Bone loss following onset of menopause may put HIV-positive women at risk for fractures

Kelly Safreed-Harmon
Published: 18 January 2010

Post-menopausal HIV-positive women may be at high risk for fractures because of low bone mineral density (BMD), according to a study appearing in The Journal of Clinical Endocrinology and Metabolism.

The article reports on significant differences observed by US researchers comparing HIV-positive post-menopausal Hispanic and African-American women to otherwise similar HIV-negative women.

The HIV-positive cohort had lower BMD than the HIV-negative cohort, and also appeared to be experiencing a faster rate of metabolic change in bone tissue.

With a growing population of HIV-positive people in their fifties and older, there is an increasingly important need to understand the interplay between HIV and ageing-related diseases.

Women and men both lose bone mineral density as they age, but women are at greater risk for osteoporosis (severe bone thinning). One reason for this is the decline in production of the hormone oestrogen after women enter menopause. High oestrogen levels earlier in life have a protective effect on the bones.

The recent US study enrolled 108 HIV-negative and 110 HIV-positive post-menopausal women over age 40, all either Hispanic or African-American. The women were patients at two New York medical centres. Approximately four-fifths of the HIV-positive women were taking antiretroviral therapy, including 28% on non-nucleoside reverse transcriptase inhibitor-based regimens and 39% on protease inhibitor-based regimens.

After adjusting for age, race/ethnicity and body mass index (BMI), researchers found that HIV-positive women had 4.5% lower lumbar spine (LS) BMD than HIV-negative women (p = 0.04). There were also non-significant trends toward lower total hip (TH) and non-dominant one-third radius (DR) BMD.

More HIV-positive women than HIV-negative women had T-scores under -1.0 (78% vs 64% at the LS; 45% vs 29% at the TH; and 64% vs 46% at the femoral neck [FN], all p < 0.05). After adjusting for BMI, HIV-positive women had significantly lower Z-scores at the LS, TH and FN as well.

T-scores are a widely used measure of how much someone’s bone density varies from the bone density found in young healthy people, with the difference described in units of standard deviation from the mean. Z-scores are based on bone density comparisons with people of the same age, sex and weight.

The BMD, T-scores and Z-scores of HIV-positive women taking antiretroviral therapy were comparable to those of HIV-positive women who were not on antiretrovirals.

Bone tissue is being broken down and replaced on an ongoing basis, and bone thinning occurs when tissue loss outpaces tissue formation. The metabolic process of renewing bone tissue can be charted with biomarkers known as bone turnover markers (BTMs).

When researchers compared a number of BTMs in the two study cohorts, they found that some BTMs differed significantly in accordance with HIV status. HIV-positive women had higher levels of N-telopeptides and C-telopeptides, two byproducts of bone breakdown, than HIV-negative women.

HIV-positive women also had significantly higher levels of serum TNFα, a protein that affects bone metabolism.

After controlling for age, BMI, race and alcohol use, researchers found HIV status to be an independent predictor of BMD at the LS and TH.

Additional analyses suggested that more rapid bone turnover and higher levels of TNFα and interleukin-6 may be mediating factors in HIV-related bone thinning.

BMD was not found to correlate with CD4 count, HIV-1 plasma RNA levels, AIDS criteria, length of time on antiretroviral therapy or class of antiretroviral therapy.

Other people have proposed that the generally lower body weight of HIV-positive people may largely account for their lower BMD levels. The study’s authors question that notion because of their observation about BMD remaining low after adjusting for BMI.

“Importantly, low body weight is a powerful risk factor for osteoporotic fracture,” they comment. “Thus, the fact that BMD is lower in HIV-positive individuals is of clinical relevance, whether or not the mechanism by which it is lower is attributable directly to HIV or mediated indirectly by effects of HIV on weight or other parameters.”

Other studies have found low BMD in HIV-positive people, but most of those studies focused on younger cohorts. It is plausible that both HIV infection and antiretroviral treatment may have detrimental effects on bone health. The authors note that BMD typically declines within the first two years of antiretroviral initiation, then levels off.

Reference

Yin MT et al. Low bone mass and high bone turnover in postmenopausal HIV-infected women. J Clin Endocrinol Metab (advance online publication, January 2010) doi:10.1210/jc.2009-0708.