Long-term extension trials to prove the efficacy and safety of bisphosphonates

Abstract

Bisphosphonates are nonmetabolizable analogs of pyrophosphates. They have a high selectivity to bone remodeling sites, become retained and recycled, providing a long duration of continual effect after discontinuation. Bisphosphonates have been registered for postmenopausal osteoporosis for 20 years. Four bisphosphonates are currently registered for postmenopausal osteoporosis – alendronate, risedronate, ibandronate and zoledronic acid. They were all registered on the evidence of fracture-risk reduction over 3 years compared with placebo. Beyond 3 years, there are very few bisphosphonate data where a placebo group has been maintained and none where the original randomized sample size for registration has been continued. Hence, long-term fracture efficacy data depends on observing the fracture-risk reduction in the group continued on long-term bisphosphonates to the risk reduction observed during the first 3 years of the clinical trial, where the placebo group was maintained. In this regard, long-term bisph...