Femoral insufficiency fractures associated with prolonged bisphosphonate therapy

Abstract

Background: Emerging evidence has linked the long-term use of bisphosphonates with femoral insufficiency fractures. It has been suggested that the prolonged effect on bone remodeling leads to the accumulation of microfractures and weakening of bone.

Questions/purposes: We investigated the association between bisphosphonate use and femoral insufficiency fractures.

Methods: We evaluated 100 patients with low-energy femoral shaft fractures before and after bisphosphonates became available for use. Twenty-one consecutive patients who presented between January 1995 and February 1997 were compared with 79 consecutive patients who presented between January 2007 and February 2009. The radiographs of all 100 patients were examined for evidence of preexisting insufficiency fractures. We identified insufficiency fractures by a transverse fracture line on the tension side of the femur with lateral cortical thickening immediately adjacent to the fracture. Relevant details from the history were recorded.

Results: Forty-one patients had an underlying femoral insufficiency fracture, all of whom had been receiving bisphosphonate therapy. Among the 21 patients with low-energy femoral fractures before the availability of bisphosphonates, none had insufficiency fractures. Of the 41 patients with insufficiency fractures, 29 (71%) had prodromal pain and 18 (44%) had bilateral insufficiency fractures. Bisphosphonate use was associated (odds ratio greater than 1000) with insufficiency fracture. The mean duration of bisphosphonate use in patients with insufficiency fractures was longer than in patients without fractures (7.1 versus 3.2 years).

Conclusion: Long-term bisphosphonate use is associated with insufficiency fractures of the femoral shaft, which commonly present with prodromal thigh pain and may be bilateral. These fractures were not seen before bisphosphonates became available for use.

Fig. 1

A low-energy femoral fracture in a 70-year-old woman can be seen on this radiograph. The characteristic insufficiency fracture pattern is evident with a transverse fracture line and lateral cortical thickening adjacent to the fracture (white arrow). The woman had been receiving alendronate therapy for 8 years and reported prodromal anterolateral thigh pain for 2 months.

Fig. 2

A 68-year-old woman who had received long-term alendronate therapy presented to her physician with prodromal pain in the right anterolateral thigh. This radiograph was diagnostic for an insufficiency fracture (white arrow). This was missed by the referring physician and radiologist and the woman presented to us with a low-energy subtrochanteric fracture at the site indicated by the arrow.

Fig. 3A–B

A 71-year-old woman presented with (A) a spontaneous nontraumatic left femoral shaft fracture while standing and was incidentally found to have (B) a femoral shaft insufficiency fracture on the right. The woman reported a 6-month history of prodromal left anterolateral thigh pain, a 2-month history of right anterior thigh pain, and a 10-year history of alendronate use. The bilateral femoral insufficiency fracture pattern can be seen (white arrows).

Fig. 4A–B

Radiographs of the right hip and pelvis, respectively, show (A) a low-energy subtrochanteric fracture on the right and (B) a previous left subtrochanteric fracture in the same patient. The bilateral subtrochanteric insufficiency fracture pattern with the transverse fracture line on the tension side of the femur and lateral cortical thickening adjacent to the fracture can be seen.