Abstract
Summary Statement
Atypical femoral fractures consist of a thin fracture line extending through the lateral cortex. The adjacent bone is undergoing resorption and mechanical abrasion and is often replaced with woven bone. The mechanical environment seems to inhibit healing.
Background
The pathophysiology behind bisphosphonate-associated atypical femoral fractures remains unclear. Histological findings at the fracture site itself might provide important clues. So far only one case describing the histological appearance of the fracture has been published.
Methods
Between 2008 and 2013, bone biopsies comprising the fracture site were collected from 8 patients with 4 displaced and 4 undisplaced atypical femoral fractures. Seven female patients reported continuous bisphosphonate use for an average of 9.5 years. One patient was a man, not using bisphosphonates. The bone biopsies were evaluated histologically, with Fourier transformed infrared imaging (FTIR) and micro-computed tomography.
Results
The 4 undisplaced fractures engaged the whole cortical thickness and comprised a 150 to 200 µm wide, meandering fracture gap filled with amorphous necrotic material. Von Kossa staining showed occasional mineralised elements with bony structure within the amorphic material. Active resorption and remodeling was common in the close vicinity of the fracture, but seldom reached into the fracture gap. In some areas, the bone adjacent to the gap appeared to undergo fragmentation and disintegration, possibly due to abrasion. Woven bone was common adjacent to the fracture gap, and appeared to have been formed in defects caused by abrasion or where resorption cavities had reached into the fracture gap. Periosteal and endosteal callus was found in all cases. Far away from the fracture, large areas of osteonal bone with only empty osteocyte lacunae were found in some samples. In one patient, the remodeling process bridged the fracture gap at some points. The fracture was otherwise similar to the other undisplaced fractures. This patient had suffered from thigh pain since her bisphosphonate treatment was discontinued 18 months earlier, when the atypical fracture was diagnosed.
Discussion
Atypical femoral fractures show signs of increased remodeling in the vicinity of the fracture gap. The narrow width of the gap and its necrotic contents suggest that micromotion leads to strains between the fracture fragments that precludes survival of ingrowing cells. Moreover, there seemed to be continuous mechanical fragmentation of the bone at the crack, and replacement of fragmented areas with woven bone. Thus, it appears that the fracture line is not static, but moves in the bone over time, like the changes in the course of a meandering river.
