The potential use of antisclerostin therapy in chronic kidney disease-mineral and bone disorder.

Abstract Sclerostin is a regulator of the osteoanabolic canonical Wnt signaling pathway, and thus helps to govern rates of bone formation. The Wnt pathway is also recognized as playing an important role in the pathophysiology of the chronic kidney disease-mineral and bone disorder (CKD-MBD). It also may serve as an interface between bone and the vascular system. Pharmacological inhibition of sclerostin has shown promise as an osteoanabolic approach to the treatment of osteoporosis. Inhibition of sclerostin is a potentially useful but unproven strategy in the management of CKD-MBD. Clinical trials with humanized monoclonal sclerostin antibodies (Scl-Ab) have shown a rapid initial increase in bone formation and a marked increase in bone mineral density. Although clinical data, to this point, in CKD are not available, animal models of low bone turnover CKD show that Scl-Ab improves trabecular bone volume and mineralization without affecting biochemical indices. Targeted clinical trials are needed to evaluate the potential effectiveness of Scl-Ab in CKD. Based upon the available data, there is potential not only for this new therapeutic class to improve skeletal health but perhaps also to have substantial cardiovascular benefits in CKD.