Higher rates of bone loss seen after menopause in HIV-positive women

Most research on changes in bone density in HIV-positive women has focused on women before they have entered menopause. Due to hormonal changes associated with menopause, women entering this phase of their life are at high risk for thinning bones.

A research team at Columbia University Medical Center in New York City has been studying bone density in both HIV-negative and HIV-positive women who have entered menopause. On average, HIV-positive women had double the annual rate of bone thinning compared to HIV-negative women. Such large decreases in bone mineral density places HIV-positive women at increased risk for osteopenia, osteoporosis and fractures as they age.

Study details

Researchers reported results from 55 HIV-negative and 73 HIV-positive women, all of whom were described as “postmenopausal” by the study team. The women had ceased to have periods and their level of estrogen was relatively low. None of the women were taking hormonal therapy or had a history of reduced bone mineral density prior to entering the study. This report focuses on the HIV-positive women.

The average profile of the HIV-positive women when they entered the study was as follows:

• age – 56  years
• time since onset of menopause – 10 years
• length of time HIV positive – 9 years
• history of AIDS – 47%
• lowest-ever CD4+ count – 195 cells
• current CD4+ count – 474 cells
• taking anti-HIV therapy (ART)– 78%
• vitamin D deficiency – 50%
• co-infected with HCV – 21%
• taking a calcium supplement – 23%

On average, women were in the study for about 18 months.

Results – Baseline

At the start of the study, HIV-positive women had thinner bones than HIV-negative women. Taking into account body mass index (BMI—a relative assessment of fatness that is derived from a formula for a person’s weight and height), HIV-positive women had significantly thinner bones at these places:

• spine
• hip
• forearm

Results – Bone turnover

Bone tissue may feel thick and hard but, at the level of the cell, bones are very dynamic, as small parts of bones are always in the process of being absorbed so that they can be repaired. This process of tearing down and repair is called bone turnover.

In the present study, researchers analysed blood samples, assessing the levels of chemical signals associated with bone turnover. They found an imbalance in chemical signals favouring the absorption of bone in HIV-positive women. This would suggest that HIV-positive women were at increased risk for osteoporosis and osteopenia.

Changes in bone over time

Researchers calculated that HIV-positive women lost about twofold more bone at the spine, hip and forearm than HIV-negative women.

Links to bone loss

Researchers took into account traditional risk factors linked to bone loss and found that factors such as race/ethnicity, age, weight and BMI were not associated with bone loss. However, HIV infection was significantly associated with thinning bones.

Among factors related to HIV, none of the following were linked to bone loss:

• lowest-ever CD4+ count
• CD4+ count at entry to the study
• having a history of AIDS

ART and bone loss

Overall, the use of ART was associated with reduced bone loss at the spine but not the hip or forearm. The reasons for this difference are not clear.

There was no difference in rates of bone loss between women taking ART based on protease inhibitors (28 women) or non-nukes (NNRTIs; 20 women).

The researchers reported that the rate of bone loss at the spine or forearm among the 12 women taking tenofovir-based regimens (tenofovir is sold as Viread and found in Truvada, Atripla, and Complera) was greater than among women who were not taking tenofovir by a factor of between two and four-fold. Even after taking into account factors such as BMI, age, race/ethnicity, CD4+ count, vitamin D levels, parathyroid hormone, phosphorus levels and so on, the rate of bone loss in the spines of tenofovir users was about twofold greater than in women who did not use tenofovir. This difference was statistically significant. However, caution must be used when interpreting this result and we will return to this finding later in our report.

Tenofovir use did not appear to affect the density of the hip bones.

Fractures

Overall, rates of fractures in women were not statistically different between HIV-positive (10%) and HIV-negative (8%) women.

When researchers assessed the severity of fractures, those fractures of moderate or severe intensity were more likely to occur among HIV-positive women (3%) than among HIV-negative women (0%). However, because of the relatively small proportion of fractures, this difference did not achieve statistical significance. Moreover, when researchers estimated the future 10-year risk of fractures among all women in the study, rates were slightly lower among HIV-positive women (5%) than among HIV-negative women (6%).

Findings in perspective

1. Overall, the research team found that postmenopausal HIV-positive women are at risk for what it called “excessive bone loss” at the spine and forearm compared to postmenopausal HIV-negative women.

2. HIV-positive women on ART did not lose as much bone mineral density as HIV-positive women who did not take ART. This suggests that, in general, ART has beneficial effects on bone density.

3. The accelerated loss of bone mineral density in the present study is probably due to the combined effects of lowered estrogen levels and HIV infection. Indeed, the HIV-positive women in this study had significantly less estrogen than the HIV-negative women, even though the HIV-positive women were about three years younger.

4. Most studies of changes in bone mineral density have focused on the spine and hip; the present study extends that to the forearm. That HIV-positive women were losing bone mineral density in the forearm suggests that this part of the body may be at increased risk for fractures.

5. Although the researchers found that use of tenofovir was associated with decreased bone mineral density, this finding must be interpreted cautiously because of the following reasons:

• This was not a randomized clinical trial. Therefore, the interpretation of its findings may be skewed by factors that the researchers did not take into account. For instance, we do not know why doctors prescribe tenofovir for some women but not others.
• The study was not specifically designed to assess the impact of tenofovir on changes in bone mineral density.
• The number of women taking tenofovir was relatively small.

However, the study’s findings with regard to tenofovir are intriguing and suggest that tenofovir should be further studied among postmenopausal HIV-positive women in a clinical trial specifically designed for that purpose. Such a trial should be large and should last for several years.

6. The study was not designed to assess fracture risk, so firm conclusions about this issue cannot be drawn from the data.

Overall, the present study, while groundbreaking for its focus on postmenopausal HIV-positive women, clearly establishes the need for a larger and longer study with this population. Such a study takes on added importance because more women with HIV are aging, and researchers, doctors and women living with HIV need to know more about the intersection of HIV and aging.

— Sean R. Hosein

REFERENCE:

Yin MT, Zhang CA, McMahon DJ, et al. Higher rates of bone loss in postmenopausal HIV-infected women: a longitudinal study. Journal of Clinical Endocrinology and Metabolism. 2012 Feb;97(2):554-62.