How do romosozumab, teriparatide, and bisphosphonates compare in head‑to‑head fracture outcomes?
Executive summary
Romosozumab and teriparatide—both osteoanabolic agents—generally outperform oral bisphosphonates for reducing vertebral and clinical fractures in high‑risk postmenopausal populations in randomized and network meta‑analyses, while romosozumab often produces larger early gains in bone mineral density (BMD) than teriparatide; however, head‑to‑head fracture outcome data remain limited and context‑dependent across trials and observational cohorts [1] [2] [3]. Observational studies of vertebral fracture healing and small cohort comparisons show mixed results: anabolic agents may reduce certain complications such as pseudoarthrosis but do not uniformly prevent short‑term “domino” vertebral fractures compared with bisphosphonates [4] [5].
1. Anabolic agents versus bisphosphonates: fracture‑reduction signal
Large network meta‑analyses and randomized trial data coalesce around a consistent message that bone‑forming therapies—teriparatide and romosozumab—reduce clinical and vertebral fracture risk more than bisphosphonates in populations at elevated fracture risk, with relative risk reductions reported across multiple pooled analyses [1] [6]. Economic evaluations note that while non‑bisphosphonates reduce vertebral fractures versus no treatment, cost and value considerations still favor bisphosphonates in many settings [6] [7].
2. Romosozumab versus teriparatide: BMD and surrogate advantages
Direct head‑to‑head studies show romosozumab produces larger, faster increases in lumbar spine and hip BMD than teriparatide—most notably in the STRUCTURE trial and several observational analyses—which translates into superior surrogate markers of bone strength at 12 months [2] [8]. Systematic reviews and a GRADE‑based meta‑analysis conclude romosozumab compares favorably to teriparatide for both efficacy and adverse‑event profiles in postmenopausal cohorts transitioning from bisphosphonates [3] [8].
3. Clinical fracture endpoints: romosozumab may edge teriparatide but data are evolving
Emerging observational cohorts—such as a nationwide Japanese study—report lower incidences of major osteoporotic fractures with romosozumab compared with teriparatide over one‑ and two‑year follow‑up in high‑risk patients, suggesting a possible clinical advantage beyond BMD [9]. Nonetheless, randomized trial evidence directly comparing fracture outcomes between these two anabolics is sparse, so definitive superiority for fracture prevention remains provisional and dependent on patient selection and prior treatment history [3] [9].
4. Vertebral fracture healing and short‑term “domino” fractures: nuanced findings
Studies focused on acute osteoporotic vertebral fractures (OVFs) paint a nuanced picture: in an observational multicenter cohort, teriparatide and romosozumab reduced unstable pseudoarthrosis compared with bisphosphonates but did not significantly lower the incidence of rapid subsequent “domino” OVFs within 3 to 12 months [4] [5]. A commentary synthesizing RCTs argues anabolic agents significantly reduce new OVFs versus bisphosphonates, yet individual trial results vary for fracture healing endpoints [10].
5. Influence of prior antiresorptive therapy and sequencing
Prior bisphosphonate exposure blunts BMD responses to anabolic agents—especially teriparatide—at the hip and may influence early fracture risk trajectories, which complicates head‑to‑head comparisons and favors romosozumab in patients switching from long‑term bisphosphonates, where romosozumab has shown greater hip BMD gains [8] [2]. Case‑control and switching studies also report that romosozumab often yields the largest BMD improvements after bisphosphonate cessation, but these are observational signals that require cautious interpretation [11] [12].
6. Limitations, safety and practical implications
Comparative fracture outcome evidence is heterogenous: high‑quality RCTs and meta‑analyses support anabolic superiority over bisphosphonates for many fracture endpoints, but direct randomized fracture comparisons between romosozumab and teriparatide are limited and observational cohorts may suffer confounding [1] [9] [4]. Safety profiles and cost‑effectiveness differ—romosozumab carries cardiovascular considerations in some trials and non‑bisphosphonate strategies are often less cost‑effective than bisphosphonates—so individual patient risk, prior therapy, and health‑system resources must shape treatment choice [12] [7].