Osteoporos Int. 2026 Apr 10. doi: 10.1007/s00198-026-07968-w. Online ahead of print.
ABSTRACT
This study compared romosozumab and teriparatide for osteoporosis treatment using real-world data. Romosozumab was linked to significantly lower mortality, especially in older adults, without added cardiovascular risk. These findings highlight romosozumab as a potentially safer and more effective option for reducing death risk in patients with osteoporosis.
BACKGROUND: Osteoporosis is a prevalent condition among older adults and significantly increases the risk of fragility fractures, particularly affecting the hip and vertebrae. Pharmacologic therapy remains central to osteoporosis management, with anabolic agents such as romosozumab and teriparatide demonstrating efficacy in increasing bone mineral density and reducing fracture risk. However, direct comparative evidence regarding their impact on mortality is limited. This study aimed to evaluate the differences in all-cause mortality between romosozumab and teriparatide in patients with osteoporosis, utilizing a large real-world dataset.
METHODS: We conducted a retrospective cohort study using electronic medical records from the TriNetX US Collaborative Network, comprising data from over 120 healthcare organizations. Patients aged ≥ 20 years diagnosed with osteoporosis between January 1, 2016, and December 31, 2023, initiating either romosozumab or teriparatide were included. Individuals with malignancies, bone neoplasms, multiple myeloma, parathyroid disorders, or cerebrovascular accidents were excluded. Propensity score matching (1:1) balanced demographic, clinical, and laboratory characteristics between cohorts. The primary outcome was all-cause mortality, with subgroup analyses performed based on age, sex, comorbidities, and treatment settings.
RESULTS: Each treatment group included 2470 matched patients. Over the follow-up period, romosozumab was associated with significantly lower all-cause mortality compared to teriparatide (hazard ratio [HR] 0.68, 95% CI 0.49-0.94). This survival advantage was particularly evident in patients aged ≥ 60 years (HR 0.65, 95% CI 0.47-0.88). Subgroup analyses consistently favored romosozumab across multiple comorbid conditions, including diabetes mellitus and chronic kidney disease, although these subgroup results did not reach statistical significance. Importantly, no increased mortality risk was observed in patients with hypertension or coronary heart disease, indicating a favorable cardiovascular safety profile in these populations.
CONCLUSION: In this real-world analysis, romosozumab was associated with a significantly lower risk of all-cause mortality compared to teriparatide among patients with osteoporosis. These findings may support the preferential consideration of romosozumab, particularly for older adults and patients at elevated fracture risk, given the inherent limitations of the study design, while highlighting the necessity of careful cardiovascular risk assessment.
PMID:41961089 | DOI:10.1007/s00198-026-07968-w