Targeting Sclerostin in Postmenopausal Osteoporosis: Focus on Romosozumab and Blosozumab.

Most current treatments for osteoporosis inhibit bone resorption and reduce total fracture numbers by about one-quarter. The identification of the osteocytic protein sclerostin as a potent regulator of bone turnover and bone density has led to the development of a new therapeutic class-agents that inhibit sclerostin activity, resulting in increased bone formation and reduced bone resorption. Romosozumab and blosozumab are monoclonal antibodies that bind to sclerostin, reducing its inhibition of Wnt signaling. They have comparable activities in phase I and II studies, doubling formation markers, halving resorption indices, and increasing spine bone density by >10% over 12 months. Only romosozumab has progressed to phase III, where the first study showed a 73% reduction in vertebral fracture risk and a 36% reduction in clinical fractures at 1 year. It was well-tolerated. A further phase III study will conclude in 2017. Romosozumab is a very promising medication in the management of established osteoporosis, but much remains to be done to determine its optimal duration and sequence of administration.