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Relationships Between Inflammation, Immune Activation, and Bone Health Among HIV-Infected Adults on Stable Antiretroviral Therapy

Erlandson, Kristine M. MD*; O'Riordan, MaryAnn PhD; Labbato, Danielle RN; McComsey, Grace A. MD†,‡

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 March 2014 - Volume 65 - Issue 3 - p 290–298
doi: 10.1097/QAI.0000000000000005
Clinical Science

Background: The aim was to determine the association between bone health and inflammation, T-cell activation, and monocyte activation among HIV-infected persons on stable antiretroviral therapy.

Methods: We performed a cross-sectional analysis of all the subjects enrolling in the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV trial with available skeletal assessments by dual-energy x-ray absorptiometry, inflammation, and immune activation markers. Analyses used were Wilcoxon rank-sum tests, Spearman correlation coefficients, and linear regression.

Results: One hundred forty-two subjects were included: 78% men, 69% African American, median age 46.3 years, CD4+ count 604 cells per microliter, and 77% with undetectable HIV-1 RNA. Twenty-three percent had osteopenia/osteoporosis at the hip, and 21% had this at the lumbar spine. Soluble vascular cell adhesion molecule-1 was correlated with hip (r = −0.22) and spine (r = −0.23) bone mineral density (BMD), and bone turnover markers (r = 0.20–0.33; all P < 0.05). No significant correlations were observed between the BMD and T-cell activation (%CD38HLA-DR on CD4+ or CD8+ T cells), monocyte activation (CD14CD16, sCD14, and sCD163), or inflammatory markers [interleukin (IL)-6, tumor necrosis factor-α, highly sensitive C-reactive protein, D-dimer, receptor activator of NF-kB ligand, osteoprotegerin, soluble tumor necrosis factor-RI and II]. In regression models including traditional bone risk factors, hip BMD was associated with age, race, and body mass index; spine BMD was associated with race, family history of hip fracture, trunk fat, tenofovir, and HIV RNA; bone resorption (c-terminal collagen crosslinks) was associated with intracellular adhesion molecule-1 and trunk fat; bone formation (P1NP) was associated with soluble vascular cell adhesion molecule-1, trunk and limb fat (P ≤ 0.05).

Conclusions: Future studies should evaluate the longitudinal association of the adhesion molecules to further elucidate potential contributory mechanisms of bone loss among HIV-infected persons on stable antiretroviral therapy.

*Department of Medicine, University of Colorado—Anschutz Medical Campus, Aurora, CO; and the Departments of

Medicine and

Pediatrics, Case Western Reserve University, Cleveland, OH.

Correspondence to: Grace A. McComsey, MD, Case School of Medicine, 11100 Euclid Ave, Cleveland, OH 44106 (e-mail:

Supported by the National Institutes of Health (NR012642 to G.A.M. and AG040594 to K.M.E.) and BMS.

G.A.M. has served as a scientific advisor or speaker for Bristol-Myers Squibb, Tibotec, Gilead, and Merck, has received research grants from Bristol-Myers Squibb, GlaxoSmithKline, and Gilead Sciences, and is currently serving as the DSMB Chair for a Pfizer-sponsored study.

Clinical Trials Registration: NCT01218802.

Received September 06, 2013

Accepted September 09, 2013

© 2014 by Lippincott Williams & Wilkins