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Endocrine Feedback Loop
EFL052 - Osteopenia as a Surgical Indication in Primary Hyperparathyroidism
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- [00:00]
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. Hello and welcome again to the Endocrine Feedback Loop podcast for our 52nd episode. For today's episode we go to the JCEM to review an observational report on the benefits of surgical cure of primary hyperparathyroidism in women with osteopenia. As clinical endocrinologists, we frequently encounter this scenario, so the conclusions of this study will have obvious implications for the care we provide. We will think carefully about the specific question the authors answer, as well as how they deal with the intrinsic limitations of this observational study design. Before I introduce our team today, I will briefly remind you that I host the Endocrine Feedback Loop podcast and work at the Vanderbilt University Medical center in Nashville, Tennessee as a general endocrinologist and medical director. Back in our virtual recording studio today is Our regular contributor is Allison Myers from the Albert Einstein College of Medicine in the Montepuor Medical center in New York City. She also works as a general endocrinologist, additionally serving as the Associate Chair for Diversity, Equity and Inclusion in the Department of Medicine at Montepuor. Her research focuses on diabetes technology and disparities in care of individuals with diabetes. With us today is our guest expert for this episode is Natalie Cusano from the Zucker School of Medicine at Hofstra and the Lenox Hill Hospital in New York. She focuses her practice on bone and calcium disorders and is the Director of the Bone Metabolism Program at Lenox Hill. She is known to you all from her extensive publications in the osteoporosis and hyperparathyroidism fields. So as you can easily tell, the perfect pair of endocrinologists joins me today to review this article. As is also always the case, everything we discuss will be our opinions only and not necessarily those of our respective institutions or of the endocrine society. Today we look at Parathyroidectomy improves bone density in women with primary hyperparathyroidism and preoperative osteopenia. The Journal of Clinical Endocrinology and Metabolism published this study in June 2024. Samuel Frey and Maxime Girard served as the first authors for this paper, which came to us from Nantesite in France. Now I will turn the discussion over to Allison. She will review the author's introduction and get Natalie to overview some key historical aspects of primary Hyperparathyroidism.
- [02:37]
B
Allison, thank you for that wonderful introduction. Chase, happy to be here with you again. Today, we're shifting gears from our typical diabetes conversation to talking about calcium and osteoporosis and bone loss. And our colleagues in France noted that 80% of the people who have primary hyperparathyroidism are asymptomatic at the time of diagnosis, which means that their labs typically show normal calcaemia, despite the fact that they have an elevated parathyroid level, also known as primary hyperparathyroidism. Or they can have hypercalcemia with a normal range pth, which is, of course, inappropriately elevated because in the setting of hypercalcemia, you would expect the PTH to be somewhere in the teens or single digits. And so, Natalie, I wanted to ask if you can give us a brief overview of some of the changes that we may see in primary hyperparathyroidism over time.
- [03:29]
C
Yeah. Thanks so much for having me on. So, before routine measurement of serum calcium, primary hyperparathyroidism presented as a highly symptomatic disease of bones, stones, GROANS AND moans as we've learned from the older literature. But since the advent of the Autoanalyzer, it has generally presented with a more mild form, with serum calcium incidentally noted as being elevated, but generally within 1 milligram per deciliter above the upper normal limit. Kidney stones do remain the most common complication in about 20% of patients, followed by bone loss and fractures. We do know that when we screen for kidney stones and vertebral fractures, we do find them in quote, unquote, in asymptomatic patients. And for that reason, the guidelines do recommend screening because this would change the recommendation for surgery. And as you mentioned more recently, we've characterized an even more biochemically mild form where patients have a high parathyroid hormone level but normal serum calcium. And this is known as normal calcium primary hyperparathyroidism.
- [04:34]
B
Thank you for that wonderful overview, Natalie. We also know when we talk about the bone effects of parathyroid disease, it causes bone catabolism because we're increasing stimulation of osteoclasts, which is leading to either osteopenia or even more severe osteoporosis. It is established that a parathyroidectomy can lead to improvements in bone mineral density for those with osteoporosis. Guidelines recommend surgical intervention in primary hyperparathyroidism with osteoporosis, but not osteopenia, with some experts suggesting that the lower the preoperative bone mineral density, the greater the expected postoperative bone mineral density gain. Natalie, can you comment on why guidelines are silent on osteopenia and primary hyperparathyroidism? And what is the current consensus on how we should approach it?
- [05:27]
C
Guidelines are complicated, so we need to look for the best evidence base for making recommendations. And recommendations can be guided by morbidity, including fracture risk in the case of primary hyperparathyroidism, but also other measures, including cost effectiveness. So, with regards to the criterion for age less than 50 years, we have great data that patients who are less than 50 years old have a greater risk for complications and progression of disease over time. So surgical therapy makes sense with regards to morbidity and cost effectiveness for younger patients. There was a study that did an analysis of quality adjusted life years and found that surgery may be cost effective even into the early 60s. But we would need more studies before changing the age recommendation for surgery. For the skeletal guideline in primary hyperparathyroidism, there are data that successful parathyroidectomy reduces fracture risk. So we have the guidance that patients who have osteoporosis and are at the highest fracture risk should be considered for surgery. However, we don't have data on reducing fracture risk specifically in patients with osteopenia, and it is certainly something that we should look into. And we have this study that's lending to the literature. But given that the majority of patients with primary hyperparathyroidism are postmenopausal women with a generally high prevalence of osteopenia, changing the guidelines would have a significant impact on the number of parathyroid surgeries performed. Just a note before we move on. The guidelines do state that patients who have a significant decline in bone density during monitoring be considered for surgery even if the osteoporosis threshold is not reached. So the guidelines don't exclude patients with osteopenia from receiving surgery if indicated.
- [07:16]
B
Thank you for that summary of the guidelines, Natalie. So, overall, this study, the aim was to evaluate bone mineral density and bone remodeling biomarkers changed in one year after surgery in women who underwent a parathyroidectomy for primary hyperparathyroidism in a prospective real life cohort of patients. Bone mineral density and bone remodeling biomarker changes after parathyroid surgery were compared between patients presenting with osteoporosis and those who had osteopenia before surgery. Now I'll turn it back to Chase to discuss the methods of the study.
- [07:54]
A
Thank you, Alison. And we will think about the study design that's used here. And I think this is best considered to be a prospective cohort study. It's how the authors describe their work. And we'll think about that in general, as we normally do. A prospective cohort study. Two key components of that, both the prospective and the cohort. To start with the cohort component of that, that implies that you have a cohort of subjects that you follow over time. The time component is a key aspect of a cohort. And what you have to do is you've got to split these individuals into multiple groups. Traditionally, that is saying somebody who has been exposed to something versus being unexposed to that. Well, we're going to have to be a little bit fluid in how we think about that when we get to that part. But traditionally that's how that would be considered. The prospective part of that simply refers to where you started the study. The setup for a prospective versus a retrospective cohort study is the same. It's where the investigators start their work that make the difference. If you are starting your study after all of the data has been collected, but you can still reproduce that time sequence, that makes it a retrospective cohort study. When you are starting your investigation before any of the outcomes have occurred, and then you are following these subjects in real time, that makes it a prospective cohort study. It's a much stronger study design and we'll get to see a little bit of that. You can define exactly what information you want because you are deciding on that before you start collecting that data. And that's what the authors used here. So. So let's now look at this study particularly, and we'll begin by taking a look at the population as the authors report that. So these are all patients who are at the University Hospital of Nantes in France. And the investigators started this study in March of 2016. And the population that they were interested in was women with primary hyperparathyroidism who underwent a parathyroidectomy with at least a year of follow up data as of March 2022. There were a few exclusion criteria. They were only looking at adults, so they excluded anybody under the age of 18. They excluded women who were pregnant, they excluded any unusual forms of hyperparathyroidism. So all secondary and tertiary. Anybody who had hypocalceuria or anybody who had concern that their primary hyperparathyroidism was a part of multiple endocrine neoplasia. All of those were exclusion criteria. And then finally, because they needed all of that data to do the analysis, you were excluded if you lacked complete clinical biochemical and radiologic data. We're going to think about how they define the bone impact of primary hyperparathyroidism. And this will be one of several places that we get Natalie's input. They defined osteopenia and osteoporosis by T scores, and I wanted to get Natalie's input and to see is this a major deal, because as we'll see in the results when we turn this back over to Allison, not all of these women were postmenopausal. So do you have any concern about deciding on osteopenia versus osteoporosis using T scores in this patient population?
- [10:56]
C
So you're correct that, yeah, for younger women and men, instead of the term osteopenia, we use bone density below the expected range for age. If the Z score is less than minus two, I don't have an issue in this case, since the majority of patients were over age 50. And certainly for women in the perimenopausal period, I do use osteopenia instead of bone density below the expected range range.
- [11:19]
A
We'll move on now to some details of the surgery itself that was done for all of these women. The investigators note that two experienced surgeons did all of the parathyroidectomies here. The indications for surgery were based on the French guidelines. Those are very similar to ones utilized in the United States and elsewhere. So we'll hit those very quickly. The first indication would be age less than 50. A second one would be symptoms or evidence of any tissue damage, with kidney stones being an example of that. Natalie mentioned that that is a frequent one. The third one would be a corrected calcium above 11.0 or a urine calcium greater than 400. And then finally, as we talked about before, if you had a bone density scan with a T score that was negative 2.5 or below, so that osteoporosis based on the DEXA scan that was also considered a surgical indication. The investigators routinely obtained preoperative imaging and cure was defined as normocalcemia six months after the parathyroidectomy, or if they didn't have data at that time, then 12 months after surgery. Another comment about the measurements that are done here, specifically around the bone mineral density. The authors note that they routinely obtained a bone mineral density scan before surgery and then also 12 months after that parathyroidectomy. Natalie wanted to get your input again here. Mostly just curious. This is a fairly frequent obtaining of the bone density scan. Would you describe this as something that is done primarily in a research setting, or do you think that this should actually be a fairly common practice in someone who has had a parathyroidectomy is getting a bone mineral density scan a year after surgery.
- [13:00]
C
Clinically, I do measure bone density one year after a successful parathyroid surgery and start pharmacologic osteoporosis therapy at that time, if the bone density remains low.
- [13:11]
A
One final comment on that bone marrow density measurement. We will talk about the least significant change. The authors here use a 0.03 grams per centimeter squared as their LSC. The statistics will be the last part of the methods that we spend some time thinking about. And I think there are several key things that we want to wrestle with here. The authors do an analysis on a couple of different levels. The first level that they do is they look at all of their patients in aggregate, and Allison's going to walk us through some of that data. But the real heart of their analysis that they do, and the part that would be classified as a prospective cohort study, is when they split these individuals into two groups. So again, this entire cohort is women who underwent a parathyroidectomy for primary hyperparathyroidism and had that follow up data. But two of the groups that they are going to spend most of their time comparing are those who had preoperative osteoporosis versus those who had preoperative osteopenia. The authors wrestle with this a little bit in their discussion. So we're doing this earlier on, but I think it fits here as we think about this study design because I wanted to get Natalie's input on this. And just thinking about this clinically, frequently, the groups that we are wrestling with, whenever we see a woman who has primary hyperparathyroidism and has osteopenia, we are trying to decide if this is somebody who should maybe have a surgery or if we should just observe. And so one of the questions that I had would be, well, is this really the right comparison? Again, this entire cohort is only people who had a parathyroidectomy, but presumably within this institution, they have access to lots of individuals who did not undergo a parathyroidectomy who just were observed alone. And I would think that that would be the real comparison that would be helpful here is to say, okay, you have somebody who has osteopenia and compare that to group of women who have normal bone mineral density to see if there's a difference in the change in bone marrow density and certainly fracture data, if you were to have access to that. But thoughts, Natalie, about this comparison Primarily osteoporosis versus osteopenia.
- [15:14]
C
Yeah, you're right. I think if they had a large cohort of women with primary hyperparathyroidism who were being observed, it would be interesting to compare medically with surgically treated patients. But it may be hard to match the two cohorts completely even if an observed cohort was available. So here in the study the authors stated that 94.4% of patients in the study had a clear surgical indication from the guidelines. So they probably would have had more clinically significant disease than a cohort that was just being observed. So it wouldn't necessarily be an accurate comparison. And I think how they did it was interesting because one of their aims was to compare the bone density response to parathyroidectomy in osteopenia versus osteoporosis and see if the increases were similar or if the patients with osteoporosis had a larger improvement in bone density.
- [16:05]
A
We will keep that in mind as we come to the results and then the conclusions shortly. A couple of other comments on the statistics. The authors report multiple potential confounders. So they report those and we will go through those with Allison and the results. One thing that I look though, typically when you measure these confounders you want to see the impact if you have two different groups and this is an observational study and it's frequent that the groups are going to be dissimilar on multiple aspects, but then you'll tend to make some adjustment for that. Natalie referenced that that concept already did not see any evidence that that happened here. So the authors report the confounders note that these groups are different but don't obviously adjust based on that. Finally, one thing that the authors point out to the very end of their methods is that many of the patients, most in fact who had urine calcium measured had it done in the form of a spot collection. So a one time collection as opposed to a 24 hour urine collection. The authors make note that for those individuals who had the spot collection, they did an imputation approach to estimate the 24 hour urine level. Nathalie, I was curious as your thoughts on that from two different perspectives. One would be just a research perspective. Do we get any concerns about having any inaccuracies with that, but then also just the clinical implications of that? 24 hour urine collections are rarely patients favorite things to do. So is this actually a viable alternative that we could be simply doing a spot collection as opposed to the more arduous 24 hour urine collection?
- [17:36]
C
Generally a random spot urine calcium is not thought to be very accurate since it can depend a lot on recent dietary or supplement intake. I was involved in a study where we could use a fasting two hour urine collection instead of a full 24 hours. It's, as you said, it is not a patient's favorite thing to be doing these collections.
- [17:58]
A
So potentially some imprecision that was introduced here. We talked before about exclusion criteria. Hypocalceuria was an exclusion criteria here, so we'll need to keep that in mind. But hard to know how much of an impact that has. All right, there's our high level overview of the methodology. We will come back to some of those points because I do think that they factor in a significant way to some of the conclusions that the authors draw, which we'll get to. But first, first want to hear from Allison. She's going to walk us through the results as presented by the authors.
- [18:27]
B
Initially, we had 326 people that were included in this cohort that was so nicely described earlier by Chase, but nearly half of them were actually excluded because they were male, gender or did not have surgery or had missing data. So in the final COHORT they had 247 women, but unfortunately, 70 of them were missing biochemical or BMI data. So their final analysis was composed of 177 persons. 20% of those had a normal bone mineral density and the remaining 80% were pretty much evenly split between either having osteopenia or osteoporosis. If we look at Table 1, which gives us the population, baseline, demographic and clinical characteristics, one of the interesting things that they did not comment on, but of course we need to keep in mind this study was done in Europe, which was not done here in the United States, is the fact that race and ethnicity of the sample were not described, which makes me suspect that the sample was pretty much all white, European women, which is of course not typical for those of us who practice in areas like in New York City, where we have a much more diverse population, where we see all comers, whether it be white, Asian, Hispanic, Latino, black or biracial, or people more than one race or ethnic group. So that was pretty interesting. Also, as noted before by Chase, there were several confounding things that they mentioned but did not include in their analysis. So some of the confounders that they mentioned include percentage of fat mass, level of physical activity, the use of steroids, smoking or alcohol, which we know can pose as risk factors for developing either osteopenia, osteoporosis but were not included in the analysis or in the baseline demographics. When we look at the actual group, the mean age of the entire group was 62. So, as mentioned earlier by Natalie, this was a postmenopausal group. Those who had osteoporosis actually had a higher mean age than those with osteopenia. So it was 66.7 years for the osteoporosis group compared to 61.8 for the osteopenia group. There was a higher mean fat percentage and a higher BMI in those with osteopenia when compared to osteoporosis. So the higher fat percentage was 40.4% versus 37.7%. The BMI difference was 27.3 versus 24.3. More of the women in the osteopenia group were postmenopausal compared to the osteoporosis group, and. And that was 94.6 versus 80.6, which was also interesting because you would have thought that you would have had more postmenopausal folks in the osteoporosis group. Those with osteoporosis, unsurprisingly, had more fractures, especially at the lumbar spine. There was no difference in other indices in terms of smoking history, labs, the pathology that was seen after surgery or oral steroid use. But again, there was no actual analysis done to account for some of these confounding things. So, Natalie, can you give us a thought or two on how these groups are so different between our osteoporosis and osteopenia groups?
- [21:44]
C
Yeah, I think these differences have to do with what we generally expect for patients who have a diagnosis of osteoporosis if patients are not being evenly matched for these factors as part of a study protocol. So, as you said, it makes sense that there is more fractures in the osteoporosis group. Also, age is a risk factor for osteoporosis, so this makes sense. And obviously, increasing age, more prevalence of postmenopausal women. Higher body mass index is also thought to be relatively protective for bones in a way, since there's more mechanical loading on the bones. So patients with a higher body mass index do tend to have a higher bone density. So I think that is not necessarily anything that they could have done to prevent those differences from being present, but it's just what we see in a cohort of women with osteoporosis versus osteopenia.
- [22:33]
B
Thank you, Natalie. Post op, there were decreases in mean serum calcium as well as median urine calcium and parathyroid levels and there was an increase in mean phosphorus. 166 patients, or 94.4%, had a serum calcium of less than 2.6 millimoles per liter six months after surgery and for people who they did not have a urine sample six months after surgery, they followed them out for a year and that was considered that they were cured. Among the 10 patients who were not cured, nine had removal of at least one pathologic gland during surgery and amine, serum calcium and medium serum parathyroid levels were significantly decreased one year after parathyroid surgery in this subpopulation. There were also statistically significant differences in the baseline and postoperative GFR and creatinine values, and despite the statistical significance there was no true clinical significance noted. There was also improved bone mineral density at all sites, greatest in the lumbar spine, followed by the femoral neck and hip, and lastly the forearm. There were no statistically significant differences seen in the absolute bone marrow density changes between groups at the different sites. Among the osteopenia group, 46 out of 53 patients or 86.8 had a significant BMD gain at the greater than one site or one site, while 7 out of 53 or 13.2% of patients had no significant BMD gain. Those with a BMD gain had a higher preoperative level of their bone turnover markers, which were P1, NP and CTX. Now I'll turn it back to Chase for discussion around our conclusion.
- [24:23]
A
We are going to move into the discussion and several key things that Allison has walked us through already that we really want to wrestle with and Natalie has alluded to this already in the introduction that potentially has a significant impact on the care that we're providing and how we think about who might meet an indication for surgery in primary hyperparathyroidism. So we'll start where the authors do as they summarize their work and they say that parathyroidectomy in primary hyperparathyroidism was associated with bone mineral density improvements and a decline in bone remodeling biomarkers one year after surgery with comparable BMD gains between osteoporosis and osteopenia. The authors then go on to note that there is a very high prevalence of osteoporosis and osteopenia in this cohort and again we've talked about this. This is a cohort of women who met some criteria for surgery and so they all had a parathyroidectomy. The authors report that with that osteoporosis and osteopenia, that that's 45 and 44%, respectively. When I did those calculations on my own, came up with slightly lower numbers, 42 and 41%, respectively. But the point being, the vast majority, over 80%, had a bone impact with either osteoporosis or osteopenia. So, Natalie, give me a sense. And this may be hard because, again, they're only looking at individuals who met surgical criteria, and these are different criteria than the ones that are used in the US at least a little bit different, but a very high prevalence of bone impact here. So as you think about other populations, as we think about potentially applying these results to other populations, do you have any sense or do you have data that would allow us to compare this to, say, a U.S. population?
- [26:00]
C
Obviously, there's multiple studies out there looking into the prevalence of osteopenia and osteoporosis in the US population. But one of the studies found that there was a prevalence of osteoporosis in imposed menopausal US women using the WHO criteria of 30% and prevalence of osteopenia of 54%. So these numbers are not outside the realm of what we would expect.
- [26:24]
A
Good. Helpful to know. And Allison pointed out some difference, at least in, say, an ethnic makeup of the groups that we're looking at here. But as far as the frequency that prevalence of bone impact of primary hip repair thyroidism may be at least in line comparing these two different populations. The authors take the next step then, of comparing some data, of referencing some other studies that show that surgical cure of osteopenic patients with primary hyperparathyroidism does actually lower a fracture risk. And then they go on to point out that a parathyroidctomy in primary hyperparathyroidism does not lead to improvements in all types of bone equally. Natalie, we thought this was a pretty obvious place to get input from you. You've done a lot of work here. The authors actually cite some of your work here. So why don't you help us understand that? Why would a surgical cure improve bone at one site more than it might at another site?
- [27:17]
C
When we look at bone density improvements after parathyroidectomy, multiple studies have demonstrated, using dexa, which is an aerial two dimensional measurement, that trabecular bone, which is the spongy bone inside, improves much more than cortical bone, which is the outer shell of bone. So the lumbar spine is primarily trabecular bone. The hip is a mix of cortical and trabecular, and the distal One third radius is primarily cortical bone. In the majority of studies in the literature, there have been significant improvements in bone density at the lumbar spine, less so at the hip, and little to any improvement at that distal one third radius. And this is in large part because cortical bone has a much lower metabolic rate compared to trabecular bone, so it doesn't turn over as rapidly. So I was involved in studies at Columbia University where we used high resolution peripheral quantitative CT, HRP, QCT, which can provide a 3D measurement of bone at the distal radius and tibia, almost like a non invasive bone biopsy. And in patients with primary hyperparathyroidism, up to two years following successful parathyroidectomy, we did find improvements in volumetric bone density, trabecular bone density, as well as improvement in cortical bone density and cortical thickness. And studies with bone biopsy have also shown improvement in cortical parameters after surgery. So there are improvements in cortical bone. If we can measure using other modalities, but using dexa, it just doesn't tend to change as much.
- [28:50]
A
And one final comment that the authors make about their findings, I think a particularly interesting one, we'll again get Natalie's input here. So they point out that those preoperative CTX and P1NP levels, those bone turnover markers, that they were higher in osteopenia patients who attained a post operative BMD gain. And so they say that this is potentially a way that you could select which osteopenic primary hyperparathyroidism patients to send to surgery. So the higher those bone turnover markers, if you have osteopenia, the more likely you are to get a improvement in your bone mineral density after a surgery. So Natalie, let's get your thoughts on this. The authors are merely suggesting, they're not concluding that we should start doing this. They suggest that more studies would be needed. But from your perspective, is this something that's at least biologically plausible? Do you think that this has the potential, with more data in the future, to turn out to be a way that we maybe parse out these groups a little bit more as we try to decide who might need a surgery in this osteopenia category?
- [29:55]
C
Definitely makes sense that patients with higher bone turnover, as evidenced by these higher levels of bone resorption measured by CTX and bone formation by P1MP, would have more of a bone density improvement from surgery. And other studies have shown this. If we improve the bone turnover after surgery, then we're going to improve bone loss and improve bone density. It is really hard to delineate a cutoff for bone turnover markers when surgery might be indicated, though, since there have been so many different assays used in the literature and it's not standardized. So I think it would be hard to come up with a specific cutoff for when surgery might be indicated. But it's definitely something that we do think about. And I measure bone turnover markers, but again, it is hard because they're not standardized across all labs.
- [30:48]
A
Natalie's already pointed out a clear reason to why we might have trouble implementing something like this. Certainly at the level of a guideline, but more to come and certainly a promising area for investigation there. We're going to wrap up with the author's limitations and they listed some, some of which we've pointed out already. The big one, from my perspective, that they do point out is that they don't have a control group. They point out, just like we talked about before, is that it would be very interesting to know with the group of women who did not undergo surgery and just were observed, how that would compare to somebody with osteopenia. We don't really know here. And so this isn't something that we can wrap our hands around a little bit more, but that a control group who did not undergo a parathyroidectomy would have been helpful here. A couple of other things that the author has mentioned as limitations. They point out that not all DEXA scans were done at their facility, so maybe a little bit of variability there. And then they also point out that they did not have any data on hormone replacement therapy in postmenopausal women. So potentially introducing a confounder there that was not measured. Well, only other thing that I would reiterate, we talked about it before, but there was not a statistical adjustment. And these two groups were different. The osteopenia and the osteoporosis group were different on more than just what their bone mineral density is. Natalie pointed it out very well. None of these differences were unexpected. I think they're entirely explained. But you would have to wonder what sort of an impact those other differences had as we look at the bone mineral density and concluding that they are not different between those two groups. We're now going to move on to where we always end and trying to wrestle with whether our practice should change. So we're going to get to that in a second. But, Allison, I first of all wanted to ask you, as you analyze this article and looked at the details, just the quality of this report, overall what were your impressions?
- [32:39]
B
My impressions is that they embarked on something that we don't know much about. So I think it's a good start. Obviously, it doesn't have the most robust sample size, but again, this is a starting point. This was never meant to be a robust randomized control type trial situation. It was a prospective cohort. So I think that what they gave us is something that we can work with. Again, their population doesn't necessarily match mine. There were a few other things that I would just want to note that they mentioned, and that was the fact that many patients didn't have wrist measurements. And I know for me, when I'm checking for patients who have primary hyperparathyroidism, that's something I'm a stickler about. In fact, I have had to stop sending patients to one center because they don't include it with their DEXA scans. And then, of course, the other thing that we have to know is that a DEXA is helpful. But to Natalie's point earlier, it doesn't really tell us about the microarchitecture of the bone. So even though someone may be quote, unquote osteopenic, we don't really know their bony microarchitecture, which can have actually worse or advanced disease. So I definitely give them an E for effort. But we definitely need to have more studies and more trials that are a little bit more inclusive of different folks from different walks of life.
- [33:50]
A
Natalie, let's get your thoughts there as well. Well, again, in a second we'll come to whether we need to be thinking about changing our practice. But just quality of the report, what was your impression of this article?
- [33:59]
C
And I agree with everything that Allison said for what this was, this prospective cohort study. It's interesting and adds to the literature, but there are a number of limitations, as we pointed out.
- [34:15]
A
Natalie, let's stick with you here as we wrap this up. And I think, as we've stated already, this is observational data. We have several clinical trials in primary hyperparathyroidism guiding where we need to be intervening, and that's likely to be our gold standard. And what's really going to move the needle on changing, say, a guideline as we've referenced before. But I would be curious in your thoughts just looking at this and where this is going. Might this start the pendulum swinging back the other way? You talked a little bit about the history of primary hyperparathyroidism, how it used to be discovered only in its severe form, but then with changes in biochemical testing, we started Detecting a lot more milder forms of primary hyperparathyroidism. That was actually the impetus for why the guidelines were needed in the first place, so we could figure out where we could observe people and where we needed to continue to intervene surgically. And then that led to observing a lot more folks. But potentially here are we moving back the other direction? Is this now saying, well, yeah, it's not just women with osteoporosis from primary hyperparathyroidism, but maybe osteopenia as well? Do we need to start thinking about that? And now are we going to be including a lot more individuals in this group of people who meet surgical criteria? What are your thoughts on that?
- [35:28]
C
Yeah, I think there's still a lot that we don't know about the disease. So obviously even things with quality of life which were not addressed here, but there's still a question of whether there are neuropsychiatric symptoms of the disease that can be cured with surgery. So I think there's just a lot that we still don't know about the disease. And so certainly for my patients who have osteopenia, who do have a decline in bone density, I do always speak about surgery. It's interesting because even though it's a relatively straightforward surgery and outpatient procedure, a lot of patients don't want to undergo surgery. They just have it in their minds that there's a lot of postoperative issues or they just don't want to have surgery. And so there's a lot that we have in the literature that is reassuring if patients are not undergoing surgery. But, yeah, I think that again, this leads to the literature that we can see significant improvements in bone density in patients who don't, who aren't at the osteoporosis threshold following surgery. I don't think it quite changes any minds in terms of the guidelines as of yet. Unfortunately, for fracture data, you really need thousands and thousands of patients. And so that's why we need population based studies to look at this more and whether it makes sense to recommend surgery before osteoporosis in terms of reducing fracture risk. And again, it probably does, but we just don't have that data. So I don't see it changing the guidelines as of yet. But certainly it's something I'll be more mindful of in when I evaluate my patients in the clinic.
- [37:05]
A
And with that, I would like to thank Allison Myers and Natalie Cusano 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 and Andrew Harmon. If you want to like and subscribe, you can find us on Apple, Spotify, or wherever you get your podcasts. We'd love to hear your feedback on this episode of the podcast itself. Please email us at podcast podcast@endocrine.org Endocrine Feedback Loop is a free service of the Endocrine Society. To learn more or to become a member, visit the society's website at www.endocrine.org.