Changes in plasma RANKL-osteoprotegerin in a prospective, randomized clinical trial of initial antiviral therapy: A5260s

Citation: Kelesidis T, Moser C,  Johnson E, Stein JH, Dubé MP, Yang O, McComsey GA, Currier  JS, Brown TT. Changes in plasma RANKL-osteoprotegerin in a prospective, randomized clinical trial of initial antiviral therapy: A5260s. J Acquir Immune Defic Syndr. 2018 Jul 1;78(3):362-366. doi: 10.1097/QAI.0000000000001679. PMID: 29533303. PMCID: PMC5997510.

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https://www.ncbi.nlm.nih.gov/pubmed/29533303

BACKGROUND:
The contributions of the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) axis to cardiovascular and bone disease in treated HIV-1 infection are not well defined.

SETTING:
Prospective, observational, longitudinal study.

METHODS:
In a subset analysis of a prospective randomized clinical trial, 234 HIV-1-infected antiretroviral therapy-naive participants received tenofovir-emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir and achieved plasma HIV-1 RNA <50 copies per milliliter by week 24 and thereafter. Associations between plasma RANKL, OPG, or RANKL/OPG ratio levels with total, hip, and spine bone mineral density (BMD) loss or progression of carotid artery intima-media thickness were assessed longitudinally over 96 weeks.

RESULTS:
Over 96 weeks, all treatment groups had similar and sustained declines in plasma RANKL, increases in plasma OPG, and subsequently, decreases in the RANKL/OPG ratio. There were no associations between plasma RANKL or RANKL/OPG ratio levels with total, hip, and spine BMD loss or progression of carotid artery intima-media thickness; however, plasma OPG in successfully treated HIV-infected patients (week 48 and 96) was associated with spine BMD loss.

CONCLUSIONS:
In virologically suppressed HIV-infected patients, the evolution of bone disease could be linked to plasma OPG levels; however, the role of plasma levels of RANKL and RANKL/OPG ratio in the prediction of morbidity in treated HIV-1 infection may be limited.

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