Real-world evidence indicates romosozumab use is associated with a greater reduction in osteoporotic fractures than PTH (1–34) analogs in women

Abstract Background To compare the effectiveness of romosozumab (ROMO) with parathyroid hormone (PTH) receptor agonists [teriparatide (TPTD)/abaloparatide (APTD)] in reducing fracture risk following osteoporosis treatment. Methods A TriNetX cohort study assessed fracture and mortality risks using Kaplan–Meier analysis with hazard ratios (HRs) and 95% confidence intervals (CIs). Results After propensity score matching (n = 2,258 pairs), ROMO users had lower risks of osteoporotic fractures (HR: 0.711, 95% CI: 0.542–0.931) and hypercalcemia (HR = 0.707, 95% CI: 0.511–0.977) compared with PTH receptor agonists. Five subgroup analyses demonstrated a reduced fracture risk in the ROMO cohort among women (HR: 0.738), patients aged ≥ 65 years (HR: 0.652), individuals with a history of prior fractures (HR: 0.659), and those without chronic kidney disease (CKD) (HR: 0.731). Sensitivity analyses confirmed the robustness of the findings across different covariate adjustments, data sources, and extended follow-up, consistently showing a lower risk of hypercalcemia and nonsignificant trends toward reduced fracture risk in the ROMO cohort. Conclusion Compared with PTH analogs, ROMO offers stronger short-term protection against osteoporotic fractures and hypercalcemia, particularly in older women with prior fractures. Nonetheless, cardiovascular safety, calcium metabolism, and sequential therapy require careful consideration for individualized treatment.