Beyond a reasonable doubt? Bisphosphonates and atypical femur fractures

In May 2011, we were privileged to debate on behalf of the ECTS and the ASBMR in a Clinical Debate hosted by the IBMS and the ECTS with the motion "Atypical femoral shaft fractures are a consequence of bisphosphonate therapy". The evidence presented for and against the motion is summarized and discussed in this joint commentary. The hypothetical chain of evidence between bisphosphonates, decreased toughness of bone, microcrack accumulation in man and atypical fractures is plausible but unproven. However, the combination of consistent clinical features (which may include a stress reaction at the site of maximum tensile load), a significant statistical association and a feasible biological mechanism gives grounds for caution especially as regards long term treatment in patients at low or moderate risk of osteoporotic fractures.