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
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
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
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
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
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 =
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
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.”