Abstract
BackgroundBy assessing the changes in concentration of soluble receptor activator of nuclear factor κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-naïve HIV-infected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery.MethodsWe used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation.ResultsSoluble RANKL changed significantly over time (overall p = 0.02) with 25% decrease (95% CI: -42 to −5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD and changes in sRANKL.ConclusionIn this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART.Trial registrationClinical-Trial.gov. id NCT00135460, August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee.
Highlights
By assessing the changes in concentration of soluble receptor activator of nuclear factor κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy in treatment-naïve HIVinfected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL levels associated with CD4+ T cell recovery
The bone loss associated with combination antiretroviral therapy (cART) initiation has been observed for all combinations of drug classes [6] Tenofovir disoproxil fumarate (TDF) containing regimens are associated with more pronounced decreases in bone mineral density (BMD) of an additional 1.4%–2.0% [3, 7]
A total of 48 patients with baseline BMD and RANKL/ OPG measurements and at least one follow-up BMD and RANKL/OPG measurement participated in the BMD RANKL sub study (23 in the nucleoside reverse transcriptase inhibitor (NRTI) sparing and 25 in the protease inhibitor (PI) sparing group)
Summary
By assessing the changes in concentration of soluble receptor activator of nuclear factor κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-naïve HIVinfected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery. HIV-infected patients experience a loss in bone mineral density (BMD) during the first 6–12 months after initiation of combination antiretroviral therapy (cART) [1,2,3,4,5]. B(RANK) expressed on osteoclast surfaces binds receptor activator of nuclear factor κ B ligand(RANKL), which is expressed on osteoblast surfaces and secreted by endothelial cells, B lymphocytes and T lymphocytes [9]. Osteoprotegrin (OPG) is produced by osteoblasts and works as a decoy receptor of RANKL inhibiting osteoclast activity [9]
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