In the HIV Research Takeaway, we provide plain talk about new data in the world of HIV-related research and explain in straightforward terms what the results mean for people living with or affected by HIV.
The Issue: Low Bone Density in People With HIV
In the 1990s the HIV metabolic issue was fat wasting. In the 2000s it was cardiovascular disease. And now, increasingly, bones are the focus of attention when considering living long-term with HIV.
Concern about the bone health of people living with HIV is not new. Plenty of studies have shown that patients presenting to HIV clinics had lower bone density than expected for their ages -- and low bone density is associated with a heightened risk of bone fractures in the spine and the hip. Other research has shown drops in bone mineralization with the start of HIV medications, especially tenofovir disoproxil fumarate (TDF), a drug found in Truvada (TDF/FTC), Atripla (efavirenz/TDF/FTC), Stribild (elvitegravir/cobicistat/FTC/TDF) and Complera (rilpivirine/TDF/FTC).
These findings have led some to suggest that screening for low bone density be performed for certain people living with HIV, such as those over age 50 or who have other risk factors. However, this recommendation is not as commonly followed as other general health maintenance guidelines. For one thing, screening typically requires a scan called a DEXA that uses X-rays to measure the density of bone. So, to get a DEXA scan, the patient has to go to a hospital or radiology center. Also, some insurance companies balk at paying for these scans.
FRAX is a computer-based tool (yes, it is also an app) that is used clinically to predict the risk of bone fracture. Similar to heart attack calculators, FRAX uses risk-factor information input by health care providers to spit out a 10-year probability of a major bone break. Those at highest risk could be evaluated for correctable causes of bone loss and be started on medication to strength their bones. How well this tool predicts fracture risk in HIV-positive people is not clear and is the question at the heart of a recent study of HIV-infected and uninfected men receiving care from the Veteran's Administration (VA).
The study appears in the Aug. 15, 2016, issue of the Journal of Acquired Immune Deficiency Syndromes. The lead author is Michael T. Yin. The title is "Fracture Prediction With Modified-FRAX in Older HIV-Infected and Uninfected Men."
The researchers looked at clinic data collected on almost 25,000 men between the ages of 50 and 70, of whom over 7,000 were HIV-infected. As expected, the HIV-positive men had more risks for low bone density than the HIV-negative men due to having had a prior fracture, previous treatment with corticosteroids (e.g., prednisone) -- which can deplete bone mineralization -- lower body mass and hepatitis C infection. After the team plugged the available data for all the men into the FRAX calculator, the predicted 10-year risk of fracture was found to be slightly but statistically higher for the HIV-infected men. However, the good news is that the fracture-risk probability for both groups was rather low at about 3%.
Next, the researchers checked the VA medical records for any mention of a fracture that could have been due to low bone density. They found that the actual recorded rate of fractures was higher than the rate the FRAX predicted -- this was true for both the HIV-positive and the HIV-negative men. The actual fracture rate was higher for those with HIV (about 4.5%) than those without (about 3.5%). To improve the ability of FRAX to predict the fractures that had happened, the researchers played with adding HIV as a risk factor and this helped improve the predictive ability of the calculation.
However, even when modified to include HIV as a risk factor, FRAX was not that useful for predicting exactly who ended up getting a fracture. FRAX missed all but a handful of both the HIV-infected and HIV-uninfected men who experienced a bone break. That is, well over 90% of the fractures that occurred were not predicted by FRAX.
Based on this study, one might wonder why in the world anyone would use the FRAX calculator if it could not predict more than nine out of ten fractures. Good question.
But, before we clinicians delete the app from our phones, it should be noted that the researchers used previously collected data, and some important information was not always present. In clinical practice this information, such as the history of bone fractures in a parent, would be more readily accessible. Also, they relied on medical records and billing codes that may not always be accurate.
Nonetheless, FRAX's poor performance suggests that more is going on than less-than perfect data inputs. The researchers note that the calculator was originally developed using data from people in Minnesota. For those who have not been up there, there are not too many people of color in Minnesota; however, over half of those included in the VA study were African American. The performance of FRAX may well be different in different populations. Also, this study was done only in men; there are many fewer women receiving care in the VA system. How FRAX does in predicting fractures in HIV-infected women remains unknown.
Overall, this study indicates there is no technological short cut for assessing bone density and fracture risk. Those 50 years of age or older living with HIV should ask their health care providers about getting a DEXA scan, especially if they also have other risks for fracture, including ever smoking, heavy drinking or having a low weight; white race; low testosterone; vitamin D deficiency; oral or IV corticosteroid treatment; and thyroid disease. If the provider pulls out her smart phone to pull up the FRAX app, you can knowledgably and politely ask her to put her phone away.
David Alain Wohl, M.D., is an associate professor of medicine in the Division of Infectious Diseases at the University of North Carolina.