Vitamin D does not modulate immune-mediated bone loss during ART initiation

Area of Science:

• Immunology
• Bone Metabolism
• Pharmacology

Background:

• Antiretroviral therapy (ART) can lead to bone loss.
• Vitamin D (VitD) and calcium (Ca) supplementation may mitigate ART-associated bone loss.
• The mechanism, particularly immunomodulation, remains unclear.

Purpose of the Study:

• To investigate if VitD/Ca supplementation affects immune cell phenotypes and receptor activator of nuclear factor kappa-B ligand (RANKL) expression during ART initiation.
• To explore the relationship between immune markers and bone mineral density (BMD) changes.

Main Methods:

• Exploratory analysis of a 48-week randomized, double-blind, placebo-controlled study (A5280).
• Characterized lymphocyte phenotypes and RANKL expression (MFI) at baseline and 48 weeks.
• Assessed changes within/between groups and correlated cellular phenotypes with BMD.

Main Results:

• T-cell activation markers (CD4, CD8) declined with ART initiation but did not differ between VitD/Ca and placebo groups.
• No significant changes in T-cell RANKL expression or MFI were observed.
• Declines in CD4 activation correlated with bone loss in both groups; CD8 activation decline correlated with bone loss in the placebo group.

Conclusions:

• ART initiation is associated with reduced T-cell activation, independent of VitD/Ca supplementation.
• VitD/Ca supplementation does not appear to mitigate ART-associated bone loss by modulating immune activation or RANKL expression.