Romosozumab versus teriparatide for risk of dementia in individuals with osteoporosis: a target trial emulation study

This target-trial emulation study sought to assess the association between romosozumab and incident dementia. We analyzed longitudinal claims data from 69,543 Japanese individuals with osteoporosis (using teriparatide as an active comparator), finding that romosozumab initiation among individuals with osteoporosis may correlate with a lower dementia risk than teriparatide initiation. PURPOSE: The neurocognitive benefits of osteoporosis treatments remain underexplored despite growing interest in the bone-brain connection. We aimed to analyze the association between romosozumab and incident dementia, using teriparatide as the active comparator. METHODS: We emulated a target trial using longitudinal commercial claims data from Japan. We identified individuals aged ≥ 50 years with osteoporosis who newly initiated either romosozumab or teriparatide between 2019 and 2023. The primary outcome was incident dementia, and the secondary outcome was Alzheimer's disease. We estimated the absolute risk reduction (ARR) and relative risk (RR) using a weighted Kaplan-Meier estimator, conducting both intention-to-treat and per-protocol analyses. RESULTS: A total of 69,543 individuals were included in the study (90% female; mean age, 81 years). In the 2-year intention-to-treat analyses, the ARR was 0.7% (95% confidence interval, - 0.1 to 1.3%), with a RR of 0.91 (95% confidence interval, 0.84 to 1.01). For Alzheimer's disease specifically, the ARR was 0.6% (95% confidence interval, 0.0 to 1.1%), with an RR of 0.88 (95% confidence interval, 0.79 to 1.00). In the 1-year per-protocol analyses, the ARR was 1.0% (95% confidence interval, 0.7 to 1.4%), with a RR of 0.76 (95% confidence interval, 0.69 to 0.82). For Alzheimer's disease specifically, the ARR was 0.6% (95% confidence interval, 0.3 to 0.9%), with an RR of 0.77 (95% confidence interval, 0.65 to 0.86). CONCLUSIONS: In this target trial emulation study, romosozumab initiation among individuals with osteoporosis may be associated with a lower risk of dementia, particularly Alzheimer's disease, than teriparatide initiation.