[Development of bisphosphonates].

Bisphosphonates (BPs), antiresorptive agents, have been established as first line drugs for treatment of osteoporosis and widely used all over the worlds. In Japan alendronate and risedronate, newer generation of BPs have been developed according to a evidence-based guideline and approved for clinical use in 2001 and in 2002, respectively. Although these BPs have been shown to have antifractures efficacy, great efforts have been made to explore convenient administration routes and schedules of BPs for individual patients. On the other hand, some of BPs are indicated for abnormal bone and calcium metabolism other than osteoporosis, including Paget's disease of bone, hypercalcemia associated with malignancy. Currently, extended indications of BPs are under development to the treatments of metastatic bone diseases, such as breast cancer, multiple myeloma, and rheumatoid arthritis. Since etidronate, first generation of BP also have the inhibitory effects on mineralization and hydroxyapatite crystal formation, application of this agent to ectopic ossification and calcification are very promising and under investigation.