Bone quality in patients with atypical femoral fractures

Bisphosphonate treatment generally reduces fracture risk in women with postmenopausal osteoporosis, but rare atypical femoral fractures reported over the last 7 years have raised concerns about risks of prolonged antiresorptive therapy. These fractures have a distinctive transverse morphology characteristic of a brittle tensile fracture. In this subset of patients, suppression of bone turnover with long durations of bisphosphonates could cause tissue embrittlement and microdamage accumulation that might degrade fracture toughness. However, direct evidence for this putative pathophysiologic mechanism has not yet been established, and relatively little is known about the bone tissue of patients with atypical femoral fractures. The long-term goals of this work are to characterize the effects of bisphosphonate treatment over time on bone tissue material properties and structural behavior and to elucidate the pathophysiologic mechanisms that contribute to atypical femoral fractures. In our lab we characterize the compositional properties of cortical tissue from postmenopausal women with atypical fractures and compare them to those of postmenopausal women with typical osteoporotic fragility fractures and without fragility fractures. Characterization of bone tissue properties from patients with atypical fractures will provide insight into the etiology of these fractures, form the basis for diagnostic markers for atypical fracture, and inform clinical management of patients on long-term bisphosphonate treatment.

Collaborators:
Joseph Lane, MD: Orthopedics, Hospital for Special Surgery
Dean Lorich, MD: Orthopedics, Hospital for Special Surgery
Deepak Vashishth, PhD: Biomedical Engineering, Rensselaer Polytechnic Institute
Ani Ural PhD, Villanova University
Robert O Ritchie, PhD, Lawerence Berkeley National Laboratory & University of California at Berkeley

Funding:
American Society for Bone and Mineral Research Junior Faculty Osteoporosis Research Award
NSF-CAREER