This phase 3 ARCH trial compared a bone-forming regimen against a standard antiresorptive in high-risk postmenopausal osteoporosis. 4093 women with prior fragility fracture received either romosozumab for 12 months followed by alendronate, or alendronate throughout. The question: does starting with a sclerostin inhibitor beat alendronate alone for preventing fractures?
For a postmenopausal woman with severe osteoporosis and a prior fragility fracture, this trial says an anabolic-first strategy beats going straight to a bisphosphonate. Romosozumab builds bone rapidly, then alendronate locks in those gains. The result is fewer vertebral, clinical, nonvertebral, and hip fractures within a single year.
The mental model: in the highest-risk patients, you may not have time to wait for slow antiresorptive protection, so front-load bone formation.
The catch is the cardiovascular signal. Serious cardiovascular events were higher with romosozumab (2.5% vs 1.9%), driven by cardiac ischemic and cerebrovascular events, and this is why the drug carries a boxed warning and is avoided in patients with recent MI or stroke.
Remember the appraisal limits: this was not a cardiovascular outcomes trial, had no placebo arm, and the event numbers were small.
This phase 3 ARCH trial compared a bone-forming regimen against a standard antiresorptive in high-risk postmenopausal osteoporosis. 4093 women with prior fragility fracture received either romosozumab for 12 months followed by alendronate, or alendronate throughout. The question: does starting with a sclerostin inhibitor beat alendronate alone for preventing fractures?
For a postmenopausal woman with severe osteoporosis and a prior fragility fracture, this trial says an anabolic-first strategy beats going straight to a bisphosphonate. Romosozumab builds bone rapidly, then alendronate locks in those gains. The result is fewer vertebral, clinical, nonvertebral, and hip fractures within a single year.
The mental model: in the highest-risk patients, you may not have time to wait for slow antiresorptive protection, so front-load bone formation.
The catch is the cardiovascular signal. Serious cardiovascular events were higher with romosozumab (2.5% vs 1.9%), driven by cardiac ischemic and cerebrovascular events, and this is why the drug carries a boxed warning and is avoided in patients with recent MI or stroke.
Remember the appraisal limits: this was not a cardiovascular outcomes trial, had no placebo arm, and the event numbers were small.