Adverse Effects of Bisphosphonates

Use of bisphosphonates has been growing steadily in the last decade. This follows the introduction of simpler dosing regimes, the availability of lower-priced generics, and concerns about the safety of hormone-replacement therapy. Bisphosphonates have a relatively good safety record and are tolerated by the majority of patients, but serious adverse events have been recorded in some cases. Only the most common of adverse effects are robustly observable in clinical trials. In general, studies were not powered to detect effects that were lower in incidence than fractures. This review of adverse events in bisphosphonate-treated patients was based on published information from case reports, case series, claims databases, national databases, surveys, adverse event reporting databases, and single or pooled clinical trials. The most common acute adverse events with bisphosphonates for osteoporosis are gastrointestinal discomfort and acute influenza-like illness. Renal complications are very rare with oral bisphosphonates and rare with i.v. bisphosphonates when used appropriately. Based on our current knowledge, skeletal events in the form of osteonecrosis of the jaw and atypical fragility fractures are rare compared with the risk of osteoporotic fractures, at least in patients with the same risk of fractures as those in the phase III trials. It is biologically plausible that atypical fragility fractures could follow from suppression of bone remodeling, but high-quality studies proving causality are lacking. Physicians are advised to critically reassess BMD and risk profile after 3-5 years of therapy to avoid treatment in patients at low risk.