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Title: Background


1
Factors Associated with Low Bone Mineral Density
(BMD) in a Large Cohort of HIV-Infected U.S.
Adults Baseline Results from the SUN Study
836
ET Overton1, K Mondy1, TJ Bush2, LJ Conley2, EM
Kojic3, K Henry4, J Hammer5, KC Wood6, KA
Lichtenstein7, JT Brooks2, and SUN Study
Investigators
1. Division of Infectious Diseases, Washington
University School of Medicine, St. Louis, MO. 2.
Division of HIV/AIDS Prevention, National Centers
for HIV, Hepatitis, STD and TB Prevention,
Centers for Disease Control and Prevention. 3.
Miriam Hospital, Providence, RI. 4. HIV Program,
Hennepin County Medical Center and the U of MN,
Minneapolis, MN. 5. Denver Infectious Disease
Consultants, Rose Medical Center, Denver, CO. 6.
Cerner Corporation, Vienna, VA. 7. University of
Colorado Health Sciences Center, Denver, CO, USA.
Comparison of Femoral Neck T-scores Among SUN
Study Participants and Matched Controls
Distribution of Low Bone Mineral Density In SUN
Study Participants
Distribution of Low Bone Mineral Density In SUN
Study Participants
Abstract (updated)
Results
Background Low Bone Mineral Density (BMD) is a
common metabolic complication associated with HIV
infection. With increasing survival in the era of
HAART, there is continued interest in the factors
influencing low BMD in HIV-infected
individuals. Methods The SUN Study prospectively
follows a cohort of HIV-infected patients at 7
U.S. clinics. At baseline, DEXA bone densitometry
and body composition, clinical data and fasting
laboratory values were obtained on all subjects.
Results were compared to persons from the NHANES
matched for age, race, gender and BMI. Results
Data were available for 625 matched pairs.
Participants had a mean age of 41.0 years, 22
were female, and 28 were African American. Among
SUN subjects, 78 were currently on HAART and 58
had an undetectable HIV viral load. Osteopenia
(T-score -1.0 to -2.5) and osteoporosis (T-score
-2.5) were identified in 323 (52) and 61 (10)
subjects, respectively. In univariate analyses,
low BMD (T-score -1.0) was associated with
older age, male gender, unemployment, lower body
mass index (BMI), higher visceral to subcutaneous
fat ratio, duration since HIV diagnosis and any
stavudine use (all plt0.01). Osteoporosis alone
was associated with older age, non-white race,
lower BMI, current tobacco use, unemployment,
lower nadir CD4 cell count and longer duration
since HIV diagnosis (all plt0.05). In multivariate
analyses, low BMD was associated with older age,
male gender, lower BMI, unemployment and no
resistance training osteoporosis was associated
with older age, lower BMI, longer duration since
HIV diagnosis, and lower nadir CD4 cell count
(all lt0.05). When compared to the NHANES cohort,
the SUN Study cohort had significantly lower mean
T-scores at the femoral neck (-0.77 vs. -0.36,
plt0.01). At this site, the prevalence of low BMD
was higher in the SUN Study cohort (52 vs. 29,
plt0.01). Conclusions In the HAART era, low BMD
remains a significant complication of HIV
infection, more prevalent than found in the
general population. In this large cohort of
HIV-infected persons, the majority of whom are
virologically controlled, the ramifications of
low BMD will become an issue of concern as they
age. HIV- and antiretroviral-related factors that
may affect BMD loss warrant longitudinal study.
  • 625 HIV-infected subjects were matched to the
    NHANES cohort.
  • Mean age 41.0 years.
  • 135 women and 490 men.
  • 378 Caucasians,173 African-American, 61
    Hispanics.
  • Mean BMI 26.4 kg/m2.
  • 466 subjects (75) were on HAART.
  • 74 subjects (12) were ART naïve.

Low Bone Mineral Density
SUN study participants Mean -0.77
Matched NHANES subjects Mean -0.36
Osteopenia (51.7)
Osteoporosis (9.8)
Proportion
Univariate Analysis among the HIV-infected
Subjects
plt0.001
T-score
Background and Methods
  • Mean T-scores were significantly lower in
    HIV-infected subjects.
  • T scores (-0.77 vs. -0.36).
  • At the femoral neck
  • Osteopenia was present in 51.7 of HIV-infected
    subjects and 29.1 of the NHANES cohort.
  • Osteoporosis was present in 9.8 of HIV-infected
    subjects and 1.0 of the NHANES cohort.

Normal (38.6)
  • Background
  • Osteoporosis is characterized by low bone mass
    leading to increased bone fragility and increase
    in fracture risk, particularly the vertebrae,
    hip, and wrist bones. Well characterized risk
    factors include race and gender (white and Asian
    women), early menopause, sedentary lifestyle,
    estrogen deficiency, family history of
    osteoporosis, heavy alcohol and caffeine intake,
    poor calcium intake, smoking, hyperthyroidism,
    renal failure, and corticosteroid use. In the
    general population, osteoporosis primarily
    affects postmenopausal white women.
  • In the HAART era, low bone mineral density,
    including osteopenia and osteoporosis, has been
    identified as a common problem among chronically
    HIV-infected persons. Several studies have
    examined the relationship between bone mineral
    density and HIV. These studies have identified
    certain risk factors for low BMD including
    duration of HIV infection, history of weight
    loss, low BMI, smoking, and steroid use. The SUN
    study provides the opportunity to evaluate the
    association between HIV and low BMD among a large
    cohort of HIV-infected subjects in the current
    HAART era.
  • Objectives
  • To determine the baseline prevalence of low BMD
    (osteopenia and osteoporosis) in the SUN Study
    cohort.
  • To describe factors related to low BMD in this
    cohort.
  • To compare prevalence of low BMD in the SUN
    cohort with a healthy cohort from the NHANES
    matched for age, gender, race, and BMI.
  • Methods
  • HIV-infected Cohort The Study to Understand the
    Natural History of HIV/AIDS in the Era of
    Effective Therapy (SUN Study) is a 5-year
    prospective cohort study designed to examine risk
    factors for complications of treating HIV and
    longer survival. There are 682 HIV-infected
    adults enrolled from 7 clinic in 4 U.S. cities.
    At enrollment, all subjects were 18 years of age
    or older. Subjects were either ARV-naïve with a
    CD4 cell count between 100 and 500 c/mm3 or HAART
    experienced with a CD4 cell count gt100 c/mm3.
  • Data Collection Sources of data included patient
    interview and laboratory data obtained at
    baseline study visit as well as abstraction of
    data from outpatient medical records. At
    baseline, all subjects receive a dual X-ray
    absorptiometry (DEXA) scan to determine bone
    mineral density. DEXA data were read at a single
    site (Tufts University).
  • HIV-uninfected Cohort SUN Study subjects were
    matched for age, race, gender, and BMI to healthy
    persons from the National Health and Nutrition
    Examination Study III cohort. From DEXA scan
    results from the NHANES dataset, T scores from
    the femoral neck were available for comparison
    with the SUN Study cohort.
  • Definitions We used definitions of osteopenia
    and osteoporosis developed by the World Health
    Organization based on the standard deviation (SD)
    between an individuals' BMD and the mean BMD at
    the time of peak bone mass among 30 year olds,
    adjusted for gender and race. Osteopenia is
    defined as a T score between -1 and -2.5 SDs
    below the mean. Osteoporosis is defined as a T
    score of less than -2.5 SDs below the mean. Low
    BMD includes all persons classified as having
    osteopenia or osteoporosis.
  • Statistics Chi-square or Fishers exact tests
    used for categorical variables. Continuous
    variables compared using the Students t-test or
    Mann-Whitney U test, for normally and
    non-normally distributed data, respectively.
    Multivariate logistic regression to identify
    independent predictors of low BMD and
    osteoporosis from among factors significant in
    univariate analyses. All p values were
    two-tailed. SAS software was used for analysis.

Multivariate Analysis of Factors associated with
Low Bone Mineral Density
Conclusions
  • There is a high prevalence of osteopenia and
    osteoporosis in the SUN cohort.
  • These prevalence rates are much higher than
    those in a matched healthy cohort.
  • Longer duration of time since HIV diagnosis and
    lower baseline CD4 cell counts in combination
    with older age and lower BMI may serve as useful
    markers for aggressive evaluation of BMD with
    DEXA scanning.
  • The SUN study will provide longitudinal data to
    determine the evolution of BMD in HIV-infected
    subjects and the role of ART and to evaluate the
    development of fragility fractures.
  • Acknowledgements We wish to gratefully
    acknowledge all SUN study investigators and their
    support staff, Cerner Corporation, and all of the
    study participants who have devoted their time
    and effort to this research endeavor.

Multivariate Analysis of Factors associated with
Osteoporosis
Continuous variables were categorized into
quartiles. For the BMI and CD4 cell count
variables, these values reflect the lowest
quartile. For the age and time since diagnosis
variables, these values reflect the highest
quartile
Visceral to subcutaneous fat ratio. Men only.
Women only.
The findings and conclusions in this poster
presentation are those of the authors and do
not necessarily represent the views
of the Centers for Disease Control and Prevention.
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