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Article Abstract
Introduction: Osteoporosis is a major risk factor for fractures, yet the contribution of immune responses to its pathogenesis remains poorly understood. This study investigates whether common viral infections, including Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and varicella-zoster virus (VZV), contribute to osteoporosis through immune-mediated pathways.
Methods: We performed two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) summary data and complemented this with observational analyses from the NHANES 2003-2004 cycle. Antibody responses to EBV, HHV-6, and VZV were examined for potential causal effects on bone mineral density (BMD) at key skeletal sites.
Results: MR analyses indicated that stronger antibody responses to EBV, HHV-6, and VZV were associated with reduced BMD, particularly at the lumbar spine and femoral neck (OR = 1.18, 95 % CI: 1.02-1.36, p = 0.040). Subgroup analyses suggested more pronounced reductions among young men with EBV and elderly women with VZV. Sensitivity tests supported the robustness of these findings.
Conclusions: Our findings suggest that common herpesvirus infections may contribute to bone loss via immune-mediated mechanisms, especially in vulnerable subgroups. These results provide epidemiological support for a viral-immune link in osteoporosis and underscore the need for mechanistic and longitudinal studies to clarify underlying pathways and guide future preventive strategies.
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