The effect of prior osteoporosis treatment on bone mineral density response to romosozumab

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BACKGROUND: Romosozumab is an osteoanabolic agent with dual anabolic and antiresorptive effects, with substantial benefits on bone mineral density (BMD) and fracture risk reduction. BMD gains are attenuated by prior antiresorptive treatment. This study aimed to compare real-world effects of romosozumab on BMD and bone turnover markers (BTM) according to prior antiresorptive treatment. METHODS: We conducted a retrospective audit of patients who completed 12 months of romosozumab treatment between April 2021 and October 2024 at a tertiary hospital and affiliated clinics. Patients were analysed according to treatment history: treatment-naïve, prior bisphosphonate, or prior denosumab. Primary outcome was percentage change in BMD at the lumbar spine (LS) over 12 months. Secondary outcomes were percentage changes in femoral neck (FN), total hip (TH) BMD and bone turnover markers (procollagen type 1 n-propeptide and c-telopeptide) over 12 months. Between-group differences were assessed using ANCOVA and linear mixed models. Subgroup analyses examined the effect of duration of prior treatment and timing of transition from denosumab on BMD. RESULTS: Seventy-two patients were included (mean age 72.4 ± 11.9 years; 83% female). 20 patients were treatment naïve, 32 transitioned from bisphosphonates and 20 transitioned from denosumab. Patients in the treatment naïve group were younger, had lower baseline BMD and fracture risk compared to the bisphosphonate or denosumab group. The median duration of bisphosphonate use in the bisphosphonate group was 48 months and the median duration of denosumab use in the denosumab group was 50 months. LS BMD gains were significantly greater in treatment-naïve patients compared to those with prior bisphosphonate or denosumab exposure (13.1% vs 8.5% vs 4.4%, p = 0.04). There were no significant differences in percentage change for FN or TH BMD across groups. A longer duration of prior antiresorptive therapy and later romosozumab initiation following denosumab were associated with smaller BMD gains. C-terminal teloptide (CTx) levels decreased in both treatment naïve and prior bisphosphonate groups but transiently increased in the prior denosumab group before stabilising by 6-12 months. CONCLUSION: In our real-world cohort, romosozumab effectively increased BMD, particularly in treatment-naïve patients. Duration of prior antiresorptive therapy and timing of transition from denosumab significantly influenced BMD gains. Prospective studies are needed to optimise transition strategies from antiresorptive agents.

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