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HIV-positive people not on antiretrovirals are prone to inflammation-related bone loss
Liz Highleyman, 2013-10-16 06:50:00
not taking antiretroviral therapy experienced more bone mineral density loss at
the hip and were somewhat more likely to develop osteopenia or osteoporosis than
HIV-negative individuals, researchers reported at the IDWeek 2013 conference held recently in San Francisco. They
also found that and bone loss amongst
people with HIV appeared to be linked to inflammation.
People with HIV are more prone than HIV-negative
people to bone loss – including osteopenia and more severe osteoporosis – but
whether this is attributable to HIV infection itself, resulting inflammatory
and metabolic changes, antiretroviral drug toxicity, or a combination of these
and other factors is not fully understood.
Certain antiretrovirals – notably tenofovir (Viread) and protease inhibitors – are
known to be associated with bone loss, but bone changes in people not yet on
antiretroviral therapy (ART) have not been extensively studied. The role of
inflammation and vitamin D in bone health is unclear and may be easier to study
in treatment-naive individuals.
Hileman from Case Western Reserve University and colleagues
looked at changes in hip and spine bone density over time, progression to
osteopenia or osteoporosis, and relationships between bone loss and inflammatory
markers and vitamin D levels.
single-site study included 47 antiretroviral-naive HIV-positive adults with CD4
cell counts greater than 400 cells/mm3 and 41 healthy HIV-negative
control subjects matched by sex, age and race.
Most (about 70%) were men,
69% were African-American, about 30% were white and the median age was 39
years. People in the HIV-positive group had been infected for four years on
average and the mean CD4 count was 625 cells/mm3. The median body
mass index (BMI) was 26 kg/m2. HIV-positive people were
significantly more likely than HIV-negative volunteers to be current smokers
(72 vs 15%) and to have hepatitis C (19 vs 2%). People with diabetes or
active infections or inflammatory conditions were excluded.
At study entry and 48 weeks later participants
underwent dual-energy X-ray absorptiometry (DEXA) scans of the hip and lumbar spine, as well as measurement of
vitamin D and inflammation biomarkers including interleukin 6 (IL-6), high
sensitivity C-reactive protein (hsCRP), soluble tumor
necrosis factor alfa receptors I and II (sTNFR-I and sTNFR-II), and the adhesion molecules sVCAM-1 and sICAM-1.
The HIV-positive group had
significantly higher baseline levels of IL-6 (3.0 vs 2.2 pg/mL, respectively),
sTNFR-II (2434 vs 1965 pg/mL), sVCAM-1 (782 vs 544 ng/mL) and sICAM-1 (300 vs
187 ng/mL), but levels of hsCRP, sTNFR-I and vitamin D (13 vs 15 ng/mL) were
Between baseline and 48 weeks, levels of vitamin
D and inflammation biomarker levels did not change significantly in either group,
nor did changes differ significantly between the two groups.
At baseline, the
HIV-positive and HIV-negative groups had similar total hip, femoral neck,
trochanter (ball of the hip joint) and spine bone density. In both groups, a
majority (62 and 68%, respectively) had normal BMD and one-third had
osteopenia (lower than normal bone mineral density); 4.4% of HIV-positive people and no HIV-negative people had
osteoporosis, but this difference was not significant.
Over 48 weeks, HIV-positive people showed a
larger percentage BMD loss at the total hip, trochanter and spine, whilst HIV-negative
people lost more at the femoral neck, but none of these differences reached
At 48 weeks, 93% of people with HIV experienced
bone loss at any site compared with 73% of HIV-negative people, a difference
that was significant after adjusting for sex, age, race, baseline BMI, smoking
and hepatitis C status. This was particularly notable at the trochanter, with
73 and 49%, respectively, showing bone loss (also significant after
Being HIV positive conferred a greater
likelihood of trochanter BMD loss, with an odds ratio (OR) of 2.8, or nearly
three-fold higher risk. Adding IL-6, sTNFR-II, sVCAM-1, sICAM-1 or vitamin D to
the analysis along with HIV status reduced the OR by more than 10%, suggesting
inflammation may explain part of the effect of HIV.
Over 48 weeks 21% of HIV-positive people
progressed to osteopenia or osteoporosis compared with 6% of HIV-negative
individuals, but the difference did not reach statistical significance. The
only independent predictors of progression in an adjusted analysis were white
race and higher baseline IL-6 level.
adults, but not [HIV-negative] controls, had BMD loss at the total hip and
trochanter sites over 48 weeks," the researchers concluded.
"HIV-positive [people] were more likely to
have bone loss at the trochanter site and this appears to be associated with
systemic inflammation," they added.