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Introduction: Cortical bone thinning and a rarefaction of the trabecular architecture represent possible causes of increased femoral neck (FN) fracture risk. Due to X-ray exposure limits, the bone microstructure is rarely measurable in the FN of subjects but can be assessed at the tibia. Here, we studied whether changes of the tibial cortical microstructure, which were previously reported to be associated with femur strength, are also associated with structural deteriorations of the femoral neck., Methods: The cortical and trabecular architectures in the FN of 19 humans were analyzed ex vivo on 3D microcomputed tomography images with 30.3 μm voxel size. Cortical thickness (Ct.Th tibia ), porosity (Ct.Po tibia ) and pore size distribution in the tibiae of the same subjects were measured using scanning acoustic microscopy (12 μm pixel size). Femur strength during sideways falls was simulated with homogenized voxel finite element models., Results: Femur strength was associated with the total (vBMD tot ; R 2  = 0.23, p < 0.01) and trabecular (vBMD trab ; R 2  = 0.26, p < 0.01) volumetric bone mineral density (vBMD), with the cortical thickness (Ct.Th FN ; R 2  = 0.29, p < 0.001) and with the trabecular bone volume fraction (Tb.BV/TV FN ; R 2  = 0.34, p < 0.001), separation (Tb.Sp FN ; R 2  = 0.25, p < 0.01) and number (Tb.N FN ; R 2  = 0.32, p < 0.001) of the femoral neck. Moreover, smaller Ct.Th tibia was associated with smaller Ct.Th FN (R 2  = 0.31, p < 0.05), lower Tb.BV/TV FN (R 2  = 0.29, p < 0.05), higher Tb.Sp FN (R 2  = 0.33, p < 0.05) and lower Tb.N FN (R 2  = 0.42, p < 0.01). A higher prevalence of pores with diameter > 100 μm in tibial cortical bone (relCt.Po 100μm-tibia ) indicated higher Tb.Sp FN (R 2  = 0.36, p < 0.01) and lower Tb.N FN (R 2  = 0.45, p < 0.01)., Conclusion: Bone resorption and structural decline of the femoral neck may be identified in vivo by measuring cortical bone thickness and large pores in the tibia., Competing Interests: Declaration of competing interest KR and GI have the patent application “CortBS: Ultrasonic method for determining pore dimensions in cortical bone” pending. JS, AR, FH, LP, CW, CCG and DP have nothing to disclose. JB reports grants and personal fees from Eli Lilly, grants and personal fees from Amgen, grants from Will Pharma, outside the submitted work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cortical pores are determinants of the elastic properties and of the ultimate strength of bone tissue. An increase of the overall cortical porosity (Ct.Po) as well as the local coalescence of large pores cause an impairment of the mechanical competence of bone. Therefore, Ct.Po represents a relevant target for identifying patients with high fracture risk. However, given their small size, the in vivo imaging of cortical pores remains challenging. The advent of modern high-resolution peripheral quantitative computed tomography (HR-pQCT) triggered new methods for the clinical assessment of Ct.Po at the peripheral skeleton, either by pore segmentation or by exploiting local bone mineral density (BMD). In this work, we compared BMD-based Ct.Po estimates with high-resolution reference values measured by scanning acoustic microscopy. A calibration rule to estimate local Ct.Po from BMD as assessed by HR-pQCT was derived experimentally. Within areas of interest smaller than 0.5 mm 2 , our model was able to estimate the local Ct.Po with an error of 3.4%. The incorporation of the BMD inhomogeneity and of one parameter from the BMD distribution of the entire scan volume led to a relative reduction of the estimate error of 30%, if compared to an estimate based on the average BMD. When applied to the assessment of Ct.Po within entire cortical bone cross-sections, the proposed BMD-based method had better accuracy than measurements performed with a conventional threshold-based approach., (Copyright © 2018 Elsevier Inc. All rights reserved.)