Current and emerging therapies for the treatment of osteoporosis

Abstract

Osteoporosis represents a weakening of bone tissue due to an imbalance in the dynamic processes of bone formation and bone resorption that are continually ongoing within bone tissue. Most currently available osteoporosis therapies are antiresorptive agents. Over the past decade, bisphosphonates, notably alendronate and risedronate, have become the dominant agents with newer bisphosphonates such as ibandronate and zoledronic acid following a trend of less frequent dosing regimens. Synthetic estrogen receptor modulators (SERMs) continue to be developed as drugs that maintain the bone-protective effects of estrogen while avoiding its associated adverse side effects. Currently available agents of this class include raloxifene, the only SERM available in the United States (US), and lasofoxifene and bazedoxifene, available in Europe. Calcitonin, usually administered as a nasal spray, completes the list of currently approved antiresorptive agents, while parathyroid hormone analogs represent the only anabolic agents currently approved in both the US and Europe. Strontium ranelate is an additional agent available in Europe but not the US that has both anabolic and antiresorptive activity. New agents expected to further expand therapeutic options include denosumab, a monoclonal antibody inhibitor of the resorptive enzyme cathepsin K, which is in the final stages of Food and Drug Administration approval. Other agents in preclinical development include those targeting specific molecules of the Wnt/β-catenin pathway involved in stimulating bone formation by osteoblast cells. This review discusses the use of currently available agents as well as highlighting emerging agents expected to bring significant changes to the approach to osteoporosis therapy in the near future.