Bone Loss in Pre- and Post-menopausal Women with HIV

		SUMMARY: Women with HIV are at risk for bone loss, especially after menopause, according to 2 recently published studies. Pre-menopausal HIV positive women had lower bone mineral density than HIV negative women, but experienced a similar modest rate of decline over 2.5 years. Post-menopausal HIV positive women, however, had lower bone mineral density, a higher rate of osteopenia, and higher levels of biomarkers of bone turnover, indicating that they could be a greater risk for fractures.

By Liz Highleyman

Pre-menopause

In the first study, described in the February 2010 Journal of Acquired Immune Deficiency Syndromes, Michael Yin from Columbia University Medical Center and colleagues used dual energy x-ray absorptiometry (DEXA) to compared bone mineral density (BMD) in younger women with and without HIV.

The analysis included 100 HIV positive and 68 at-risk HIV negative pre-menopausal women in the Women's Interagency HIV Study (WIHS). As a group, HIV positive women were slightly older on average than the HIV negative women (40 vs 36 years) and more likely to be coinfected with hepatitis C (31% vs 12%).

About 60% were taking antiretroviral therapy (ART), including 22% on protease inhibitor-based regimens, 25% on NNRTI-based regimens, and 6% on nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) only. In addition, 15% were treatment-naive and 26% had used ART in the past but were currently off treatment.

The researchers measured BMD at the lumbar spine (lower back) and femoral neck (the narrow section of the thigh bone below the ball joint of the hip) at an initial visit and again at a follow-up visit after a median 2.5 years.

Results

	At the index visit, HIV positive women had BMD within the normal range, but approximately 5% lower than HIV negative women at the lumbar spine and femoral neck.
	Over the duration of follow-up, HIV positive women experienced small but significant decreases in BMD at the lumbar spine and femoral neck (-1.9% at both sites).
	However, annual percentage decreases in BMD did not differ significantly between HIV positive and HIV negative women at the lumbar spine (-0.8% vs -0.4%, respectively) or femoral neck (-0.8% vs -0.6%).
	Mean T scores (a standardized measure of bone density) were within the normal range (> -1.0) in both groups, but significantly lower among HIV positive women.
	Z scores (another standardized measure) were also in the normal range for age (> -2.0) in both groups, with a trend toward being lower in HIV positive women.
	Changes remained similar after adjusting for age, body weight, and BMD at the index visit.
	9% of HIV positive women showed osteoporosis at the lumbar spine, but none at the femoral neck; HIV negative women had no osteoporosis at either site.
	Similar proportions of HIV positive and HIV negative women experienced rapid bone loss, defined as more than a 3% decrease in BMD per year (14% vs 10% at the lumbar spine; 10% vs 6% at the femoral neck).
	Among HIV positive women, low BMD was significantly associated with lower body weight and heavier alcohol use.
	In a multivariate analysis controlling for other factors, bone loss was significantly associated with vitamin D deficiency and opiate/opioid drug use.
	However, there was no significant association with current CD4 cell count, CD4 nadir (lowest-ever level), AIDS diagnosis, overall exposure to ART, class of antiretroviral drugs used, or exposure to tenofovir (Viread, also in the Truvada an Atripla combination pills).
	Mean parathyroid hormone (PTH) and vitamin D levels were similar in HIV positive and HIV negative women; in both groups, however, vitamin D levels were well below the optimal level for bone health (32 ng/mL).
	The incidence of self-reported fractures was 0.74 per 100 person-years among HIV positive women (3 fractures), similar to the rate of 1.03 per 100 person-years (2 fractures) among HIV negative women.

"In pre-menopausal HIV positive women, index BMD was lower than comparable HIV negative women," the study authors summarized. "[H]owever, rates of bone loss at the lumbar spine and femoral neck were similar over 2.5 years of observation, irrespective of antiretroviral therapy."

"Our data suggest that in contrast to advanced untreated HIV infection or initiation of ART, cytokine levels and bone turnover markers are not elevated in ART-experienced pre-menopausal women, and rates of bone loss are modest in such women," they elaborated in their discussion.

The researchers noted that limitations of the study include lack of hormone level measurements, body composition analysis, or nutritional assessment. In addition, the small sample size of the longitudinal analysis did not permit inferences about the effects of specific antiretroviral drugs on BMD.

"Our results provide some reassurance that short-term bone loss is modest in the majority of pre-menopausal, weight stable HIV positive women," they concluded. "However, a cumulative annual 1% decrease in young women, given the expected acceleration during the menopausal transition, may predispose these women to premature fragility fractures as they age."

Columbia University Medical Center, New York, NY; Data Solutions LLC, Bronx, NY; University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, CA; Stroger (formerly Cook County) Hospital and Rush University, Chicago, IL; New York Medical College, Valhalla, NY; Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Montefiore Medical Center, Bronx, NY.

Post-menopause

In the second study, reported in the December 4, 2009 advance online edition of the Journal of Clinical Endocrinology & Metabolism (Abstract), Yin and a different team of colleagues looked at bone mineral density and bone turnover among older, post-menopausal women with HIV.

This prospective cohort study included 92 HIV positive and 95 HIV negative post-menopausal Hispanic and African-American women. The investigators assessed BMD by DEXA, fracture prevalence, serum levels of inflammatory cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 6 [IL-6]), bone turnover markers (N-telopeptide and C-telopeptide), calciotropic (calcium affecting) hormones, and estrone.

As a group, the HIV positive women were significantly younger (56 vs 60 years) and had lower body mass index (28 vs 30). About 80% of the HIV positive women were on ART, including 39% taking protease inhibitor-based regimens and 28% taking NNRTI-based regimens.

Results

	HIV positive women had 4.5% lower BMD at the lumbar spine compared with HIV negative women.
	HIV positive women were significantly more likely than HIV negative women to have T scores < -1.0 at the lumbar spine (78% vs 64%), total hip (45% vs 29%), and femoral neck (64% vs 46%).
	Z scores adjusted for BMI were lower among HIV positive women at all 3 sites.
	Serum TNF-alpha, N-telopeptide, and C-telopeptide levels were significantly higher in HIV positive women, particularly those receiving ART, compared with HIV negative women.
	HIV status was independently and negatively associated with lumbar spine and total hip BMD after adjusting for age, race/ethnicity, body mass index, and alcohol use.
	Again, BMD was not significantly associated with CD4 count, HIV viral load, AIDS diagnosis, duration of ART, or class of antiretroviral drugs.
	HIV positive and HIV negative women had similar frequency of fractures at the spine, hip, and forearm; however, HIV positive women reported significantly more fractures at other sites including ribs, ankles, shoulders, and pelvis.

"The lower BMD, higher prevalence of low BMD, and higher levels of bone turnover markers detected in HIV positive post-menopausal minority women could place them at high risk for future fractures," they study authors concluded.

The researchers suggested that differences in BMD might be due to the fact that HIV positive women have higher bone turnover and higher levels of inflammatory cytokines.

"Importantly, low body weight is a powerful risk factor for osteoporotic fracture," they elaborated in their discussion. "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."

Columbia University Medical Center, New York, NY; Bronx-Lebanon Hospital Center, Bronx, NY; Weill Cornell Medical College, New York, NY.

2/2/10

References

MT Yin, D Lu, S Cremers, and others. Short-Term Bone Loss in HIV-Infected Premenopausal Women. Journal of Acquired Immune Deficiency Syndromes
53(2): 202-208 (Abstract). February 2010.

MT Yin, DJ McMahon, DC Ferris, and others. Low Bone Mass and High Bone Turnover in Postmenopausal Human Immunodeficiency Virus-Infected Women. Journal of Clinical Endocrinology & Metabolism (Abstract). December 4, 2009 (Epub ahead of print).

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