Low bone density present in young men taking HIV therapy

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HIV infection in young men is associated with reduced bone mineral density, US investigators report in the online edition of Clinical Infectious Diseases. Antiretroviral therapy based on a protease inhibitor was especially associated with reduced bone density.

“We report evidence of low bone mass in behaviorally HIV infected young men on ART [antiretroviral therapy], particularly those on ART regimens that include a PI,” comment the authors. “This is the first report of low bone mass among youth who acquired HIV infection relatively recently, presumably after the onset of sexual debut during the late stages of puberty, and have relatively little exposure to ART.” 

Low bone density is a well-recognised complication of HIV infection. There is uncertainty about the exact causes. The inflammation caused by HIV is one possible explanation, but bone loss has also been observed in people after they start antiretroviral therapy. Specific classes of anti-HIV drugs, most notably protease inhibitors, as well as some individual drugs, especially tenofovir (Viread, also in the combination pills Truvada, Eviplera and Atripla) have also been implicated.



In HIV, an individual who is ‘treatment naïve’ has never taken anti-HIV treatment before.

bone mineral density (BMD)

The higher your bone mineral content, the denser your bones are. And the denser your bones, the stronger they are and the less likely they are to break. A bone density test uses X-rays to measure how many grams of calcium and other bone minerals are packed into a segment of bone. The bones that are most commonly tested are in the spine, hip and sometimes the forearm. 


A person who has never taken treatment for a condition.

control group

A group of participants in a trial who receive standard treatment, or no treatment at all, rather than the experimental treatment which is being tested. Also known as a control arm.


The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

Peak bone mass is achieved in adolescence and early adulthood and is the key factor governing bone mass during adult life. Little is currently known about the effects of HIV infection on bone mineral density in people who acquired the virus during this vital stage for bone metabolism.

Investigators from the US therefore designed a cross-sectional, case-controlled study comparing bone mineral density in 199 HIV-positive men aged between 14 and 25 years and 53 age-matched HIV-negative people as controls.

Just over half the HIV-positive patients were antiretroviral naive. In all, 52 people were taking therapy based on a non-nucleoside reverse transcriptase inhibitor (NNRTI) and 42 individuals were treated with a protease inhibitor-based regimen. Prevalence of tenofovir use was similar among the NNRTI and protease inhibitor groups.

The patients and controls had a median age of 21 years. The antiretroviral-naive participants had been HIV positive for a median of 1.3 years. The median duration of infection for people taking an NNRTI was 1.9 years, whereas those treated with a protease inhibitor had been HIV positive for a median of 2.2 years. Some 92% of people taking an NNRTI had an undetectable viral load (below 400 copies/ml) compared to 72% of individuals on a protease-inhibitor-based regimen.

Prevalence of risk factors associated with low bone density, such as smoking and alcohol consumption, was similar between the HIV-positive participants and the controls. However, the HIV-infected individuals were significantly more likely to have ever used cocaine (23 vs 8%; p = 0.01).

Bone mineral density, content and body composition were assessed using DEXA scanning.

The HIV-negative participants were heavier (p = 0.002), and had a higher BMI (p = 0.006) and greater total lean body mass (p = 0.005), when compared to the antiretroviral-naive participants and those taking an NNRTI.

Total body bone mineral density was lower in the participants taking antiretroviral therapy (NNRTI and protease inhibitor-based regimens), compared to both the treatment-naive patients and controls (p = 0.019 and p = 0.035). Bone mineral content Z-scores were lower in the patient groups compared to the control group (p = 0.005).

Further analysis showed that total bone mineral density in the hip was significantly lower in both HIV treatment groups compared to the controls (p < 0.001) and the participants who were yet to start antiretroviral treatment (p < 0.001). Total hip bone density Z-scores were also lower in the patients compared to the controls (p = 0.001) and in the treatment-experienced participants compared to those who were treatment naive (p < 0.001).

In the femoral neck, both total bone density and bone density Z-scores were lower in the protease inhibitor group than in the control group (p = 0.003 and p = 0.005).

Overall, bone mineral density in the spine was marginally lower in the HIV-positive people compared to the control group. When analysis was restricted to the HIV-positive participants, the investigators found that this measure of bone density was lower in people on antiretroviral therapy – especially when based on a protease inhibitor – than the treatment-naive participants (p = 0.025).

Total spine bone mineral density Z-scores were lower than expected in all groups, including in the HIV-negative control group, but were markedly lower in the HIV-positive people, especially those taking a protease inhibitor.

There was some evidence that antiretroviral therapy, rather than HIV infection, was the cause of bone loss. The investigators highlight that they “saw little evidence of loss or impaired accrual of bone” in the HIV-infected participants who were still treatment naive. “In these youths who had acquired HIV infection relatively recently, the effect of HIV infection per se on bone mass appeared to be minimal.”

Although the authors were uncertain about the long-term consequences of their findings, they nevertheless believe that action to protect the bone metabolism of young HIV-positive men is required: “Risk reduction through changes in diet and lifestyle is warranted.”


Mulligan K et al. Low bone mass in behaviorally HIV-infected young men on antiretroviral therapy: Adolescent Trials Network (ATN) Study 021B. Clin Infect Diseases, online edition, 2012.