TDF ups fracture risk in older patients with chronic hepatitis B

Tenofovir disoproxil fumarate (TDF) is associated with a higher fracture risk vs entecavir (ETV) after 2 years of treatment in older patients with chronic hepatitis B (CHB), a territory-wide cohort study has shown.

“Although TDF is an effective [CHB] treatment, it is known to be associated with a decrease in bone mineral density [BMD],” said Professor Grace Wong of the Department of Medicine & Therapeutics, Chinese University of Hong Kong (CUHK). “However, data on the impact of TDF on long-term incident clinical fracture remains scarce.” [J Hepatol 2024;80:553-563]

Using data from the Hospital Authority’s Clinical Data Analysis and Reporting System (CDARS), the researchers conducted a territory-wide cohort study of 41,531 patients with CHB aged ≥60 years (mean age, 69.8 years; male, 61.6 percent) between January 2005 and December 2022 who were receiving ETV (n=39,897) or TDF (n=1,634).

After propensity score matching, the cumulative incidence rates of fracture in the first 2 years were comparable between the TDF and ETV groups (2.3 percent vs 2.6 percent; weighted subdistribution hazard ratio [sHR], 0.99; 95 percent confidence interval [CI], 0.56–1.73, p=0.96).

“The incidence rates started to diverge after 2 years [weighted sHR, 1.80; 95 percent CI, 1.11–2.93; p=0.019], reaching 10.2 percent in the TDF group after 8 years of treatment [vs 6.8 percent with ETV],” highlighted Dr Jimmy Lai of the Department of Medicine & Therapeutics, CUHK.

“Results remained robust in sensitivity analyses in patients aged ≥65 years and ≥70 years, showing increased risks of incident fracture after 2 years of treatment with TDF [weighted sHRs, 2.43 and 2.50 for patients aged ≥65 years and ≥70 years, respectively],” noted Dr Terry Yip of the Department of Medicine & Therapeutics, CUHK.

Apart from well-known risk factors for fracture (ie, rheumatoid arthritis, osteoporosis, history of fracture), cardiometabolic conditions such as diabetes, hypertension, and congestive heart failure were found to be additional risk factors for fracture in CHB patients taking TDF (all p<0.005).

“Comprehensive assessment of health status should be conducted in older patients with CHB before antiviral prescription,” advised Lai. “The cardiometabolic risk factors should not be overlooked, and selection of nucleos[t]ide analogues [NAs] should be individualized based on age and comorbidities.”

“Tenofovir alafenamide [TAF], the newest first-line NA, is a better treatment option than TDF in patients with CHB and underlying risk factors for osteoporotic fractures,” wrote the researchers.

The phase III Study 108 and Study 110 showed that switching from TDF to TAF resulted in high rates of viral suppression, no resistance, and improved renal function and BMD after 5 years. A recent cohort study in South Korea also confirmed a significantly reduced risk of osteoporotic fracture with TAF vs TDF (HR, 0.68; 95 percent CI, 0.55–0.85; p=0.001). [Am J Gastroenterol 2024;119:486-496; Aliment Pharmacol Ther 2023;58:1185-1193]

The CUHK researchers did not include TAF in the current analysis as the duration of treatment was too short to support a meaningful comparison. “A head-to-head comparison between these NAs should be a research priority in the future,” they suggested.