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Introduction: In 2010, experts in osteoporosis and bone densitometry were convened by the Space Life Sciences Directorate at NASA Johnson Space Center to identify a skeletal outcome in astronauts after spaceflight that would require a clinical response to address fracture risk. After reviewing astronaut data, experts expressed concern over discordant patterns in loss and recovery of bone mineral density (BMD) after spaceflight as monitored by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). The pilot study described herein demonstrates the use of QCT to evaluate absence of recovery in hip trabecular BMD by QCT as an indicator of a clinically actionable response. Methodology: QCT and DXA scans of both hips were performed on 10 astronauts: once preflight and twice postflight about 1 wk and 1 yr after return. If trabecular BMD had not returned to baseline (i.e., within QCT measurement error) in 1 or both hips 1 yr after flight, then another QCT hip scan was obtained at 2 yr after flight. Results: Areal BMD by DXA recovered in 9 of 10 astronauts at 1 yr postflight while incomplete recovery of trabecular BMD by QCT was evident in 5 of 10 astronauts and persisted in 4 of the 5 astronauts 2 yr postflight. Conclusion: As an adjunct to DXA, QCT is needed to detect changes to hip trabecular BMD after spaceflight and to confirm complete recovery. Incomplete recovery at 2 yr should trigger the need for further evaluation and possible intervention to mitigate premature fragility and fractures in astronauts following long-duration spaceflight. [ABSTRACT FROM AUTHOR]

Introduction : Cortical bone is affected by metabolic diseases. Some studies have shown that lower cortical bone mineral density (BMD) is related to increases in fracture risk which could be diagnosed by quantitative computed tomography (QCT). Nowadays, hybrid iterative reconstruction-based (HIR) computed tomography (CT) could be helpful to quantify the peripheral bone tissue. A key focus of this paper is to evaluate liquid calibration phantoms for BMD quantification in the tibia and under hybrid iterative reconstruction-based-CT with the different hydrogen dipotassium phosphate (K 2 HPO 4) concentrations phantoms. Methodology : Four ranges of concentrations of K 2 HPO 4 were made and tested with 2 exposure settings. Accuracy of the phantoms with ash gravimetry and intermediate K 2 HPO 4 concentration as hypothetical patients were evaluated. The correlations and mean differences between measured equivalent QCT BMD and ash density as a gold standard were calculated. Relative percentage error (RPE) in CT numbers of each concentration over a 6-mo period was reported. Results : The correlation values (R2 was close to 1.0), suggested that the precision of QCT-BMD measurements using standard and ultra-low dose settings were similar for all phantoms. The mean differences between QCT-BMD and the ash density for low concentrations (about 93 mg/cm3) were lower than high concentration phantoms with 135 and 234 mg/cm3 biases. In regard to accuracy test for hypothetical patient, RPE was up to 16.1% for the low concentration (LC) phantom for the case of high mineral content. However, the lowest RPE (0.4 to 1.8%) was obtained for the high concentration (HC) phantom, particularly for the high mineral content case. In addition, over 6 months, the K 2 HPO 4 concentrations increased 25% for 50 mg/cm3 solution and 0.7 % for 1300 mg/cm3 solution in phantoms. Conclusion : The excellent linear correlations between the QCT equivalent density and the ash density gold standard indicate that QCT can be used with submilisivert radiation dose. We conclude that using liquid calibration phantoms with a range of mineral content similar to that being measured will minimize bias. Finally, we suggest performing BMD measurements with ultra-low dose scan concurrent with iterative-based reconstruction to reduce radiation exposure. [ABSTRACT FROM AUTHOR]

Elevated bone principal strain (an indicator of potential bone injury) resulting from reduced cartilage thickness has been suggested to contribute to patellofemoral symptoms. However, research linking patella bone strain, articular cartilage thickness, and patellofemoral pain (PFP) remains limited. The primary purpose was to determine whether females with PFP exhibit elevated patella bone strain when compared to pain-free controls. A secondary objective was to determine the influence of patella cartilage thickness on patella bone strain. Ten females with PFP and 10 gender, age, and activity-matched pain-free controls participated. Patella bone strain fields were quantified utilizing subject-specific finite element (FE) models of the patellofemoral joint (PFJ). Input parameters for the FE model included (1) PFJ geometry, (2) elastic moduli of the patella bone, (3) weight-bearing PFJ kinematics, and (4) quadriceps muscle forces. Using quasi-static simulations, peak and average minimum principal strains as well as peak and average maximum principal strains were quantified. Cartilage thickness was quantified by computing the perpendicular distance between opposing voxels defining the cartilage edges on axial plane magnetic resonance images. Compared to the pain-free controls, individuals with PFP exhibited increased peak and average minimum and maximum principal strain magnitudes in the patella. Additionally, patella cartilage thickness was negatively associated with peak minimum principal patella strain and peak maximum principal patella strain. The elevated bone strain magnitudes resulting from reduced cartilage thickness may contribute to patellofemoral symptoms and bone injury in persons with PFP. [ABSTRACT FROM AUTHOR]

Abstract: To examine the effects of race and sex on bone density and geometry at specific sites within the proximal femur and lumbar spine, we used quantitative computed tomography to image 30 Caucasian American (CA) men, 25 African American (AA) men, 30 CA women, and 17 AA women aged 35–45yr. Volumetric integral bone mineral density (BMD), trabecular BMD (tBMD), and cross sectional area were measured in the femoral neck, trochanter, total femur, and L1/L2 vertebrae. Volumetric cortical BMD (cBMD) was also measured in the femur regions of interest. Differences were ascertained using a multivariate regression model. Overall, AA subjects had denser bones than CA subjects, but there were no racial differences in bone size. Men had larger femoral necks but not larger vertebrae than women. The AA men had higher tBMD and cBMD in the femur than CA men, whereas AA women had higher femoral tBMD but not higher femoral cBMD than CA women. These data support the idea that higher hip fracture rates in women compared with men are associated with smaller bone size. Lower fracture rates in AA elderly compared with CA elderly are consistent with higher peak bone density, particularly in the trabecular compartment, and potentially lower rates of age-related bone loss rather than larger bone size. [Copyright &y& Elsevier]

Hip fracture is a serious and common injury that can lead to permanent disability, pneumonia, pulmonary embolism, and death. Research to help prevent these fractures is essential. Computed tomographic (CT) scan-based finite element (FE) modeling is a tool that can predict proximal femoral fracture loads in vitro. Because this tool might be used in vivo, this study examined whether FE models generated from CT scans in situ and in vitro yield comparable predictions of proximal femoral fracture load. CT scans of the left proximal femur of two human cadavers were obtained in situ and in vitro, and three-dimensional FE models employing nonlinear mechanical properties were generated from each CT scan. The models were evaluated under single-limb stance-type loading by applying displacements incrementally to the femoral head. The FE-predicted fracture load (FFE) was the maximum femoral head reaction force. FFE for the in situ-derived models for the two subjects were 5.2 and 13.3% greater than for the in vitro-derived models. These results demonstrate that using CT scan data obtained in situ instead of in vitro to generate FE models can lead to substantially different predicted fracture loads. This effect must be considered when using this technology in vivo. [Copyright &y& Elsevier]

Abstract: Fracture of the proximal femur due to metastatic disease is a significant cause of morbidity and mortality among breast cancer patients. Prophylactic surgical fixation is advised for patients at risk of fracture and typically involves placement of an orthopaedic implant. We propose that some proximal femora with metastases can be repaired by removing the lesion and filling the resulting defect with bone cement (polymethylmethacrylate), a procedure that could be performed percutaneously without the use of hardware. We studied the strengths of 12 matched pairs of cadaveric proximal femora under single-limb stance loading. One femur from each pair remained intact, while a simulated metastatic lesion, measuring approximately 75% of the neck diameter, was burred into the neck of the contralateral femur. The defects were repaired using a procedure similar to the one proposed. Femoral strength was measured via mechanical testing to failure. The strengths of the repaired femora averaged 94.7% of the strength of their respective contralateral intact femur (standard deviation, 8.7%). These findings suggest that the proposed procedure may be useful for some patients with metastases in the femoral neck. If the proximal femur could be safely repaired using the proposed technique in place of conventional surgical fixation, the patient would benefit from a shorter and less invasive surgical procedure, less pain and discomfort, greatly reduced recovery time, and a shorter hospital stay—all at a much lower cost. [Copyright &y& Elsevier]

Physical activity enhances proximal femur bone mass, but it remains unclear whether the benefits translate into an enhanced ability to resist fracture related loading. We recently used baseball pitchers as a within-subject controlled model to demonstrate physical activity induced proximal femur adaptation in regions associated with weight bearing and increased strength under single-leg stance loading. However, there was no measurable benefit to resisting common injurious loading (e.g. a fall onto the greater trochanter). A lack of power and a small physical activity effect size may have contributed to the latter null finding. Softball pitchers represent an alternative within-subject controlled model to explore adaptation of the proximal femur to physical activity, exhibiting greater dominant-to-nondominant (D-to-ND) leg differences than baseball pitchers. The current study used quantitative computed tomography, statistical parametric mapping, and subject-specific finite element (FE) modeling to explore adaptation of the proximal femur to physical activity in female softball pitchers (n = 25). Female cross-country runners (n = 15) were included as symmetrically loaded controls, showing very limited D-to-ND leg differences. Softball pitchers had D-to-ND leg differences in proximal femur, femoral neck, and trochanteric volumetric bone mineral density and content, and femoral neck volume. Voxel-based morphometry analyses and cortical bone mapping showed D-to-ND leg differences within a large region connecting the superior femoral head, inferior femoral neck and medial intertrochanteric region, and within the greater trochanter. FE modeling revealed pitchers had 19.4% (95%CI, 15.0 to 23.9%) and 4.9% (95%CI, 1.7 to 8.2%) D-to-ND leg differences in predicted ultimate strength under single-leg stance loading and a fall onto the greater trochanter, respectively. These data affirm the spatial and strength adaptation of the proximal femur to weight bearing directed loading and demonstrate that the changes can also have benefits, albeit smaller, on resisting loads associated with a sideways fall onto the greater trochanter. [Display omitted] • Physical activity adapts the proximal femur, but is it stronger? • Softball pitchers are a within-subject controlled model of unilateral loading. • The proximal femur opposite the throwing arm had enhanced mass and structure. • Changes enhanced strength to single-leg stance and a fall on the greater trochanter. • Data demonstrate physical activity can enhance resistance to fracture-related loads. [ABSTRACT FROM AUTHOR]

This work investigates how changes in cortical bone microstructure alter the risk of fragility fractures. The secondary osteons of non-osteoporotic (by DXA) women with fragility fractures have reduced lamellar width and greater areas of birefringent brightness in transverse sections, a pathological condition. We used hierarchical finite element (FE) models of the proximal femur of two women aged 67 and 88 (younger and older) during one-legged stance. At specific locations of the anterior-inferior neck (ROI), we analyzed micro-models containing osteons comprised of alternating birefringent extinct and bright lamellae. The plane of lamellar isotropy (XY) was transverse to the osteon longitudinal axis (Z) which was parallel to the femoral neck axis. To evaluate changes in fracture risk with changes in microstructure, we investigated principal and von Mises stresses, and planar stress measures that accounted for transverse isotropy. For both younger and older femurs, 48% to 100% of stress measures were larger in models with healthy architecture than in models with pathological architecture, while controlling for type of lamella and osteon. These findings suggest that bone adaptation reduces stress at most pathological lamellar sites. However, in the bright lamellae of the younger femur, the pathological tensile, compressive and distortional stresses in the transverse plane and distortional stress in the longitudinal planes were larger than the non-negligible corresponding stresses in 6 of the 28 osteon models with healthy architecture, in 5 of the 7 locations. Therefore, a minority of sites with pathological architecture present greater stress, and therefore, greater fracture risk. [ABSTRACT FROM AUTHOR]

In multicenter studies and longitudinal studies that use two or more different quantitative computed tomography (QCT) imaging systems, anthropomorphic standardization phantoms (ASPs) are used to correct inter-scanner differences and allow pooling of data. In this study, in vivo imaging of 20 women on two imaging systems was used to evaluate inter-scanner differences in hip integral BMD (iBMD), trabecular BMD (tBMD), cortical BMD (cBMD), femoral neck yield moment ( M y ) and yield force ( F y ), and finite-element derived strength of the femur under stance (FE stance ) and fall (FE fall ) loading. Six different ASPs were used to derive inter-scanner correction equations. Significant ( p < 0.05) inter-scanner differences were detected in all measurements except M y and FE fall , and no ASP-based correction was able to reduce inter-scanner variability to corresponding levels of intra-scanner precision. Inter-scanner variability was considerably higher than intra-scanner precision, even in cases where the mean inter-scanner difference was statistically insignificant. A significant ( p < 0.01) effect of body size on inter-scanner differences in BMD was detected, demonstrating a need to address the effects of body size on QCT measurements. The results of this study show that significant inter-scanner differences in QCT-based measurements of BMD and bone strength can remain even when using an ASP. [ABSTRACT FROM AUTHOR]

Abstract: Fractures of the proximal femur are the most devastating outcome of osteoporosis. It is generally understood that age-related changes in hip structure confer increased risk, but there have been few explicit comparisons of such changes in healthy subjects to those with hip fracture. In this study, we used quantitative computed tomography and tensor-based morphometry (TBM) to identify three-dimensional internal structural patterns of the proximal femur associated with age and with incident hip fracture. A population-based cohort of 349 women representing a broad age range (21–97years) was included in this study, along with a cohort of 222 older women (mean age 79±7years) with (n=74) and without (n=148) incident hip fracture. Images were spatially normalized to a standardized space, and age- and fracture-specific morphometric features were identified based on statistical maps of shape features described as local changes of bone volume. Morphometric features were visualized as maps of local contractions and expansions, and significance was displayed as Student's t-test statistical maps. Significant age-related changes included local expansions of regions low in volumetric bone mineral density (vBMD) and local contractions of regions high in vBMD. Some significant fracture-related features resembled an accentuated aging process, including local expansion of the superior aspect of the trabecular bone compartment in the femoral neck, with contraction of the adjoining cortical bone. However, other features were observed only in the comparison of hip fracture subjects with age-matched controls including focal contractions of the cortical bone at the superior aspect of the femoral neck, the lateral cortical bone just inferior to the greater trochanter, and the anterior intertrochanteric region. Results of this study support the idea that the spatial distribution of morphometric features is relevant to age-related changes in bone and independent to fracture risk. In women, the identification by TBM of fracture-specific morphometric alterations of the proximal femur, in conjunction with vBMD and clinical risk factors, may improve hip fracture prediction. [Copyright &y& Elsevier]

Pathologic fracture of the hip due to metastatic lesions in bone is a serious problem. This study examined the effect of metastatic lesions on the material properties and quantitative computed tomography (QCT) data of trabecular bone. Twelve distal femora were obtained, four with lytic and/or blastic metastatic lesions (group L), four without lesions but from donors who died from breast, prostate, or lung cancer (group NL), and four from donors with no cancer (group NC). Each specimen was CT scanned, and 56, 15×15×15-mm cubes of trabecular bone were cut. QCT density (ρQCT), compressive elastic modulus (E), compressive yield and ultimate strengths (Sy and Su), and ash density (ρash) of each cube were determined. Regression analysis was performed between ρash and E, Sy, Su and ρQCT, and analysis of covariance was used to identify differences between groups. Power relationships that did not depend on group (p&ges;0.1) were found between E and ρash (0.74&les;r&les;0.84; p<0.001) and between strength (Sy and Su) and ρash (r&ges;0.94; p<0.001). ρash was strongly related to ρQCT (r&ges;0.99; p<0.001). These results indicate that metastatic disease does not significantly impair the ability of QCT to provide an accurate and precise estimate of ρash that can be used to estimate mechanical properties of trabecular bone with and without metastases. [Copyright &y& Elsevier]

Breast, prostate, lung, and other cancers can metastasize to bone and lead to pathological fracture. To lay the groundwork for new clinical techniques for assessing the risk of pathological fracture, we identified relationships between density measured using quantitative computed tomography (ρQCT), longitudinal mechanical properties, and ash density (ρAsh) of cortical bone from femoral diaphyses with and without metastatic lesions from breast, prostate, and lung cancer (bone with metastases from six donors; bone without metastases from one donor with cancer and two donors without cancer). Moderately strong linear relationships between ρQCT and elastic modulus, strength, and ρAsh were found for bone with metastases (0.73, P<0.05). After accounting for differences in ρQCT, the elastic modulus, compressive strength, tensile yield strain, and ρAsh of bone with metastatic lesions differed from those of bone from donors without cancer (P<0.01). However, differences in tensile strength or compressive yield strain, after controlling for ρQCT, were not found. Thus, these cancers degrade the elastic modulus and compressive strength, but not the tensile strength, of cortical bone beyond the amount that would be expected from decreased density alone. The ρQCT-mechanical property relationships reported may be useful for evaluating bone integrity and assessing the risk of fracture of bone with metastases. [Copyright &y& Elsevier]