Anti-Sclerostin Antibodies in Osteoporosis and Other Bone Diseases

Abstract

The Wnt pathway is a key element of bone remodeling; its activation stimulates bone formation and inhibits bone resorption. The discovery of sclerostin, a natural antagonist of the Wnt pathway, promoted the development of romosozumab, a human monoclonal antibody directed against sclerostin, as well as other anti-sclerostin antibodies. Phase 3 studies have shown the efficacy of romosozumab in the prevention of fractures in postmenopausal women, against placebo but also against alendronate or teriparatide and this treatment also allows bone mineral density (BMD) increase in men. Romosozumab induces the uncoupling of bone remodeling, leading to both an increase in bone formation and a decrease in bone resorption during the first months of treatment. The effect is attenuated over time and reversible when stopped but transition with anti-resorbing agents allows the maintenance or reinforcement of BMD improvements. Some concerns were raised about cardiovascular events. Therefore, romosozumab was recently approved in several countries for the treatment of severe osteoporosis in postmenopausal women with high fracture risk and without a history of heart attack, myocardial infarction or stroke. This review aims to outline the role of sclerostin, the efficacy and safety of anti-sclerostin therapies and in particular romosozumab and their place in therapeutic strategies against osteoporosis or other bone diseases.