A Nomogram for Predicting Tenofovir-Associated Osteoporosis in Chronic Hepatitis B

Background/Objective: Long-term tenofovir disoproxil fumarate (TDF) therapy is associated with progressive bone mineral density loss in patients with chronic hepatitis B (CHB), yet existing fracture risk algorithms, such as FRAX, were not designed for this population. We aimed to develop and internally validate a clinical nomogram for identifying TDF-associated osteoporosis using penalized regression on demographic, virological, and biochemical predictors. Methods: In this single-center retrospective cohort study, 237 adult CHB patients receiving TDF for at least 12 months underwent dual-energy X-ray absorptiometry (DXA). Osteoporosis was defined as a T-score of -2.5 or lower at the lumbar spine or femoral neck. Thirteen candidate predictors were evaluated using LASSO regression with 10-fold cross-validation; selected variables were entered into an unpenalized multivariable logistic regression model; internal validation employed bootstrap resampling with 200 replications to derive optimism-corrected estimates of discrimination and calibration. The clinical utility was assessed using decision curve analysis (DCA). Results: Osteoporosis prevalence was 15.2% (n = 36). LASSO selected three predictors: prior fragility fracture (OR 11.45, 95% CI 4.82-27.15), the Charlson Comorbidity Index (OR 1.45 per unit, 95% CI 1.15-1.85), and alkaline phosphatase. The model demonstrated strong discrimination (apparent C-index 0.860; optimism-corrected 0.845) with excellent calibration (slope 0.94, intercept 0.02; Brier score 0.095). At a 0.15 probability threshold, sensitivity was 86.0%, specificity 78.0%, and negative predictive value 97.0%. DCA confirmed superior net clinical benefit over default strategies across the 0.10-0.30 threshold range; a pre-specified sensitivity analysis excluding fracture history retained meaningful discrimination (corrected C-index 0.791). Conclusions: This nomogram offers a clinically actionable, disease-specific tool for stratifying osteoporosis risk in TDF-treated CHB patients, particularly well suited for safely deferring DXA imaging in low-risk individuals. External validation in multicenter and ethnically diverse cohorts is required before widespread implementation.