Differences in microarchitectural and nano-mechanical properties of bone between patients with and without atypical femoral fracture after prolonged bisphosphonate treatment

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Conference Proceeding

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Journal of Bone and Mineral Research


It is well-known that a small group of patients on long-term bisphosphonate (BP) therapy are predisposed to sustain atypical femoral fracture (AFF). However, the mechanism(s) resulting in AFF remains unclear. The purpose of this study is to determine the association of AFF with bone microarchitecture and remodelling, and its mechanical propertiesIliac bone biopsies were obtained after double tetracycline labeling from 20 age-matched postmenopausal women with ≥2-year BP treatment, 10 with AFF (aged 67.4 ± 5.36) and 10 without AFF (aged 67.3 ± 6.83). The 5 μm sections were used to measure bone microarchitecture and remodeling status. Nanoindentation was performed on each bone block.As shown in Table, there was very little difference in cortical bone volume (BV/TV), and the nominal difference in cancellous BV/TV between patients with and without AFF was not statistically significant. Interestingly, wall thickness (W.Th) in all bone compartments (cancellous, cortical and endosteal) was significantly decreased in AFF patients. In contrast, erosion surface (ES/BS) and osteoclast surface (Oc.S/BS) in all bone compartments were numerically increased in AFF patients, but only the increase in OcS/BS in cortical bone reached statistical significance. Based on numerical data, the insignificant results may have been due to small sample size. Nano-indentation showed that the elastic modulus (E) of cortical bone was significantly increased in AFF patients.In summary, two morphological changes of bone (especially cortical bone) were noted in AFF patients: decreased W.Th and increased osteoclasts and bone resorption areas. Others have reported increased number of osteoclasts after 3 years of alendronate treatment, but approximately 1/3 were giant hyper-nucleated osteoclasts detached from bone surface (NEJM 2009;360:53-62). These osteoclasts have low capacity for bone resorption, producing shallow resorption cavities. Accordingly, accumulation of such abnormal osteoclasts may increase resorption area, but decrease resorption depth. The shallow resorption cavities would reduce W.Th, leading to an expansion of interstitial bone area with higher mineralization degree that may raise elastic modulus. Our previous work indicated that microdamage are much more likely to accumulate in the interstitial areas of cortical bone. Therefore, the increase in fragile interstitial bone is probably a crucial factor for the development of atypical fracture in femoral diaphysis.




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