Comparison of Receptor Activator of Nuclear Factor Kappa-B Ligand and Osteoprotegerin with Other Serum Biomarkers for Bone Homeostasis in People Living with HIV.

Abstract

Introduction: This study evaluated Bone Mineral Density (BMD) and examined the associations of serum Receptor Activator of Nuclear factor kappa-B Ligand (RANKL), Osteoprotegerin (OPG), and the RANKL/OPG ratio with Dual-energy X-ray Absorptiometry (DXA) findings and clinical parameters in people living with HIV (PLWH) receiving Antiretroviral Therapy (ART).

Methods: In this prospective cross-sectional study, adults living with HIV were consecutively recruited at a tertiary care center. Participants underwent DXA, measurement of serum RANKL and OPG levels, and routine biochemical and hematological testing. Clinical and laboratory variables were compared according to BMD status, and multivariable linear regression analyses were performed to identify factors associated with RANKL, OPG, and the RANKL/OPG ratio.

Results: Low BMD was identified in 20 participants (25.0%), including 14 (17.5%) at the femoral neck and 12 (15.0%) at the lumbar spine. Participants with low BMD were older than those with normal BMD (median 54.0 vs 35.0 years, p = 0.017). Serum RANKL, OPG, and the RANKL/OPG ratio did not differ significantly according to BMD status. In multivariable models, hemoglobin and age were independently and inversely associated with the RANKL/OPG ratio (p = 0.028 and p = 0.041, respectively), whereas age and neutrophil percentage were independently and inversely associated with serum RANKL (p = 0.001 and p = 0.048, respectively) and OPG levels (p = 0.002 and p = 0.023, respectively).

Discussion: These findings suggest that circulating RANKL and OPG may not adequately reflect DXA-derived skeletal status in ART-treated PLWH and may be influenced by broader systemic, inflammatory, and hematologic factors.

Conclusion: Direct densitometric assessment remains central to skeletal evaluation in PLWH receiving ART.