Romosozumab following denosumab improves lumbar spine bone mineral density and trabecular bone score greater than denosumab continuation in postmenopausal women

J Bone Miner Res. 2024 Nov 1:zjae179. doi: 10.1093/jbmr/zjae179. Online ahead of print.

Abstract

Romosozumab following anti-resorptive can be an effective sequential treatment strategy to improve bone strength. However, whether the transition to romosozumab after denosumab is associated with greater improvement in bone mineral density (BMD) and trabecular bone score (TBS) compared to denosumab continuation remains unclear. In this propensity score-matched cohort study, we analyzed data from postmenopausal women who initiated denosumab between 2017 and 2020. Individuals who were transited to 12 months of romosozumab after denosumab were 1:1 matched to those who continued an additional 12 months of denosumab (n = 86 for each group; denosumab-romosozumab [DR] and denosumab-denosumab [DD]). Mean BMD gain by denosumab treatment in matched DR and DD groups from denosumab initiation to transition (median 4 times [range 2 to 8]) was +4.8% and + 2.0% in the lumbar spine and total hip. DR group showed greater LS BMD gain compared to the DD group (+6.8 vs. +3.3% point, P<.001) for 12 months post-transition independent of the duration of prior denosumab treatment, yielding greater overall LS BMD gain in DR compared to DD (+11.6% vs. +8.0%, P<.001). DD group showed continued improvement of hip BMD, whereas hip BMD was maintained but not improved in the DR group. DR group was associated with greater TBS improvement than the DD group (2.9% vs 1.0%, P=.042). One month after the transition to romosozumab from denosumab, P1NP immediately increased above the level of denosumab initiation with relatively suppressed CTx, creating a transient anabolic window. For 12 months follow-up, one incident morphometric vertebral fracture and one patella fracture were observed in DD, whereas one ankle fracture was observed in the DR group. Romosozumab following denosumab improved lumbar spine BMD and TBS greater than denosumab continuation in postmenopausal women.

Plain language summary

Osteoporosis weakens bones and increases fracture risk, especially in postmenopausal women. Denosumab effectively boosts bone density and reduces fractures, but stopping it quickly reverses these benefits. Anti-resorptive therapy can help, but may not fully protect patients, and for those at high fracture risk, continuing denosumab might be the best option. This study compared patients who switched from denosumab to romosozumab with those who continued denosumab. We found that switching to romosozumab improved spinal bone density and trabecular bone score more than continuing denosumab, suggesting it may be a promising follow-up treatment, though more research is needed on fracture outcomes.