Fracture risk associated with chronic use of bisphosphonates: evidence today.

IMPORTANCE OF THE FIELD: Bisphosphonates are the most widely used antiresorptive agents for the treatment of osteoporosis. However, the cumulative bisphoshonate exposure and its association with atypical fragility fractures, and the optimum duration of treatment remain obscure. AREAS COVERED IN THIS REVIEW: This review article focuses on the existing evidence relevant to the development of stress fractures following prolonged administration of bisphosphonates. Furthermore, the optimal duration of bisphosphonate treatment and the real risk of associated stress fractures are discussed. WHAT THE READER WILL GAIN: A detailed overview of the cases reported thus far in the literature. In addition, the reader will become aware that the currently available observational studies and clinical trials are not powered to detect complications of very low incidence such as atypical insufficiency fractures. TAKE HOME MESSAGE: It is unknown whether the pathophysiology of these atypical insufficiency fractures is related to the mode of action of bisphosphonates, or else if they represent an unusual osteoporotic fracture manifestation. Clinicians should be aware that patients on long-term treatment may develop this side effect. The decision to maintain a patient on therapy beyond 5 years should be taken on a case-by-case approach, guided by individual overall fracture risk, and the drug's efficacy and safety profile.