Analysis of cortical bone quality in long-term bisphosphonate users with atypical femur fracture (AFF)
Farlay D, Rizzo S, Ste-Marie LG, Michou L, Morin SN, Qiu S, Chapurlat R, Rao SD, and Brown J. Analysis of cortical bone quality in long-term bisphosphonate users with atypical femur fracture (AFF). Bone Reports 2020; 13.
Purpose: Atypical Femur Fractures (AFF) are associated with long-term bisphosphonates (BPs) therapy, but it is unclear if cortical bone quality is altered in AFF. Accordingly, we analyze cortical bone quality in BPs-treated patients with or without AFF.
Material and methods: Two groups of 26 transiliac bone biopsies from postmenopausal women treated with BPs with AFF and without AFF were analyzed. Histomorphometry revealed low remodeling in all patients. Degree of mineralization of bone (DMB) and heterogeneity index (HI) of mineralization were measured using digitized microradiography. Microhardness (Hv) was calculated with a Vickers microindenter. Quality of mineral phase and organic matrix were assessed using Fourier transform infrared microspectroscopy (FTIRM). Mann-Whitney and Spearman correlation tests were performed.
Results: Women with AFF were treated significantly longer (9.7±3.3yrs) than women without AFF (7.9±2.7yrs, p=0.026). Cortical DMB was significantly higher in AFF than in non-AFF (p=0.001) and HI was significantly lower (p=0.050) implying a denser and more homogeneous cortical bone in AFF vs non-AFF. Increase in cortical DMB persisted even after adjustment for treatment duration (p=0.007). Hv and quality of mineral phase and organic matrix (FTIRM) were not modified. Cortical DMB was positively correlated with treatment duration (r'=0.468; p< 0.020) in AFF group only. In contrast, denosumab, a more potent antiresorptive, lead to higher cortical DMB and lower HI as reported by us with the same methodology in 2-3 years denosumab treated women (Dempster et al. JCEM, 2018). However, Hv was significantly increased (unpublished) leading to beneficial effect on bone resistance.
Conclusions: Cortical DMB was higher and HI lower in AFF than in non-AFF, but these results do not appear to be solely due to a lower bone turnover in AFF. Therefore, the combination of a higher DMB (and lower HI) and absence of higher hardness could explain the propensity for AFF in long-term BP users.