Bisphosphonate Duration of Therapy for Management of Osteoporosis

Abstract

Recent controversy has raised questions about the duration of therapy with bisphosphonates for the treatment of osteoporosis. The optimal duration of use has not been established. In post-menopausal women with osteoporosis and high risk of fractures the potential benefits of treatment have outweighed the likely risks. Bisphosphonateswere shown to reduce the risk of fracture by as much as 60% in registration trials (Table 1). The study information reviewed by the U.S. Food and Drug Administration (FDA) for initial drug approval was based on treatment durations of 3 years in which clear evidence of vertebral fracture risk reduction with alendronate, risedronate, ibandronate, and zoledronic acid was demonstrated. Reduction of non-vertebral fracture was demonstrated for all of the bisphosphonates except ibandronate. Since then, longer term extension trials have shown a small but statistically significant benefit to continued treatment with alendronate, risedronate, and zoledronic acid beyond the initial treatment periods. No long-term safety concerns were identified in these trials. There are no extension trials with ibandronate. In the last few years, reports of osteonecrosis of the jaw and femoral head fractures have led the Food and Drug Administration (FDA) as well as bone and mineral clinicians to rethink long-term bisphosphonate therapy. The FDA safety review focused on trials in which the bisphosphonate was administered at least 3 years and fracture data were captured systematically and completely. Thus, the Fosamax Fracture Intervention Trial Long-term Extension (FLEX), Reclast Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT), and the Actonel Vertebral Efficacy with Risedro-