simply is a disease of aging usually that is, uh, associated with a decrease in, um, bone mass, the amount of bone we have. And, um, how much bone we have is usually determined by that balance between formation versus resorption. And as we age, the resorption starts to accelerate a little more. In women, after menopause, it accelerates even more. That's why women are more prone, uh, to having osteoporosis. It's a very common, uh, disorder. So probably half of women over the age of 50 and um, a quarter of men, uh, can expect to have a fracture due to osteoporosis sometime in their lifetime. Uh, so it's quite common.
[00:08:34] Russ Altman: So, tell me, what are the kind of clinical manifestations, uh, uh, how does somebody know that they should even be worried about this? Hopefully before they have a pathological fracture or something that really is life changing. We'll get to that as well. But, but what, what are the symptoms or so to speak of osteoporosis?
[00:08:50] Joy Wu: Well, so one of the tricky things about um, diagnosing osteoporosis is there are really very few symptoms. It's a little bit like high blood pressure, right? It's something that we call silent. So, um, for that reason we often do clinical screening with, um, bone density scans or DEXA scans. Um, uh, usually, you know, the warning signs, unfortunately, other than that, than that, are fractures. So, what we call fragility fractures. So, fractures that happen without, uh, a major trauma. So of course, if you were in a, a terrible car accident or if you fell off, you know, the roof of a building, you would expect to have some fractures. But, um, you know, I trained in New England and so if you slipped on the ice and uh, fell on your wrist, uh, many people have hip, uh, wrist fractures then. Um, and that's, that's the sign that maybe the bones are more fragile than they should be.
[00:09:36] Russ Altman: Are there, are there risk, other risk factors? Uh, you mentioned women after menopause. I was surprised to hear that 25% of men, 'cause I don't think of osteoporosis as a disease of men. So, um, what are the kinds of risk factors, uh, earlier in your life or any time in your life that you can kind of be aware of?
[00:09:54] Joy Wu: So, uh, some things are other diseases like some endocrine disorders, hyperthyroidism, hyperparathyroidism. Um, some medications. Glucocorticoids are a very common cause of osteoporosis. Um, so treatment for inflammation. Um, and, uh, the area that I specialize in is, uh, largely, uh, breast cancer patients. So, women undergoing endocrine therapy because you're blocking the estrogen signaling, they're at, uh, significant risk for bone loss and fractures. Um, and otherwise, uh, you know, excessive alcohol, uh, current smoking, um, it's one of the diseases for which being thin is actually, uh, a risk. So, people who are, um, on the thinner side of average, uh, can have higher risk of fractures. Um, and then, uh, there's some genetics. So particularly if you've had a parent who's had a hip fracture, uh, your own risk of a fracture goes up.
[00:10:48] Russ Altman: Great. Great. Now a couple of questions about that. One is, you mentioned glucocorticoids. Um, many people are on puffers, like, uh, um, for their asthma or for their COPD. Does that increase the risk, or does it have to be systemic pills?
[00:11:04] Joy Wu: Yeah, that's a great question. So mostly we think about, um, the systemic, so oral or IV, uh, steroids and, and really, we're talking about pretty high doses for prolonged periods of time, more than three to six months, um, continuously. So, um, in the days, for instance, in, um, many rheumatologic disorders, before they had all of these new, um, immune modulatory agents, it was quite common for patients to have very high doses of steroids for months or years on end. Uh, thankfully we're seeing less of that now. I think many of the diseases that used to be treated predominantly with high dose steroids, there are a lot of other alternatives now.
[00:11:40] Russ Altman: Great. And, and another thing is, uh, as someone myself who is, uh, let's just say not getting younger, um, I'm, uh, very aware of increased recommendations for weight-bearing exercise. And you're, you're seeing more people at 50, 60, 70 years old going to a gym and lifting weights. Um, I presume this is at least partially motivated by bone health reasons. Is that, is that right?
[00:12:01] Joy Wu: Yeah. No, I think of it as the opposite of, you know, when we send astronauts up into space, they actually lose a tremendous amount of bone density because of being in microgravity. So, um, we do need to, uh, continuously load our bones. They're very responsive to mechanical forces. So, one of the ways that you can mitigate bone loss is to really be diligent about strength training. And one of the things that's become clear is that, um, you always want to challenge yourself. So even as you get older, um, you know, you, you might not be lifting the same amount of weight as you did when you were 20 years old, but it should still be enough to constantly challenge, uh, and, and build, um, build strength.
[00:12:40] Russ Altman: Great. So, okay, now the, now I have one personal anecdote, which is that yesterday at my doctor's appointment, uh, I was one and a half inches shorter than my peak height, uh, when I was, you know, a young man, let's say 30 years ago. And, and, and I was very surprised that my doctor offered me, he actually wound up not recommending it, but he said, oh, maybe we should think about a DEXA scan. And I was surprised by this, but he said, because of my loss of height, you know, this would probably, might be because of my vertebrae, kind of, I guess, kind of getting squished. Um, and so, um, is this loss of height, is this something that people are paying, obviously I'm very concerned about it all of a sudden. Uh, I knew this was happening, of course, this wasn't the first measurement, but um, it reached an inch and a half of yesterday and so it was kind of like, wow. Um, I'm gonna have to like, change my driver's license. So, so I guess my question is, uh, is this a normal process, a little bit loss of height and does that indicate a, an increased risk for, um, osteoporosis? I'm now thinking about my 25% of brethren, uh, which I might be joining.
[00:13:44] Joy Wu: Yes, exactly. So, I mean, it is an important point that I always try to make that, um, we think of osteoporosis mostly as a disease of women. Um, but it is something that affects men. It tends to be later, um, in life than for women because there is not really a menopause equivalent. Um, but it is underdiagnosed and undertreated for men. Um, so usually, you know, I start to really think about it when the height loss is two inches or more. Um, but it's, you know, I think not, not a bad idea to, um, get screening because it is often underdiagnosed in men and because there are a lot of things that we could do to sort of mitigate the bone loss. There are a number of reasons why people can lose height over time. But I think the one that, um, you're worried about and, uh, and I would be wanting to rule out as well is, uh, spine fracture. So, your vertebra should be rectangular boxes, but over time they can, um, sometimes compress slightly, sometimes compress all the way. Uh, and those are the, you know, spine fractures, vertebral compression fractures, uh, and those, those are definitely a sign of fragility and osteoporosis. So, um, it's something to think about for men.
[00:14:46] Russ Altman: Yeah. Well, thank you. I was, I was blaming my running because of the pounding on the, on the, uh, asphalt. But we'll see, we'll see. And that's a story that we'll, we, we won't have to go into anymore. Okay. Let's get to one of the areas of, I know of your, uh, strongest interest, and you mentioned it briefly before, which is especially the interaction of bones with cancer, and we think about this in many ways. You already mentioned that some sorts of chemotherapies can reduce the calcification and the strength of the bone. We all have heard about bone metastases being a kind of terrible outcome of some cancers, so maybe give us the landscape of the, uh, the relationship between bones and cancer, which I'm sure is quite complex and is what you focus on.
[00:15:25] Joy Wu: Yeah, so, um, it's, it's an area where sort of my clinical practice in my, uh, laboratory-based research really dovetail, uh, quite, uh, in a very satisfying manner. So, uh, clinically, I think there's sort of, uh, two major issues that we're very interested in. One of course, is that when cancer is, um, metastatic or widespread, stage four, uh, one of the most common sites that cancers of many types like to go is to the bone. And there are a variety of reasons for that. Um, it's thought that since, uh, under normal circumstances, your bones are supporting hematopoiesis, um, and those interactions between osteoblasts and blood cells, uh, it's thought that cancer cells can somehow hijack those molecular signals. Um, and that might be why cancer cells are somehow, um, recruited, enticed to go to the bone marrow and sort of take up residence and become metastasis.
[00:16:14] So, um, certainly there's a, a very strong interest because it is such a common feature of widespread, um, advanced late-stage cancers that, uh, it's something that, you know, we've as a field been really working hard to try to understand so that we can prevent. Um, more commonly, at least within breast cancer, you know, 95% of women are thankfully diagnosed when it's still early stage, so localized, um, still to the breast. Um, but because the majority, uh, of breast cancers are estrogen or progesterone receptor positive, the good news is that we can use endocrine therapy, hormone blockade, to try to reduce the recurrence. Um, and of course, that's, uh, the predominant goal. Um, but that comes at the cost that when you reduce estrogen in bone, uh, bone loss is a well-known effect. Uh, and so my clinical practice is largely based on, um, trying to mitigate the bone loss in women who are undergoing endocrine therapy for their breast cancer.
[00:17:09] Russ Altman: Yeah. So, what kind of tools do you have? I can see that this is like a, a terrible dilemma because of course, curing the cancer and hitting it as hard as the patient can tolerate to try to clear it is the number one goal, but then if you're successful, there's a, there's a lifetime of, of bone health, that becomes a very important issue. Um, how are the medications for helping, uh, build bone, uh, especially in the, the folks who are at having osteoporosis, either from, uh, what I'll call natural causes or because of intensive chemotherapy or the cancer process itself.
[00:17:41] Joy Wu: Yeah, and sometimes those overlap, uh, a lot of women who are diagnosed with breast cancer are in fact postmenopausal. Uh, and so you could already have underlying causes for bone loss that are then aggravated by the endocrine, uh, therapies. So fortunately, we have really good medications that we can use to manage this process. So, uh, I tell patients that the treatment of osteoporosis is pretty straightforward. We have two choices. We can either block bone resorption by the osteo class or we can promote bone formation, uh, by the, um, osteoblasts. So, the first class of medications are the antiresorptives. And they are by far the most commonly prescribed for routine osteoporosis. Um, but also, they work very effectively in patients with cancer who might be losing, uh, bone either directly because of chemotherapy or because of endocrine, um, blockade, uh, as we were discussing. So those medications work really well. Um, in the lab, one of the things we're really interested in is that, uh, the anabolic treatments for osteoporosis, the ones that stimulate bone formation.
[00:18:43] Russ Altman: Yes.
[00:18:44] Joy Wu: Um, the physicians are still not quite sure whether they're safe in cancer, and the reason is because, at least in animal studies, um, the original anabolic agent was recombinant parathyroid hormone. And there's quite a bit of interest in PTH acting on the bone marrow microenvironment to stimulate hematopoiesis. In fact, it's one of the things that we study in the lab. And so, there's,
[00:19:06] Russ Altman: Hematopoiesis is just the creation of blood cells that happens in the bone marrow.
[00:19:10] Joy Wu: Correct. Thanks for clarifying. Right. So again, the osteoblasts are really important for supporting the production of these, uh, blood cells in the marrow. And, uh, there's a lot of evidence from animal studies that, um, parathyroid hormone, and its receptor in bone, play an important role in that process. And so, the worry is that if you use recombinant, uh, parathyroid hormone to promote bone formation, um, and I mentioned earlier that maybe cancer cells like to hijack some of these signals within the bone marrow. Maybe we're actually making the bone marrow microenvironment more welcoming to cancer. That's a theoretical concern. Um, but it's, uh, because of the lack of safety data, it's something that, um, uh, physicians have been reluctant to use bone forming medications in cancer patients. Um, but it's one of the things we've been studying in the lab and actually we found that if you're a mouse with breast cancer, we can actually decrease bone mets, um, by treating with, uh, recombinant PTH. So, we're trying to understand sort of the mechanisms and hopefully someday translate that for patients.
[00:20:10] Russ Altman: And of course, one thing that I, I think you said it already, that promotes bone growth is estrogen, but giving that to a woman with breast cancer, right, is, uh, kind of out of the question because of its potential role in stimulating the, the breast cancer cells.
[00:20:25] Joy Wu: Right. So, um, so we certainly don't wanna give estrogen itself. Um, there are some very cool pharmacology in the selective estrogen receptor modulators or SERMs, um, like Tamoxifen, which, um, acts as a sort of partial agonist in bone, but an antagonist in breast. And so, um, the, uh, they're used very effectively to, um, both prevent and, and limit the recurrence of breast cancer, uh, because again, they block the effects of estrogen in the breast while being somewhat protective in the bone.
[00:20:56] Russ Altman: This is The Future of Everything with Russ Altman. We'll have more with Joy Wu next. Welcome back to The Future of Everything. I'm Russ Altman and I'm speaking with Joy Wu from Stanford University. In the last segment, we got a tutorial about the basics of bone biology. Say that 10 times fast. In this segment, Joy's gonna tell us about some exciting work with stem cells. You can take a skin cell and turn it into a bone cell. It's a miracle. Joy can do it, and she'll tell us what's the status of getting more bone cells to build up bone more quickly and effectively in patients who need it.
[00:21:45] So Joy, I know that you have an active research effort in the use of stem cells and, and, and my guess is that you talked about the osteoclasts, which break down bone and the osteoblasts. And it seems to me that maybe, and you can tell me if I'm right, getting more of those osteoblasts and having them be more aggressive in the creation of bone would be a great thing in some cases. So where are we and tell me about the stem cells in, in bone biology?
[00:22:10] Joy Wu: Um, yeah, you're absolutely right, Russ, we're really interested in how to have osteoblasts make more and stronger bone, um, and how to stimulate them. One of the limitations of the bone building medications I mentioned earlier is that at the moment they all have to be delivered by a needle, which, um, as you can imagine, makes them less popular. So, some are daily self-injections, some are monthly injections in the clinic. Wouldn't it be great if we had, um, a, a pill, for instance, that could stimulate bone formation. So, we've been interested in a number of approaches in the lab. Um, the first is just understanding the signaling pathway. So why is it that recombinant parathyroid hormone works to, um, activate your osteoblast and is there a way that we can accomplish the same thing?
[00:22:50] Um, again, maybe in a pill form or, um, bypassing. One of the sort of conundrums in the clinical world right now is that the effects of PTH only work for about a year or two. Um, and so you can build bone for about, uh, two years and then it sort of levels off. Um, and so there seems to be some kind of set point the body, uh, recognizes. And, and the other challenge is that once we stop the anabolic agent, that bone goes away very quickly unless we immediately follow it with a, um, anti-resorptive medications. So, um, you know, one of the great mysteries is how do we build new, new bone, um, make bones stronger and then keep it there? Um, and so that's one of the things we're studying from a signaling perspective.
[00:23:31] Russ Altman: So, let, so let me ask about that if I could. I'm sorry to interrupt. The, um, what you said it works for a year or two and then stops. Is it stopping because it's gotten you to a normal bone density and so we all should be perfectly happy, and it won't go past normal? Or is it not even getting to normal and for some reason just petering out before you get to the, the point that you would say, this is a perfectly normal bone.
[00:23:55] Joy Wu: Yeah, it's a great question. Um, you know, whether the set point is recognizing some sort of normal, I think, um, for the most part it seems to be, you know, uh, more, just as much as you can get over, uh, one to two years and then it plateaus. And there's a lot of, um, theories in the field right now. One of them is that maybe the stem cells that give rise to osteoblasts got exhausted and you just simply ran out of the, you know, uh, workhorses of bone formation, and so you need a little time to recover. Um, there, there does seem to be some sort of set point recognized because as I mentioned, if you stop the medication without doing anything else, uh, it, it will all disappear very quickly. The osteoclasts will sort of, uh, break down the bone again, and, and you'll basically go back to where you started. So, um, you, you don't wanna spend two years giving yourself injections every day only to end up where you were before you did that.
[00:24:49] Russ Altman: Good. Well, I'm sorry about that interruption. I just was very interested. But you were talking then about the signaling systems and, and, and what you're studying to try to, um, get around all this.
[00:24:58] Joy Wu: Yeah. So, um, so certainly understanding how parathyroid hormone works, uh, it intersects with another pathway called Wnt signaling. So those two right now are the targets for the two classes of bone building medications that we do have available. So clearly, they're very effective at building bone and we're trying to understand how they work and whether we can, um, accomplish them in a, in a safe and sustained manner. Um, the other approach we're taking is, um, like many other labs, trying to see if we can harness the power of stem cells, uh, to make osteoblast. So, we've tried a number of approaches. We've used, um, embryonic stem cells.
[00:25:34] Um, what we call induced pluripotent stem cells where you take, uh, skin cells and reprogram them. And we, we can make bone, we can make osteoblasts in the lab. It takes a really long time and, uh, it's a very low yield, so not super-efficient. Something that we're a little bit more excited about more recently is, uh, direct reprogramming. So that's, um, an approach where we can actually take skin cells. Uh, right now we can do it in mice, uh, and we can basically, uh, convert them directly into bone forming osteoblasts, uh, much more quickly, um, and more efficiently. Uh, and so that's,
[00:26:09] Russ Altman: So, lemme make sure I understand. So, in the old fashioned, so to speak, reprogramming, you took the skin cell, you turned it into a, what you called an induced pluripotent cell. This is like a, a, a cell that can turn into many things. Neural tissue, muscle tissue, and then you turned it into bone. But now there's this new kind of shortcut it sounds like, where you go directly and it also, by the way, sounds like a miracle where you go from a skin cell directly to an osteoblast, uh, by injecting various factors into the cells and, but, and so that's exciting because then this is derived from the patient's own body, like this, the patient's skin, and then a presumably it would be then injected back into that patient. So, there should be no issue of rejection. But I think what you were saying a moment ago is that your yields are still low, so you might try this thousands of times and only get a few of these osteoblasts. And so is, I just wanted to make sure I'm, I'm hearing properly.
[00:27:02] Joy Wu: Um, so, uh, it seems to be much more efficient. Uh, the problem with the original approach where you took skin cells and turned them into pluripotent stem cells is it takes several weeks for that step alone. Then you need to redirect them into, um, as you were describing, bone forming osteoblasts. And that itself takes another several weeks. Now by sort of sending them directly into the bone forming path, uh, it's much faster, um, and more efficient so we can get a much higher yield of cells. And, um, and then having a source of osteoblast gives us a lot of options. So, um, we probably can't inject them into all of the bones. Um, but if somebody had a localized, uh, non-fracture, uh, non-union, we might be able to use them there. We might be able to use them for treating, uh, a local sort of trauma or a destruction by tumor. And then you could certainly use them for, uh, high throughput screening of drug libraries to look for new medications and new approaches to treatment. So, uh, lots of options once we have sort of a, you know, inexhaustible supply of osteoblasts.
[00:28:09] Russ Altman: So, yeah, that, so your last comments lead to two questions. Uh, the first one is do these osteoblasts when you make them, are they perfectly good osteoblasts? So, like, you know what the normal osteoblasts that are produced by bone, uh, by bones, uh, look like. When you analyze these ones that come from skin cells, are you satisfied that they look like perfectly good osteoblasts, or do they have important differences?
[00:28:32] Joy Wu: So, we've done a number of tests to try to answer that question, and so far, we're, um, doing these studies in mice. So, we can certainly show that they, uh, behave like osteoblasts. So, in culture, they can make what we call mineralized bone nodules, and they express the genes that look like osteoblasts and probably most importantly, when we put them in living mice and, um, try to have them form bone, they can actually make bone. So, I think there's still a long way to go before we say these, these are true osteoblasts, um, uh, able to make bone in, in vivo, in the, you know, natural setting. But, uh, I think we're making good progress.
[00:29:11] Russ Altman: And, and the other question that I, I had, which was triggered by your statement that you need to put them in local places in order to get the effect of the osteoblast is do these divide or are they kind of, um, so if they divide it, then I would say once you have one, you could then have a bunch because you, but it sounds like maybe they don't divide fast enough so that you get an ample supply.
[00:29:32] Joy Wu: That's a great question. So. Uh, you know, the dogma has been that once cells are fully differentiated into osteoblasts, that they're probably not dividing, uh, certainly not at very high rates. That was one of the reasons we thought to use stem cells to begin with. We thought that if you could have, um, you know, an, uh, infinite supply that you could then start with a large number of stem cells and, uh, even if you lose yield along the way, that you could then get to, um, a large number of osteoblasts. Uh, so I think it remains to be seen whether they have some, uh, power to divide, but probably not in the way that, um, you're thinking of it's themselves, you know, replenishing themselves.
[00:30:10] Russ Altman: So, so getting that skin to osteoblast highway moving is, is a, is a good option, uh, right now. Well, in the last minute or so, I just wanted to end with, um, you're a bone doctor and people are always concerned about their own bones. I was wondering if you could just kind of end with some do's and don'ts for those of us who want to optimize our, our bone health and I guess this what, you might give slightly different advice to the young people versus the people who are older, because the young people might still be building their bones, whereas the, the rest of us are just trying to hang on. So, what's the advice that you give to patients and, and perhaps listeners?
[00:30:44] Joy Wu: So, I think, um, to have good bone health, there are a number of things that we can do from a lifestyle perspective. So, um, making sure that we have adequate calcium and vitamin D, those are the two supplements that have been pretty well documented to be important for, uh, bone health. So, you know, two to three servings of dairy products. Um, otherwise if you're older, at risk for bone loss, maybe thinking about some supplements, uh, in discussion with your doctor. Um, as we mentioned earlier, vitamin D is important 'cause that's what helps us absorb the calcium. The other, uh, super important lifestyle, um, option of course is exercise. So, in general there are so many benefits to exercise. So, um, you know, the recommendations are 30 minutes of moderate, um, activity a day. Um, specifically for bone health, I think it's really important to do strength training two to three times a week. Um, that helps to stimulate the bones to keep, um, keep up the bone formation.
[00:31:39] Uh, it's also important to work on things like balance, um, and coordination because part of why people fracture as they get older is that they fall, um, more easily. Um, and then that brings me to my final point, which is, um, particularly for older adults, uh, at risk of fracture, sort of looking around the house and trying to limit things that can cause falls. So, um, throw rugs that are not, uh, tacked down on the floor are a common example. Maybe having a, a nightlight in the middle of the night if you're having to get up, um, maybe to use the restroom so that you're not stumbling around in the dark where you might fall. Um, and then a good choice of shoes. So, um, things that are stable and, and again, to limit your chance of falling. I used to tell people to be careful not to fall until I realize no one's ever trying to fall. So, I think it's more important to limit the things that might, you know, lead to a fall.
[00:32:31] Russ Altman: Fantastic. So, this is great. We've gone from stem cells to good old, uh, fashioned country doctor advice. So, thank you so much, uh, to Joy Wu.
[00:32:39] Joy Wu: Thanks, Russ, for having me.
[00:32:41] Russ Altman: Thanks to Joy Wu. That was the future of bone health. Thank you for listening to this episode of The Future of Everything. Don't forget, we have zillions of episodes in the back catalog, and you can spend all day and all-night listening to old episodes, old, but still good, of The Future of Everything. Please remember to follow us in whatever app you're listening to right now that'll guarantee that you never miss the future of anything. You can connect with me on many social media platforms, including LinkedIn, Bluesky, Mastodon, and Threads @RBAltman, or @RussBAltman. You can also follow Stanford School of Engineering @StanfordSchoolOfEngineering, or more simply @StanfordENG.
