Sequential therapy following romosozumab: real-world comparison of denosumab and bisphosphonates with 2-year...

Sequential therapy is required to maintain bone mineral density (BMD) gains after romosozumab treatment; however, the optimal sequential therapy remains unclear. This study compared denosumab with bisphosphonates as sequential therapy following romosozumab treatment in real-world practice.

This retrospective observational study analyzed 315 patients with osteoporosis who received 12 months of romosozumab at Mutsu General Hospital (April 2019-April 2024) with a minimum 12-month follow-up. Sequential therapy was chosen by the physician and patient after consideration of renal function, gastrointestinal tolerance, adherence, and patient preference. The total enrollment was 315 patients: denosumab plus vitamin D (n = 158), bisphosphonates plus vitamin D (n = 95), no sequential therapy (n = 13), or other regimens (n = 49). For BMD analysis, 12-month data were available for 264 patients (denosumab n = 157, bisphosphonates n = 95, no sequential n = 12). The primary outcomes were BMD changes at the lumbar spine and total hip.

Sequential therapy was implemented in 92.7% of the patients. At 12 months, both the denosumab and bisphosphonate groups showed significant BMD increases, with no statistical difference (lumbar spine: +12.8% vs. +13.6%, p = 0.565; total hip: +3.8% vs. +4.0%, p = 0.926). At 24 months, denosumab showed greater continued increases (lumbar spine: +5.9% vs. +2.2%; total hip: +5.8% vs. +4.0%). Patients without sequential therapy experienced a BMD decline from year 1 to 2 (lumbar spine: -5.4%). TRACP-5b (a bone resorption marker) decreased by approximately 30% in both sequential therapy groups (medians: denosumab -30.3%, bisphosphonates -30.6%). Incident fracture rates were similar between denosumab (6.3%) and bisphosphonates (6.3%) but numerically higher in the group without sequential therapy (15.4%).

Sequential therapy following romosozumab administration is essential for preventing BMD loss and reducing fracture risk. Both denosumab and bisphosphonates were effective, with denosumab showing superior sustained BMD gains in the second year.