Bisphosphonates Linked to Risk of Rare Fractures

Long-term therapy with bisphosphonates is linked with an increased risk of atypical femoral fractures (AFFs) due to lower crack-initiation toughness and less crack deflection at osteonal boundaries, according to the results of a recent study.

For their study, the researchers examined biopsies of proximal femoral cortical bone adjacent to fracture sites from postmenopausal women during fracture repair surgery. Based on their fracture morphology and history of bisphosphonate treatment, the women were grouped into 5 categories: long-term bisphosphonate therapy with AFF (n=12), long-term bisphosphonate therapy with typical fractures (n=10), long-term bisphosphonate therapy with no fracture (n=5), bisphosphonate-naïve women with typical fractures (n=11) and bisphosphonate-naïve women with no fractures (n=12). The researchers noted that women in the long-term bisphosphonate treatment group had received treatment for 6 to 8 years, which is longer than the FDA recommendation of 3 to 5 years of treatment.
_______________________________________________________________________________________________________________________________________________________________________

Using vibrational spectroscopy and nanoindentation, the researchers found that tissue from bisphosphonate-treated women with AFFs was harder and more mineralized than tissue from bisphosphonate-treated women with typical osteoporotic fractures. Fracture mechanics measurements showed that tissue from bisphosphonate-treated patients had deficits in fracture toughness, lower crack-initiation toughness, and less crack deflection at osteonal boundaries that in bisphosphonate-naïve patients.

“Together, these results suggest a deficit in intrinsic and extrinsic toughening mechanisms, which contribute to AFFs in patients treated with long-term bisphosphonates,” the researchers concluded.

—Michael Potts

Reference:

Lloyd AA, Gludovatz B, Riedel C, et al. Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance [