Association Between Chronic Hepatitis B Virus Infection and Risk of Osteoporosis: A Nationwide Population-Based Study

The effect of hepatitis B virus (HBV) infection on bone mineral density in patients without advanced liver disease remains unclear. Hence, we assessed the association between HBV infection and the risk of osteoporosis. From 2000 to 2011, patients older than 20 years with HBV infection were identified from the Longitudinal Health Insurance Database 2000. Of the 180,730 sampled patients, 36,146 and 144,584 patients were categorized into HBV infection and comparison cohorts, respectively. Compared with the comparison cohort, the HBV infection patients had a higher risk of osteoporosis (adjusted hazard ratio [aHR]: 1.14, 95% confidence interval [CI]: 1.03–1.25) after adjusting for age, sex, frequency of medical visits, and comorbidities of diabetes, hypertension, hyperlipidemia, heart failure, cirrhosis, chronic kidney disease, thyroid diseases, medication of steroid, PPI, warfarin, aspirin, and estrogen replacement therapy. The patients with HBV infection exhibited a 1.13-fold (95% CI = 1.03–1.25) higher risk of developing osteoporosis, but the risk of osteoporotic fracture was comparable between patients with HBV infection and the comparison cohort (aHR = 1.20, 95% CI = 0.77–1.86). The incidence of osteoporosis increased with the increment of age (age ≤ 49: aHR = 1; age 50–64: aHR = 5.67, 95% CI = 5.09–6.32; age ≧ 65: aHR = 13.3, 95% CI = 11.8–14.9) and coexisting cirrhosis (aHR = 1.62, 95% CI = 1.24–2.12). However, the osteoporosis risk contributed by HBV infection decreased with age and the age-specific risk analyses showed that patients with HBV infection exhibited the highest risk of osteoporosis than patients without HBV infection for the patients aged ≤49 (aHR = 1.42, 95% CI = 1.19–1.70). Furthermore, the osteoporosis risk contributed by HBV infection has decreased with the presence of comorbidity (aHR = 1.27, 95% CI = 1.09–1.48 vs aHR = 1.04, 95% CI = 0.91–1.15). HBV increases the risk of osteoporosis, but HBV infection may be less influential than other risk factors. Moreover, HBV has no detrimental effect on osteoporotic fracture in this study.