Emerging therapies for osteoporosis

Abstract

Osteoporosis is a condition which affects approximately one in four postmenopausal women and one in ten elderly men. Fractures resulting from the decrease in bone mass which characterises this disease are very costly in both financial and human terms. It has been known for many years that oestrogen treatment, or hormone replacement therapy (HRT), prevents bone loss and osteoporosis. However, many women do not tolerate the numerous side effects, or are concerned by the possibility of increased rate of breast cancer. Calcitonin has also been used for some years to treat osteoporosis, in spite of the drawbacks associated with a protein therapeutic. Since 1996, alendronate, a member of the bisphosphonate class of antiresorptive agents, has been available for the treatment and, subsequently, the prevention of osteoporosis. Despite a difficult dosing regimen and gastrointestinal side effects, alendronate is widely prescribed. The more recent introduction of a selective oestrogen receptor modulator, raloxifene, provides an additional option for both prevention and treatment of the disease. However, there remains a need for highly efficacious antiresorptive agents with an excellent safety and tolerability profile. In addition, there are no bone-forming agents currently available, which are needed to treat patients with very low bone mass who are at high risk of fracture. There are currently numerous agents in clinical development in the classes mentioned above. In addition, there are many novel approaches to the modulation of bone resorption and formation in the discovery and/or early development phases. These include inhibitors of osteoclast adhesion, protease and kinase inhibitors, and receptor antagonists as well as some protein agents. The status of these emerging therapies is discussed in this review.

• antiresorptives
• bisphosphonates
• bone formation
• calcitonin
• oestrogen
• osteoblasts
• osteoclasts
• osteoporosis
• parathyroid hormone
• SERMs
• therapeutic targets