Dr. Kirsten Patrick:
Welcome to a special episode of the CMAJ podcast. I'm Kirsten Patrick, editor-in-chief of CMAJ. This episode is another installment in our occasional series on updates to practice guidelines.
Dr. Roland Grad has led the development of a Canadian Task Force on Preventive Healthcare guideline, entitled, “Recommendations on Screening for Primary Prevention of Fragility Fractures”. Dr. Grad is Associate Professor in the Department of Family Medicine at McGill University, a practicing family physician, and a member of the Canadian Task Force on Preventive Healthcare.
Hi, Roland. Thanks for joining me today.
Dr. Roland Grad:
Good morning, Kirsten. Thanks for having me.
Dr. Kirsten Patrick:
Okay, so let's start with the definition of a fragility fracture, because if we're going to be talking about screening for them, our listeners should know what we're talking about screening for.
Dr. Roland Grad:
Okay, so we're talking about preventing a first fragility fracture among older people living in the community, and fragility fractures result from a minor impact, like a fall from your own height. And normally, these wouldn't happen, but when they do, we call them fragility fractures. Some people call them major osteoporotic fractures. They can involve the radius, the vertebrae, the humerus, in addition to the hip, and in the case of vertebral fractures, we considered only the clinically apparent ones, not those vertebral fractures that are sometimes detected on radiography.
Dr. Kirsten Patrick:
So Roland, I've got elderly parents, and my mom broke her hip falling from a standing position. I think we're all familiar with how that happens, but the other ones that you're talking about, when people are falling from their own heights. A fragility fracture in a vertebra, for example, might happen, would you say, if somebody slips on ice and lands on their buttocks, perhaps?
Dr. Roland Grad:
Yeah, it is not that uncommon for people to come in with back pain, and we find compression fractures, and it was the kind of thing that you wouldn't normally expect. So I guess that is another example of fragility fracture, exactly, Kirsten.
Dr. Kirsten Patrick:
Okay, and the guideline is about preventing these from happening. What motivated the task force to produce this new guideline at this time?
Dr. Roland Grad:
I guess there were more than one thing that motivated us. Frankly, we started work on this prior to the pandemic, and at that time, I'll be honest with you, I was a little bit confused about how one should go about preventing fragility fractures. I trained at a time when we talked a lot about osteoporosis. It was a binary thing: yes/no. We didn't consider people's risk for fracture very much. We didn't do very much shared decision-making at the time, and this was already more than 20 years ago.
So as things evolved, we realized there was a need for updated guidance on screening to prevent fragility fractures. We were also aware of new evidence from the publication of new screening trials in females older than 65, and this is an important topic. As you mentioned, your mom suffered a fracture. These are consequential events for individuals and for the healthcare system.
Dr. Kirsten Patrick:
So you mentioned that you've been working on this guideline since before the pandemic in 2019, and that was around the time of the emergence of new trials. If we think about what physicians in Canada have been doing up to this point to screen for fragility fractures, if anything, what would that have been?
Dr. Roland Grad:
So actually, screening is common in Canada. Family doctors like me have been requesting BMD or bone mineral density tests for their patients since the last century, so that's been going on for decades. And if you look at some of the statistics, it's interesting, Kirsten, because after 65, about two-thirds of women in this country report having had at least one BMD test, and about a third of women under 65 report having had at least one BMD test, and many have been diagnosed with osteoporosis. For example, the prevalence among women 65 to 79 in Ontario is estimated at 40%, so this is a common thing.
But screening to prevent fragility fractures, it can be done using what we call a Risk Assessment First strategy, and we hope this guideline will improve how doctors think about screening to prevent fragility fractures. We should allow our patients to get more involved in this process. Our patients need to gain some insight into their risk for a fragility fracture, and to what extent can preventive treatment alter that risk? And I think we need to let go of the idea of screening for osteoporosis, which is actually just one of several risk factors for fragility fracture.
Dr. Kirsten Patrick:
I'm just going to pick up on something that you mentioned before. So you were talking about understanding personal risk and pointed out, very pertinently, that BMD is just one aspect of multifactorial risk, really. So what did you look at when you were looking at the evidence that's emerging, in terms of risk factors for fragility fractures?
Dr. Roland Grad:
So in terms of risk factors for fragility fracture, the task force involved the Evidence Review and Synthesis Centre at The University of Alberta to conduct evidence reviews. Actually, they conducted four systematic reviews and one overview of reviews. I'll just go into each of those briefly, if that's okay.
One of the systematic reviews they conducted was on the accuracy of tools like FRAX, which is a tool that allows the clinician and the patient to look at how multiple variables influence the risk of fragility fracture. So these are things like age, sex, height, weight, smoking, alcohol, and it goes on. There's at least 10 of them. So that was one systematic review, which was how accurate are tools like FRAX to predict the occurrence of fractures in the future, like hip fracture?
The Evidence Review and Synthesis Centre also conducted a systematic review on screening trials, so the trials about screening.
They did another review on the trials of treatment, like with bisphosphonates, to prevent fractures. Those were the treatment trials, not necessarily on screened people.
And finally, they did a systematic review on patient values and preferences, to try and understand what people want.
Dr. Kirsten Patrick:
So in these evidence reviews, Roland, let's go through them one at a time. What did you find, in terms of the evidence for the FRAX tool, screening trials, treatment trials, and patient preference?
Dr. Roland Grad:
Okay, so for those four things, maybe I'll just give you a high-level summary, because it's actually quite complex, and it can all be found in a publication in the Journal of Systematic Reviews.
So first, I guess we will start with the accuracy of tools like FRAX. We found that the Canadian FRAX tool was reasonably well-calibrated to predict the occurrence of fragility fracture and hip fracture in 10 years' time. So the diagnostic or predictive accuracy was adequate for the FRAX.
We found three screening trials. These were all conducted in females, after the age of 65 years, who were invited by mail to participate in screening, so not exactly the typical approach that we would have as clinicians in office practice. These were willing participants who took up an offer of screening by mail. These trials have great names, like SCOOP, SALT, and ROSE, and are also summarized in the systematic review. And the benefits of screening were greater than zero, so I would describe them as small, but statistically, significantly different from zero, so there was a benefit.
We found no trials that showed benefit for screening males of any age. We found no trials of screening females from 55 to 64 years of age, and we found only a single trial of females from 45 to 64 that was published in 2010. So there's a gap, actually, in our knowledge. We don't really know what to do for these subgroups of the population and very important groups of the population.
Dr. Kirsten Patrick:
That is a surprising evidence gap, actually. Blows me away, a little.
Dr. Roland Grad:
Yes, it does. Me, too, and anyways, I don't want to editorialize here, but clearly, those who advocate for screening in men, for example, should be encouraged to actually conduct the trial in the first place.
Dr. Kirsten Patrick:
Absolutely.
Dr. Roland Grad:
Yeah, it's eminently doable and needs to be done. And finally, for patient values and preferences, we found, I think, two things that are quite interesting. First, females from 50 to 65 are actually curious and interested in screening, but when it comes to preventive treatment, their preferences vary widely. So there's an important kind of resistance towards preventive treatment, and it's variable. Some people want it; some people don't, which is why we think shared decision-making becomes more important in this particular guideline.
Dr. Kirsten Patrick:
Did the trials give any sense as to the reason, or was it just people's views on being treated vary?
Dr. Roland Grad:
I guess that's the first main point, is that they vary: that some people want treatment; others do not want treatment. And I think what is very interesting is that when you explain to people what is the chance of benefit from treatment, it's typically much lower than what they would want in order to initiate treatment. In other words, the patient wants treatment to reduce their probability by 50%, but in reality, it might only reduce their probability by 3%. So it's not zero. There is some benefit, but it's much lower than what they would consider to be important for initiating preventive treatment.
Dr. Kirsten Patrick:
So given this evidence, what has the task force recommended? Can you walk us through the recommendations of the new guideline?
Dr. Roland Grad:
Yes, I can. So number one, we recommend screening females after 65 using a strategy based on the FRAX tool, without bone mineral density or BMD. We call this a Risk Assessment First strategy. And then once your patient understands their risk and sees the potential to benefit from preventive medication, and if they would consider this preventive treatment, we then recommend a second step, which involves a BMD test and re-estimation of fracture risk, using that FRAX tool again, using the femoral neck T-score. This is a conditional recommendation, and the implications of that for practice are shared decision-making is the way to go, in terms of implementing this recommendation at the point of care.
Second, we do not recommend screening in females under 65 without clinical risk factors or for males of any age. That's a strong recommendation. This means that shared decision-making will not typically be needed at the point of care.
And of course, clinicians need to remain alert to changes in patient health. They will recognize these changes, and this may trigger testing as needed, but this testing for people whose health changes is case-finding, not screening.
Dr. Kirsten Patrick:
Right, that makes sense. So you outlined some risk factors for fragility fractures very early in our talk. Can you list them again for our listeners?
Dr. Roland Grad:
Yes, and the Canadian task force, supported by the Knowledge Translation Group at St. Michael's Hospital in Toronto, has put together a great little fragility fracture decision aid, which lists all of these variables. And the URL for that decision aid is available in the guidelines, so I'd encourage our listeners to have a look at this tool that we've developed, which is meant to be used at the point of care.
So doctors don't have to keep all of this in their heads, because in my mind, it's too complex to do, and that's why we have these tools in the first place. And interestingly, I see it as being very analogous to talking with people about preventing cardiovascular disease, where we have a Framingham calculator. So it's not just the cholesterol level that matters; it's a series of variables like your age and sex, your height, and your weight.
In the case of preventing fragility fracture, whether or not you smoke, how much alcohol you drink, if your mother or father had a fragility fracture, and there's a few conditions, like rheumatoid arthritis, that are also listed in there, which are known to elevate the risk for fragility fractures.
Dr. Kirsten Patrick:
How long does it take to run this interactive tool and have a discussion with a patient?
Dr. Roland Grad:
I think what you're raising is an important question around the issue of clinician time and how is that time best spent? We haven't actually timed people, in terms of running this, but we think that it, in the long run, when you look at the two strategies available, we think that this strategy of Risk Assessment First, using a tool to estimate risk, will not take more time than ordering BMD tests. And that's because once you start ordering BMD tests, you re-order them periodically, and prior guidelines, for example, have suggested that one to three years be the interval to repeat test ordering.
So if you take a long view of this, and this is what family doctors are doing, because we are in this as a long game, it's 25 years, let's say, that we're going to follow somebody. And during those 25 years, we think that having two or three discussions about fracture risk and the ability of treatment to reduce that risk would actually take less time than repeatedly ordering BMD testing every two to three years, for example.
Dr. Kirsten Patrick:
Makes sense. Makes very good sense to me. And talking about the practical application of these recommendations, how is a family doc going to use these recommendations? What's their thinking going to be, after having read this guideline, when they see a patient that they think they might want to screen?
Dr. Roland Grad:
Right, well, let's run through an example, and I picked a real person out of my practice. Her name is not Maria, but let's call her Maria. And she takes no medication. She's Caucasian, and a non-smoker. Has no history of prior fragility fracture. Let's assume her weight is 65 kilograms, height 170 centimeters. And Maria comes in at the age of 58 and asks me: "Should I have a bone mineral density test?" This is not such an unusual scenario after the menopause. In my practice, it happens.
And what I think we should do, when patients initiate that before the age of 65, is to have a discussion about their fracture risk, and that discussion would be guided by the Fragility Fracture Decision Aid, that tool that I talked about. And when you plug in, it takes just a minute or two to plug in the variables, because you already know her height and weight, because she's your patient, and you know about her past medical history, and if not, you can ask.
And once you run that FRAX tool in that decision aid, what you'll see is that for people like Maria at 58, bisphosphonate treatment almost has no effect. It prevents one major osteoporotic fracture per 100 females just like her over 10 years. So very quickly, Maria, age 58, realizes this is not worth it. No BMD test is done, and you decide that you're going to discuss this again. When to discuss this again is another interesting issue. We did not find any trials that look at screening intervals. So we do know that there's observational data that shows no benefit from doing this more often than once every eight years, because you are what you are, unless you get sick, in which case that needs to be re-evaluated.
But if you're not sick, then Maria remains in your practice. She ages along with you and comes back, let's say, 10 years later, and at the age of 68, she asks you ... Well, actually, at this point, I would ask her if she would be interested in re-discussing, because now she's after 65 years of age. And conditionally, on shared decision-making, we recommend initiating discussions, so I would initiate this time. And I would run that same tool one more time, and I would show Maria that this time, bisphosphonate treatment for five years would prevent two major osteoporotic fractures over 10 years.
I would like to add that it's possible that Maria is interested in preventive treatment. Maybe yes; maybe no. She needs to know what she could get from this intervention, and if she is interested, potentially, then I would do a BMD test. And if the BMD test comes back with a T-score of minus 2.5, I would re-estimate her fracture risk using that T-score. That's a T-score from the femoral neck, and I would learn the treatment, instead of preventing two, now prevents three major osteoporotic fractures and one hip fracture per 100 females just like her, over the next 10 years.
So the BMD test really didn't change much, but it confirmed that you're in the right ballpark, that you're going to prevent two or three fractures over 10 years. And I would ask Maria, "Is that important for you to take this treatment?" She would then ask me, "What are the side effects?" I would mention to her briefly what they are, and a decision would be made.
Just to end off, I'll say that it gets even more interesting if she decides not to take treatment at 68 but comes back 10 years later, in her late 70s. At that point, the benefits of treatment are even more clear. So when you look at this, it's really once you get into the 70s that preventive treatment starts to become more interesting.
Dr. Kirsten Patrick:
Okay, that's interesting. So one thing that you said triggered a question for me, and that was you said she ages, and you age along with her, and it made me think. The doctor that she sees when she's 68 may not be the one that she sees at 58. Do you tell Maria at 58, "Don't think about it until you're over 65, and if another doctor suggests that you be screened or you go for bone mineral density testing before age 65, you should say no?"
Dr. Roland Grad:
Well, saying no is an interesting and maybe challenging one. Let me start first with the easier one. I would definitely say to Maria, age 58, that we should re-discuss this after 65, because people have this sense of the annual visit as being some sort of marker for when you should talk about things. But really, the annual frequency is not helpful, and it is only after some time has passed, maybe eight years, that one should reconsider, assuming that Maria's health has not changed.
And I do sometimes have discussions about why things are being done. If another doctor orders a test for my patient, and I don't think that test is clinically indicated, I wouldn't hesitate, if the timing was right, to bring it up, because I want my patients to know that they can talk to me about tests that other people are ordering for them.
Dr. Kirsten Patrick:
Roland, I know that when folks do systematic reviews, part of that work is to try to anticipate evidence that is due to come out in the future, so by searching trial registries, et cetera. And I wonder if you have any sense of how the evidence landscape may change in the next five to 10 years, in this particular area.
Dr. Roland Grad:
Well, I do know that The University of Alberta Evidence Review and Synthesis Centre did an update and did not find any important new evidence as of 2021. So we are not aware of any landmark studies in progress, so I don't think it's likely to change, certainly not in the next year or two or three. And we have already mentioned that trials need to be done, and they take years to get going, so yeah, I think it's going to be a while.
Dr. Kirsten Patrick:
Absolutely. Now, I wonder if you could give our listeners a take-home message. What's the one thing that you would want them to know about this new guideline and how it should change their practice?
Dr. Roland Grad:
Well, if I had to pick one thing, I think it's that we should move towards discussions about fracture risk with our female patients after 65 and what can be done about it. This means a move away from the idea of screening for osteoporosis, which is based on an arbitrary threshold of minus 2.5 or lower. And labels like osteoporosis, I should say, are unfortunately associated with potential for harm: harms from over-diagnosis, harms from over-treatment. So I think we need to get more nuanced and engage our patients in this process.
We built a decision aid, Kirsten, to guide this discussion, to help people understand their risk. What can happen if you don't take preventive medication, and what are the potential benefits if you do? So I guess that would be my take home message, Kirsten.
Dr. Kirsten Patrick:
Okay, discussions. Sounds good to me. I am a person who's approaching this age in the next decade-and-a-half, and I look forward to the discussions with my doctor. Thank you for joining me today, Roland. It's been great to talk to you.
Dr. Roland Grad:
Thank you, Kirsten. It's been a pleasure.
Dr. Kirsten Patrick:
Dr. Roland Grad is a practicing family physician, associate professor at McGill University, a member of the Canadian Task Force on Preventive Healthcare, and a co-author of a new guideline published at cmaj.ca, entitled, “Recommendations on Screening for Primary Prevention of Fragility Fractures”. A link to the decision aid that Dr. Grad mentioned in this interview is provided in the show notes.
Thanks for listening to this special episode of the CMAJ Podcast. Jola and Blair will be back in two weeks with our regular content. If you found this podcast useful, please like and share it or leave a comment. I'm Dr. Kirsten Patrick, editor-in-chief of CMAJ.