Association between HBV DNA levels and bone mineral density in antiviral-naive chronic hepatitis B patients

Recent studies have shown that patients with chronic hepatitis B (CHB) have an increased prevalence of osteoporosis. However, the direct relationship between hepatitis B virus (HBV) DNA (representing the viral replication level) and bone mineral density (BMD) remains undefined. We aimed to investigate the association between HBV DNA levels and BMD in middle-aged and elderly CHB patients without prior antiviral therapy.

This cross-sectional study recruited 362 untreated patients with CHB (men aged ≥50 years and postmenopausal women) who underwent both HBV DNA testing and dual-energy X-ray absorptiometry (DXA) within a 6-week interval. Based on bone mineral status, patients were categorized into three groups: normal BMD, osteopenia, and osteoporosis. Multiple regression and generalized additive models (GAMs) were applied to analyze associations between HBV DNA and BMD, whereas Receiver operating characteristic (ROC) curve analysis was employed to evaluate the discriminatory ability of HBV DNA levels to distinguish patients with osteoporosis. Exploratory mediation analysis of β-CTX and CRP was performed to assess indirect statistical associations linking HBV DNA with BMD.

Patients with osteoporosis had considerably higher HBV DNA levels than those with osteopenia or normal BMD. In multivariable analyses, each 1 log₁₀ IU/mL increase in HBV DNA was associated with a 0.22-unit decrease in BMD T-score in the total cohort, with a stronger inverse association observed in males (β = -0.32) than in postmenopausal females (β = -0.16). GAMs revealed a continuous negative association between HBV DNA levels and BMD across the spectrum from normal bone density to osteoporosis (P for trend <0.001). HBV DNA demonstrated good between-group discriminatory ability for differentiating osteoporosis, with superior accuracy in males (area under the ROC curve = 0.847; optimal cut-off: 2.857 log₁₀ IU/mL). Exploratory mediation analyses suggested that β-CTX and CRP may contribute to the association between HBV DNA and BMD in the total cohort; however, only β-CTX demonstrated a notable mediating effect in males. Notably, the direct association between HBV DNA levels and BMD remained evident across all mediating models.

Higher HBV DNA levels are independently associated with lower BMD and demonstrate discriminatory ability for osteoporosis status in patients with CHB. Longitudinal studies are warranted to determine the predictive value of HBV DNA in predicting osteoporosis risk.