The preclinical discovery and development of romosozumab for the treatment of people with severe osteoporosis who are at high risk of fracture

In postmenopausal women, the administration of romosozumab over one year decreased the risk of vertebral and clinical fractures versus placebo and versus alendronate. Furthermore, sequential treatment, switching romosozumab over to denosumab, reduced the risk of vertebral fractures compared to switching the placebo to denosumab. Meanwhile, switching romosozumab to alendronate reduced the risk of vertebral, clinical, nonvertebral, and hip fractures compared to continuous alendronate. An imbalance in cardiovascular events was found when using romosozumab in comparison to alendronate but not versus placebo. Romosozumab was eventually approved by EMA and FDA in 2019 for the treatment of patients with very high risk of fractures while considering their cardiovascular risk and is available and reimbursed in many countries.