Body Composition, Soluble Markers of Inflammation, and Bone Mineral Density in Antiretroviral TherapyNaive HIV-1Infected Individuals

Brown, Todd T. MD, PhD*; Chen, Yun MSc; Currier, Judith S. MD, MSc; Ribaudo, Heather J. PhD; Rothenberg, Jennifer MS§; Dubé, Michael P. MD; Murphy, Robert MD; Stein, James H. MD, FACC#; McComsey, Grace A. MD**

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 July 2013 - Volume 63 - Issue 3 - p 323–330
doi: 10.1097/QAI.0b013e318295eb1d
Clinical Science

Objective: To determine the association among bone mineral density (BMD), inflammatory markers, and alterations in fat and lean mass in untreated HIV-infected individuals.

Design: Cross-sectional analysis of antiretroviral therapy–naive persons enrolled into a randomized clinical trial.

Methods: Dual-energy x-ray absorptiometry for BMD and lean and fat mass and a laboratory assessment were performed. Soluble biomarkers included adipocytokines (leptin and adiponectin), inflammatory markers (high-sensitivity C-reactive protein and interleukin 6), and markers related to bone metabolism [osteoprotegerin (OPG)], receptor activator of nuclear factor κB ligand. BMD at the lumbar spine, total hip, and femoral neck was expressed as a Z score (number of standard deviations away from age-, race-, and sex-matched reference population).

Results: Three hundred thirty-one subjects had a median (Q1, Q3) age of 36 (28, 45) years, were 89% men, and 44% white. The prevalence of low BMD (Z score ≤ −2 at any of the 3 sites) was 10%. No associations were detected between Z scores and high-sensitivity C-reactive protein, interleukin 6, or receptor activator of nuclear factor κB ligand (P ≥ 0.1). In a linear model adjusting for age, gender, race, and total fat mass, lower lumbar spine Z scores were associated with lower total lean mass, higher serum adiponectin, and lower OPG. Results at the total hip or femoral neck were similar.

Conclusions: Among antiretroviral therapy–naive HIV-infected individuals, lower BMD was associated with lower lean mass, higher adiponectin, and lower OPG, but not HIV disease variables or any of the inflammatory markers. These findings may have implications for bone metabolism in untreated HIV, in which hypoadiponectinemia and higher OPG may mitigate bone loss.

*Department of Medicine, Johns Hopkins University, Baltimore, MD;

Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA;

Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA;

§Social & Scientific Systems, Inc., Silver Spring, MD;

Department of Medicine, Keck School of Medicine at the University of Southern California, Los Angeles, CA;

Department of Medicine, Northwestern University, Chicago, IL;

#Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI; and

**Department of Pediatrics, School of Medicine, Case Western Reserve University, Cleveland, OH.

Correspondence to: Todd T. Brown, MD, PhD, 1830 East Monument Street, Suite 333, Baltimore, MD 21287 (e-mail: tbrown27@jhmi.edu).

Supported by NIH grants (HL095132, HL095126, AI068636, AI068634, AI69471, and AI56933). Study drug and additional support were provided by Gilead, BMS, Jansen, and Merck.

T. T. B. has served as a consultant for BMS, GSK, Merck, Abbott, Gilead, and ViiV Healthcare and has received research funding from Merck and GSK. J. S. C. has served as a consultant for Gilead and has received research funding from Merck. R. M. has served as a consultant for Gilead and serves on a Data Safety Monitoring Board for Gilead. J. H. S. serves on a Data Safety Monitoring Board for Abbott, Lilly, and Takeda. G. A. M. has served as a consultant or received research grants from BMS, Pfizer, and GSK. H. J. R. and Y. C. and J. R. have no Duality of Interest disclosures.

Received December 03, 2012

Accepted March 26, 2013

© 2013 Lippincott Williams & Wilkins, Inc.