Body composition, soluble markers of inflammation, and bone mineral density in antiretroviral therapy-naive HIV-1-infected individuals

Abstract

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.

Conflict of interest statement

Conflicts of Interest

Dr Brown has served as a consultant for BMS, GSK, Merck, Abbott, Gilead, ViiV Healthcare and has received research funding from Merck and GSK. Dr. Currier has served as a consultant for Gilead and has received research funding from Merck. Dr. Murphy has served as a consultant for Gilead and serves on a Data Safety Monitoring Board for Gilead. Dr Stein serves on a Data Safety Monitoring Board for Abbott, Lilly, and Takeda. Dr McComsey has served as a consultant or received research grants from BMS, Pfizer, and GSK. Dr Ribaudo and Ms Chen and Rothenberg have no Duality of Interest disclosures.

Figures

Figure 1

Distribution of Z-scores at Hip, Femoral Neck, and Lumbar Spine in ART-naïve persons compared to the expected distribution of Z-scores. Pair-wise Correlation of Z-scores at the 3 BMD sites.

Figure 2

Multivariable Linear Regression Models for Bone Mineral Density Z-scores

Figure 2

Multivariable Linear Regression Models for Bone Mineral Density Z-scores