Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis B

J Med Virol. 2019 Jul;91(7):1288-1294. doi: 10.1002/jmv.25433. Epub 2019 Feb 27.

Abstract

Background: Recent studies have suggested a potential increase in the incidence of osteoporosis for patients receiving tenofovir disoproxil fumarate (TDF), but this issue remains controversial.

Methods: The retrospective cohort study of 1224 Asian chronic hepatitis B (CHB) patients greater than 18 years without baseline osteopenia/osteoporosis seen at four US centers from 2008 to 2016. Patients were categorized into three groups-treatment-naive patients who initiated therapy with TDF (1) or entecavir (ETV) (2), or untreated patients (3). Patients were followed until the development of osteopenia/osteoporosis or end of the study.

Results: Of the 1224 study patients, 276 were treated with TDF, 335 with ETV, and 613 were untreated. The prevalence of cirrhosis was lower for untreated patients (2.6% vs 16.3% for TDF and 17.6% for ETV; P < 0.001). The 8-year cumulative incidence rate of osteopenia/osteoporosis was 13.17% for TDF, 15.09% for ETV, and 10.17% for untreated patients, with no statistically significant difference among the three groups ( P = 0.218). On multivariate Cox regression controlling for demographics, osteoporosis risk factors, albumin, and hepatitis B virus (HBV) DNA levels, neither TDF (adjusted hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.34 and 1.59) nor ETV (adjusted HR = 0.98; 95% CI: 0.51 and 1.90) were associated with increased osteopenia/osteoporosis risk compared with untreated patients.

Conclusions: Our retrospective study suggests that there is no significant increase in the incidence of osteopenia/osteoporosis for patients with CHB treated with TDF or ETV during a median follow-up of about 4 to 5 years. However, further study with longer follow-up is needed as an anti-HBV therapy, which is often lifelong or long-term and the development of osteopenia/osteoporosis can be a slow process.

Keywords: entecavir; hepatitis B; osteoporosis; tenofovir; viral hepatitis.

MeSH terms

  • Adult
  • Antiviral Agents / adverse effects*
  • Asian People*
  • Bone Diseases, Metabolic / chemically induced*
  • Bone Diseases, Metabolic / ethnology
  • Female
  • Follow-Up Studies
  • Guanine / adverse effects
  • Guanine / analogs & derivatives
  • Hepatitis B, Chronic / complications*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / ethnology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Osteoporosis / chemically induced*
  • Osteoporosis / ethnology
  • Proportional Hazards Models
  • Retrospective Studies
  • Tenofovir / adverse effects
  • Treatment Outcome
  • United States

Substances

  • Antiviral Agents
  • entecavir
  • Guanine
  • Tenofovir