Bone Disease and HIV/AIDS: More Common Than You Think -- This Month in HIV
An Interview With Todd Brown, M.D., Ph.D., and Ben Young, M.D., Ph.D.
Bonnie Goldman: Why do you think so little attention is being paid to the issue of bone disease in HIV-positive people? Dr. Young?
Ben Young: The short answer is: I don't know. I think that there has been a compelling amount of evidence, starting maybe even in 1999/2000, that certainly the bone mineral density issue was very common in our patients.
I think there are two points. Number one is that the fracture frequencies to date have been low and, in part, owing to the relative younger age of our patients.
It takes a large patient population to see sufficient numbers of fractures to begin to connect the dots, in terms of fracture risk. I think that there's a disconnect between the recognition of a common, let's say, laboratory abnormality and the potentially very serious clinical event, meaning fractures.
"A lot of the continuing medical education that we receive is often sponsored by pharmaceutical companies. And pharmaceutical companies have largely not connected their bone health franchises with their HIV franchises."
-- Ben Young, M.D., Ph.D.
Even in our clinic, where we had these fractures, it took us a number of years to begin to realize there was some connection between the fractures and the abnormal bone mineral density.
The second one is a little more challenging, I think. It speaks to the idea that, for better or worse, a lot of the continuing medical education that we receive is often sponsored by pharmaceutical companies. And pharmaceutical companies have largely not connected their bone health franchises with their HIV franchises.
That's not to say that everything in the world was driven by pharma, but it is a large component of the drum beating, so to speak.
So that we've heard a lot about heart disease that was amplified by medical education sponsored by pharmaceutical companies. I think that bone disease in the HIV-positive population has fallen between the cracks.
However, there is a palpable increase in the number of scientific articles and posters at conferences and such related to bone health. I think that people's awareness of it is starting to very significantly increase, and I'm grateful for that.
Todd Brown: I agree. I think that more and more attention has been paid, and as the understanding gets better, more people will become interested.
"HIV-infected patients may be at higher risk for falling, for reasons that aren't related to bone density at all. For example, peripheral neuropathy is a big risk factor for falling and we know that HIV-infected populations have a high risk of peripheral neuropathy."
-- Todd Brown, M.D., Ph.D.
The other issue that we haven't really talked about -- I think Ben might have mentioned it earlier -- is the non-skeletal risk factors for fracture.
Most fractures occur when people fall. HIV-infected patients may be at higher risk for falling, for reasons that aren't related to bone density at all. For example, peripheral neuropathy is a big risk factor for falling and we know that HIV-infected populations have a high risk of peripheral neuropathy.
So I think that those issues also need to be addressed, and also need to come out in consultations with patients who are concerned about bone health.
There are some practical things that people can do to decrease their risk of falling: for example, wearing certain shoes; making environmental changes, such as picking up piles of paper, making sure that there are no rugs that slip; really watching themselves while walking on slippery surfaces. All these things are also very important in preventing fractures.
Bonnie Goldman: Dr. Brown, can you explain why peripheral neuropathy would make someone more likely to fall?
Todd Brown: You rely on your feet. When we walk around, we don't really realize what we're doing, but we have a sense of where our feet are in space. So we can walk down the street, and we can talk to people while we're walking down the street, and we will automatically bring our foot up to go over the curb. But it's because we have a sense of where our feet are in space.
People with peripheral neuropathy may not have that sense as well, and so they might be more likely to stumble and fall as a result.
Bonnie Goldman: So that, compounded with low bone density, would cause the fracture?
Todd Brown: Absolutely.
Bonnie Goldman: The European HIV guidelines just came out, and they have a whole section about bone disease diagnosis, prevention and management. [Click here to view.] Yet there are no such recommendations in the U.S. guidelines. Are you hoping that the U.S. guidelines will include something like that in the future?
Ben Young: Yes. I actually went to the European AIDS Clinical Society meetings in Cologne, Germany, where they did, indeed, present what I believe to be the first management guidelines for bone health, prevention and such, in HIV patients.
They speak specifically about issues relating to the screening for bone disease, vitamin D and calcium supplementation, and so on. I think that these are a very welcome advance, and provide good guidance for clinicians as to how to take care of people for their long-term health.
I'll point out as well that the Europeans were, I think, quite prescient, including guidelines for managing other health issues in their compendium, such as diabetes and lipid problems [click to view], cardiovascular disease [click to view] and cancer [click to view].
People can go to the European AIDS Clinical Society Web site and look at these guidelines.
Todd Brown: I haven't seen the published version, or the presented version, of the guidelines, but I did see an earlier draft. One important thing to realize is that, even in the general population, European recommendations for screening for osteoporosis are different than the U.S. guidelines. I think it's important to keep this in mind when you're trying to apply the European guidelines to U.S. populations.
Ben Young: Good point, Todd. Actually, I'd love to hear your thoughts. The principal screening tool that they recommend is the use of the FRAX equation, which is available through online calculators, and is adjusted for both race and country. I want to get your thoughts as to whether that's a reasonable tool for us to be using, absent DXA scans.
Bonnie Goldman: Just a note: FRAX is a fracture risk assessment tool.
Todd Brown: This is a way of trying to figure out for a given person what is his or her risk of having a fracture in the next 10 years.
This gets at this idea that I mentioned before between your risk in relation to someone your own age versus your absolute risk of having a fracture.
You plug risk factors into this Web-based algorithm [click here to view]. Anyone can do it themselves. If you Google "FRAX" and log on to the site in Sheffield, England, you can plug in risk factors. At the end, you press a button and you get the 10-year risk of fracture. It's broken down in two ways: either all osteoporotic fracture or hip fracture, specifically.
You can look to see what your risk of fracture is. You could either use it in conjunction with a bone density test (that's how FRAX is used in the U.S.) or use it without a bone density test to determine who should get a screening DXA scan -- you use just your body weight and height as a surrogate.
There are differences in how people in the U.S. and how people in Europe use this tool. The concern that I have is that most of the data that FRAX is built on -- and a lot of work went into trying to figure out the factors that are associated with fractures, and the various populations -- but most of the data is in people older than 50. I have some reservations about using those data in making clinical decisions, because the reference database from which FRAX calculates the fracture risk really wasn't very robust at low ages. That's my general concern with using FRAX.
Bonnie Goldman: How do we get health care providers to add the prevention and management of bone disease to the long list of things they are already doing as part of primary care in people with HIV?
Todd Brown: I personally would take an age-stratified approach. For older HIV-infected patients -- and I use 50 as a cut point -- I think that there should be an emphasis on obtaining a baseline bone density test, in addition to talking about other issues related to bone health -- calcium intake, vitamin D intake, activity level, smoking cessation, making sure that the alcohol intake is not excessive.
These latter factors, not the bone density issues, would also be a discussion that could be had with younger patients. But other people have different strategies, in terms of screening.
Ben Young: I agree with all of the points, except for -- and again, I accept the uncertainty regarding -- the age threshold at which you deploy screening methodology. The prevalence of abnormal bone mineral density in the HIV population is greater than it is in the general population and there is at least some data that suggest that it's also prevalent in younger individuals.
I certainly caution people from drawing too many conclusions from individual anecdotes -- but through these earlier studies, we identified people who were under age 25, who had no obvious risk factors, who had osteoporosis.
Thinking prospectively -- from this perspective of how much harm is done by trying to screen and address secondary or reversible causes versus the harm done by ignoring the potential risk in having fractures -- I will err, at the moment, on the side of more aggressive screening and prevention. But I accept that the data set and the national guidelines to date don't address the risk/benefit equation for men with bone disease and people of either gender who have HIV and bone risk.
There are a lot of unknowns and a lot that needs improvement, but at least for the moment, this clinician's view is to try to address the concerns with as many patients as possible and, if appropriate and relevant, DXA scan the patients.
Todd Brown: Just to follow up on one idea, which hasn't come out: We all reach our peak bone mass at around age 30 and bone density declines thereafter. Your bone density at, say, age 55 or 65 in part depends on whether or not you've reached your peak bone mass.
For people who are younger than age 30, it's a really crucial time to build bone. There's concern, as well as some studies, showing that there may be a failure in HIV-infected children and adolescents to get up to that peak bone mass.
I think that the approaches, in terms of calcium and vitamin D, are really important. There are some concerns about using DXA in this population. It can be difficult to interpret clinically. So that's one of the big drawbacks.
Bonnie Goldman: Dr. Brown, is there any ongoing or future research regarding bone disease in HIV-positive people that you're particularly excited about?
Todd Brown: There are a couple of areas of research that are important -- the first is really trying to nail down the actual risk of fractures.
At this year's retrovirus meeting there are going to be some studies that will look at this in more detail, and I know Ben is part of one of them. I think that it is crucial to try to understand what the risk of fracture is. We can talk about bone density and DXA scans, but what we really care about at the end of the day is whether people are breaking bones, and what the risk factors are for breaking bones.
The next thing is looking at some of the mechanisms of why HIV-infected patients may be more likely to have lower bone density and have an increased fracture risk.
I had mentioned that there is a drop in bone mineral density in the first two years of antiretroviral therapy. Why that is, really, is not clear. Generally, inflammation is considered to be bad for the bone. With antiretroviral therapy, markers of inflammation invariably go down. So why would you get a decrease in bone density? And this has been seen consistently in many, many studies. I think that that's a very interesting thing to look at.
Of course, the goal here would be to try to prevent this drop in bone density. To see if there are various agents that may be less associated with this drop in bone mineral density is another important goal.
Also, can we do things to mitigate, or decrease, this loss? For example, if we supplement people with calcium and vitamin D, can we decrease the amount of bone that's lost in the first two years of antiretroviral therapy?
Then, I think that trying to understand bone disease for aging HIV-infected patients is crucial. I had talked briefly about non-skeletal risk factors -- so, not related to bone density -- that are very important in fractures, and mostly, fall risk. I think that those issues need to be clearly studied in HIV patients.
Also, I think that getting more data to try to make better decisions about who should be screened would be very important, and to go through some of these cost benefit type analyses, to see if it makes sense on a population level to screen people with HIV infection across the board with DXA scans.
Bonnie Goldman: I guess we'll get some more information at the end of February, after CROI [Conference on Retroviruses and Opportunistic Infections].
Todd Brown: That's right.
Bonnie Goldman: Thank you both for taking the time to talk with me, and for providing such a terrific update on bone disease and HIV.
This transcript has been lightly edited for clarity.
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