Prodromal Symptoms in Patients with Bisphosphonate-Associated Atypical Fractures of the Femur

Symptoms have been reported to precede bisphosphonate-associated atypical fractures (AFs) of the femoral shaft. We aimed to determine the frequency and clinical characteristics of such prodromal symptoms. We searched the Swedish national database of spontaneously reported adverse drug reactions for all cases of AF associated with bisphosphonates from January 2006 to March 2013. To confirm diagnostic accuracy and to characterize and determine the frequency of any prodromal symptoms we retrieved copies of medical journals and radiographs for patients who consented to participate in the study. The frequency of prodromal symptoms was compared with that of patients where information was based only on narratives from the adverse drug reaction case reports. A total of 45 reports of AF were identified. We were able to obtain medical records and x-rays for 21 cases and diagnostic accuracy was confirmed for all. Medical records revealed prodromal symptoms in 86 % (n = 18), most commonly pain in the ipsilateral thigh (14 out of 18 patients) preceding the fracture for weeks or longer. Awareness of such symptoms may facilitate early diagnosis and possible prevention of the AF.