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

## TL;DR

A study found that romosozumab reduces osteoporotic fractures more effectively than PTH drugs in women and older adults.

## Contribution

This study provides real-world evidence that romosozumab is more effective than PTH analogs in reducing fracture risk in specific patient subgroups.

## Key findings

- Romosozumab users had a 28.9% lower fracture risk compared to PTH users (HR: 0.711).
- Benefits were strongest in women, older adults, and those with prior fractures.
- Romosozumab also reduced hypercalcemia risk compared to PTH drugs.

## Abstract

To compare the effectiveness of romosozumab (ROMO) with parathyroid hormone (PTH) receptor agonists [teriparatide (TPTD)/abaloparatide (APTD)] in reducing fracture risk following osteoporosis treatment.

A TriNetX cohort study assessed fracture and mortality risks using Kaplan–Meier analysis with hazard ratios (HRs) and 95% confidence intervals (CIs).

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.

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.

The online version contains supplementary material available at 10.1186/s13293-025-00817-1.

Osteoporosis is a disease that makes bones weak and more likely to break, especially in older adults and women after menopause. This study compared two types of bone-strengthening medicines: romosozumab (ROMO) and parathyroid hormone (PTH) drugs, including teriparatide and abaloparatide. Researchers used a large health database to see which treatment better prevented bone fractures. They found that people taking ROMO had fewer fractures and fewer cases of high calcium levels in the blood than those taking PTH drugs. The benefits of ROMO were strongest in women, people aged 65 and older, and those who had fractures before. These results suggest that ROMO may offer stronger short-term protection against fractures compared with PTH drugs. However, doctors still need to consider possible side effects and each person’s overall health before choosing the best treatment. This study provides helpful information for patients and doctors in deciding how to manage osteoporosis and reduce the risk of fragility fractures.

The online version contains supplementary material available at 10.1186/s13293-025-00817-1.

Compared romosozumab (ROMO) with parathyroid hormone (PTH) receptor agonists for fracture prevention in osteoporosis.

ROMO users had lower risks of fractures and hypercalcemia after patient matching.

Benefits were greater in women, adults ≥ 65 years, those with prior fractures, and without kidney disease.

Findings were consistent across data sources and sensitivity analyses.

ROMO offers stronger short-term protection, though safety and treatment sequencing need consideration.

The online version contains supplementary material available at 10.1186/s13293-025-00817-1.