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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

Jacobson, Denise L PhD, MPH*; Spiegelman, Donna DSc*†; Knox, Tamsin K MD; Wilson, Ira B MD, MSc§

JAIDS Journal of Acquired Immune Deficiency Syndromes: November 2008 - Volume 49 - Issue 3 - p 298-308
doi: 10.1097/QAI.0b013e3181893e8e
Epidemiology and Social Science

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

From the Departments of *Biostatistics; and †Epidemiology, Harvard School of Public Health, Boston, MA; ‡Department of Public Health and Family Medicine, Tufts University School of Medicine, Boston, MA; and §Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts Medical Center, Boston, MA.

Received for publication October 22, 2007; accepted August 5, 2008.

Supported by National Institute of Diabetes and Digestive and Kidney Diseases (P01DK45734); General Clinical Research Center funded by the National Center for Research Resources (M01RR00054); Lifespan/Tufts/Brown Center for AIDS Research (P30A142853); National Institute of Allergy and Infectious Diseases (1K24 A1055293); National Institute of Drug Abuse (1P30DA13868); National Heart, Lung, and Blood Institute of the National Institute of Health (R01HL65947); and National Centers for Research Resources (K24 RR020300).

Presented as an abstract at the 12th Conference on Retroviruses and Opportunistic Infections, February 2005, Boston, MA.

All authors on this article had full access to all the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.

Correspondence to: Denise L. Jacobson, PhD, MPH, Department of Biostatistics, Center for Biostatistics and AIDS Research, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115 (e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.