Evolution and Predictors of Change in Total Bone Mineral Density Over Time in HIV-Infected Men and Women in the Nutrition for Healthy Living Study

Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 11/2008; 49(3):298-308. DOI: 10.1097/QAI.0b013e3181893e8e
Source: PubMed


Osteopenia is common in the era of effective antiretroviral therapy (ART), yet the etiology is unclear. We evaluated the association of host factors, disease severity, and ART to changes in total body bone mineral density (total BMD) over time in HIV-infected men (n = 283) and women (n = 96).
Total BMD was measured annually by whole-body dual-energy absorptiometry (DXA), and medical, dietary, and behavioral history was collected. The median time from first to last DXA was 2.5 years (range 0.9-6.8 years). Using a repeated measures regression model, we identified variables independently associated with percent change in total BMD between consecutive DXA exams (n = 799 intervals), adjusted for age, race, sex, menopause, and smoking. We estimated percent change in total BMD over an average interval (1 year) standardized for representative levels of each determinant in males, premenopausal women, and postmenopausal women.
Median baseline age, CD4, and viral load were 42 years, 364 cells per cubic millimeter, and 2.7 log10 copies per milliliter, respectively. The estimated change in total BMD for those not on ART was -0.37% per year [95% confidence interval (CI) -0.76 to -0.02] for men, -0.08% per year (95% CI -0.49 to 0.33) for premenopausal women, and -1.07% per year (95% CI -1.86 to -0.28) for postmenopausal women. Greater loss of total BMD was associated with lower albumin, lower body mass index, prednisone/hydrocortisone use, tenofovir use, and longer duration of didanosine. Strength training and long duration of d4T and saquinavir prevented or mitigated bone loss. For those on ART for 3 years (not including the above agents), the rate of loss was -0.57% per year (95% CI -1.00 to -0.14) for men, -0.28% (95% CI -0.71 to 0.15) for premenopausal women, and -1.27% (95% CI -2.07 to -0.47) for postmenopausal women. Postmenopausal women had greater loss than premenopausal women and men.
Low body weight, low albumin, catabolic steroid use, and menopause may accelerate bone loss, and strength training may be protective. Tenofovir and didanosine may also have a deleterious effect on BMD.

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    • "We did not find evidence that the extent of immune reconstitution, as measured by CD4 + count increase at 16 weeks, was associated with BMD change after controlling for baseline CD4 + count. There are conflicting reports in the literature on the relationship between baseline CD4 + count and the risk for BMD loss on ART [17, 18]. Our study benefits from the large number of included subjects and the comprehensive data that were gathered on subjects in the setting of clinical trials. "
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    ABSTRACT: Background: Bone mineral density (BMD) decreases 2%-6% in the 2 years after antiretroviral therapy (ART) initiation. Pre-ART immune deficiency and early immune recovery may contribute to this loss. Methods: We pooled data from 3 studies of ART initiation in treatment-naive patients in which serial whole-body dual-energy X-ray absorptiometry scans were performed. We used linear regression to evaluate effects of baseline CD4(+) and 16-week CD4(+) change (both absolute and relative) on 96-week total BMD change from baseline. We performed multivariable linear regression to assess associations between baseline variables of age, sex, race/ethnicity, body mass index (BMI), hepatitis C status, parent study, human immunodeficiency virus type 1 (HIV-1) RNA level, and assignment to a protease inhibitor (PI)- or tenofovir-containing regimen on 96-week total BMD change. Results: The included 796 subjects had mean 96-week total BMD loss of 2.0%. In multivariable analysis, baseline CD4(+) cell count was significantly associated with 96-week BMD loss; individuals with baseline CD4(+) <50 cells/µL lost significantly more BMD compared to those with CD4(+) ≥500 cells/µL. A greater relative, but not absolute, 16-week increase in CD4(+) count was significantly associated with greater declines in BMD, but not after controlling for baseline CD4(+) count. In multivariable analysis, older age, female sex, lower BMI, higher HIV-1 RNA levels, and PI and tenofovir assignment were also associated with greater BMD decline. Conclusions: Low pretreatment CD4(+) count, but not greater CD4(+) count increase, is a strong and independent risk factor for bone loss after ART initiation. ART initiation at higher CD4(+) counts may reduce the burden of osteoporosis and fragility fractures.
    Preview · Article · Aug 2013 · Clinical Infectious Diseases
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    • "In this way, it is quite possible that strength training reduces bone loss in HIV-infected patients, the same as happens in non HIV infected people. As a matter of fact, maintaining adequate weight and engaging in physical activity has been reported as a strategy that may help to preserve and perhaps improve bone mass density in HIVinfected patients[55]. In this way, thirty minutes of exercise (including jogging or walking) at least 3 days a week has been recently recommended[56]as a useful measure to prevent osteoporosis in HIV people. "

    Full-text · Article · Jan 2012 · Journal of AIDS & Clinical Research
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    • "HIV-infected individuals have an increased risk of osteopenia compared to HIV-uninfected people. This risk is increased further by the use of TDF [Jacobson et al., 2008]. It is not yet clear whether patients receiving TDF also have an increased bone-fracture risk. "

    Full-text · Chapter · Oct 2011
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