Bone Fractures More Likely in HIV-Positive Postmenopausal Minority Women
By Nancy Fowler Larson
Medscape Medical News
January 7, 2010 — HIV-infected postmenopausal minority women are at greater risk for bone fractures because of decreased bone density and higher bone turnover markers, according to a study published online January 6 in the Journal of Clinical Endocrinology Metabolism.
"Low bone mineral density (BMD) is commonly reported in young men and women with [HIV] infection, and fracture rates may be higher," write Michael Yin, MD, MS, from the Columbia University Medical Center, New York City, and colleagues. "Hypothesizing that postmenopausal women might be particularly vulnerable to any adverse effects of HIV infection or [antiretroviral therapy] (ART) on the skeleton, we initiated a longitudinal study to assess the prevalence of osteoporosis/osteopenia, determinants and etiology of low BMD and rates of bone loss in HIV+ postmenopausal Hispanic and African American women, who constitute the majority of new infections in women in the United States."
The now-widespread use of ART has substantially increased the lifespan of HIV-positive patients. The authors predicted that by 2015, more than half of HIV-positive persons in the United States will be older than 50 years, and therefore subject to diseases of aging, including osteoporosis.
In 2002, the researchers launched their longitudinal study of bone health in 92 HIV-positive and 95 HIV-negative postmenopausal (>1 year of amenorrhea and follicle-stimulating hormone [FSH] > 30 mIU/mL; FSH > 20 mIU/mL and estradiol < 30 pg/mL; or age > 55 years, regardless of FSH and estrogen) minority women. The study authors assessed the participants' BMD, fracture prevalence, calciotropic and gonadal hormones, bone turnover markers, and serum levels of inflammatory cytokines (tumor necrosis factor alpha [TNFα], interleukin 6). Dual x-ray absorptiometry was used to measure BMD of the lumbar spine, femoral neck, total hip, and nondominant one third radius, along with body mass index (BMI).
Examining results collected through 2007, the authors found that unadjusted BMD (g/cm2) was 5.9% lower in HIV-positive subjects at the total hip. There was no significant difference at the spine, femoral neck, or radius between the 2 groups. After adjusting for several major BMD predictors, including age, race/ethnicity, and BMI, BMD was 4.5% lower in HIV-positive women at the lumbar spine, and a trend emerged toward a 3% to 4% lower BMD at the radius and total hip.
In HIV-positive women, the prevalence of T scores lower than ?1.0 was higher in 3 sites: the spine (78% vs 64%; P < .05), total hip (45% vs 29; P < .05), and femoral neck (64% vs 46%; P < .05). When adjusted for BMI, Z scores were lower in HIV-positive women in the same locations. HIV-positive participants had much higher serum TNFα, N-telopeptide, and C-telopeptide levels — a finding most notable in women receiving ART. After allowing for age, ethnicity, BMI, and alcohol use, HIV-positive status was independently and negatively associated with spine and hip BMD.
"The lower BMD, higher prevalence of low BMD and higher levels of bone turnover markers detected in HIV+ postmenopausal minority women could place them at high risk for future fractures," the authors write.
The researchers also noted higher bone turnover markers and TNF-α in HIV-positive women receiving ART and posited that multivariate modeling may mediate HIV's effect on BMD.
The authors stated several limitations to their study:
The control group's excellent health may have contributed to the greater BMD differences between HIV-positive and HIV-negative women because healthier women naturally have a higher BMD.
The HIV-positive women were significantly younger (56 ± 1 vs 60 ± 1 years; P < .01), which may have resulted in a different bias of higher BMD in the HIV-positive group.
The small sample size prohibited detailed analysis of specific ART regimens.
The study did not incorporate measurement of visceral adipose tissue through computed tomography scans.
Reasons for bone loss in HIV-positive women remain unclear, although it may be related to increased levels of proresorptive cytokines. By continuing to follow up the study subjects, researchers hope to further comprehend the relationships among HIV status, ART, and bone health.
"Completion of the ongoing longitudinal study should permit assessment of whether increased bone turnover associated with ART translates into accelerated bone loss and increased fracture rates in aging postmenopausal women," the authors write.
The National Institutes of Health supported the study. The study authors have disclosed no relevant financial relationships.
J Clin Endocrinol Metab. Published online January 6, 2010.