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In clinical studies, high resolution peripheral quantitative computed tomography (HR-pQCT) is used to separately evaluate cortical bone and trabecular bone with an isotropic voxel of 82 µm 3 , and typical cortical parameters are cortical density (D.comp), thickness (Ct.Th), and porosity (Ct.Po). In vitro, micro-computed tomography (micro-CT) is used to explore the internal cortical bone micro-structure with isotropic voxels and high resolution synchrotron radiation (SR); micro-CT is considered the 'gold standard'. In 16 tibias and 8 femurs, HR-pQCT measurements were compared to conventional micro-CT measurements. To test modality effects, conventional micro-CT measurements were compared to SR micro-CT measurements at 7.5 µm 3 ; SR micro-CT measurements were also tested at different voxel sizes for the femurs, specifically, 7.5 µm 3 versus 2.8 µm 3 . D.comp (r  =  -0.88, p  <  10 -3 ) was the parameter best correlated with porosity (Po.V/TV). The correlation was not affected by the removal of pores under 130 µm. Ct.Th was also significantly highly correlated (r  =  -0.89 p  <  10 -3 ), while Ct.Po was correlated with its counterpart Po.V/TV (r  =  0.74, p  <  10 -3 ). From SR micro-CT and conventional micro-CT at 7.5 µm 3 in matching areas, Po.V/TV and pore diameter were underestimated in conventional micro-CT with mean  ±  standard deviation (SD) biases of  -2.5  ±  1.9% and  -0.08  ±  0.08 mm, respectively. In contrast, pore number (Po.N) and pore separation (Po.Sp) were overestimated with mean  ±  SD biases of  +0.03  ±  0.04 mm -1 and  +0.02  ±  0.04 mm, respectively. The results from the tibia and femur were similar when the results of SR micro-CT at 7.5 µm 3 and 2.8 µm 3 were compared. Po.V/TV, specific surface of pores (Po.S/Po.V), and Po.N were underestimated with mean biases of  -1.7  ±  0.9%, -4.6  ±  4.4 mm -1 , and  -0.26  ±  0.15 mm -1 , respectively. In contrast, pore spacing was overestimated at 7.5 µm 3 compared to 2.8 µm 3 with mean biases of 0.05  ±  0.03 mm. Cortical bone measurements from HR-pQCT images provided consistent results compared to those obtained using conventional micro-CT at the distal tibia. D.comp was highly correlated to Po.V/TV because it considers both the micro-porosity (Haversian systems) and macro-porosity (resorption lacunae) of cortical bone. The complexity of canal organization, (including shape, connectivity, and surface) are not fully considered in conventional micro-CT in relation to beam hardening and cone beam reconstruction artifacts. With the exception of Po.V/TV measurements, morphological and topological measurements depend on the characteristics of the x-ray beam, and to a lesser extent, on image resolution.

In assessing osteoporotic fractures of the proximal femur, the main objective of this in vivo case-control study was to evaluate the performance of quantitative computed tomography (QCT) and a dedicated 3D image analysis tool [Medical Image Analysis Framework--Femur option (MIAF-Femur)] in differentiating hip fracture and non-hip fracture subjects. One-hundred and seven women were recruited in the study, 47 women (mean age 81.6 years) with low-energy hip fractures and 60 female non-hip fracture control subjects (mean age 73.4 years). Bone mineral density (BMD) and geometric variables of cortical and trabecular bone in the femoral head and neck, trochanteric, and intertrochanteric regions and proximal shaft were assessed using QCT and MIAF-Femur. Areal BMD (aBMD) was assessed using dual-energy X-ray absorptiometry (DXA) in 96 (37 hip fracture and 59 non-hip fracture subjects) of the 107 patients. Logistic regressions were computed to extract the best discriminates of hip fracture, and area under the receiver characteristic operating curve (AUC) was calculated. Three logistic models that discriminated the occurrence of hip fracture with QCT variables were obtained (AUC = 0.84). All three models combined one densitometric variable--a trabecular BMD (measured in the femoral head or in the trochanteric region)--and one geometric variable--a cortical thickness value (measured in the femoral neck or proximal shaft). The best discriminant using DXA variables was obtained with total femur aBMD (AUC = 0.80, p = .003). Results highlight a synergistic contribution of trabecular and cortical components in hip fracture risk and the utility of assessing QCT BMD of the femoral head for improved understanding and possible insights into prevention of hip fractures., (Copyright © 2011 American Society for Bone and Mineral Research.)

Cortical bone is a multiscale composite material. Its elastic properties are anisotropic and heterogeneous across its cross-section, due to endosteal bone resorption which might affect bone strength. The aim of this paper was to describe a homogenization method leading to the estimation of the variation of the elastic coefficients across the bone cross-section and along the bone longitudinal axis. The method uses the spatial variations of bone porosity and of the degree of mineralization of the bone matrix (DMB) obtained from the analysis of 3-D synchrotron micro-computed tomography images. For all three scales considered (the foam (100 nm), the ultrastructure (5 microm) and the mesoscale (500 microm)), the elastic coefficients were determined using the Eshelby's inclusion problem. DMB values were used at the scale of the foam. Collagen was introduced at the scale of the ultrastructure and bone porosity was introduced at the mesoscale. The pores were considered as parallel cylinders oriented along the bone axis. Each elastic coefficient was computed for different regions of interest, allowing an estimation of its variations across the bone cross-section and along the bone longitudinal axis. The method was applied to a human femoral neck bone specimen, which is a site of osteoporotic fracture. The computed elastic coefficients for cortical bone were in good agreement with experimental results, but some discrepancies were obtained in the endosteal part (trabecular bone). These results highlight the importance of accounting for the heterogeneity of cortical bone properties across bone cross-section and along bone longitudinal axis., (2010 Elsevier Ltd. All rights reserved.)

Background: The incidence of osteoporotic hip fractures increases with age, more sharply in women than in men, as a result of qualitative and quantitative bone alterations. Mineralization (a qualitative parameter) showed no differences with age or sex in cancellous bone in earlier studies. Few studies assessed such differences in cortical bone, a major contributor to femoral bone strength. The aim of this in vitro cross-sectional study of a large group of human femoral midshafts was to look for age- and sex-related differences in the degree and distribution of cortical mineralization that might be implicated in bone fragility., Methods: Cortical bone specimens from 193 femurs were studied using quantitative microradiography, with an aluminum step-wedge reference. The femurs were from 99 females and 94 males in a Caucasian anthropological collection covering a broad age spectrum. We determined the mean degree of mineralization of osteons (On.DMB-Al), interstitial tissue (Int.DMB-Al), and total bone (Tt.DMB-Al), and representative parameters of density histograms. Results were expressed as relative values. Age- and sex-related differences in DMB-Al values were evaluated using non-parametric tests., Results: Degree of tissue mineralization (Tt.DMB-Al) decreased significantly with age in females (r=-0.257; P=0.010) but did not change in males. Tt.DMB-Al was higher in females than males until 50 years of age (P=0.001) but was lower in elderly females than elderly males (P=0.016). DMB-Al distribution varied significantly with sex and age. The first DMB-Al quartiles in osteons and interstitial tissue were not different between males and females, but the third quartile and interquartile range differed significantly (P=0.032 and P=0.000, respectively). The mineralization difference between the two tissues indicated greater bone heterogeneity in females than males (P=0.000)., Conclusions: In this in vitro cross-sectional study of anterior midfemoral cortical specimens, the degree and distribution of mineralization varied with age and sex. In females, mineralization started at a higher level than in males but was lower in the sixth decade, falling below the level in males. Mineralization was far more stable throughout life in males. In elderly females, the lower degree and greater heterogeneity of mineralization may have consequences on bone strength and the risk of fracture.

The relevance of Finite-Element models for hip fracture prediction should be increased by the recent subject-specific methods based on computed tomography (CT-scan), regarding the geometry as well as the material properties. The present study focused on the prediction of subject-specific mechanical parameters of cortical bone (Young's modulus and ultimate strength) from the bone density measured by CT. A total of 46 compression and 46 tension samples from 13 donors (mean age+/-S.D.: 81.8+/-12.7 years) were harvested in the femoral mid-diaphysis and tested until failure. The Young's modulus and ultimate strength were linearly correlated with the bone density measured by CT, for tension as well as compression (0.43

Thirty-eight slices of pure trabecular bone 1-cm thickness were extracted from human proximal femurs. A pair of 1-MHz central frequency transducers was used to measure quantitative ultrasound (QUS) parameters in transmission [normalized broadband ultrasound attenuation (nBUA), speed of sound (SOS)] and in backscatter [broadband ultrasound backscatter (BUB)]. Bone mineral density (BMD) was measured using clinical x-ray quantitative computed tomography. Site-matched identical region of interest (ROIs) of 7 x 7 mm2 were positioned on QUS and QCT images. This procedure resulted in 605 ROIs for all the specimens data pooled together. The short-term precision of the technique expressed in terms of CV was found to be 2.3% for nBUA, 0.3% for SOS and 4.5% for BUB. Significant linear correlation between QUS and BMD were found for all the 605 ROIs pooled, with r2 values of 0.73, 0.77, and 0.58 for nBUA, SOS, and BUB, respectively (all p < 0.05). For the BUB, the best regression was obtained with a polynomial fit of second order (r2 = 0.63). An analysis of measurements errors was developed. It showed that the residual variability of SOS is almost completely predicted by measurements errors, which is not the case for BUA and BUB, suggesting a role for micro-architecture in the determination of BUA and BUB.

Three-dimensional accurate evaluation of the geometry of the proximal femur may be helpful for hip fracture risk evaluation. The purpose of this study was to apply and validate a stereo-radiographic 3D reconstruction method of the proximal femur, using contours identification from biplanar DXA images. Twenty-five excised human proximal femurs were investigated using a standard DXA unit. Three-dimensional personalized models were reconstructed using a dedicated non-stereo corresponding contours (NSCC) algorithm. Three-dimensional CT-scan reconstructions obtained on a clinical CT-scan unit were defined as geometric references for the comparison protocol, in order to assess accuracy and reproducibility of the 3D stereo-radiographic reconstructions. The precision of a set of 3D geometric parameters (femoral-neck axis length, mid-neck cross-section area, neck-shaft angle), obtained from stereo-radiographic models was also evaluated. This study shows that the NSCC method may be applied to obtain 3D reconstruction from biplanar DXA acquisitions. Applied to the proximal femur, this method showed good accuracy as compared with high-resolution personalized CT-scan models (mean error = 0.8 mm). Moreover, precision study for the set of 3D parameters yielded coefficients of variation lower than 5%. This is the first study providing 3D geometric parameters from standard 2D DXA images using the NSCC method. It has good accuracy and reproducibility in the present study on cadaveric femurs. In vivo prospective studies are needed to evaluate its discriminating potential on hip fracture risk prediction.

Objective: Accurate three-dimensional (3D) geometry of the proximal femur may be helpful for fracture risk evaluation, as well as for planning and assisting surgical procedures. The purpose of this study was to apply and validate a stereoradiographic 3D reconstruction method on the proximal femur from radiographic contours identified on bi-planar radiographs., Materials and Methods: Twenty-five excised non-pathologic proximal femurs were investigated using a low-dose digital radiographic device. Three-dimensional personalized models were reconstructed using the Non-Stereo Corresponding Contours (NSCC) algorithm. Three-dimensional CT-scan reconstructions were defined as geometric references for the comparison protocol, in order to assess the accuracy and reproducibility of the personalized 3D stereoradiographic reconstructions. In addition, the reliability of a set of 3D parameters obtained from stereoradiographic models was evaluated., Results: This study demonstrated the validity of the NSCC method when applied to the proximal femur, with good results for accuracy (mean error = 0.7 mm) and reproducibility (Wilcoxon test: p > 0.28). Moreover, a precision study for the set of 3D parameters yielded a coefficient of variation lower than 5%., Conclusions: Once this approach has been validated in vivo, it should find multiple applications in therapeutic fields (e.g., for surgical planning, computer assisted surgery, etc.), as well as in diagnostic contexts (e.g., equilibrium studies or osteoporosis fracture risk assessment).

The purpose of this study was to describe the age-specific distribution of midfemoral intracortical porosity throughout the cortical width in males and females. Microradiography and an automated image analysis system were used to study midfemoral cortical bone specimens from 163 white people, including 77 males and 86 females, in a recent anthropological collection covering a broad age range. In each specimen, porosity (percentage of the cortical bone area occupied by pores), pore number, and pore size were measured throughout the entire cortex and in three cortical subregions of equal width labeled the periosteal, midcortical, and endosteal subregions. For each gender, relationships linking age to porosity, pore number, and mean pore size were assessed using regression analysis. In addition, age- and site-related changes in these three variables were tested for significance using two-way analysis of variance (ANOVA). Age explained 52% of the porosity variance in females and 13.5% in males. In each gender, there were significant age- and site-related differences in porosity, pore number, and pore size. In adults aged 60 years or younger, both pore size and pore number increased with increasing age, whereas in adults older than 60 years, pore size continued to increase but pore number decreased. In males, the age-related changes in pore size and pore number were proportionally similar in the three cortical subregions. In females, in contrast, the changes predominated in the endosteal subregion and resulted in significant cortical thinning.

Purpose: To determine whether computed tomography (CT) can be used to quantify age- and site-related changes in cortical bone mineral density (cBMD) at the middiaphyseal femur and whether cBMD differences are related to intracortical porosity., Materials and Methods: Cortical bone specimens from 163 femurs were studied with CT and microradiography. Femurs were from 77 males and 86 females in a white anthropologic collection covering a broad age spectrum. In each sample, the cBMD was measured in the entire cortical width and in periosteal, midcortical, and endosteal subregions of interest. Age- and site-related changes in cBMD were tested for significance by using a two-way analysis of variance for both sexes. By using linear regression, cBMD was compared with porosity in the entire cortical width and in each subregion., Results: There were significant age-related differences in cBMD (P <.001 in females, P =.008 in males). In addition, cBMD values were significantly different between the three cortical subregions (P <.001 for both sexes), decreasing from the periosteum to the midcortex to the endosteum. The cBMD values were closely related to porosity, and porosity contributed to 71.6% of the variance in cBMD in the overall population., Conclusion: CT is effective in the measurement of age- and site-related changes in cBMD. Decreases in cBMD are closely correlated with increased cortical porosity.