Welcome to Zoe science and nutrition, where world leading scientists explain how their research.

Can improve your health.

Today, we discuss a disease that causes fragile bones and which many of us remain unaware of until it's too late. This disease is osteoporosis, and it leads to more time in hospital than many of the other major diseases. For women over the age of 45, this means more hospital time than breast cancer, heart attack or diabetes. And one in five men over 50.

Will break a bone because of osteoporosis.

This can lead to debilitating and life changing disability and even early death. However, osteoporosis is both preventable and treatable. Here to tell us how are two leading experts on osteoporosis, Professor Cyrus Cooper and our own professor, Tim Spector. Cyrus is president of the International Osteoporosis foundation and a professor of rheumatology at the University of Southampton in the UK. Tim is one of the world's top 100 most cited scientists, a professor of.

Epidemiology and my scientific co founder at.

Zoe, Cyrus and Tim, thank you for joining me today.

Nice to meet you.

Great to be back.

So we have a tradition here at.

Zoe Cyrus, where we always start with a quick fire round of questions from our listeners. And we have these very strict rules.

You can say yes or no, or.

If you absolutely have to, you can give us a one sentence answer. It's intentionally very difficult for professors. Are you willing to give it a go?

Certainly.

Brilliant. Will as many as one woman in.

Three have a fracture in later life due to weaker bones?

Yes.

Is osteoporosis mainly genetic? No. Does menopause cause osteoporosis?

It doesn't cause it. It's the point at which bone density declines more sharply than it was before.

Okay. Is it possible to reverse osteoporosis?

Without doubt.

Can I improve my symptoms through diet alone?

You can do something with diet alone, but you won't be doing as much as you could if you used other things, too.

Are there new treatments we have today.

That are much better than in the past?

Absolutely.

And last question, and you're allowed a whole sentence. What's the biggest myth about osteoporosis?

That you hear that it is an inevitable consequence of aging.

So I think that's fascinating that, in fact, something that maybe I just grew up with thinking was inevitable isn't.

And on the other hand, I was.

Completely shocked by how many people will end up living with osteoporosis. And also this huge number of people, particularly women, who are going to have a fracture later in life. Like, one in three is enormous. And I was struck also quite a lot of men I understood from our research. So again, it's not only women, so just I'm surrounded by myths. So I'm really excited to get into this. Can you start by explaining, like, what osteoporosis is? And I suspect you're going to have to start by helping us to understand actually, really what bones are.

Osteoporosis is the commonest bone disorder worldwide and it's associated with reduced bone density, a disruption of the micro architectural content of bone and an increased risk of fracture. The fractures that typically arise from osteoporosis are fractures of the hip, the spine and the distal forearm or wrist. Those three fracture sites account for about half of all fractures in older people, and the other half are from all the other sites combined around the skeleton.

The places you're talking about feel to me like not the most common places that people tend to break their bones when they're children or in their twenties or thirties. Is that so?

That's exactly correct. In their twenties and thirties, trauma plays a much bigger role than bone density.

This is like falling out of a.

Tree or having a road traffic accident.

Breaking a nose.

Yeah. Whereas as you get to later life, particularly for women above the age of 50, the average age of menopause, and men more so after age 70. Low trauma, or in fact absent trauma, is associated with many of the fractures, and those truly are ones due to bone fragility.

So what does it mean to break.

A bone without trauma? I think of it always being like you.

No, it means just rolling over in bed, for example. You can actually trigger a vertebral fracture.

Wow.

Just by doing that or twisting in a certain way.

Most of our vertebral fractures present on an incidental finding on a radiograph and a vert.

Just help me out. A vertebral fracture. Where am I?

Spine. And typically the bones that break in your spine. The spine contains small vertebral bodies all the way down the mid thoracic, which is the middle part of the back, and the lower lumbar, which is down towards the pelvis. Those are the main sites at which osteoporotic vertebral fractures occur.

That's a wedge. So you have these sort of square looking vertebrae, lots of them, all on the spine, which act as these sort of shock absorbers. And when you get a fracture, it sort of crunches in on itself. And so if it does it in a certain direction, you can end up with a bent spine.

That's your example of us thinking about in the past, like old ladies sort of being bent over.

And some of these old ladies don't feel any pain. It just gradually comes on. They don't notice it happens at night or whenever you can have, you know, five or six of these without any pain at all. And that's why it's often called the silent epidemic, which for this reason that people actually getting fractures without knowing about it and not realizing what the cause is and not realizing that it's preventable.

So it's slightly terrifying idea that you might just roll over and, you know, things break in your bones. Could you help me, Cyrus, to understand what's going on? Why does this start to happen now? But, you know, nobody in their twenties is worried about this happening.

All of us gain bone density through our childhood and adolescence.

What does bone density mean?

So if we were to look inside a bone, we'd find that there are layers of collagen and those collagen protein layers have gaps in them within which the calcium sits. In osteoporosis, there's a reduced amount of collagen and there's also a reduced amount of mineral, and that's what makes the bone weak.

Why are you talking about these fractures in these particular bones? Right, like, I've got bones all over. Why? Why these ones?

Well, these fractures are particularly rich in what is called trabecular bone, which is a honeycomb end of the long bones, which loses bone fastest, and which, when it gets subjected to trauma fractures earlier.

So I'm thinking about my very simple, you know, almost cartoon picture of a skeleton with like, long bones, little round bits at the end. And you're describing sort of those round bits at the end of the things.

That are getting just beneath the round bit at the end, that part of the bone. So the fractured neck of femur, the area just underneath the head of the femur, which is what gives way and breaks.

So it's a combination of actually the mechanical weak point. So that's where the hip, you know, it's got a long bone, but obviously the longer the bone, the more likely pressure is going to be able to break it. Plus it's also what's going on inside the bone, where it's at its weakest, so that you can. It's less dense, less thick. And we have this idea that your skeleton is renewing all the time. So I think it's around ten to twelve years. You completely replace your skeleton with new bone.

Amazing.

All our body is renewing all its proteins all the time, but it's slower with bone. And this happens at different rates, at different people, and also slightly within your bone. It can happen at different points. So we often think that the weakness in bone is also because it might be a point that's renewing even more rapidly.

What's remarkable is that we developed this bone turnover cycle, or bone remodeling cycle, in order to get rid of bad bone, bone that's accumulated micro cracks in it, and replace that with good bone.

If you'd asked me 20 minutes ago, I'd be like, oh, no, I just have my bones for the rest of my life. Like my teeth.

It's completely not like that, okay? It's actually, the skeleton that you walked in with is going to be different to the skeleton that you walk out of this room with. And the reason we can do that is we have cycles of bone. Cells that are two different cells, one cell that makes bone, and one cell that resorbs bone. And throughout all our bones, there are these little microscopic foci where a cell takes out a piece of bone and then rests for a bit and then fills it with new bone. And that's the basis that has allowed us to develop interruptions to that remodeling cycle that eventually can become treatments for osteoporosis.

Another analogy is, you know, our bones are remodeling, and throughout all our bones, you've got these little teams of workmen, one digging a hole and the other one coming along and filling it in.

I love this. So it's a bit like somebody repaving the road outside my house.

Exactly. So it's continuously being dug up and renewed, but it takes twelve years to actually finish the job. A bit like the local council, but as Cyrus is saying, the drugs we've got interfere with the speed at which those things happen, so that if you can do that properly, you end up with more the workmen who are filling in the holes working faster than the ones who are digging the holes out.

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Why does anyone get osteoporosis? So you just showed me this picture, which sounds brilliant, which is like, I'm in my late forties. I really like the idea I might have done bits of damage to my bone, your micro fractures, like you said, and I'm going to get them all fixed. But it sounds like, in fact, for a lot of people, this fixing is no longer working properly.

Yeah. So two good examples of that relating back to the cycle of bone formation and resorption are of the menopause in women, where there's a step change in the ability of the cells to turn over because of the deficiency of estrogen. And the other would be inadequacy of calcium absorption by vitamin D in the gut, which happens with advancing age and which leads to, again, people being unable to maintain calcium balance and be at increased risk of fracture.

So tell me about the menopause for a minute. I feel like there's a lot of listeners who are saying this catalog of things that happen. It just sort of gets more and more depressing. So this is not one we've talked about before. We had this little metaphor that Tim had about digging up the road and replacing the road. What is going on as someone is going through perimenopause?

And what is, when you have low estrogen, the cells that are digging the road carry on being active. If anything, they're a little bit more active, whereas the cells that are filling the holes in become less active and the whole cycle slows down. So it accentuates the loss of burn.

And do we have any idea why that might be the case, given that, obviously, menopause is like a normal part of.

Well, one of the earliest observations about estrogen and bones in the laboratory showed that they're covered, particularly in estrogen receptors. And the use of estrogen and estrogen like products has been attested to in clinical trials that show retardation of bone loss.

Can you just help us to imagine what life is like for someone who is living with osteoporosis?

The different three common fractures manifest really in different ways. So a hip fracture typically would occur at age 81. That's the average age in western countries, the US, Asiania, and Europe. Typically, the person has a fall and bangs the outside of the right hip or the left hip, and that fall is typically backwards or to the side. And indeed, the falls have been studied well enough that some people suggest that, say, institutionalized or nursing home residents might benefit from using hip protectors, which shield the greater trochanter from. From damage. So whether or not that's taken up as a large scale public health measure. It shows that the hip fracture requires the traumatic episode to its outside, that then takes the weakened bone and it breaks. A vertebral fracture, as we've discussed before, actually manifests for most people on an x ray. They have no symptoms. They might have had some pain on use of their spine, but typically there's no trauma. If there is trauma, it's the sort that you're in the hotel lobby, lift your suitcase wrongly and find that there's sudden back pain in the lower part of the spine. And then the wrist fracture typically occurs when you're walking outdoors on icy pavements, have a slip, fall backwards, because you.

Just put your wrist out to support yourself and it just doesn't have the strength to take you.

And I think that's really interesting, because if you did that, you fell over, you tripped over a paving stone. When you're 30, you put your hand out, you might sprain it or bruise it, but it doesn't usually break, whereas you get to over 50 or over 60. You know, men and women, then that doesn't happen. What's really interesting is when you get to 70 or 80 and the same thing happens, your reflexes generally don't allow you to stick your hand out, and so you fall onto your hip, fracturing your hip. So it's really interesting how these, you know, the same fall at different times of life can lead to a different, different outcome.

We talk quite a lot about women. Can men get osteoporosis as well?

Absolutely. So, for example, men of the age of 70, there'll be a significant proportion, let's say seven to 10%, who will have low bone density. And one in ten men from the age of 50 will sustain an osteoporosis related fracture in the remainder of their lifetime. So they definitely will, just not at the levels at which women, because you're.

Saying, like, one in ten of men, but one in three of women will have a fracture caused by this weakened bone, which is. So it's still a lot of men, but it's not almost half as you're describing with women.

A lot of them get missed because doctors don't expect men to get it. And patients often don't think about osteoporosis if they're male as well. And so many of them are much more amiss than in women.

If you're listening to this and you're worrying about yourself, or maybe you're worrying about a loved one, is there a.

Way to find out if you have.

This osteoporosis because you're saying it's like, hidden away inside the bones. Inside my body.

Absolutely. So that the assessment of future fracture risk has become a very topical area in the last 15 years, before we understood that age and a previous fracture were definite markers of a future risk of fracture. And those people, particularly those with a past fracture, needed to be evaluated even before 15 years ago. In 2008, we developed a global tool that mixed risk factors for osteoporosis, just from a questionnaire, height and weight, and a Dexa scan to derive for an individual patient the ten year risk of a hip or any osteoporotic fracture. And that ten year risk is now incorporated in multiple rules, which are often dependent on different healthcare systems in different countries, but the principle of which is to target treatments according to people's fracture risk.

And if you were a woman listening to this, at what point would you start to. Because I think I'm hearing nobody, almost no one in their thirties, would this make sense? When do you start to worry about this?

A person who had a 20% chance of having a major osteoporotic fracture or a 3% chance of having a hip fracture meet the criteria for the cost effectiveness of drugs that retard their future risk of fracture.

So it's like the statin story. So, in a way, what the osteoporosis world have done is come up with a sort of table of risks proportional to your age and sex. To say, at this point, it's worth worrying about it. And each country's got its own levels, but it really varies a lot with age, so exactly the same risk factors, but just ten years older, you're much more likely to have a fracture. It's much more important to get some intervention.

And so if you're a man or a woman listening to this, I guess my question is, at what age would you say? I think I should have a conversation with my doctor to discuss this, because it sounds like this is something that is changed a lot with age.

Absolutely. Ever since the development of DEXA scanning, DXA scanning, there has been discussion about when we should use that bone density measurement. And early on, the most discussion was directed to at the time of the menopause, at age 50, say, in women, of course, that's actually an inappropriate time to undertake mass screening. It's much better when age has caught up the fracture rates to around 70 to 80 years. For individuals on a large scale to benefit from knowing what their bone density.

Is, what's interesting is just before COVID I was still doing osteoporosis clinics and I was actually undiagnosing more people than I was diagnosing.

Undiagnosing meaning saying you don't have osteoporosis?

Yes.

Did a Dexa scan and the T score was high. They were at low risk of osteoporosis.

But just to make sure, you did a scan and it said you looked into their little honeycomb bones and you're like, actually, they're all looking good.

It's rather strange because there's many people out there who are undiagnosed with osteoporosis, particularly in their seventies or eighties, who aren't thinking about it. But there's many people between 40 and 60 who are told they've got osteoporosis because their bones are slightly lower than average and their risk is really low in the next ten years of getting a fracture. So as far as I'm concerned, they don't have clinical osteoporosis anything to worry about at the moment. These are the people that are coming to their doctors and using all these resources that are actually slightly inappropriate because they're not at the high risk group. And so that's why I ended up saying, you know what? You're average for your age. Don't worry about it. Come back and see me in ten or 15 years time. So I think it's really important how important age is in this whole factor, and I think it's not emphasized nearly enough.

And the use of the new technology, the bone dead stomach, in this way, has been shown in large scale trials in the Netherlands, in Denmark and in the UK, that showed that over a five year period, after such a GP screening approach for primary prevention of hip fracture, there was a reduction of hip fracture by 28%. So a really meaningful impact of treatment in the older age group, when bone density was found to be low.

And just before I talk about treatment, because I think you've talked a lot about the hip fracture, but haven't really talked about what that means. And I know that in the research the team was showing to me, actually having a hip fracture was a pretty terrible thing to happen. Could you just, again, paint the story of what this means and therefore why you're saying this is so important? Yeah.

So, first of all, almost 90% of hip and vertebral fracture patients report their symptoms as the most severe on any of the scales of impact of quality of life. So these are major events for people who sustain them. And in one or two of the studies people even describe osteoporotic fractures after they've had them as being worse than death itself. So this is something that the patients take seriously themselves.

They can't judge that. It's hard to judge that.

I agree. I agree. But that paper was in the BMJ and it was. It caused a ripple.

Isn't it more like the other important factors that, you know, 25% mortality.

Yeah.

Related to the fracture, which people don't think about fractures. You think, oh, well, you were patched up in hospital, but actually, about a quarter die of it and about half never go home. I think they're the frightening steps.

And 50% never walk again that were walking before. So for a hip fracture, it's a catastrophic effect on mobility and quality of life. For vertebral fractures, it's really the height loss and back pain that are the two main consequences of osteoporosis and fracture.

Some people have none back pains. It's only in a percentage of them, and it usually disappears. They forget about it and then don't get treatment.

What are the most common myths that.

You hear about how you can treat this risk of osteoporosis? And I still have a feeling that you're gonna talk to me about calcium. Cause that's how I was brought up, which is just as long as you drink a glass of milk every day and, like, maybe two of them, if you're going through menopause, then you'll be fine. And I know from Tim, which is there's also been a lot of conversation about popping vitamin D pills as a.

Way to solve this. Yeah. So I think with regard to calcium, my own view is that we have developed ways of absorbing calcium, which even at really quite low intakes of calcium, we can maintain adequacy. So it's only when you get to very low levels of calcium in, say, a strict vegan diet, where you might wish to think about calcium supplementation for vitamin D. Sunlight is the major determinant of vitamin D in the skin, which then gets converted in the liver and kidney to the active form of vitamin D. And other than absence of sunlight, it's only for groups of institutionalized, elderly immigrant groups that have suddenly encountered much less sunshine than they were exposed to before. Those are the groups where we think about giving widespread vitamin D supplementations, contrary.

A to government advice, and b, what goes on in every osteoporosis clinic in the country, as you and I both know. So where's it all gone wrong? Why do people not listen to the research data. And how have we got into this mess? That, as Jonathan says, calcium and vitamin D are the, you know, oh, that's the first thing everyone should take to make sure they're healthy. And that keeps these companies really rich and powerful.

Yeah, I feel like there are a lot of people listening to this. Particularly, I think menopause is a great example because you've just said, no, there really is this increased risk of menopause that your little workers are no longer laying down the bones. So you need to eat lots of things with calcium, and if not, pop, you know, some sort of calcium pill every day. And what does this mean 30 years ago?

That's what Cyrus and I believed. I think we'd be on saying, yes, calcium and vitamin D bound to work. Give it to everybody. Can't be anything wrong with it. It's going to work. And the trials, Cyrus, haven't shown that.

They don't. They don't show that. And if anything, one or two of the observational studies suggest that there might be problems associated with giving calcium supplementation to do with cardiovascular disease.

So what would you be saying to somebody thinking about taking calcium if they.

Had a pint of milk today, or the equivalent in terms of yogurts, cheese, puddings, cakes and biscuits, which are the main sources of calcium? I wouldn't go for calcium supplementation.

Because you think it might actually be harmful.

Yeah, I'd go even further, I'd say. I used to say that, and I was worried about vegetarians and vegans. But looking at the data, you get plenty of calcium from vegetables and other sources as well. And leafy vegetables, green leafy, the ones that Zoe is trying to promote. And if you have a good, diverse plant diet, there's no evidence you're going to be calcium deficient. And absolutely no evidence from the trials that giving extra calcium in the form of these artificial tablets is going to help your fracture risk.

Is that true even for people who would be eating a vegan diet? So, like, no calcium from, you know, the yogurts or things like that, that a lot of people listening to this would probably be having some of, even if they're not having any milk, I.

Think if they have a diverse plant diet, that is, they're thinking about their diet consciously and they are getting a variety. I mean, you can get calcium from just having many italian mineral waters. It's in many things that you don't think about, and we don't actually need that. Our body is pretty good at absorbing what little there is. And most of the world doesn't have dairy products and they don't get fractures.

The only caveat I'd add to that discussion, which we are in agreement with, is that when people are taking the drugs, particularly the. Against resorption drugs, the trials have shown that calcium and vitamin D at relatively low amounts should be given with the drugs that are used.

But you would agree with Tim, that actually, for most people listening, if they're not obviously in treatment with their doctor.

We think calcium and supplementation is not something that I would want to promote as a. Wouldn't give public health, as one of our colleagues, as you reminded me, said.

What does the latest science say? Because again, I think many of us who live in more northerly climates are used to the government saying, we're all low on vitamin D, we all need to be taking supplementation. What is the.

And the recommendations, again, are sometimes out of step with the evidence. So the evidence from what are called observational studies, that vitamin D is deficiency is linked to a whole host of outcomes, including even early death, frailty and fracture.

So that sounds pretty bad. Cyrus, that has me straight for the vitamin D supplementation.

Yes. That's not good for it when you take the trials into account, because the trials don't echo the observational data, they actually suggest that if there is any beneficial effect, it's a really rather small one, perhaps a five to 7% reduction in the risk of all fractures. And even that is quite a discrepant evidence base.

Didn't you do some trials that actually showed it made it worse?

Cyrus? We did. And explanations were forthcoming from our colleagues in the industry that produced vitamin D supplements to explain that worsening.

Can I just make sure I've understood that right, because you're smiling, but it's really shocking. You're saying these were quite old people, so we're at quite a lot of risk of fracture. You split them into two groups. You only gave vitamin D to one of those groups. You presumably thought it was going to make them healthier and reduce the number of fractures. And actually they were worse off.

And that on its own, would enter the realm of, oh, bad luck. You know, the one that went the other way. Except that an australian study echoed pretty much the same findings.

Take it all together. The trials are really either negative or detrimental. Only a few are pointing the right direction. But if you discount some of those early trials in the 1980s, which were a bit dodgy, there's no good evidence that vitamin D supplementation for the vast majority of people is beneficial. It doesn't mean that no people will benefit.

And is there anything because we're obviously talking about osteoporosis. Would there be anybody listening to this saying, oh, well, that's true for osteoporosis, but it's got these other really important benefits? Or is this just basically across the board that you think people do not need this vitamin D unless they got very, very low?

I think because of those other trials and mortality being evaluated now in large vitamin D trials all over the western world, one would have to hold judgment on a mass program of desupplementation to older people.

Cyrus is arguing against this, but we actually have government guidelines from what used to be Public Health England saying, everybody.

Over the UK, you're saying in the UK?

In the UK. And I think other countries also have some of these guides. I'm not quite sure what the US guidelines are on vitamin D, but I.

Think they're similar, 400 to 800 units daily given to older people, you know, and that seems a blunderbuss approach at best, and possibly when the aggregate is all looked at in the round, something that might have a negative impact.

We did a podcast on vitamins a little while ago, which only listeners were interested could take a look at. One of the things that shocked me was his feedback that sometimes vitamins can actually be harmful because we are used to seeing in our stores, like super doses. Ten times are recommended dose. And I think we all assume from this, well, you know, if one is good, ten must be better. I think what you're saying is here we talk about both calcium and vitamin D. Actually, even within the recommended dose might be harmful with the latest evidence. So we need to be really thoughtful about supplementation rather than just assuming that there's no possible downside and we should just take them. I just want to make sure that that's what you're saying the latest data on vitamin D and calcium is saying.

And I think it's also because it's in a different form to the way our evolution has allowed us to absorb these vitamins. Vitamin D, which isn't actually a vitamin, you know, is produced in our skin from sunlight for a reason. We're able to absorb it that way. And that's where calcium, we get it from plants and, you know, dairy products, we don't get it from. We're not designed to get it from a giant chunk of a gram capsule that suddenly dropped like an atomic bomb into our gut and overwhelms our system. So it's the way these vitamins are sold or processed. That may be the problem, because by definition, a vitamin is something you need a minute amount of in order to service the body and keep it functioning normally.

The other thing I would add is that it's this whole area of vitamin D metabolism throughout the life course is a subject for research rather than translation to policy. So our studies over a period of 15 or 20 years have shown that the mother at the time of, before and during pregnancy is susceptible to the offspring having an enhanced trajectory of bone mass during childhood. If the mother is supplemented before and during pregnancy with vitamin D at relatively low dose, you know, 1000 units daily.

Just want to make sure I understood that. I think you were saying that if you're pregnant and taking vitamin d supplements, that might be a good thing, because that might actually mean that your child ends up having better bones over time.

Absolutely. And raises the possibility that there might be some enhancement of the peak bone mass, something that we never thought of as an outcome from vitamin D supplementation.

And Cyrus, I have a few children, but my youngest is four. Is it too late for me to do anything for her in terms of ensuring that her bone density is going to be great when she goes through actually for that?

Sadly, the studies that have been done in childhood, vitamin D supplementation, so long as you get an adequate dairy intake and vitamin D nutrition, are not so good for giving all school kids vitamins again.

And I shouldn't be pushing, it sounds like I don't have to particularly be pushing a glass of milk to her either, from what I'm hearing.

Well, I think that becomes a more complicated issue because it's the protein that provides the benefit in the glass, but.

There'S not the calcium. Not the calcium back again. There will be a lot of people listening to this who are saying, oh, maybe I want to go and speak to my physician, my doctor, get checked. They will have this scan and maybe they'll say, actually you are seeing these signs of osteoporosis. You mentioned the fact that there are some real treatments. Could you help at the highest level to understand what you can do?

Sure.

So the first line of treatment would be a drug class called the bisphosphonates. And examples of bisphosphonates are alendronate or resedronate. Those are taken in tablet form once per week with adjunctive, as I'd mentioned before, calcium and vitamin D as part of the trial regimen. And those drugs will reduce over a three to five year period and indeed longer. With follow ups of the trials by 50%, the number of fractures.

Oh, well, so you can just take a tablet once a week and you can actually halve the number of fractures.

But only while you're taking it.

You've got to keep it.

That's a caveat. We used to think, oh, if you treat people for five years, you know, you've got everything, you've pushed everything five years away. It doesn't seem to be true. It's only while you're taking it are you protected. And that's sort of the problem, because you're actually slowing the bone down while you're on it. So that's why we have these drug holidays. You go on, and so every five years you have a little break for a year, let your bone recover, and then you go back on it.

Indeed. That's the regimen. That would be the first line. Then you can use intravenous of the same type of drug, zoledronic acid, it's called, but it's a bisphosphonate given once a year, and that allows the bone resorption to be reduced in a much more marked manner than the oral bisphosphonates. Then the next line would be the last of the anti resorptive agents, which is called denozumab, and that is given once every six months with a subcutaneous injection, those will reduce by 50 or 60%.

I feel like if. If you're listening to this and you're concerned, you would. You definitely want to know your state.

And perhaps I should also mention HRT, which we mustn't forget about, which was the first one before.

This is hormone replacement therapy, estrogen replacement.

Therapy in the US.

What.

What does that do above the age of 60, 65? There's been a sort of discussion that perhaps the risk of heart disease become prohibitive on general use of HRT. But in someone who's had a fracture, they are going to be benefiting from their bone densities. Point of view. And from age 50 to 60 is the current controversy, which is perhaps we should be looking at HRT as a whole in those ages in women, because of the risk benefit balance being, and.

It has a significant reduction in the risk of fracture.

Yeah, it's nearly as good as the bisphosphonate does. And for many people going through menopausal symptoms, it provides extra protection as well, and might actually reduce heart problems as well. So I think a lot of the data and the worry in this field was that all the data we had was based on the old regimens of HRT, which used different combinations of the progesterone and the estrogen, rather than estradiol, rather than having estradiol patch, and then new types of progesterone, new ones which are much safer for the heart. So I think the jury's still out on the exact risk benefit. But for most people, if they are taking HRT, they should still be getting the benefit. They will be getting the benefit on the bones, and generally, they are getting a fair bit of protection for their skeleton. At the same time, I would just.

Add very quickly that the new class of bone forming agents have an even more profound effect on rapid changes in bone density. They're more recently developed and used much less widely today, but are likely to become part of this armamentarium. The bottom line is that we have a whole variety of therapeutic interventions for people at different levels of severe osteoporosis.

So it's really encouraging that there are these effective treatments on offer.

Cyrus, can I ask, are there any downsides or side effects to these treatments?

Absolutely. The major side effect from oral bisphosphonates are problems with the esophagus. They can induce an esophagitis, an inflammation of the gullet, which can lead to the drugs having to be withdrawn. That's an indication to move to the intravenous or subcutaneous agents for both of the antiresorptive drugs as a whole, there has been a lot of activity, particularly legal activity, about rarer side effects of long term suppression, the bone cells that eat away bone. The first problem is called osteonecrosis of the jaw. And although it's got an incredibly low frequency, it has been sensitized by the legal cases in the United States, which have led to dentists not wanting to treat patients with the bisphosphonates. And guidelines have now been drawn up that are adhered to about information regarding bisphosphonates and what is called ONJ. The other is second and subsequent atypical fractures, which happen when, again, the skeleton has been exposed to long duration of bisphosphonates and denozumab. And there we undertake those drug holidays that we talked about earlier that enable us to continue with bisphosphonate therapy if the patient needs it after a period of time in which it leeches out of the bone.

Yeah. So there are these side effects, and, like this frozen bone is the other sort of colloquial term for it, where the drugs are doing such a good job that they're just slowing everything down, which means it doesn't repair, and therefore, you can get these consequences as Sara said, this rare necrosis of the jaw, where bone in the jaw gets sort of eaten away, or you get these really rare fractures that come out of nowhere that look really odd on x ray, but they're incredibly rare. So one atypical fracture and no jaw problem in about 25 years. So I think the lawyers have exaggerated this problem and caused problems. But this is one reason we don't just give everybody, age 30 these drugs.

For life, because there are side effects. And even if rare, you wouldn't therefore want to give them to everyone, because then you're giving it to hundreds of millions of people.

And there's also the idea if you give all these drugs too early, they might not work when you need them to. So that's the other thing. If you just give it 20 years too early, then it's not going to be really effective at the time when you're in your seventies and you really need that protection. So they're the sort of subtleties about this. So the drugs really work, but it's all about timing. That's the crucial thing. When do you give it to that person to maximize benefit and minimize risk?

Let me tell you a quick story. So Wednesday last week, I went for dinner with my wife, Justine. Now, this would have been a source of anxiety for me in the past, and that's because some foods would leave me feeling really tired and sick for hours afterwards. And as a result, I actually followed quite a restrictive diet. Then I did Zoe and discovered that I'm prone to blood sugar spikes. From my Zoe digital coach, I learned that this doesn't mean I have to restrict what I eat, I just have to be smarter about my food choices. So back to last week at the restaurant, we were eating Italian, which before Zoe, would have left me feeling terrible. But my Zoe coach helped me make choices that consider my blood sugar. I started the meal with a delicious italian salad and then enjoyed some pasta afterwards, drenched in olive oil, of course. And after dinner, I felt great, energized by my food and by the fact that now I don't have to limit the foods I eat and choose between a healthy and a happy life. Whether I'm eating out or cooking, my Zoe digital coach helps me make smarter choices every day.

Honestly, it's transformed how I feel. And according to the scientists who continue to develop, the digital coach, making these choices now could give me many more healthy years. Why not join more than 100,000 other people giving Zoe membership per shot and tell me what you think? To take the first step towards the possibility of more energy, less hunger, and more healthy years. Take our quiz. To help identify changes to your food choices that you could make right now, simply go to zoe.com podcast. Whereas a podcast listener, you can also get 10% off.

And it sounds like you haven't really said this, but it sounds like this is another example where if we were living the sort of highly active lifestyle that our ancestors had, it sounds like, in fact, it's quite likely that far fewer people would have this osteoporosis at 70 or 80 because of all that impact of exercise would probably have meant that they had significantly stronger bones.

Cyrus and I wrote a paper together in the 1980s.

We did.

It was show tracking in the US activity levels and fracture levels. And they sort of absolutely mirror each other as people from the 1960s onwards did less and less, and fractures just sort of just went up through the roof.

I think what's so interesting is this is the exact opposite of how I was brought up as a child, which is that when someone becomes older, they're supposed to take it easy. Like, you should take all the luggage away from them, they should just sit down. And I think what's fascinating is this is done with love and caring, right? And actually, it's terrible advice. And we're actually hurting the people that we love because actually they shouldn't be going around carrying things and walking up the stairs. And you're saying, like bouncing and all these things that we're scared of.

Get your granny to carry the suitcases. That's the rule.

And they should be out dancing, it sounds like. And generally, yes, and carrying the suitcases and all the things that we thought made you old are actually the things that we're probably keeping you young.

I think that's absolutely right.

This would not be like a Zoe podcast if we didn't want to talk about the lifestyle factors that people can use. Could we maybe start with diet and nutrition? And maybe just at this point, maybe Tim, start with you.

So diet has a big role to play in osteoporosis. And if you looked at some meta analyzes where you're combining lots of these studies together from all these cohorts around the world, you find that once you've accounted for lots of other factors, the quality of the diet has a big impact on the risk of fracture. And it's not things like the amount of calcium in the diet, it's not things zinc or any one item. It's the sort of things we talk about in this podcast all the time, having plenty of vegetables, being protective it's about having small amounts of processed food. It's not having lots of junk food, not having lots of fizzy drinks. So it's that health quality aspect which has come out globally. When you look at the meta analyzes as being really important and it's significant.

Is it this difference between a high quality diet and an average diet, 2% that only scientists can see?

No, we're talking sort of 30, 40% differences. These are really big ones. But it's highlighting that the same things that are good for many other diseases are also good for osteoporosis and bone. But it's also telling us that it's not, as we used to think, all about calcium or all about protein. It's actually the quality of the diet, the combination of foods, rather than these individual ingredients which people use to sell supplements completely.

That's right.

And this is true at all ages, as far as I know. So, I mean, you've done some of.

This work, children, adolescents, older adults. The move towards dietary quality as compared with micronutrients that are specific for bone health has definitely been the direction.

I think that's really interesting, because I think one of the things that was most surprising to me in my journey from Zoe over the last seven years is seven years ago, I assumed that there are these very specific vitamins because they're the things that are on the, you know, the back of the pack and that you see being sold in the stores and that those were really mattered everywhere. And I think I've substantially discovered that, you know, there's 100,000 chemicals in food and all these other sorts of things, even before they hit your microbiome and they make all these other things. But I had at least until this morning, thought, well, at least calcium is really important for bones. You know, I'm sure I learned that when I was eleven. And what you're saying, I think, is, even there, your total diet may be really important, but it's not because there's calcium in that diet. It's something to do with all the different things.

Just because the calcium is in the bone does not mean that modifying it by increasing its level in your stomach will actually have any impact on your bones.

And sars nebula had been brought up on this myth that calcium was all important, and we just assumed it was a factory. And it's only really in the last ten years, with all these massive analyzes and people starting to look at diet differently, a more global, holistic way of looking at food, that we start to see that actually calcium doesn't even make the list of contenders. So it doesn't matter whether you actually drink milk or not. It's about the quality of your diet.

It's really interesting. What you're saying is the calcium does really matter in my bones. Like, I need to have the calcium, is what you're saying. But in order to get more calcium ion bones, eating or drinking more casino doesn't help. You're saying, like, if the road's dug up outside, I can't just give you a bunch of asphalt that doesn't make it happen. Like, I need someone to come with that fancy machine that lays it. And so I sort of need to pay the person who's going to lay it, rather than just say, oh, I'll eat some asphalt. This will solve.

Eat more gravel.

Yeah, that's fascinating. Now, I think one question a lot of people will be saying is, is there anything specifically, however, that I should be thinking about adjusting? So, imagine that maybe I'm going through perimenopause, I've been through menopause. Is there anything that we know about sort of way that I might want to think about changing my diet? Or is this just like, overall, I need to care more about the quality of my diet, perhaps, than when I was younger?

I think the number one message is care more about the quality of diet. Try and get more plants in there, because they are all these sources of other minerals. As you said, there are 100,000 different chemicals in food. So the more diversity we get, the more we are going to get a balance of these things. And so that's why a rich balance of, particularly plants is going to give you all these, whether it's zinc or magnesium or phosphate, in exactly the right amounts that your body needs, because we're evolved to take it up and absorb it in those ways. That's more important than any saying, okay, I'm going to forget all that. I'm just going to take some vitamin D capsules and drink a pint of milk. So I think, in a way, that's where we've got it wrong. In the past, we've said, well, there's one quick fix here where actually it's going back to, you know, there isn't a quick fix. It's this holistic idea. Again, it comes back to food quality and. But I think get the food quality right, and then Cyrus will tell us, there's some really good exercise tips now that at all stages of life that are really important.

So could you talk about that? Because actually, we haven't mentioned exercise yet.

One of the reasons we things have a skeleton and bones is for the muscles to work off and for locomotion, for walking around, running, evading hunters. In the olden days, that role of exercise is very close to the starting function of the skeleton itself. We already know that when we start in the earliest stages of life, weight bearing, we can start to see an acceleration in the mineralization of the skeleton at those very early stages.

Toddlers first steps.

Yes, absolutely.

So you're saying once the toddler starts walking, suddenly their bones get stronger?

They've been weightless in utero, they come out and they start to. To ambulate, and you can see a discernible change in their mineral accrual from the blood, if you like, into the skeletal tissue. Thereafter, there's a rapid gain up to age 25. Examples? The serving arm of a tennis player is 15% to 20% higher bone density than the non serving arm. A stroke or reason for paralysis of a limb leads to massive demineralization of the bones in your.

So I just want to make sure, because everyone, everyone sort of is familiar with the idea that their muscles shrink if they're not using them. But what you're saying is that if I use my arm, for example, your tennis example, is like, I'm using that arm more and hitting something with it, my bone is actually going to get bigger and stronger, or denser and stronger.

Absolutely. That's exactly what happens.

That's crazy.

If you send someone into space, their skeleton will dissolve with calcium, leaving the bone and being passed out in the urine.

Because they're weightless.

Because they're weightless, and therefore no action of the muscles on the bone.

Weight bearing exercise is crucial, really, at all stages of life, and I think that's the sort of number one lesson people need to learn. And, and what we also learned from another experiment is it doesn't have to be huge amounts of time. You don't have to run marathons or anything.

That's the point. Of course, you'll do well if you run marathons, but if you just walk an hour, three days a week, as an older person, you'll still have an improvement in both your bone density and your falls risk your muscle function and falls risk such that you'll have an impact on fracture.

And what about actually weight bearing exercise? This has come up on a lot of podcasts here, often talking a lot about sort of the muscle benefits, but it seems here you're talking about impact.

Weight bearing or weight lifting.

I'm talking about weight lifting here where you're actually doing exercise that involves, like, resistance and something.

This was always controversial, weightlifting. And there was, in the early days, a lot of information suggested that things like swimming and weightlifting didn't give you as much benefit as jumping up and down, skipping. I used to tell my patients to skip for two minutes a day and there are some studies to show that just that is as effective as doing an hour's sort of weightlift.

For sure. It's the operationalization of realistic activity schedules for someone who's interested and uses swimming as a hobby, for example, you wouldn't want to discourage them from going swimming, but just point out to them that the evidence would suggest rather more, that weight bearing rather than non weight bearing is better for the skeleton.

I want to clarify because it's not really clear to me, so, you know, I do go to the gym a few times a week because I'm told it's really good for my health and a lot of that is resistance. I'm, you know, doing stuff with weights because I'm also told that's really good for my health. What will the impact of that be on my skeleton?

From the research that's been done, it would have a measurable effect on your bone density, but we have no idea what it would do to your risk of fracture.

Okay, so the bone density will improve, but it's not. There isn't the studies out there to show what that will do in terms of fracture risk.

And it probably wouldn't improve as much as if you were playing tennis every day.

Right? I agree. That's right.

Could you help to understand that?

Because the weight bearing.

Could you explain? I think it's because I don't understand what weight bearing is.

I think it's just jumping up and down. So putting extra pressure on your limbs for bone.

The sensitive part of the bone cycle is the change, the delta in the force being applied to the bone. So jumping up and down is giving lots of stimulus to the bone forming cell. Swimming is giving very little stimulus to the bone forming. So.

So it's like. That's why two minutes of skipping may be as good as an hour of walking gently. If you walk briskly, you're going to be putting more load, therefore it's better.

So what would I do? Let's say somebody's listening to this. You know, they're motivated to improve their health. They're worried about osteoporosis, maybe because they've been told that there's some risk or there's some risk in their family. What would be the exercise that you would be saying is, I deal.

So the first thing I'd say to a patient is, do not be sedentary. Some exercise is going to be better than sitting in the armchair and watching the tv. Once you've decided to take exercise, even walking half an hour a day for five days a week is going to do some good to your balance and bone density and risk of fracture. And then if you want a tailor made exercise regime for osteoporosis, you go and consult a physiotherapist, which we have as part of our team, and they provide you with the specific exercise regimen that is appropriate for you.

I always told my patients, do something you enjoy because you're more likely to do that for long periods of time. And if it's weight bearing, if you can do it brisker, if you can do it with a bit more bounce, if you hate exercise, or you, for example, can't do it for very long, my example of skipping is actually quite a good one. Or some people who even have arthritic problems can't do that. There was something called heel raising, which was really big about 20 years ago, where basically you just go up and down on your toes, swinging your arms, and you put your heels down on the ground so you're not moving far at all. There's no risk of falling, really, just swinging up and down. And as your heels go down on the ground, you just do that for five minutes a day. And that has been shown to have some benefit on it. So, in a way, what we're saying is there's some exercise for everybody, whether it's running, whether it's walking slow or brisk, skipping heel strikes or any other activity or sport they like doing.

Brilliant.

Final question for you both having sort of pulling all of this together. If you're going to advise our listener on the top three actions that they could take today to improve their bone.

Health, what would you say?

Maybe starting with you, Cyrus, I certainly.

Feel they should have a healthy lifestyle. And in parentheses for that, I would have a prudent diet, an appropriate level of exercise, and avoidance of lifestyle aspects which are poor for skeletal health, including smoking and very heavy alcohol. The second thing I would do would be assess your risk. And number three would be to treat that risk appropriately, because there are so many agencies now available to us to reduce it significantly.

Tim, what would your three be?

As Cyrus says, work out what your likely risk is, which will depend on your age and what you need to do. People in their twenties are going to very different advice than in their sixties. The two key things are eating well and avoiding ultra processed food, having a rich variety of vegetables that, according to the epidemiology studies, could reduce your risk by 30%. Just really following Zoe advice and having an exercise regime that you do that's good for bone health, and even if you are a swimmer, you just add in something that's also going to be good for your bones. And if you do those three things, then you're maximizing your chance of reducing a fracture and you're setting yourself up to have the least amount of problems in your life.

Amazing. I would like to try and do a little summary. There's been lots of fun, and correct me if I got any of this wrong, so we started by saying osteoporosis is incredibly common. And you described the fact that one in three women and one in ten men will have a fracture caused by weak bones. So there's a huge number of people who are listening to this. You said there are a number of fractures you could have, but particularly if you have a hip fracture, this is a really major event that half of people, after this hip fracture, will never go home again, they'll never walk again, and a quarter of people will die within twelve months of having a hip fracture. So that's really serious. What we're talking about starts off quite scary. And then I think the good news is, for a lot of things we talked about is there's a lot you can do. We talked a bit about bones and I discovered, to my amazement, that all my bones have been replaced every twelve years. And I've got this beautiful image of like the workman taking them away and then the workman putting it back, that they're for taking out this calcium and collagen and you need to put that calcium and collagen back.

And that if we don't do that, that's where you start to have this osteoporosis that explains all of these risks, and that one of the things that happens at menopause is suddenly you keep taking it out, but you're not putting it back as well. And hence this real shift for women after menopause. The good news is you really can diagnose it. You said, particularly, you can now use this Dexa scan, which I know is quite common. It's something I did when I did the first Zoe studies with Tim. So you can diagnose that and really understand what your risks are.

And then we said almost everything that.

The listener knows about how to deal with osteoporosis is wrong and actually downright harmful. So calcium, you don't need to take lots of calcium supplements. And in fact, you both said that you wouldn't take calcium supplements. There's a good, really good evidence that if you're eating a decent diet, there is no value from adding calcium supplements. And I think, Tim, you said, actually, even if you're vegan, then if you're having a good, diverse diet, there's no evidence. I think you said there are all these people elsewhere in the world who don't really eat any dairy products and they're not all having higher fractures. So that's one thing that's out.

And then you said on vitamin D.

Cyrus, even more amazingly, you did a three year study where you separated people into two groups, and the group that you gave vitamin D to actually had more fractures than the group without. And that has been repeated elsewhere. So from your perspective, the evidence suggests that vitamin D could even be harmful if you're taking it as a supplement. In terms of bones, am I saying that fairly? Which I find extraordinary because at the same time you also said, oh, by the way, lots of governments in the US and the UK tell everybody to take these vitamin D supplements. And this feels like another example, as we see with a lot of our food, where there's a real mismatch between government advice and the latest science. And of course, this show, we can't give official advice, but we can share what is the latest science. Having said all of that, Cyrus, you did say that vitamin D supplementation during pregnancy might actually be great for your children and could actually reduce their risks long term. So I guess another example where the situation in pregnancy can be quite different from everywhere else. The good news is there's a lot of medical treatments that are out there and that actually there was quite nice pop a pill or maybe even have an injection once a year could halve your risk.

And that also taking estrogen, supplementation, HRT, as well as all the other benefits that we've talked about on other podcasts, could have a significant reduction in risk of osteoporosis as well. And then I think we talked about diet and lifestyle. And I think the really good news here is that diet can have a really big effect. Tim, I think you said maybe a 30% to 40% reduction in risk, but it's not about taking calcium or zinc or protein. It's actually about an overall high quality diet. Lots of vegetables, limiting ultra processed foods, trying to have more plants. And your key message was. It's an example of why you might want to care more about this during perimenopause and menopause, for example, because suddenly, like, this is a higher risk and you can deal with it. And I think we wrapped up talking about exercise, where I think, for me, the really interesting thing was you were really focusing on this idea that you need to put pressure on your limbs. And that's quite different, maybe from putting pressure on your muscles. So swimming puts quite a lot of pressure on your muscles, right. You're pushing, but you're saying, well, it doesn't do anything for your bones because they're not banging.

And so you need to think about exercise where, you know, you were describing skipping or jumping or any of these things which you described as weight bearing. And so that activity that's giving these sort of shocks is really important for your bones, which, again, I guess, says there's not always one exercise that solves everything. And you need to get this advice here.

Well done.

Brilliant. I thought that was really interesting. Thank you so much. I think it's one of those things where it's a little scary what you're describing. But on the other hand, there is a lot that you can do, which is really exciting. And I guess one of the key measures is this is something you'd really like to understand about your risk for yourself or your loved ones early, because there's really a lot you can do. It's not something where you find out this information, but there's nothing you can do about it.

That's right. At different times of life. So you might want to find out at age 50 and then revisit age 70. I think the decisions you take will be different.

Amazing.

Thank you both very much.

Thank you.

Pleasure.

I really enjoyed my conversation with Cyrus and Tim today.

I learned an enormous amount and I hope that you did too, and that you heard plenty of valuable tips for preventing or managing osteoporosis. I certainly did. Now, you also heard from Cyrus and Tim how important nutrition is to our health. And if youd like personalized advice and support on how you can eat the best food for your body, then why not try a Zoe membership? Zoe can help you feel better now.

And live healthier in the years to.

Come, backed by real clinical studies. To find out more about what Zoe membership entails and get 10% off your membership, head to Zoe.com podcast right now. I'm your host, Jonathan Wolf. Zoe Science and nutrition is produced by yellow Hewins, Martin, Richard Willen and Sam Durham. As always, the Zoe Science and nutrition podcast is not medical advice. It's for general informational purposes only. If you have any medical concerns, please consult your doctor and see you next time.