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- [00:01]
A
This is endocrine feedback loop. I am your host Chase Hendrickson and welcome you to this Journal Club Podcast series brought to you by the Endocrine Society. Thanks for joining us as we explore an important article recently published in one of the Society's clinical journals. Welcome back to the Endocrine Feedback Loop podcast for our 73rd episode and the start of our seventh season. For this episode of the podcast, we look at a JC&M paper that reports a secondary analysis of an RCT that studied the effects of zoledernate infusions every five or ten years. We as endocrinologists often think of antiresorptive therapy being fairly standardized, so this study that offers zoledronate more broadly and less frequently raises some interesting questions for us to wrestle with. We will give you our impressions as we walk through this paper and as always, we will end with our thoughts on whether these results should change our clinical practice. Before I introduce our team to you, I remind you that I host the Endocrine Feedback Loop and work at Vanderbilt Health as a general endocrinologist and medical Director. Back today as this episode's regular contributor is Amal Shibley Rahal. She comes to us from the University of Iowa where she is a master educator in endocrinology, currently serving as an Associate Dean for the Carver College of Medicine. She serves as the lead endocrine educator for their internal medicine residency, having also been the Fellowship director in the past. Her clinical practice focuses on bone and calcium disorders with many publications in this field and in endocrinology in general. Today's guest expert hails from Duke Health. Tom Weber will be a familiar name to you listeners from his many papers and talks in the field of bone health. His expertise ranges from male and postmenopausal osteoporosis to rare bone disorders like X linked hypophosphatemic rickets and tumor induced osteomalacia. So as you can tell, the perfect pair of endocrinologists joins me today to discuss a paper on osteoporosis. As usual, everything we discuss will be our opinions only and not those of our respective institutions or the endocrine society. This month we discuss anti fracture efficacy of 5 or 10 yearly zoledronate in women aged 50 to 60 secondary analyses of a randomized trial, which was published by the Journal of Clinical Endocrinology and Metabolism in April 2026. Mark Boland served as the first author of this manuscript and was joined by colleagues also at the University of Auckland in New Zealand. I will now hand things over to Amal. She will go through the author's introduction and the main points that they make, as well as getting Tom to share insights along the way.
- [02:41]
B
Amal thank you, Chase. As Chase mentioned, I will start by presenting the author's introduction to this paper. Current practice guidelines recommend that most fracture prevention strategies target people at high risk of fracture, such as older individuals and those with low bone mineral density or prior fractures. Tom, I'm going to stop for a minute here and ask you to comment about the varying definitions of risk and about the traditional approach to treat those at high or very high risk of fracture.
- [03:16]
C
Thank you, Amal, for that introduction. I think that when you think about risk for osteoporosis, it's important to quantify it by obviously risk of fracture is why we treat, and we can glean that from bone density testing, but also from estimation of fracture risk with fracture risk calculators like frax. And then there are guidelines with regards to level of fracture risk, moderate, high, very high, that we use to decide on osteoporosis treatments. In clinical practice. What we typically will look at is the estimate of fracture risk based on all the clinical factors, not just the bone density, but also aggregate risk factors, to give us what's called a frax, which is an online fracture risk calculator estimate of fracture risk to help give guidance in terms of treatment.
- [04:02]
B
Thanks, Tom. So that is the traditional approach to treating or evaluating patients at risk of fracture or with osteoporosis. What's different about this paper is that it challenges this approach or presents a counterargument that basically asks the question whether earlier treatment of people who are at lower fracture risk might have long term benefits in terms of decreasing the chances that they will progress to high fracture risk or actually sustain a fracture. To test this hypothesis, the authors of the current paper published a study in 2025 in the New England Journal of Medicine where they treated women between the ages of 50 and 60 who had osteopenia and they gave them infrequent doses of zoledronic acid and showed that this approach decreased the risk of fracture as evaluated 10 years later. The current publication is a report on the same study that looks more closely at fracture risk at different time points and tries to correlate that with certain risk predictors in their patient population. Now I'm going to ask Chase to walk us through the design and the methods that they used, so we'll first
- [05:18]
A
of all think about RCTs in general. Now again, this is a secondary analysis so we're going to get to that in just a second. But first of all, as we think about RCTs, we always hold those up as the gold standard because they do a couple of things that are really great that get around problems that show up in observational studies. They are typically in the name. So with an rct, the R is randomization. And the key with that is when you randomize individuals to be treated or not treated, you deal with confounding. Confounding still shows up. It can still be an issue here. But if you have enough subjects and you've randomized correctly, you should be able to balance your confounders. So you could think of them essentially as canceling each other out. You don't have to worry about them affecting your results. So that's one of the real benefits. The other benefit comes from blinding. And the reason that that is so helpful is that it gets over the concerns around bias. So a bias in biomedical research is when you treat a subject differently because you know what group that individual is with blinding. You don't know whether a person is being treated or not treated. So you can't treat them differently. And that applies to the subjects themselves, but also anybody participating in the investigation. So that's an rct. And that's why we always hold these up as the gold standard, typically in these investigations. Now, a subgroup analysis goes further. So you take, generally speaking, an rct, but then you ask the question of would it be different when I come up with different conclusions if I was looking at some baseline characteristic. Age is a good example. That's almost always one that's thought about is, well, if I see that an intervention is beneficial, would it be different if I split people into different ages and said, well, was it more effective if you're older, is it more effective if you're younger? And that's the idea of a subgroup analysis, is you're trying to understand a differential effect of an intervention. So that's what this is. Now, we're going to first of all start just by thinking very broadly about the larger, the original rct, and that was published several months ago. So just to hit that at a high level, that was a 10 year double blind RCT. And you heard a little bit about it already. But that study enrolled women ages 50 to 60 who had T scores that were between 0 and negative 2.5. So we would consider them as having osteopenia or actually normal bone density. Then there were three groups there. So there was a placebo group. So it was a placebo controlled trial. There were two intervention groups. So one of them, the subjects, receives electronate just at baseline at year zero. And then in the other intervention group, they also received a zoledronate infusion at that baseline at year zero, but then again five years later. The outcomes of that rct, the primary outcome was looking at new vertebral fractures that were identified on plain films. They had a few secondary outcomes. The first one was incidence of fragility fractures. The second one was any fracture. And the third of the secondary outcomes was a major osteoporotic fracture. Tom, I thought you could maybe help us here. Still thinking about the larger study, that initial rct, but help us understand fractures, how those are defined in these sort of studies, if they're thought about differently. Just anything that we would need to have in mind as we think about how fractures are used as outcomes in RCTs.
- [08:34]
C
Thank you, Chase. It's a very good question. And the primary endpoint of most osteoporotic trials throughout the past three decades has been vertebral fractures. The reason for that is that they occur more commonly and they're a little bit easier to detect with plane imaging, what are called morphometric fractures. And the protocol for this study followed that with a little bit of a twist. They talked about changes in vertebral morphology by 0.5123 in terms of severity, as well as at least a 20% loss of vertebral height in the anterior, mid or posterior vertebral height. And that's how we define morphometric fractures. Now, these fractures can occur without any pain whatsoever. In fact, two thirds of vertebral fractures, when they occur, don't cause acute pain. That's why it's important to look for them radiographically. But they still predict a higher risk for fractures going forward. So it's important to identify vertebral fracture. Definition, I think, was pretty standardized. And with regards to the other comments and fractures, they captured major osteoporotic fractures, which we use in frax calculations, although they included pelvis and I'm not quite sure why, but they included that in the definition as well. And they talked about then all fractures. And that would include fractures of the face, skull, fingers, hands, toes and feet. And that's another parameter which is captured in some trials of osteoporosis as well.
- [09:57]
A
We're now going to think about this secondary analysis, this subgroup analysis. So we've just been talking about the initial study that initial RCT So for this paper, the subgroups that they looked at, first of all, as they thought about the outcomes, they assessed the time to a fracture. So what they did is they pooled fractures together based on when they occurred, whether they occurred in that 0 to 5 years or that 5 to 10 years. And then specifically the four subgroups that they looked at, age was the first one gave that as an example earlier. That's often looked at. The other one was estimated fracture risk. Tom talked about that a little bit in the introduction about, wow, that's important, how we can do that. We'll come back to that. But that was another subgroup that they looked at. The third subgroup was the baseline bmd, and then the fourth one was the change in the BMD throughout the study. Those are the four subgroups. Just one last word on the methods here is that they did not adjust for multiple testing in their P values that they report. But the authors address that later on. So we'll come back to that in a little bit. So very high level. We didn't want to get too much in the weeds of the statistics here. It's a relatively sophisticated approach when you do these subgroup analyses. But we wanted to make sure that we were wrestling with the results and what conclusions the authors draw from those. So in order to do that, I'm going to hand things back over to Amal and she's going to spend some time walking us through these results.
- [11:19]
B
The study included 1053 women. 352 were randomized to receive 5 mg of zoledronic acid at baseline and 5 mg five years later. 351 subjects received the 5 mg of zoledronic acid at baseline and a placebo infusion at five years. And 351 subjects received placebo infusions at both time points. The baseline characteristics of the subjects are presented in Table 1. The mean age was 56 years. 85% of them were from European descent. And remember, this study was conducted in New Zealand. The average T score at the time of enrollment in the study was minus 0.5. So very mild osteopenia, so to say, on average. Now I would like to direct your attention to Figure 1, which shows the time course of fractures during the study. First we will look at vertebral fractures and those are shown in panel a of figure 1. Between years 0 and 5, there were very few vertebral fractures. As a result of that, there were no differences between the three groups. Between years five and ten those who received just one dose of zoledronic acid at baseline experienced a 57% reduction in fracture risk. And those who received two doses of zoledronic acid at baseline and at five years experienced a 58% reduction compared to the group that only received placebo at both timelines. If the average risk reduction that we are seeing between years 5 and 10 were to be averaged over the full 10 year study period, we see that with one dose of zoledronic acid, there was an overall 41% reduction in fracture risk and the reduction was 44% with two doses of zoledronic acid. And as a reminder, this is all talking about vertebral fractures at this point. So I will turn back to Tom and ask you, Tom, how these results compare with the vertebral fracture reduction observed with traditional dosing of zoledronic acid, such as with the Horizon trial.
- [13:39]
C
Thank you, Amal. I think it's important to recognize the differences between trials when we start to do this comparison. The Horizon Pivotal Fracture trial included women whose mean age, I believe was in their 70s, early 70s, so a much older group. And actually at baseline, based on bone density as well as prevalent fractures and level of fracture risk, they were much more severely affected. Having said that, there was about a 70% reduction of vertebral fractures in the Pivotal Fracture trial with Horizon 1.5% in zoleduric acid versus 3.7% in placebo. What was interesting is that fracture risk reduction was seen within the first year and it increased as time went on as well, such that it became 3.3% for zoledronic acid treated subjects and 10.9% for placebo. So I think that the numbers are comparable. What's interesting though is the onset was more acute with regards to the Horizon Pivotal Fracture trial and not as much so with no significant effect in the first five years. And that raises the question of is it a cumulative effect of zoledronic acid has to occur in this population that was studied versus the Horizon trial? And those are interesting questions to ask.
- [14:50]
B
Now we will look at the risk of major osteoporotic fractures. And as a reminder, this was defined as the combination of wrist, spine, shoulder, hip or pelvis fractures for this study. And the results are shown in panel c of Figure 1. Again, there was no statistically significant risk reduction between years 0 and 5. However, there was a little bit of a trend toward less fractures in those who received zoledronic acid at baseline compared to those who who received placebo. The ones who received zoledronic acid had a 9% less risk compared to those who received placebo at baseline. Now, between years five and 10, there was a statistically significant decrease in the risk of major osteoporotic fractures in the two zoledronic acid groups. And those who only received one dose of zoledronic acid, there was a 39% reduction. In those who received two doses of zoledronic acid, there WAS a 57% reduction. And this is between years 5 and 10. If we take those risks and average them again over the full 10 year span of the study, we see that those who received a single dose of zoledronic acid experienced a 29% risk reduction over a 10 year span and those who received two doses of zoledronic acid experienced a 40% reduction in risk. The researchers also looked at the risk of any fracture and this is shown in panel b of figure 1. Between years 5 and 10, there was a non significant trend toward fracture reduction of 20% in those who received a baseline dose of zoledronic acid compared to those who got placebo between years five and 10. Those with one dose of zoledronic acid experienced a 30% risk reduction and those who received two doses experienced a 40% risk reduction. And these changes were statistically significant. Again, if we average these reductions over the full 10 year span of the study, the reduction would be around 23% for people who received a single dose of zoledronic acid and about 30% for those who received two doses of zoledronic acid. Tom, I will ask you a similar question now. You know, how do these results in general compare with the reduction that we see in non vertebral fractures when zoledronic acid is used in the more traditional way?
- [17:24]
C
Thank you, Amal. So, slight differences between all fractures and nonvertebral fractures in terms of the definition, but fairly comparable. And the numbers in terms of the percent reduction is fairly similar as well. The Horizon pivotal fracture trial was associated with about a 25% reduction in nonvertebral fractures. So I would say that the results are fairly comparable between studies.
- [17:47]
B
Now we will move on to the next aim of this study, which was to look at fracture risk correlations with risk variables. For these analyses, the investigators only studied correlations with the risk reduction of any fracture. So they did not look at vertebral fractures or major osteoporotic fractures in isolation here. Tom, why do you think they focused on the risk reduction for quote, unquote, any Fracture as opposed to vertebral fractures or major osteoporotic fractures?
- [18:16]
C
That's a good question, Amal. There are some that think that any fractures can be osteoporotic nature. And one thing I didn't mention earlier is that in the fractures that were captured within this trial, they did capture them, irrespective of the degree of trauma. And there's an older literature suggesting that patients who fracture with high trauma have lower bone densities. And so it's important to note that maybe that doesn't distinguish the true fragility fractures versus all fractures. So I think that they were trying to capture that aspect of biology as well.
- [18:48]
B
Great. Thank you. Okay, so let's look at the results. The results of these analyses are shown in Figures 2 and 3. For those of you who have the study in front of them, in Figure 2, they assess if differences in baseline characteristics that are categorical variables affected the risk of, quote, unquote, any fracture risk reductions observed. They did not find any statistically significant correlations between fracture risk reduction and the variables that they examined, such as baseline weight, height, bmi, physical activity, falls, smoking status, or bone mineral density, turtiles. And again, they looked at all of these variables as a categorical variable for this particular analysis. Now, in Figure 3, they do similar correlations, but this time they focus on continuous variables, and particularly they focus on age. T score at the lumbar, spine, T score at the hip, and baseline estimations of fracture probability based on frax. Here we see the expected correlations between these variables and the risk of fracture, meaning that the risk of fracture increases with age, the risk of fracture increases with lower T scores. The likelihood that someone will experience a fracture during the 10 years of the study is higher if their baseline FRAX calculation showed a higher probability of fracture. For each one of these variables that they studied, the risk line is highest in those subjects who received two doses of placebo, followed by the subjects who received one dose of zoledronic acid and one dose of flip placebo. And the lowest risk line was for the subjects who received two doses of zoledronic acid. However, these three risk lines for the three different groups are parallel, meaning that there were no interactions between the risk variables that they assessed and the treatment arm. Chase, can you please remind us what interactions means in this setting?
- [20:57]
A
Yes. So this really gets back to the whole idea of a subgroup analysis and what you're trying to understand. And the idea of that is to try to understand if the treatment here, if the effectiveness of it really varies by any of these subgroups that you're looking at. And one of the challenges with a subgroup analysis is that it's often not adequately powered. When you're trying to decide in your initial RCT how many subjects you want in that rct, you're doing your power calculations based on this larger study. The challenge is always is when you start looking at smaller groups, you will often not have enough individuals in there to confidently say that you've got enough, that you can show a difference. Now, if you see a clear distinction. So if you do a subgroup analysis going back to that example of age and you can say, oh, yeah, clearly this intervention is very effective in older individuals, but we don't see that at all in younger individuals, then fine, then the power is not a concern. It's always a problem. When you don't see a difference, can you conclusively say, yeah, we don't see a difference, there's no change here, or is it just, well, we didn't have enough individuals to be able to see that. And I think that's one of the reasons that the authors are showing this as putting these lines together to be able to say they're really parallel. So it's not even that there's a trend. And, ah, maybe if we just had more individuals, we'd be able to clearly see that there was a difference. They're able to demonstrate here that, well, these lines are all quite parallel, so we wouldn't anticipate there being a difference, a meaningful one, even if we had a lot more subjects. So I think that's what they were attempting to illustrate with those graphs.
- [22:23]
B
Thank you, Chase. Now we move to the final section of the analysis where the authors focus on changes in bone mineral density over the study period. In Figure 4, we see the percentage of subjects who experienced an increase in bone density at the total hip within each treatment arm between years 0 and 5 and between years 5 and 10. In summary, the group that received two doses of placebo had the lowest percentage of individuals who experienced an improvement in bone mineral density, followed by quite a bit of improvement in the group that received just one dose of zoledronic acid and even more improvement in the group that received two doses of zoledronic acid. Figure 5 tries to correlate the increase in bone mineral density at the total hip with fracture risk reduction and essentially shows no clear patterns or trends, meaning that the increase in bone mineral density does not consistently predict the degree of fracture risk reduction in this group of subjects. This suggests that regular monitoring of Bone mineral density in this group may not necessarily be helpful in predicting fracture benefit. Tom, this reminds me of a study that was published in the New England Journal of Medicine many years ago that suggested that regular bone mineral density monitoring in patients with osteopenia in general was not necessary. A couple of sentences. Can you remind us of that study? Even though those subjects were not on therapy? So it's a different group of people to some degree.
- [24:05]
C
Thank you, Amal, for that. I do remember that study well, and what it did is they took one of the original osteoporosis cohorts from the study of osteoporotic fractures and tried to determine with certain degrees of osteopenia or normality how long it took for those individuals, 10% of them, to convert to osteoporosis, how many years? And for patients who had normal bone density, it took 17.4 years. For patients with mild osteopenia, T score between minus 1 and minus 1.5, it took 16.5 years. For moderate osteopenia, which was minus 1.5 to minus 2, it took 4.6 years. And for more advanced osteopenia, from minus 2 to minus 2.5, it only took 1.0 years for 10% of that population to convert to osteoporosis. So the bottom line is, from the study that they suggested is that we do not need to test for bone density very often at all in patients who are more mildly affected in terms of their bone density. Truth be told, I actually had a conversation with the lead author on a study, and I asked her if she used that study in her clinical practice, and she said, no, it's not practical when you're taking care of patients. They're not going to wait 15 years for another bone density study to be done. So while it was very interesting intellectual study to do, I don't think it really changed practice all that much.
- [25:25]
A
We are now going to move on to the discussion, and I'm going to keep posing some tough questions for Tom for him to wrestle with for us. Okay, so I'm going to start with where the authors start as they summarize some of their results. And they say that the effect of zoledronate on fracture incidence is greater during years five to 10 than zero to five, with a nearly 60% reduction in years five through 10 for the treated groups. And they also point out that 56% of women in the group treated at baseline and five years had an increased bone mineral density, but the effects on fracture incidence did not vary. By that change in bone mineral density. So, Tom, thoughts about this? Does this stand out to you as surprising or is this. Yeah, no, this is kind of what we would expect with what we've seen in other studies and in clinical practice.
- [26:15]
C
Thanks, Chase. No, I think this is expected. I wouldn't expect bone density to have a dominant effect in a patient's population at very low risk for fracture. So I think this is consistent with observations from previous studies.
- [26:28]
A
The authors then go on to compare their work to other studies. They do point out that other studies that enrolled older individuals with a higher fracture risk did show increasing risk reduction as those trials progress. So trying to compare that to some of the results that they found here, the authors also point out that in this population of women at a low risk for fracture, that the treatment effects did not vary based on the studied baseline variables. So, Tom, one thing I wanted to get your input on here, because when we've looked through these numbers, when Amal walked us through them, there's a lot of an emphasis here on a relative risk reduction, and that's what the comparisons are. But another key component of this is an absolute risk reduction. So just as we're wrestling with some of these numbers, how do we need to keep in mind absolute risk reduction when we're working through a bunch of relative risk reduction?
- [27:21]
C
Thank you, Chase. That's really, really important. And as it relates to absolute risk reduction, that's how we determine the number of subjects needed to treat to prevent one event. It's one over the absolute risk reduction. So if we look at this trial, again, the relative risk reductions for most of these fracture outcomes are very impressive. With regard to morphometric vertebral fractures, the absolute risk reduction is 5%. So that would be a number needed to treat of about 20, which is not unreasonable in osteoporosis trials. But again, this is over a 10 year period that we're looking at for major osteoporotic fracture risk reduction, including the pelvis, as I mentioned earlier, 8.1% absolute reduction, which is about a 1 in 12 patients to treat to prevent one fracture over 10 years. And then any fracture risk reduction, the absolute risk was 10.6%, and that would be an NNT of about 10. So these are not unreasonable NNTs. But I think what's left out of this trial is a calculation, and there was very little conversation about it in the discussion about harm and the number needed to harm. They did talk about episcleritis and scleritis affecting a number of patients. I Calculated the absolute risk was 1.3% in the treatment groups. There were no cases in the placebo group. So again, that's not a large number needed to harm, but still a number which I think has to be taken into account. There was also no discussion about acute phase reactions, some of which can be very severe in patients who have never taken bisphosphonates or even if they have taken oral bisphosphonates before. And that can be debilitating, as Amal will know, in our clinical patients. And there's no discussion on these parameters. So you need to look at the full picture, harm versus benefit, when you're trying to make a decision with the patient about what's best for them to do.
- [29:09]
A
One interesting comment that the authors make to recognize something that many of us have encountered is they point out that the average bone mineral density in the twice treated group remains stable over the study. But, and I'll quote them here, there was a tail of individuals whose BMD decreased by more than 1% per year. And the authors then point out that that reflects a clinical scenario that is encountered, not infrequently in our patients. The authors then go on and point out that since a baseline fracture risk can be assessed without a bone mineral density, Tom alluded to that before. And that since the change in bone mineral density is not associated with fracture risk, it's unclear of whether bone mineral density testing is as helpful as we think it is. And so, Tom, we've touched on this already, but let's come back to that. What are your thoughts? Again, this is an unusual approach. They're treating people in an atypical way, at least compared to usual practice practice. But it's feeding in this information that we have that maybe we do a lot of BMD testing, and it's not giving us as much helpful information as we think it might be. So given all those caveats, how do you take this and what are your thoughts about that, particularly as it relates to the care we provide? Thanks, Chase.
- [30:23]
C
No, I think that it's always a question that comes up. And the question that Amal brought up from the previous study is about frequency of testing. Do we need to do it as frequently as we should? I think as bone specialists and endocrinologists, improvement in bone density is great, but we're looking for patients who are not responding to therapy. That's really the outcome. We're making sure that with what they're doing, they're not losing ground. We know declining bone density and the rate of decline predicts A higher risk for fracture. So we're trying to head that off with regard to frequency of testing. I did not mention this earlier, but my clinical practice, what I'll see is when I check a density, I will repeat the density at the appropriate amount of time, depending on the skeletal side involved and the expected rate of change. But once that's done, once I establish that patient's biology, I back off on frequency and, you know, whether it's two or three years, and if they're still the same, maybe it's four to five years after that. So there's a pragmatic approach to bone density testing that I think we can adopt. We don't have to measure every one to two years in patients. That would make a lot more sense.
- [31:23]
A
A bunch of interesting ideas for problems that we encounter a lot that we try to think through. Let's move on now to the conclusions that the authors leave us with, and then we will try to come up with some conclusions of our own. First of all, the authors, they point out that infrequent zoledronate use prevents fractures in low risk women aged 50 to 60, with the greater impact being between five to 10 years after treatment has started. And then finally, another point, they say that the benefits of treatment appear independent of baseline bone mineral density and changes in bone mineral density. Okay, so, Amal, let's start with you. So before we get to whether this should change our practice, just give me your sense quality of this report overall. What has been your impression of it?
- [32:07]
B
Chase, as you hinted to earlier, quite complex analyses and too many analyses. And at some level you're not sure you know how that would apply to your patient. The fact it's a randomized clinical trial, the fact, you know, they did have the kind of half placebo and full placebo arm, are very helpful. I think the quality is good. As far as a study design goes, I wish there was a little bit more in depth evaluation of the risks because we are treating low risk group. So the side effect of the drug mix is more important in this setting overall, however, as a study, I think it's of good quality. We'll come back to that later. You know, in terms of its clinical applications. We can discuss that later.
- [32:54]
A
Tom, any thoughts that you would add on the quality of the report Overall?
- [32:59]
C
I agree with Amal. I think it's a quality study. I do think that consistent with some of the other observations we've had from this group, every 18 month dosing in patients with osteopenia, many of whom had prevalent Fractures is effective in terms of the bone density effect and fracture risk reduction. But it is a younger population with a low risk of fracture. And the question of risk benefit has to come into play with regards to ultimately how we treat these patients.
- [33:28]
A
All right, so let's go there now. I'm trying to think about how we're going to treat our folks. So, Amal, you alluded to some of this before, but what are your thoughts? Will this change your practice? What can we glean from this? That not only your practice, but endocrinologists in general. What should we be doing differently based on this information?
- [33:42]
B
To be honest, and I'd be very curious to hear what Tom will have to say about this, I haven't quite figured out how to incorporate this study into my day to day practice. Tom just alluded to an older study from this group that looked at every 18 months dosing of zoledronic acid and that I found much more clinically useful because it was a higher risk population at baseline that you would want to treat, but maybe not over treat. This is a pretty low risk population. So I haven't found a clear application for this study in my practice. I have found a couple of applications that are not exactly consistent with the study itself and that would be patients who otherwise I would treat with a traditional approach or maybe with 18 months dosing of zoledronic acid. But the patient themselves do not want to take treatment because of concerns about atypical femoral fractures or osteonecrosis of the jaw, which are very, very small, long term risks. So in a couple of patients, I found this study as an in to, you know, get them on something, even if we're not doing it frequently, you know, where I can tell them, you know, the risk of subtrochanteric, you know, atypical femoral fractures and ONJ are going to be quite minuscule in this setting with this use. But maybe I'm giving you, you know, some fracture benefit, even though I don't know when that's going to happen with this design. Is it going to happen between 0 and 5 or 5 and 10? But these patients where I've used this approach are a little bit higher risk than the study population. So it's a little bit of an extrapolation on my end and otherwise sort of patient who's reluctant to receive treatment. I wonder, Tom, if you found other applications in your practice for this study.
- [35:31]
C
Thank you, Amal. No, I think that we practice similarly. I think there are patients who are reticent, many Patients are reticent to take any therapy for osteoporosis, but specifically bisphosphomus, both oral and iv. And this is a situation. And I can hearken back to the recurrent fracture trial under horizon. The drug was given versus placebo to men and women after a low trauma hip fracture. And one dose of zoledronic acid in that trial reduced clinical fractures over three years. So we do have again, different population perhaps than the younger population that we look at. But in the patients that we see, many of them are older at a higher risk. So there is applicability from that standpoint, I think with this trial and with the prior trials as well. So I think that's true. Amal, in terms of my practice, I haven't incorporated it. It's hard to find a way to incorporate it. And I think again, getting back to the risk benefit of treating a 52 year old woman who is normal density or is a T score of -1.2 and saying we're expecting you to have this benefit and it's a hard sell, I think. And I think that that's why we're all kind of struggling with that, I
- [36:35]
B
guess to circle back to what I said and I haven't encountered that scenario, but the reverse scenario could be applicable in that you may have say, a 53 year woman who's otherwise low risk, who's say gynecologist, you know, decided to do a DEXA scan because, you know, she went through menopause a year ago or two years ago and she does have slightly low bone density. And you may not feel very strongly about treatment, but the patient themselves herself might feel extremely scared about having osteopenia. So I could see how this study might be, you know, sort of an in between solution in a way. I personally haven't used it in that setting, but, you know, I could imagine myself potentially doing that if I were to encounter that situation.
- [37:19]
A
And with that, I would like to thank them all, Shibli Rahal and Tom Weber for joining me for this month's edition of Endocrine Feedback Loop. I hope that you all learned as much as I did and that you will join us again next month. And now you're in the loop. This has been Endocrine Feedback Loop. Endocrine Feedback Loop is brought to you by the Endocrine Society with Production Oversight by Brandy Brown. If you want to like and subscribe, you can find us on Apple, Spotify or wherever you get your podcast. We'd love to hear your feedback on this episode of the podcast itself, please email us@podcastren.org
- [37:55]
C
Endocrine Feedback Loop is a
- [37:57]
A
free service of the Endocrine Society.
- [37:59]
C
To learn more or to become a member, visit the society's website at www.endocrine.org.