Associação do desbalanço de RANKL/OPG na perda óssea em pessoas vivendo com HIV

Abstract

The advent of antiretroviral therapy (ART) has markedly improved the health of people living with HIV/AIDS (PLWHA), allowing them to achieve greater longevity. However, aging in this population has been accompanied by a progressive decline in physiological integrity, including loss of bone mass. This cross-sectional observational study aimed to investigate the imbalance in the production of RANKL/OPG and CD4⁺ T helper cell cytokines of the Th1, Th2, and Th17 profiles in PLWHA. A total of 23 participants over 50 years of age were enrolled and underwent bone mineral density (BMD) assessment by densitometry and blood collection for plasma analysis. Of these, 8 had normal bone density and 15 were classified with osteopenia (7 women and 8 men). The cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-10, IL-17A, and IL-6 were quantified by flow cytometry (CBA). Within the Th1 profile, men without bone disease exhibited higher concentrations of IFN-γ and IL-2 compared with the control group. Regarding the Th2 response, IL-4 was increased both in men without bone disease and in those with osteopenia. For the Th17 profile, IL-6 levels were significantly elevated in men without bone disease, men with osteopenia, and women with osteopenia, all compared with controls. Serum quantification of receptor activator of nuclear factor kappa-B ligand (RANKL) in men with osteopenia revealed reduced concentrations, whereas osteoprotegerin (OPG) was increased, resulting in lower RANKL/OPG ratios. This pattern suggests preferential expression and consumption of RANKL at local sites of chronic inflammation rather than persistence in circulation. IFN-γ exhibited a central role, showing moderate to strong correlations with IL-2, IL-10, and IL-17A, as well as a direct correlation with IL-4 and IL-10. In contrast, the correlation pattern in men with osteopenia was less structured, including a negative correlation between OPG and TNF-α, suggesting immunoinflammatory dysregulation. The reduced RANKL/OPG ratio further reflects disruption of this axis conditioned by HIV infection. Taken together, our findings suggest that Th1-type responses, particularly the balance within this profile, may act on the immuno-skeletal interface to mitigate the effects of bone resorption. In conclusion, our study demonstrates that even in PLWHA with clinical stability and sustained viral suppression, bone loss emerges as a silent, multifactorial, and progressive process in which immune modulation and imbalance of the RANKL/OPG axis play a central role.