Bisphosphonate adverse effects, lessons from large databases

To review the latest findings on bisphosphonate safety from health databases, in particular sources that can provide incidence rates for stress fractures, osteonecrosis of the jaw (ONJ), atrial fibrillation and gastrointestinal lesions including esophageal cancer. The main focus is on bisphosphonates used for osteoporosis.

Register studies have so far not confirmed a shift from classical to nonclassical femur fractures with bisphosphonates. However, studies were either small or without X-ray adjudication. Two new studies found no increase in jaw surgery for inflammatory conditions - a proxy for ONJ - with oral bisphosphonates, but the risk of jaw necrosis was increased almost eight times in those receiving i.v. bisphosphonates. The risk of atrial fibrillation with alendronate may be increased in the first weeks of treatment, but no excess risk was seen in long-term users. Two studies have found decreased risk of esophageal cancer in patients taking oral bisphosphonates.

Compared with the reduction in classical osteoporotic fractures, the risk of harm caused by bisphosphonates is low, according to information presently available from clinical trials and from health databases. However, database studies have limited specificity and sensitivity for atypical fractures and ONJ. Clinical case control studies are recommended.