Summary of Clinical Use

Romosozumab received Japanese PMDA approval in January 2019, and FDA marketing authorisation in April 2019 [4], following completion of Phase 3 clinical trials in subjects with osteoporosis (pivotal trials included NCT01575834, NCT01631214 and NCT02016716). EMA approval was granted in December 2019. Romosozumab is approved for use in postmenopausal women at high risk of bone fracture, who have a history of osteoporotic fracture, and who have an inadaquate response to or are intolerant of other osteoporosis therapies. Because romosozumab therapy is associated with an increased risk of heart attack, stroke and cardiovascular death it must not be prescribed for patients who have suffered a heart attack or stroke within the previous 12 months. The bone forming effects of romosozumab diminish following 12 monthly doses, at which point patients should be moved on to osteoporosis treatments that reduce bone loss if continuing therapy is required.

Mechanism Of Action and Pharmacodynamic Effects

Romosozumab binds to sclerostin, an osteocyte protein which normally inhibits Wnt signalling and decreases bone formation by osteoblasts [1,3,5] as part of the regulatory system controlling bone mass equilibrium. Neutralisation of sclerostin activity leads to improved bone mineral density and bone formation [2,4,6].