Recent advances and current trend in the pharmacotherapy of postmenopausal osteoporosis

Abstract

Estrogen deficiency (most especially low level of β-estradiol isoform) is the major contributing factor to bone loss after menopause. Supplementation with calcium and Vitamin D is an essential baseline therapy for osteoporosis prevention and treatment. Newer emerging agents that will further expand osteoporosis therapeutic options include strontium compound (a bone selective calcium-sensing receptor [CaSR] agonist or calcimimetic which is currently licensed for use in Europe but not in the US that has both osteoanabolic and antiresorptive activity); Lasofoxifene (a new selective estrogen receptor modulator [SERM] or estrogen agonist-antagonist [EAA] with partial agonist activity at both estrogen receptors ERα and ERβ); odanacatib and balicatib (inhibitors of the resorptive enzyme cathepsin K); abaloparatide (a parathyroid hormone [PTH]-related protein analog); ostabolin-C (a new cyclicised PTH analog); romosozumab and blosozumab (monoclonal antibody inhibitors to sclerostin) which are currently undergoing clinical trial for Food and Drug Administration approval. Other agents in preclinical development include anti-dickkopf antibody (BHQ880) which targets specific protein molecules of the Wnt/β-catenin pathway involved in stimulating new bone formation by osteoblast cells; parathyroid selective short-acting calcium-sensing receptor antagonists or calcilytics (SB-423562, SB-423557, JTT-305/MK-5442, and NPS-2143) that will lead to a transient release of PTH from the parathyroid glands; and saracatinib (a novel orally available competitive inhibitor of the enzyme Src kinase and Abl kinase family shown to inhibit osteoclast-mediated bone resorption). This review article discusses these newer evolving agents that will introduce and incorporate remarkable improvements into the management of postmenopausal osteoporosis in the nearer future.