Lower weight explains why HIV-positive patients have a risk of lower bone mineral density

HIV-positive individuals have lower bone mineral density (BMD) than their HIV-negative peers because of lower body-weight, investigators conclude in a paper published in the online edition of the Journal of Clinical Endocrinology and Metabolism.

But the researchers, from the university of Auckland, New Zealand, found that this could be explained because HIV-positive patients tended to have lower body weight than HIV-negative individuals. When they controlled for body weight, the difference in bone density between HIV-positive and HIV-negative individuals ceased to be significant.

Approximately 30 cross-sectional (or snap-shot) studies have shown a relationship between HIV infection and low BMD. Indeed, a meta-analysis of studies conducted before 2005 found that HIV-positive patients were over six times more likely than HIV-negative controls to have low BMD and almost four times more likely than controls to have osteoporosis.

But a study conducted at the University of Auckland showed that white, male HIV-positive patients were over 6kg lighter than age-matched HIV-negative controls. When the investigators took this difference into account, they found that the difference in BMD between HIV-positive and HIV-negative individuals ceased to be significant.

Because of these findings the New Zealand investigators decided to conduct a second meta-analysis looking at the relationship between HIV infection and BMD. But unlike the previous meta-analysis this one sought to control for differences in body weight between HIV-positive and HIV-negative individuals.

A literature search was conducted to identify studies and abstracts published before 2007 using the search terms ‘HIV’, ‘AIDS’, ‘osteopenia’, and ‘osteoporosis’. To be included in the meta-analysis, the study had to include patients aged over 18, have a control group of HIV-negative individuals, and have data on either body weight or body mass index (BMI) for both groups.

In total, nine published studies and one abstract met the investigators’ requirements. The total number of HIV-positive patients included in these studies was 1371 and there were 1644 HIV-negative controls.

HIV-positive patients were an average of 5kg (p

Preliminary analysis showed that HIV-positive patients had lower BMD than the controls in the lumbar spine region (5% lower, p

But controlling for weight or BMI had a dramatic effect on these results. The difference in BMD in the lumbar spine region ceased to be significant (2% lower in HIV-positive patients, p = 0.12), BMD in the hip was only 2.4% lower (p = 0.031), and BMD in the femoral neck was 5% lower in patients with HIV (p = 0.013).

Unadjusted BMD was a statistically significant 5.5% lower in HIV-positive patients (p = 0.006), but after weight adjustment the relationship between HIV infection and low BMD ceased to be significant (p = 0.11).

The areas with most pronounced difference in BMD between HIV-positive patients and HIV-negative controls was the femoral neck. This size of this difference was largely explained by a single study, which only contributed a small number of patients. The investigators therefore excluded this study from a further set of analysis. After doing this, the weight-adjusted difference in BMD between HIV-positive and HIV-negative individuals fell to 3%, a difference which was no longer statistically significant.

Studies conducted since the introduction of effective anti-HIV therapy in the late 1990s tended to find a lower difference in BMD between HIV-positive patients and controls. This is consistent with the investigators’ hypothesis, as weight gain is a positive effect of antiretroviral therapy. The investigators also note that longitudinal studies have failed to find an association between the duration of HIV infection and loss of BMD, and HIV-infection is not an independent risk factor for fractures.

“Low body weight in HIV-infected patients can largely account for the high occurrence of low BMD in HIV-infected patients, and that HIV infection in the absence of low body weight is not a risk factor for low BMD”, conclude the investigators.