Bisphosphonate therapy associated with bilateral atypical femoral fracture and delayed union

The aim of this study was to identify the risk factors for developing atypical femoral fractures (AFF) and to examine the effect of bisphosphonate (BP) therapy on delayed bone union and bilateral fractures.

Between January 1^st, 2012 and December 31^st, 2020, a total of 74 AFF patients (8 males, 66 females; mean age: 75.4±7.2 years; range, 51 to 94 years) were recorded in two centers and retrospectively analyzed. A control fragility fracture group (n=143) was compared to the AFF group according to fracture characteristics, surgical fixation methods, comorbidities, and medications. The AFF patients were selected and subdivided according to their BP therapy: Group 1 (without BP) and Group 2 (with BP). Group 2 was further classified into Group 2a (<5 years of BP) and Group 2b (<5 years of BP).

The multivariate logistic regression model showed that, BP drug use was the most significant risk factor in development of AFF (p<0.001, odds ratio= 10.749, 95% confidence interval: 3.886-29.733). The patients on BP showed longer bone union (Group 2 - 8.3±3.5 vs. Group 1 - 6.4±3.1 months, p=0.02; Group 2b - 9±3.8 vs. Group 2a - 7.3 ±3.9 months, p=0.09). Of all 19 cases of bilateral fractures, 14 were in Group 2 with BP use (p=0.11). Of 74 cases, 26 (35%) contralateral femoral X-rays were taken on admission and 24 (92%) showed AFF minor criteria signs. Of these 24 patients, 10 (42%) developed contralateral AFF.

The most significant risk factor in development of AFF was BP drug use. Longer BP therapy (>5 years) showed longer delayed bone union, which was not significant. There was a relatively high risk of developing AFFs and bilateral fractures on BP therapy. In case of an AFF, a contralateral femoral X-ray must be always performed for signs of an impending fracture.