FDA Report: Fosamax Safety and Efficacy

Fosamax Benefits Not Seen After Five Years

The FDA released a report in preparation for an Advisory Panel Meeting scheduled for September 9, 2011 to review and discuss the available data regarding the long-term (greater than 3 – 5 years) use of Fosamax for the treatment and/or prevention of osteoporosis. In light of safety events that appear to potentially be associated with the long-term use of bisphosphonates (Fosamax-type medications), in March 2010 the FDA Division of Reproductive and Urologic Products (DRUP) requested submission of all available controlled clinical trial data supporting long-term use from all bisphosphonate sponsors with products approved for osteoporosis indications. The report includes sections on Efficacy and Safety, including adverse effects such as:

• Hypocalcemia
• Gastrointestinal Disorders
• Musculoskeletal Pain
• Acute Phase Reaction
• Inflammatory Eye Disease (such as iritis, uveitis, or scleritis)
• Atrial Fibrillation
• Renal Adverse Events
• Atypical Subtrochanteric and Femoral Diaphyseal Fractures
• Osteonecrosis of the Jaw
• Esophageal Cancer

According to the report prepared by FDA officials in advance of the meetings, Fosamax benefits in protecting against osteoporosis and bone density are not seen beyond five years. In order to maximize the benefits and minimize the risks of these adverse effects, the panel recommended that women should only take Fosamax for five years. In regards to safety, the committee concluded:

The safety of long-term bisphosphonate therapy continues to be unclear as study results are conflicting as to whether or not ONJ, atypical femoral fractures or esophageal cancer are associated with use of bisphosphonates for the prevention and treatment of osteoporosis. The epidemiologic evidence concerning ONJ is suggestive of an increased prevalence of ONJ and ONJ-like findings with increased duration of exposure to oral bisphosphonates, with the highest prevalence observed at 4 or more years of use. However these results would need to be confirmed by additional larger studies. Atypical fractures with radiographic features defined by the ASBMR Task Force appear to have a strong association with bisphosphonates but there is no current consensus on the extent to which cumulative use of bisphosphonates increases the risk of this rare type of fracture. Finally, no definitive evidence is available to support an association between esophageal cancer and long-term use of bisphosphonates.