Romosozumab operates through a novel dual mechanism by targeting sclerostin, a protein that normally suppresses the Wnt signaling pathway critical for bone metabolism. This monoclonal antibody simultaneously increases bone formation while reducing bone resorption, distinguishing it from traditional osteoporosis treatments that primarily focus on preventing bone loss. Clinical trials in postmenopausal women showed significant fracture risk reduction compared to both placebo and the standard bisphosphonate alendronate over one year of treatment.
This represents a meaningful advance in osteoporosis therapeutics, particularly for patients at very high fracture risk who may benefit from bone-building rather than just bone-preserving approaches. The discovery pathway—from rare genetic bone diseases to Wnt pathway research—exemplifies how studying extreme phenotypes can yield therapeutic insights. However, the cardiovascular safety signal observed when compared to alendronate (though not placebo) requires careful patient selection and monitoring. Sequential treatment protocols, transitioning from romosozumab to other agents like denosumab or alendronate, appear to optimize long-term outcomes by capitalizing on the initial bone-building phase before switching to maintenance therapy.
