About AVT
Browse Articles
Authors
Customer Services

Original article

Bone turnover, osteoprotegerin/RANKL and inflammation with antiretroviral initiation: tenofovir versus non-tenofovir regimens

Todd T Brown, Allison C Ross, Norma Storer, Danielle Labbato, Grace A McComsey

Corresponding author name: Todd T Brown
Corresponding author e-mail: tbrown27@jhmi.edu

Citation: Antiviral Therapy 2011; 16:1063-1072
doi: 10.3851/IMP1874

Date accepted: 21 February 2011
Date published online: 02 August 2011

Abstract

Background: Bone mineral density decreases with antiretroviral therapy (ART) initiation, although the pathogenesis, including the role of tenofovir (TDF), is unclear. This study assessed changes in bone-turnover markers, osteoprotegerin (OPG), soluble receptor activator for nuclear factor-κβ ligand (sRANKL), and inflammation in subjects initiating TDF- versus non-TDF-containing regimens, and determined the relationship between bone turnover, OPG/sRANKL and inflammation.

Methods: This was a longitudinal observational study comparing levels of bone turnover markers (C-terminal telopeptide of type I collagen [CTX] and osteocalcin [OC]), OPG, sRANKL and inflammatory cytokines (soluble tumour necrosis factor [TNF]-α receptor [sTNFR]-I, sTNFR-II and interleukin-6) prior to ART and 6–12 months after ART initiation with a TDF- versus non-TDF-containing regimen in HIV-infected subjects 18–50 years old.

Results: A total of 87 subjects were enrolled (TDF n=44 and non-TDF n=43). Groups were similar except subjects on TDF had a lower CD4+ T-cell nadir (P<0.01) and were more likely to receive a protease inhibitor (PI; P=0.03). At pre-ART, 35% and 1% of subjects had CTX and OC above the normal range, respectively. Both increased with ART initiation, whereas OPG, sRANKL and inflammatory markers significantly decreased. In multivariate models, increases in OC were associated with TDF use, PI use and pre-ART levels of sTNFR-I, whereas increases in CTX were associated with CD4+ T-cell nadir <50 cell/mm3. Increases in bone markers were unrelated to pre-ART levels of OPG/sRANKL and changes in OPG/sRANKL after ART initiation.

Conclusions: TDF use, PI use, TNF-α activity and advanced HIV disease are associated with changes in bone turnover markers, underscoring the complicated interaction between ART, bone turnover, inflammation and immune status, which extend beyond the OPG/RANKL system.

<< BACK

Copyright © Nucleus Global 2015. Part of Nucleus Global.
Design and Technology by Nucleus Global
Company registration No. 321 0712 (England & Wales). Registered Office address: Admiral House 76-78 Old Street, London EC1V 9AZ.