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HIV+ People on ART Have Stable Bone Density after Short-term Loss

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People with HIV tend to experience a loss of bone mineral density soon after starting antiretroviral therapy (ART), but the decline reaches a plateau after about 1 year and remains quite stable thereafter, according to a meta-analysis of nearly 40 studies described in the September 2011 Journal of Clinical Endocrinology and Metabolism.

A considerable body of research suggests that HIV positive people tend to experience bone loss, sometimes progressing to osteopenia or the more severe osteoporosis. But there is not much information about longitudinal changes in bone density over time in this population.

The reasons for low bone density in this population are not fully understood. Some drugs -- notably tenofovir (Viread, also in the Truvada and Atripla combination pills) -- have been linked to bone loss, but chronic viral infection itself and the resulting persistent inflammation may also play a role.

Mark Bolland from the University of Aukland and colleagues sought to shed more light on bone changes over time in HIV positive people who were either already on or just starting combination antiretroviral treatment, or HAART.

Bolland's group search data sources including MEDLINE, EMBASE, and the Web of Science for English-language studies published between 1966 and September 2010, and conference abstracts presented between 1997 and 2010.

They selected longitudinal studies that looked at bone mineral density changes over time, reporting measurements taken at least 48 weeks apart. The primary analysis included 6 studies that compared HIV positive adults to comparable HIV negative control groups; 3 included pre-menopausal women, 1 looked at post-menopausal women, and 2 looked at men. In addition, 31 uncontrolled studies were included in a secondary analysis.

Results

  • The primary analysis of 6 controlled studies, with follow-up periods ranging from 1.5 to 2.7 years, showed the following:

o      No significant difference between HIV positive and HIV negative participants in percent change from baseline in total hip bone density;

o      No significant difference in percent change from baseline at the femoral neck (top of the thigh bone);

o      Bone density decreased by 0.6% at the spine in HIV positive participants.

  • A secondary analysis of 37 studies (31 uncontrolled + 6 controlled) found that among HIV positive people who were already on combination ART at baseline:

o      Bone mineral density was stable or increased slightly at 1 year;

o      Bone density was stable or decreased slightly at 2 years;

o      Bone density remained stable at 2.5 years or later.

  • Among treatment-naive HIV positive participants who started combination ART at baseline:

o      Accelerated loss of bone mineral density was observed at all 3 time points;

o     Bone density decreases ranged from 2.1% to 3.2% at 1 year, and from 2.4% to 4.4% at 2 years.

o      The annual rate of bone density change was greatest at 1 year, but declined thereafter.

Based on these findings, the researchers concluded, "BMD [bone mineral density] is stable in HIV cohorts established on HAART, whereas cohorts initiating HAART have short-term accelerated BMD loss followed by a longer period of BMD stability/increases."

Given the overall stability in bone density over time, especially among people on long-term treatment, they suggested, "Routine monitoring of BMD in many HAART-treated patients may not be necessary."

An important limitation of this meta-analysis is that only 3 studies included  patient groups taking tenofovir, which is now one of the most widely used antiretroviral drugs. A small study of people already on ART at baseline saw no change in spine bone density but a 3.3% decrease at the hip at 1 year. In a study of treatment-naive patients starting ART, bone density decreased by 3.6% at the spine and 2.4% at the hip at 1 year. Another treatment-naive study that followed participants for more than 5 years saw bone density decreases of 3.3%, 2.3%, and 1.7% at the spine, and 3.2%, 2.8%, and 3.3% at the hip, at 1 year, 2 years, and 5.5 years, respectively.

The researchers noted that while HIV infection, use of antiretroviral drugs, and traditional bone loss risk factors such as smoking, alcohol use, and hypogonadism (low testosterone or estrogen) may contribute to changes in bone density, it is "difficult to explain the pattern of early accelerated BMD loss followed by BMD stability/increases" when these factors remain consistent over time. They also pointed out that bone density changes may in part be explained by changes in body weight, for example as ART enables immune recovery and reversal of wasting.

"[O]ur results suggest that low BMD should not be a concern for the majority of younger and middle-aged individuals with HIV, who are adequately treated with antiretroviral therapy and well nourished," the authors elaborated in their discussion. "Determining whether this also applies to older cohorts of HIV-infected people is an important question to be addressed."

"Decisions about investigating and treating low BMD in HIV-infected patients should be made using guidelines available for the general population, with particular focus on addressing modifiable risk factors for low BMD or fractures such as alcohol use, cigarette smoking, and low body weight," they recommended. "Effective antiretroviral treatment and avoidance of undernutrition remain the two most important factors in optimizing skeletal health in HIV-infected individuals."

Investigator affiliations: Boneand Joint Research Group, Department of Medicine, University of Auckland, Auckland, New Zealand.

9/13/11

Reference

MJ Bolland, TK Wang, A Grey, and IR Reid. StableBone Density in HAART-Treated Individuals with HIV: A Meta-Analysis. Journal of Clinical Endocrinology and Metabolism 96(9):2721-2731 (abstract). September 2011.