French study further mystifies causes of bone loss in people with HIV

Antiretroviral treatment has no significant effects on bone mineral density (BMD) in men with HIV, according to French investigators writing in the January 30^th edition of AIDS. The study showed that a lower viral load was associated with bone problems, but that it was not linked to the effects of antiretroviral medication.

Osteopenia is a decrease in bone mineral density that can lead to osteoporosis (a thinning and weakening of the bones) and an increased risk of fractures. An increased prevalence of bone problems has been seen in HIV-positive patients, but the reasons behind it are not fully understood.

There have been few studies into the factors that could be associated with bone metabolism, including the use of antiretrovirals, in people living with HIV. The studies that have been conducted show conflicting results. Researchers have struggled to find an over-riding factor leading to bone changes, suggesting that there may be many causes.

In order to estimate the prevalence of reduced bone mineral density and to investigate the factors associated with it, a cross-sectional (or snap-shot) survey within a large cohort of French HIV-positive patients was conducted. The cohort, known as the Aquitaine cohort, is a prospective cohort that includes patients who receive their HIV care at five hospitals in south western France.

Researchers recorded various patient characteristics including gender; age; HIV transmission route (intravenous drug use, homosexual or heterosexual intercourse); date of HIV diagnosis; alcohol and tobacco use; and use of anti-HIV drugs and other medication. All of these variables were extracted from the cohort database and a questionnaire was used at the first clinic visit during the study period to document body mass index, calcium consumption and physical activity. If women were menopausal, this was also recorded due to associations with the menopause and lower bone mineral density.

Bone mineral density was measured for the total body, lumbar spine and femoral neck (close to the hip joint).

A total of 492 patients were included in the investigators’ analysis. Of these 359 men (73.0%) and 133 women. A total of 31 (23%) women were menopausal. The average age was 43 years and most (93%) were taking antiretroviral therapy. The prevalence of lipodystrophy was 29%.

Osteopenia was diagnosed in 264 patients (54%). When analysed by gender, 55% of men had osteopenia and 51% of women. Osteoporosis was diagnosed in 132 patients (27%), with a prevalence of 3-4% among men and 8% in women. As expected, osteoporosis was seen at higher rates in menopausal women than in premenopausal women (22.6% and 3.9%).

When analysing the data to determine factors linked to bone problems, the investigators looked at men and women separately.

Factors found to be associated with the diagnosis of osteoporosis in men were older age, homosexual HIV transmission, low body mass index and low HIV plasma viral load ( below 500 copies/ml). Only older age and lower body mass index were marginally associated with osteopenia.

In women, all bone disorders were pooled together without the distinction between osteopenia and osteoporosis because there was lower number of diagnoses of each of the subgroups. Only older age and low CD4 cell count nadir (lowest ever recorded) were identified as factors associated with reduced body mass index.

Among these factors found to be associated with low body mass index, some were expected, such as older age or lower body mass index, but others were new, including homosexual HIV transmission group, low HIV viral load and low CD4 cell count nadir.

The researchers speculated that the link with homosexual transmission could indicate that this is a proxy for the use of recreational drugs that might damage the bone metabolism or the presence of coinfections, such as human herpes virus 8.

The finding of an association between lower bone mineral density and lower viral load contradicts some previously published reports whichsuggested that prolonged and high viremia might affect bone formation. In this study, low viral load was the consequence of successful anti-HIV therapy. While this was initially thought to indicate a harmful effect of antiretroviral treatment on bone mineral density of , investigations into the effect of antiretroviral treatment, unadjusted for viral load, did not show significant differences.

The investigators commented, “An effect on bone of antiretroviral drugs does not explain why a plasma viral load <500 copies/ml arose as a risk factor for the osteoporotic men.”

Analysis was carried out for each different drug class but none showed a significant effect on bone mineral densities. They concluded that the use of antiretrovirals was not related to osteoporosis.

The potential effect of CD4 cell count nadir may indicate that prolonged periods of immune suppression are a risk factor for bone mineral loss, due to immunological changes that disrupt bone tissue metabolism.

Another possible explanation of the effect of the CD4 cell nadir is the possibility that patients with a low CD4 cell nadir have been treated for a longer period with antiretroviral drugs, and that the association between CD4 cell nadir and bone loss . This might indirectly support a negative role for antiretroviral drugs on bone metabolism in women.

Neither lipodystrophy nor reduced physical activity was associated with early bone problems.

The investigators noted that limitations in interpreting their data could have resulted in a higher than expected number of bone problems in men. They had no reference point for average French male bone mineral densities and so American figures were used which could have skewed the results.

“The Americans have a diet that is richer in vitamin D than the French and so have a higher bone mineralisation peak,” the investigators explained. “Ongoing studies will provide better knowledge of the physiopathological mechanisms at the initiation of early demineralization among HIV-infected patients, thus allowing better diagnostic, preventive and therapeutic evaluation to support care for this chronic infection in the coming years.”