Over the past decade, reports have emerged of age-related complications occurring at a younger than expected age in some HIV-positive people. Scientists around the world are studying these age-related issues and trying to find possible causes in HIV-positive people.
In Amsterdam, researchers have established a large cohort, called AGEhIV, of both HIV-positive and HIV-negative people of similar age and risk behaviours.
The latest analysis from AGEhIV has focused on thinning bones. The mild form of bone thinning is called osteopenia and the more severe form is osteoporosis. Having thin bones can increase the risk of them breaking during falls or accidents.
According to the scientists with AGEhIV, osteoporosis was significantly more common among HIV-positive people than HIV-negative people. When the scientists took into account several factors related to the medical history of the men as well as behavioural factors, they found that HIV by itself was not specifically linked to the loss of bone. However, issues such as smoking and being underweight rose in importance. Furthermore, young MSM in this study, regardless of HIV infection, were surprisingly at risk for having thinner-than-normal bones.
Study details
There are many potential reasons why the loss of bone mineral density (BMD) can occur in people.
To better understand the potential causes of reduced BMD, scientists in Amsterdam compared health-related data from the following two groups of people:
- 581 HIV-positive people
- 520 HIV-negative people
(These figures differ somewhat from the previous CATIE News story on the AGEhIV database, as in the present study we are focusing on participants who had bone density scans available for analysis.)
A major strength of the AGEhIV cohort is that participants were from the same geographic region and had similar social, economic and behavioural backgrounds.
All participants in this analysis received low-dose X-ray scans called DEXA (dual-energy X-ray absorptiometry). Additionally, participants underwent detailed interviews and had blood drawn for extensive tests.
Overall, most participants were men (86%) and 72% were men who had sex with other men (MSM). Most (95%) HIV-positive men in this study were taking ART and consequently had a low viral load and a CD4+ count of around 565 cells/mm3.
The data for the analyses on bone health were gathered between 2010 and 2012.
Results
DEXA scans revealed that 13% of HIV-positive people had decreased bone density in the hip, hip joint and spine compared to HIV-negative (8%) participants. This difference was statistically significant.
When researchers took into account many potential risk factors for bone thinning, HIV infection by itself was not linked to decreased BMD. Rather, the following risk factors were linked to decreased BMD:
- smoking (this particularly affected the density of the spine and hip joint)
- having a less-than-ideal body weight
- having a history of symptoms of HIV disease, including AIDS
Exactly how having a less-than-ideal body weight could have affected the BMD of bones in the men is not clear from this study. However, the Dutch scientists suggested that at some point in the past, some of these men had developed serious weight loss due to life-threatening infections that are the hallmark of AIDS. Part of the treatment of AIDS-related infections, particularly those that affect the lungs, brain and other major organ-systems, includes the use of a class of drugs called corticosteroids. These drugs help to suppress the sometimes dangerous degree of inflammation that can be incited by AIDS-related infections. While corticosteroids can be part of a treatment regimen that helps to rescue a person from an AIDS-related infection, doctors now know that such drugs can also cause bones to become thinner.
Aspects of ART
The present study did not have a sufficient number of people to assess the impact of particular anti-HIV drugs on bone health. Furthermore, participants were not given HIV treatment regimens in a randomized fashion, so robust conclusions about the impact of ART on bone health cannot be drawn from the AGEhIV data.
BMD in MSM
The Dutch scientists found that bone mineral density was “surprisingly low” in younger MSM, regardless of their HIV status. They made the following statement:
“We speculate that the younger MSM within this cohort may have had a different historical pattern of engagement in active sports, diet, use of anabolic steroids or recreational drugs compared to older MSM, possibly at an age before reaching peak [bone mineral density].”
Other studies have reported reduced BMD in both HIV-positive and HIV-negative MSM in San Francisco and Amsterdam. This suggests that perhaps the issue of thinning bones may have begun prior to the onset of HIV infection in some MSM.
In context
The findings from the present study are cross-sectional in nature. Such studies cannot prove cause and effect. However, the findings from this study are similar to those of other studies. A major strength of the present Dutch study is that the HIV-negative participants who were recruited and used as a comparison were very similar to the HIV-positive participants.
The puzzle
The findings from the Dutch study about the loss of BMD in both HIV-negative and HIV-positive younger MSM are intriguing. Combined with findings from other studies, they suggest that some young MSM may be at risk for low BMD. Additional research with HIV-negative MSM is required to better understand this finding.
Care recommendations
The Dutch scientists warn doctors caring for HIV-positive MSM that such patients may be “particularly prone to developing osteoporosis/osteopenia” after the initiation of ART. A rapid decrease in BMD following initiation of ART has been seen in several studies. However, this loss of BMD then stabilizes after several years. The Dutch scientists recommend that “supportive [bone] treatment” with calcium and vitamin D3 be considered for MSM who are initiating ART. In a randomized, placebo-controlled clinical trial presented at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014), participants who initiated ART and who were given 4,000 IU/day of vitamin D3 and 1,000 mg/day of calcium reduced bone thinning by 50% compared to other participants in this study who were not given such supportive therapy.
Resource
Bone health – TreatmentUpdate 189
—Sean R. Hosein
REFERENCES:
- Kooij KW, Wit FW, Bisschop PH, et al. Low bone mineral density in patients with well-suppressed HIV infection is largely explained by body weight, smoking and prior advanced HIV disease. Journal of Infectious Diseases. 2014; in press.
- Grijsen ML, Vrouenraets SM, Wit FW, et al. Low bone mineral density, regardless of HIV status, in men who have sex with men. Journal of Infectious Diseases. 2013 Feb 1;207(3):386-91.
- Liu AY, Vittinghoff E, Sellmeyer DE, et al. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS One. 2011;6(8):e23688.
- Yin MT, Zhang CA, McMahon DJ, et al. Higher rates of bone loss in postmenopausal HIV-infected women: a longitudinal study. Journal of Clinical Endocrinology and Metabolism. 2012 Feb;97(2):554-62.
- Overton ET, Chan ES, Brown TT, et al. High-dose vitamin D and calcium attenuates bone loss at ART initiation: Results from ACTG A5280. In: Program and abstracts of the 21st Conference on Retroviruses and Opportunistic Infections, 3-6 March 2014. Abstract 133.