Comparison of bone mineral density changes between denosumab and bisphosphonates in tenofovir-exposed chronic hepatitis B patients with osteoporosis

Summary: This study compared denosumab and bisphosphonates for osteoporosis in tenofovir-exposed chronic hepatitis B patients. Both denosumab and bisphosphonates increased bone mineral density (BMD) at year 1. However, denosumab resulted in a greater BMD improvement and a more pronounced reduction in procollagen type 1 N-terminal peptide (P1NP) compared to bisphosphonate. These findings suggest that while both drugs have beneficial effects, denosumab may be the more effective therapeutic option in this population. Background: Tenofovir disoproxil fumarate (TDF), a first-line antiviral for chronic hepatitis B (CHB), is a risk factor for osteoporosis. This study aimed to compare the effectiveness of denosumab and bisphosphonates for osteoporosis in TDF-exposed CHB patients. Methods: CHB patients who were treated with either denosumab or bisphosphonates for newly diagnosed osteoporosis during > 1 year of TDF treatment between 2010 and June 2024 were included from two tertiary centers in Korea. The primary outcome was bone mineral density (BMD) change at year 1 in the lumbar spine (LS) and femoral neck (FN). Secondary outcomes included changes in two bone turnover markers, procollagen type 1 N-terminal propeptide (P1NP) and C-telopeptide of type 1 collagen (CTX). Results: A total of 155 patients were included: 79 received denosumab and 76 received bisphosphonates. The median time from TDF initiation to osteoporosis diagnosis was 4.8 years. After balancing baseline characteristics using propensity score matching, the denosumab group showed a significant increase in BMD at the LS and FN (denosumab vs. bisphosphonates: LS, 11.7% vs. 6.4%, P = 0.001; FN, 4.9% vs. 1.7%, P = 0.008) at year 1. The denosumab group had a greater reduction in P1NP levels at 6 months (-72.7% vs. -63.8%, P = 0.001), with no significant difference in CTX changes (-70.8% vs. -71.4%, P = 0.74) compared to the bisphosphonates group. The inverse probability of treatment weighting analyses reproduced a similar trend. Conclusions: In TDF-exposed CHB patients with osteoporosis, denosumab outperformed bisphosphonates in the LS and FN BMD at year 1. The reduction in P1NP level was also more prominent in the denosumab group.