, Volume 468, Issue 12, pp 3384-3392
Date: 31 Aug 2010

Femoral Insufficiency Fractures Associated with Prolonged Bisphosphonate Therapy

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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.


We investigated the association between bisphosphonate use and femoral insufficiency fractures.


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.


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).


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.

Level of Evidence

Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.
Each author certifies that his or her institution has approved the human protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research, and that informed consent was obtained.