Bone Health and Osteoporosis in Men and Women: Doug Bauer and Stanley Birge

Eric 00:00

Welcome to the GeriPal Podcast. This is Eric Widera.

Alex

This is Alex Smith.

Eric

And Alex, today we’re going to be talking about bone health in older adults, all things osteoporosis, low bone mass, osteopenia in men and women. Who do we have to talk about this?

Alex 00:33

We are delighted to welcome Stan Birge, who is a geriatrician and former director of the Division of Geriatrics at Barnes-Jewish Hospital and Washington University, and author of one of the papers we’ll discuss today in JAGS titled Vitamin D: What’s the Proper Dose? He was also part of the AGS working group On the Vitamin D Consensus Statement. Stan, welcome to the GeriPal Podcast.

Thank you.

And we are delighted to welcome Doug Bauer, a primary care general internist who’s an emeritus professor at UCSF. He has served on and serves currently on an FDA advisory committee on bone health, is author of many papers on vitamin D and bone health, including a paper we’ll discuss today. In JAMA Internal Medicine called Screening for Osteoporosis in Men: Getting Closer to Yes. Doug, welcome to the GeriPal Podcast.

Doug 01:34

Thanks, gents. I’m really glad to be here.

Eric 01:37

We’ll find out how close we are in this podcast before we jump into all of these great topics. Stan, I think you have a song request for Alex.

Stan 01:46

Yeah. Turn, Turn, Turn by Pete Seeger

Eric 01:50

Why did you pick this song?

Stan 01:51

Oh, I think first of all, the melody is one of those that just stays in your brain and pops up at every odd moment. Uh, but also the lyrics and, uh, the closing lines, for example, are a time to love, a time to hate, hate, a time for peace. I swear it’s not too late.

Alex 02:20

Yeah. Great choice. Here’s a little bit.

Alex 02:29

(singing)

Doug 03:25

Wonderful. Terrific.

Stan 03:26

Okay.

Eric 03:27

I’m gonna start off with a little bit of just about you first, Stan. How did you get interested in bone health, osteoporosis?

Stan 03:36

Well, I was interested in vitamin D metabolism and, uh, started my career in basic research and was using old aged rats for my research, but they became so expensive that I figured it’d be much cheaper to use humans in the clinic. And so that kind of launched my career in geriatrics as well as osteoporosis.

Eric 04:09

Thank you. How about you, Doug?

Doug 04:12

Oh gosh, you know, I was, um, yeah, in private practice for a few years after I finished my residency, and one of the honors that I had was to, uh, go see, uh, patients in the ER in the middle of the night who had broken their hip because the surgeons were going to take them to the OR the next morning.

And yeah, I was just blown away by how frequent that was in an elder general medicine practice. Lots of, lots of nights in the ER with these folks. So I’ve been interested in osteoporosis ever since. And when I went back to UCSF to do my research training, it was really clear what I wanted to do and what I wanted to study. And that’s been true for almost 40 years.

Eric 04:50

Wow. When was that?

Alex 04:52

Eric, I just have to say, because I forgot to say it in the intro, Doug, I believe, is our second, like, parent-child guest on Jerry Bell. Because we had Scott on a few years back talking about lower urinary tract symptoms in men. So just wanted to point that out. We had Alex as a daughter on just a few weeks ago on our podcast.

Eric 05:13

Mary Lynn McPherson. Yeah.

Alex 05:13

Yeah.

Doug 05:14

Well, I’m sure glad because my son talks a lot of smack about how he’s been on this podcast and I haven’t, so I’m glad to rectify that.

Alex 05:23

Love

Eric 05:24

it. All right, so maybe we could just start off with some basics for me. What exactly is osteoporosis, osteopenia, and this low bone mass? Doug, I’m going to start off with you.

Doug 05:39

Sure. Well, you’ve hit a really important question because, to be honest with you, a lot of people are confused about this. It’s defined, you know, pathologically. It’s bone that is susceptible to fragility because it’s lost its integrity and it’s lost its calcium content.

But unfortunately, it’s been defined and mostly understood clinically on the basis of a bone mineral density test, which is, you know, a radiographic test that assesses what’s the mineral content of your bone, typically your hip or your spine or your forearm. So when we say osteoporosis, we mean someone who has abnormally fragile bone. In fact, it’s quantified by bone density tests. And many people also talk about a bone density which is sufficiently low, it falls into the category of osteoporosis.

Eric 06:29

And that sufficiently low is less than -2.5 on a T-score.

Doug 06:34

Right. And just remember, that’s the T-score. T-scores are the number of standard deviations below normal. So that’s how many standard deviations you are below a normal 30-year-old of your same gender and ethnicity. But of course, no one really understands that. So that’s why we prefer to talk about probabilities rather than, than T-scores.

Stan 06:54

And I think, uh, just to interrupt that, uh, you alluded to this, uh, Doug, that it’s not just a decrease in bone mass, uh, but it’s a decrease in the integrity of the, uh, bone. And that we can’t really measure, uh, with a bone density. Uh, there are other factors that, uh, are contributing to the weakness of that bone.

Doug 07:22

Yep, absolutely. And then there are a couple techniques you can measure that bone structure, microarchitecture is what we call it. Um, but they’re really research-based and they’re really not ready for prime time in clinical medicine, at least widely. Um, often involve more radiation than a simple DEXA test, which is simple, cheap, and unbelievably predictive of who’s going to have a fracture.

Eric 07:42

And to be diagnosed with osteoporosis, so you have a bone mineral density scan of less than -2.5 on the T-score, so comparing to young 30-year-olds.

Doug 07:55

Right.

Eric 07:56

Or you have a fragility fracture, right?

Doug 08:00

Classically, it’s hip or spine. Those are the sort of the classic osteoporotic fractures. But actually, that’s sort of that designation of what’s an osteoporotic fracture breaks down because all fractures are related in some way to lower bone mineral density, even fingers, toes, and ribs and all these other things.

Eric 08:16

Yeah.

Doug 08:17

So,

Eric 08:18

but not like an automobile accident. Like if I had a rib and spine crushed on an automobile accident, we’re not calling that a fragility fracture.

Doug 08:28

Well, that is true. But the problem is, particularly in the elderly, it’s really hard to ascertain what is, what’s the trauma. Yeah. And somebody who’s in a Safeway parking lot and is in a fender bumper and hits the steering wheel and breaks 3 ribs, they might very well have osteoporosis, even though, you know, an 18-year-old would’ve done just fine and bounced off the steering wheel. So I really encourage people not to think about trauma. A fracture is a fracture, and the older you get, the more likely it is to really portend a recurrence as well as other bad outcomes.

Alex 08:59

And let me ask you, if you trip, like an older adult trips on the carpet and they fly off and hit the ground, hard. That’s a traumatic event, but they break their hip.

Doug 09:09

The question is, is would you have, if you fell off the carpet and…

Eric 09:12

Don’t ask Alex about breaking bones.

Alex 09:15

Uh-uh. Yeah. Doug follows me on Strava, so, which is a social media site for athletes. So he had seen many of the x-rays posted to Strava from my bicycle accidents. My goal on Strava is to not post any more x-rays. And interesting fact, dear listeners, uh, my PCP, who I listen to, I try not to doctor my PCP, said, You’ve had so many fractures, you should get a bone mineral density. And it showed that I have osteopenia with a T-score of…

Doug 09:41

And cyclists traditionally have lower bone density than those that don’t cycle, that do other exercise like running, for example. But that’s for another podcast. Right. But you’re absolutely right, Alex. But my point is trauma is really difficult to ascertain clinically. It’s even difficult in research studies to do it. And so I think that you’re more likely to make an error if you quantify something as being traumatic versus not traumatic.

The general rule of thumb is anything, any fracture over age 50 increases your risk of future fractures and therefore could be called osteoporotic. But in fact, we don’t do that typically. It’s really the big players, hip or vertebral fracture, and Colles fractures in particular.

Eric 10:21

So you get somebody, chest X-ray or abdominal X-ray, and you see an asymptomatic compression fracture. You have no idea how long it’s been. that is osteoporotic fracture or not?

Doug 10:35

Well, you’re, you are parsing, uh, where the data gets really sparse. As you know, as you say, we don’t know the duration of the age of many of those fractures, but we do know if you have had a recent one of those, you are at really high risk of having a subsequent fracture. So it is hard. And young people say, look, I was thrown from a horse when I was 22 years old.

And I, you know, I had a backache. I never got an X-ray. Who knows? And then they come in and they have an asymptomatic vertebral fracture. it’s hard to say, okay, well, you have osteoporosis because you have this. On the other hand, if you’re a betting man or a betting woman, it’s possible that they do have fragility because there may be a proportion of people out there that if they’d had high bone, higher bone density, they wouldn’t have had that fracture. Yeah. No matter what age.

So it’s, it’s difficult. It’s where epidemiology really meets, you know, public health. And in general, I encourage people to try not to get too tripped up on ascertaining trauma and was the event a traumatic event. Clearly, if you’re in a motor vehicle accident and you’ve broken 10 bones on the highway, sure. Yeah. That, that’s, that’s bad luck or bad driving. But everything else, boy, I’d be loath to say it hasn’t, it’s unrelated to osteoporosis. Okay.

Eric 11:47

I got another question for both of you. Are we still calling it osteopenia like Alex? Is it low bone mass? Is it something else? And exactly what the heck is that?

Stan 11:58

I prefer to Doug.

Doug 12:00

Well, yeah, it’s, uh, it’s really a labeling issue. And so no, the short answer is we prefer to use low bone mass as opposed to osteopenia, which, uh, comes from the Greek word, you know, low mineral in the bone, which is true. But then you label someone, you say you’re osteopenia, and there’s clearly a health impact on their quality of life knowing that they are diseased because they have osteopenia.

So, I think it really is much more clear to patients and providers that this is a labeling that may or may not have any implications whatsoever for their, for their life. So low bone mass is between -1 and -2.5. If you’re less than -2.5, then that’s labeled as osteoporosis. All

Eric 12:47

right. Last, last question on terminology.

Doug 12:50

Yeah.

Eric 12:50

What if you just have a very high FRAX score, But you haven’t done a, uh, bone mineral density. You don’t know about a fracture. I’ve seen some people say a high FRAX score is also osteoporosis, or is that not the case?

Doug 13:06

No, I don’t think so. That doesn’t mean I wouldn’t treat that person, but they don’t, may not have osteoporosis in the sense of meeting one of the traditional criteria, which is less than -2.5, or they have already fractured a classic site, such as a hip or a vertebral fracture.

Eric 13:22

Okay.

Doug 13:23

Those people are often labeled as having osteoporosis as well.

Eric 13:26

Okay, Stan, I got a question for you. Why does it happen? And you did a great paper on, is this a brain disorder and how it’s related to frailty? Would you just mind summing that up? We’ll have a link to that in our show notes, by the way.

Stan 13:41

Yeah, well, I think the presence of a fracture after the age of 50 is an opportunity to identify the possibility that that person, and even with just osteoporosis as defined by the bone density, that this person has the frailty syndrome. And this is a syndrome that we see in older adults characterized by a decrease in muscle strength, lean body mass, Cognitive impairment, weight loss, and these individuals are at increased risk of falling.

And it’s the fall that leads to that hip fracture or a Colles fracture. And I think when we see these fractures, this is an opportunity to identify these patients because the frailty syndrome, in a lot of cases, is reversible, particularly if it’s simply due to vitamin D deficiency or a B vitamin deficiency or other nutritional deficits.

Eric 14:53

Let me ask you this. Do you worry at all if somebody, if we just focus on osteoporosis, that you may miss the bigger picture of frailty that’s going on in the patient?

Stan 15:04

I do worry, and I think this is the problem today that, and I think Doug can address this too, is that we don’t follow up on these patients who have fractures. Yeah. A very small percent go on to get a bone density, a smaller percent go on to get appropriate treatment. Such as the bone-enhancing drugs that we have available today.

Eric 15:39

Yeah.

Stan 15:39

And, and more importantly, I think we don’t treat their underlying vitamin D deficiency or B vitamin deficiency.

Eric 15:49

We will get to vitamin D. I’m gonna hold off on that for a second because the other thing, so we’re starting to both think now about like who to treat, and I wonder if we can take a little step back and just start talking about who to screen first for osteoporosis. Doug, who should we screen for osteoporosis?

Doug 16:10

Well, the good news is that there’s lots and lots of women in data, so I can be really dogmatic about screening women because we know your risk goes up dramatically in a postmenopausal state with a loss of estrogen, and that risk really kicks upwards in an ex-natural function after age 65. And that has been shown in lots and lots of studies. Where it’s less clear, and so therefore, the targeting of screening ought to be at people at highest risk, or when you… and it depends a little bit about what you’re going to do in terms of preventative therapies.

But the U.S. Preventative Services Task Force has really now come up and sort of clearly joined the rest of the world in terms of the osteoporosis risk factors. If she has risk factors for osteoporosis, and these are the classic ones you think about, family history, underweight, use of medications that cause osteoporosis like corticosteroids or, you know, certain men, you know, androgen, anti-androgen therapy, then you should get a bone mineral density and risk stratify them. Then you should typically either use the bone density itself, and if it’s less than -2.5, that’s an automatic evaluation, or at least a potential evaluation for taking a medication in addition to repleting calcium and vitamin D, as Stan said.

Where the problem has been, unfortunately, is that there’s so much less evidence in men, the U.S. Preventive Services Task Force has not really blessed screening as an appropriate thing to do, even if you have risk factors. So what that means is that the, at least in the U.S., that means that there are funders of much of the care of osteoporosis, which is Medicare, does not approve bone mineral density tests in older men. And therefore you have to tell your patient, if you’re going to screen, here’s something that you’re going to have to potentially pay out of pocket for.

Alex 18:10

Hmm.

Doug 18:10

And it is really, that’s not an issue in women. Women are paid for because the U.S. Preventive Services Task Force has blessed it. So that’s the issue. That’s the crux of the issue for screening in men. And the question has always been all along, and appropriately, the U.S. Preventive Services Task Force doesn’t just say yes for no good reason. You have Yeah. Substantial, high-level, good evidence. And they don’t feel that that really exists yet in men.

Eric 18:35

I gotta ask, ’cause I always think about follow the money. Like if you were a drug company and you had 50% of the population that is not getting screened and you have this drug that you can make billions of dollars on, I would’ve assumed that they would’ve done these big trials and if it worked, it would’ve showed decrease in hip fractures. But they really haven’t. So it kind of tells me that the big money did not put money into this.

Doug 19:02

Yeah, no, I, I, I buy into that argument actually. But then in fact, the pharma did spend a huge amount of money to develop the drugs in the target population at high risk, i.e., postmenopausal women. Yeah. And then with the hope that then that they would be a bridging study or some sort of, you know, understanding based on something other than fractures, like bone mineral density, that could allow them to get an indication. So no, there are no hip fracture studies in men, period.

There are vertebral fracture studies and at least one non-spine fracture where they, you know, do the summation of all sorts of clinical fractures, but not hip. And so you have to assume, well, do we infer from women? Do we think men are different in a variety of reasons? What do you do? And the U.S. Preventative Services Task Force says, Not enough evidence. We’re not going to condone it.

Alex 19:53

I have a couple of follow-up questions here. One is, I was listening to a Curbsiders podcast. We can link in the show notes about bone health. I think the guest was from UCLA and they were saying one quarter of older women who should be screened for bone health are not being screened. And that’s where we need to put our emphasis because they are the population most at risk. And that’s a huge segment of the population, right?

Doug 20:19

Yeah.

Alex 20:20

It’s like one quarter of women and one eighth overall of older women. So any thoughts on that or where we’re missing the boat, why we’re not screening? What’s, what’s, how are this, how is this falling through the cracks?

Doug 20:32

Oh, come on, Alex. This is an asymptomatic condition until something, you know, catastrophic happens. You know, it’s not that different than getting your cholesterol screened or screening for blood pressure. It’s one of a million things that a primary care doctor needs to do. In a very short and increasingly difficult, you know, 15 or 20-minute visit. And there haven’t been a lot of system-based interventions to do this because we are way behind what our European colleagues do.

They have been actually much more successful at getting the population screened. Having the U.S. Preventive Services Task Force say every woman, regardless of ethnicity or other medical factors, should be screened at age 65 is a huge plus. And really, that’s … that is a metric that you can hang your hat on. Every woman over age 65 should be screened for osteoporosis if she hasn’t already been screened and isn’t already on a bone-active medication or on estrogen, for example. Men, it’s the Wild West. Yeah. Some men get screened, some don’t, some get treated, a lot don’t.

But there’s the usual preventative medicine conundrum that it’s difficult to implement systems to screen for asymptomatic conditions and even harder to get them to … on effective therapy, particularly when there’s scary side effects that are rare and unpredictable.

Stan 21:54

Well, just to follow up on Alex’s question, we know that a hip fracture certainly is a risk for underlying osteoporosis. And in men, the morbidity mortality is significantly greater than it is for a woman who has a, uh, hip fracture. Yep. And again, I think this is an opportunity to, uh, identify, uh, the underlying disease process, which may not be simply osteopenia or osteoporosis. Mm-hmm. And, and I think in many cases, the osteoporosis is secondary to the frailty syndrome. And one of the characteristics I failed to mention is, uh, an increase in inflammatory cytokines, which can be measured by, uh, a CRP blood test.

Eric 22:51

Mm-hmm.

Stan 22:52

And, uh, uh, we know that inflammation, uh, is associated with osteoporosis, but it’s also associated with, uh, uh, the frailty syndrome and, uh, The changes in the brain that involve the processing of information and the speed at which we process that information. And I think to a large extent, a hip fracture is indeed a brain disease reflecting this slowing of central processing speed.

Eric 23:28

Huh. So I think it…

Alex 23:30

I think you answered my second question about screening in men and where are we. Well, do you, do any of you have a strong opinion like that wants to go against the US Preventive Service Task Force and say that we do have enough evidence, enough evidence now to institute screening in men in this, with these select, you know, age group or risk factors?

Eric 23:48

I’m just gonna read a quote from Doug. Let’s see if he still agrees with it. This is from his JAMA IM article that I wrote down. A reasonable approach is to consider bone density testing at ages 70 to 75 years in men with one or more established risk factors for fracture. In the setting of a history of previous fracture, obtaining a screening bone mass measurement at a younger age, perhaps 65, is also reasonable. Doug, would you still agree with that?

Doug 24:12

Absolutely. Absolutely.

Eric 24:14

If you were in charge though, would you say, let’s just have the exact same thing we do for women, 65 plus?

Doug 24:22

Uh, no, I wouldn’t. Uh, because, um, if you… a population-based screening of men is much less efficient than it is of women. So, yeah. 4 times more common in women to reach that osteoporosis threshold of -2.5 than it is for men. But the ringer is that if you have an osteoporotic fracture, as Dan was mentioning, you’re 4 times more likely to die of your hip fracture if you’re a man than if you are a woman.

Eric 24:48

Yeah.

Doug 24:49

So it’s a more consequential bad outcome. Hip fractures are always a bad outcome no matter what your gender, but it’s really bad if you’re a man.

Eric 24:58

Is there an age or a setting like a nursing home, like 75 in a nursing home where you think we should just do universal screening for MED?

Doug 25:08

I don’t really think it’s,

Eric 25:10

no,

Doug 25:11

there’s much reason to distinguish nursing home versus, you know, non-nursing home. What is important is to understand life expectancy.

Eric 25:18

Yeah.

Doug 25:19

And if you are at the point of your life based on morbidity or other things that you think that your life expectancy is very short, then you’re not going to benefit from the drugs which take a couple of years at least to have some effect. Although, you know, there’s probably some benefit really within the first year.

Eric 25:35

Great point.

Doug 25:36

So think about that time frame. You would argue, yeah, that’s, that’s an incredibly high-risk population because they fall. And when they fall, they end up in the ER and they, with their, you know, broken hip and they go to the, to surgery. And most of them, if they don’t die, never really regain their mobility or their quality of life.

Alex 25:53

So, and we’ll link to our prior podcast with James Dierdorf and Sei Lee where they published this paper in JAMA Internal Medicine on lag time to benefit for Yeah. Bisphosphonates to prevent osteoporotic fracture.

Doug 26:04

Yeah.

Alex 26:05

Stan, any thoughts from you about screening for osteoporosis in men?

Stan 26:13

Yeah, well, I agree with Doug, but I do want to get back to that nursing home population because they are at much greater risk of a hip fracture. than women or men living in the community.

Eric 26:31

High rates of frailty, high rates of comorbidities.

Alex 26:33

They’re also older and have limited life expectancy.

Stan 26:37

Well, even age-matched, community-living older adults have a much lower risk of hip fracture. And I think the nursing home population, again, reflects the fact that the prevalence of the frailty syndrome in the nursing home population is is much greater, as well as the prevalence of cognitive impairment and dementia, which is a significant risk factor for hip fracture and, and of course, falls, as Doug mentioned.

Eric 27:12

All right. I want to make sure we have a little bit of time to talk about treatment. Any general thoughts on non-pharmacological things that you encourage your individuals with osteopenia, osteoporosis to do?

Stan 27:24

Well, I would like to ask Doug what he thinks of hip pads, because this is potentially an intervention in which you get protection immediately in contrast to the various drugs.

Doug 27:40

Yep. No, Stan, you’re right. We talk about hip protector pads in my, in my talks, and yet I have yet to meet anyone who actually wore one, agreed to take one. And it’s interesting because, you know, they are made out of a material which is supposed to absorb the energy of your falling on your greater trochanter and prevent your hip fracture. But the problem is they make you look like you have fat hips.

And in fact, I think the aesthetics has trumped fear of fracture in this particular case. And I, Stan, are you closer to this than I am? But I think that’s been even been true in institutionalized adults. They’ve had a very poor We do know that if you are wearing a hip pad and you fall, you are much less likely to break your hip than if you aren’t wearing that hip pad.

Eric 28:25

Wasn’t there a study a long time ago where they had the sham hip protector on one side and the hip protector on the other side? And there was, I think it was a negative study.

Stan 28:34

Well, let me, okay.

Doug 28:35

I don’t know about that one. I do know of trials that have actually randomized people to hip protector pads, but have not been successful because they couldn’t get people to comply with them. And when they did a per-protocol analysis, though, when they looked at those that actually wore the things, in fact, there was a substantial reduction in hip fractures, about 50% is what I, the number that I remember. I think this is just a matter of technology. Eventually we are going to have thinner, more resilient compounds that you can form over your hip that probably should be lovely. But as of right now, it’s really difficult to get to.

Eric 29:08

What were you going to say, Stan?

Stan 29:09

Yeah, I want to address your question. I was a, author on that paper. And we published in the New England Journal of Medicine that hip protectors were not effective. But as Doug alluded to, when we did a protocol analysis and factored in compliance, then they were protective. And we have done other studies which have not been published in which We were able to get compliance in a nursing home chain. Yeah. And, uh, and they showed pretty significant reduction in, uh, in hip fractures.

Eric 29:50

So I’m assuming we all encourage people and talk to people about exercise and physical therapy, adequate nutrition. Where does…

Alex 29:59

Avoiding alcohol, cigarettes.

Eric 30:01

Avoiding alcohol, cigarettes.

Alex 30:03

Or reduced alcohol at least.

Doug 30:05

Yeah, exactly.

Eric 30:05

Where does vitamin D fit into all of this, Dan? Your vitamin D intake supplements?

Stan 30:13

Well, I think vitamin D is incredibly important and the keystone for our treatment. And again, let’s go back to my comments about the role of vitamin D in falls. And we know from multiple studies that vitamin D does prevent dementia in most studies.

Eric 30:38

Wait, wait, prevents dementia or people who are vitamin D deficient, it may help?

Stan 30:44

Well, the, the one study that I’m referring to by Gargamani, these were not vitamin D deficient necessarily. It was a population of about 12,000 individuals, some of whom were vitamin D deficient. But there were others, there were all comers. But if you look at the general population, uh, Ann Haynes’ report demonstrated that 68% are vitamin D deficient.

Eric 31:15

Yeah.

Stan 31:16

So,

Doug 31:17

yeah. But Stan, the problem is there’s been, it’s been really difficult to show clinical outcomes. I have prescribed oodles and oodles of calcium and vitamin D in my career, uh, including giving a lot of Tums to perimenopausal women when back in my earlier years. And I’ve just been impressed how hard it has been to do large randomized trials that show improvement when it’s compared to placebo. And I know there’s methodologic issues, clearly, and also patient selection. I know a lot of it has to do with where your vitamin D was when you were randomized to either take placebo or vitamin D, but I’ve just been impressed how difficult it is to show…

Eric 31:54

I’ve also been impressed that there seems to be more meta-analyses on vitamin D than there are randomized studies on vitamin D.

Doug 32:00

With and without calcium, by the way. Yeah. Which further complicates the matter. So, yeah.

Stan 32:04

Well, but in that Gagrimani study, they did show a 40% reduction in dementia, particularly of the Alzheimer’s type. The difference from a lot of these studies is that they followed these patients for 10 years. And if you’re going to have an impact on Alzheimer’s disease, you have to recognize that the disease starts some 10, 20 years before there are clinical manifestations. And I think it’s informative that one of the most widely cited negative studies of vitamin D in preventing dementia is the Finnish Vitamin D trial. And the initial trial followed these patients for 4.2 years and showed no effect on dementia. But they did have a follow-up study where they monitored these patients.

Eric 33:12

Yeah.

Stan 33:13

Subjects for an additional 4.6 years and The group that received the highest dose, that was 3,200 international units per day, there was a significant decline in dementia.

Eric 33:31

Uh, we’ll have links. I don’t want to get too bogged down in dementia. Again, this is again about bone health, but we’ll have links to that. People can kind of read the article. Was that a randomized controlled trial or just the observation?

Stan 33:41

Yes. No, it, the Finnish vitamin D trial was randomized to placebo. 1,600 milligrams and 3,200 milligrams.

Eric 33:51

All right. I, I wanna make sure we have time to talk about other treatments besides vitamin D real quick. Stan, what is your like one-liner on what you recommend people do with vitamin D?

Stan 34:01

Well, that’s a complicated question ’cause there is no simple answer. It, it depends on the individual.

Eric 34:08

Yeah.

Stan 34:09

If you are a, a lean, healthy individual, good diet, The average recommended dose is about 2,400 units per day. In our consensus conference, we figured that the requirement for vitamin D is around 4,000 units per day. But then you need to subtract from that dietary intake, sun exposure, but also weight. BMI is …

Eric 34:42

Yeah.

Stan 34:42

Really important factor. And if you’re obese, BMI in the 30s, 35 and greater, your requirement for vitamin D probably doubles. So there, there is no one dose recommendation. But the other important point that I made in that editorial is that we have a pretty good idea what’s required for bone health. But what’s required for the prevention of breast cancer, colon cancer, for autism, for… Well,

Eric 35:19

we’ll save that for another episode. We’re gonna be focusing on bone health. Doug, how about you? Where, where, where do you fall on vitamin D? You seem to be a little bit more negative on it.

Doug 35:29

I, I, I would say I’m agnostic more than negative, but I am a strong believer that if you are going to prescribe someone pharmacologic doses of a medication to prevent osteoporosis, primarily bisphosphonate, it’s incumbent upon you to make sure that they get adequate calcium and vitamin D.

Eric 35:47

Yeah.

Doug 35:48

So in other words, you need the building blocks.

Eric 35:50

Do you check vitamin D levels or you just give everybody vitamin D?

Doug 35:53

Oh, I pretty much give everybody vitamin D. And then if I really feel like they’re frail, they’ve been institutionalized, uh, other issues, then I might check on vitamin D, but I’ve really gotten away from doing routine screening of vitamin D levels. Just because I’m not clear that everybody needs it. Now that’s for the skeletal outcomes, and I’ll wait with great interest for more evidence about non-skeletal outcomes.

But really for skeletal outcomes, I think that we’ve spent a lot of money on vitamin D assays and supplementing people who probably didn’t need it. Yeah. In my practice, it’s people that can’t take calcium that really get into most trouble, I think, you know, because they have lactose intolerance, for example, and they Never touch a dairy product.

Eric 36:33

Do you do 800 international units for vitamin D? What’s your…

Doug 36:36

Yeah, I think that’s fine. And I would be more than happy to, you know, see my patients take more. I don’t, you know, I think it’s safe and easy to do. On a population base though, you know, I’ve just been impressed that we’ve been really difficult to take relatively unselected and frankly, relatively healthy people, give them calcium and vitamin D and looked at all sorts of outcomes in the The VITAL study did this and really it’s been very difficult to show any clinical outcomes that improved.

Eric 37:04

Bisphosphonates. Let’s real quick, we’re going to do lightning round because we only got… when we’re thinking about bisphosphonates, go-to is oral first.

Doug 37:13

That would have been true to me a few years ago, but I, I really think that you should think intravenous first and talk yourself out of it if you can and want to. Compliance is not an issue when you get a once a year dose or even longer of intravenous zoledronic acid. The efficacy is as good, if not better, than oral medications, but that’s confounded by compliance.

I mean, it’s hard for people to take a pill every day or every week for year after year after year. And so I really do like the intravenous zoledronic acid and offer that as the first line because it’s easy to do at UCSF. You know, we have an infusion center.

Eric 37:50

Do you have to worry more about dental health and risk for… No.

Doug 37:55

There’s no evidence that it’s any worse. Now, the problem is these are really rare outcomes. So…

Eric 38:00

Osteonecrosis of the jaw. That’s what…

Doug 38:02

Yeah, exactly. Especially osteonecrosis of the jaw is incredibly rare. If you get oncologic doses, absolutely. And, you know, that’s where the issues of high doses start reaching a prevalence that is notable. But in an unselected osteoporosis population, you know, I like to tell people that you’re much more likely to be killed on Highway 101 driving home from the office than you are to get osteonecrosis process of the jaw, which is, is true. The other one though, which is more serious and I think more worrisome, but frankly easier to study because it is more common, is atypical femoral fractures.

So right now we’re doing a huge NIH-funded study to look at the prevalence and risk factors for atypical femoral fractures, including do they occur in men, which right now there’s zero evidence in men. We don’t know. And to get enough people to look at the study, we’ve had to get the entire country of Sweden Get the entire country of Denmark and all of Kaiser Southern California and pool those across 3 studies to get enough of these AFFs to say anything intelligent about them.

Eric 39:04

Is that one where the longer they’ve been on the bisphosphonate, the greater the risk, or is there…

Doug 39:08

Exactly. Yeah.

Alex 39:09

So it’s time dependent.

Doug 39:11

Clearly it is dose response. And particularly after 5 to 8 years, then the risk goes up quite dramatically.

Eric 39:18

Given that you do…

Doug 39:18

I’ve been getting that bisphosphonate for 5 years now and I…

Eric 39:21

Do you do, well, yeah. What’s your duration of a bisphosphonate?

Alex 39:24

3 years?

Doug 39:25

Uh, you know, the, the studies show that you are, what the question is, is what’s the, um, what’s the downside? The downside is if you start, stop too soon, you may increase their risk of, of an osteoporotic fracture. And we think the best evidence is because bisphosphonates stick around in your system a long, long time.

Eric 39:41

Yeah.

Doug 39:41

Particularly the intravenous. Stopping after 5 years is probably a reasonable thing to do. Intravenous, you could stop, probably stop after 3, after 3 successive doses of intravenous.

Eric 39:51

Um, oh wow.

Doug 39:52

And then, um, now the question that we don’t know is, what do you do then? Uh, we watch people, we tell ’em if they have a fracture, come talk to us. Some clinicians use bone mineral density or bone turnover markers. I think that’s not, uh, really well, um, established as being a useful way to predict who’s going to have bad outcomes after they stop their, uh, treatment. But, um, you know, clinicians don’t like to stop the drugs and then do nothing.

Eric 40:13

Yeah.

Doug 40:14

And it’s, okay, don’t worry, I’m following you and everything’s going to be fine because your bone mineral density has stayed fine or your bone turnover markers have stayed suppressed. But in fact, we really don’t know. And this is an ongoing area of investigation, which we don’t know. We do know people are scared to death of having these long-term complications of the bisphosphonates, and the use of bisphosphonates has gone… went down dramatically in the late ’90s, early 2000s, because people were afraid of these side effects.

Eric 40:41

Yeah, it’s a long list.

Doug 40:43

It’s a long list. And, but remember, They are really rare events, and you’re much more likely to prevent a hip fracture or a non-spine fracture with your bisphosphonate than you are to cause either an atypical femoral fracture or osteonecrosis of the jaw. So the risk-benefit is still strongly, strongly positive.

Eric 41:00

Let me ask you another question for both of you. In 2018, a New England Journal study came out on osteopenia in women over 65 and giving them zoledronic acid. Which showed a decrease in symptomatic and non-symptomatic fractures. Do you treat osteopenic women or Alex Smith with, uh, zoledronic acid for osteopenia? Stan, what do you do?

Stan 41:26

Well, I think that depends on the, again, the individual, their life expectancy and, uh, other, uh, factors. But, uh, uh, you know, if they’re otherwise healthy, good life expectancy, uh, I think, uh, Uh, one can consider looking at other risk factors for osteoporosis. Yeah. Uh, that can be treated. And if that is really approaching, uh, the 2.5 standard deviation of the T-score,

Eric 41:56

yeah,

Stan 41:56

then I would recommend, uh, uh, treating. But I just wanna pick up on what, uh, Doug said. Uh, I, I’m opposed to the oral forms. Because, uh, they are associated with gastric ulcers and, uh, esophageal ulcers. ‘Cause you’re supposed to be upright for 30 minutes after you take it.

Eric 42:17

Yeah.

Stan 42:18

And that’s not doable in a nursing home.

Doug 42:20

Yeah. Yeah. Yeah. So that New Zealand study, um, it was a single study, very good osteoporosis researchers in New Zealand did that study. And it did indeed show that even 18 months, I believe, of interval of zoledronic acid reduced non-spine fractures. The rub is if we’re worried about the total amount of bisphosphonate that you give someone over a lifetime, maybe you should save that for when you really need it.

Eric 42:44

Oh.

Doug 42:45

On the other hand, if a woman is scared to death because she watched her mother have a hip fracture and she says, I am 55 years old and I am really worried about my bone health, other than once we’ve done all the non-pharmacologic things, including everything we’ve talked about on the podcast, then I don’t think it’s unreasonable to, um, do a bone density and offer them a single dose of intravenous bisphosphonate. zolendronic acid, which may be just fine for the next 5 or 10 years.

Eric 43:12

I heard when they came up with the definition for osteoporosis, it was during a WHO Rome meeting.

Doug 43:18

Yes.

Eric 43:18

And they, they, they couldn’t finalize what number that they were going to use. And finally, like, that was a hot, like, Wednesday afternoon. I’m not sure if either. And they just picked 2.5. Like, there’s nothing magic about -2.5. Is that right?

Doug 43:33

It was based on the fact that about 20% of the population was screened, had -2.5. So basically it was a pure you know, a decision that was made just to make a decision and move forward. It has stood the test of time though. That’s what’s incredible about that is that as you think about this, not many other proposals have improved on that -2.5. But what I would encourage everybody to do is to think about your probability of having a fracture as opposed to your T-score, which is really much easier for patients and frankly clinicians to get their arms around.

Eric 44:03

Oh yeah. One last question for both of you. This is one that, ’cause we talk about drug holidays for Bisphosphonates. Denosumab, so our second-line therapy, is there a drug holiday there, or what do you do with it? I don’t know. No, you’re just, you’re on it for life.

Doug 44:20

Either you are on it for life, or you have to really be careful stopping, because there’s clearly a marked increase in the risk of rebound fractures, particularly vertebral fractures, which can be catastrophic. And everybody is at risk who stops their denosumab, whether it’s because your doctor tells you to stop, Or because you decide to stop yourself, or because you’re non-compliant.

It’s a terrible drug. I, I just find it unbelievable. Uh, and I don’t use it, uh, unless I am convinced that someone’s going to be on that the rest of their life. And I think the story about ONJ and, um, atypical femur fractures is out for denosumab. We just don’t know.

Eric 44:57

So we don’t know what the long-term side effects are from denosumab with atypical fractures?

Doug 45:02

It’s from observational studies. It’s all from observational studies. And the randomized controlled trials all stopped at 3 years. Um, If you’re interested, Chris Ensrud and I, who’s another general internist, wrote a piece about denosumab in JAMA. It was about a year ago. And from a primary care perspective, I’m not saying it’s not useful in some specialty practices where people have tried other things, but I’m telling you, in the general practice, I just can’t imagine why anybody would take someone who’s doing well on a bisphosphonate and switch them to a denosumab.

Eric 45:30

Yeah.

Doug 45:30

Because you are, you’re going to obligating that person either to take it for life or to go through a period of pain. I increase risk when they stop.

Eric 45:37

Well, I want to thank both of you. I realize that we’re out of time. Maybe we’ll just do a little bit more Stan’s song, Turn, Turn, Turn.

Alex 45:50

(singing)

Eric 46:45

Man, we could have gone for 2 hours on this podcast, Alex. Thank you, Doug. Thank you, Stan. Sorry we had to cut it, but we’re going to have to have you both on another time. So thank you very much for being on this podcast.

Doug 46:57

Our pleasure. It was great fun.

Stan 46:58

Our pleasure.

Eric 47:00

And thank you to all of our listeners for your continued support.

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