Long-term use of tenofovir disoproxil fumarate increases fracture risk in elderly patients with chronic hepatitis B

Background & Aims: The use of tenofovir disoproxil fumarate (TDF) is associated with a reduction in bone mineral density and an increase in bone metabolism biomarkers. However, data on clinical bone fractures remain limited. We evaluated the impact of TDF compared to entecavir on the risk of fracture in elderly patients with chronic hepatitis B (CHB). Methods: Patients with CHB aged >-60 years receiving entecavir or TDF between January 2008 and December 2022 were identified using a territory -wide database in Hong Kong. The risk of incident fracture in entecavir- and TDF-treated patients before and after month 24 were compared after propensity score matching. Results: A total of 41,531 patients with CHB (mean age 69.8 +/- 7.8 years, 61.6% male) receiving entecavir (n = 39,897 [96.1%]) and TDF (n = 1,634 [3.9%]) were analysed. At a median follow-up of 25.3 (9.1-58.5) months, 1,733 (4.2%) patients developed incident fracture. Patients with incident fracture were more likely to have diabetes, hypertension, congestive heart failure, rheumatoid arthritis, osteoporosis, and a history of fracture. Compared with propensity score -matched entecavir-treated patients, the risk of incident fracture in TDF-treated patients was comparable in the first 24 months (weighted subdistribution hazard ratio [sHR] 0.99, 95% CI 0.56-1.73, p = 0.960) but increased after month 24 (weighted sHR 1.80, 95% CI 1.11-2.93, p = 0.019). The 24-, 60-, and 96 -month cumulative incidences (95% CI) of fracture in TDF-treated and entecavir-treated patients were 2.3% (1.6%-3.4%) vs. 2.6% (1.9%-3.5%), 6.4% (5.0%-8.2%) vs. 4.7% (3.8%-6.0%), and 10.2% (8.3%-12.6%) vs. 6.8% (5.4%-8.5%), respectively. Conclusions: The risk of fracture increased with TDF treatment for >-24 months in elderly patients with CHB. Selection of nucleos(t)ide analogues should be individualised based on age and comorbidities. (c) 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.