Cortical Bone Mapping Research Articles

Population trends in human rib cross-sectional shapes.

Rib fractures remain the most frequent thoracic injury in motor vehicle crashes. Computational human body models (HBMs) can be used to simulate these injuries and design mitigation strategies, but they require adequately detailed geometry to replicate such fractures. Due to a lack of rib cross-sectional shape data availability, most commercial HBMs use highly simplified rib sections extracted from a single individual during original HBM development. This study provides human rib shape data collected from chest CT scans of 240 females and males across the full adult age range. A cortical bone mapping algorithm extracted cross-sectional geometry from scans in terms of local periosteal position with respect to the central rib axis and local cortex thickness. Principal component analysis was used to reduce the dimensionality of these cross-sectional shape data. Linear regression found significant associations between principal component scores and subject demographics (sex, age, height, and weight) at all rib levels, and predicted scores were used to explore the expected rib cross-sectional shapes across a wide range of subject demographics. The resulting detailed rib cross-sectional shapes were quantified in terms of their total cross-sectional area and their cortical bone cross-sectional area. Average-sized female ribs were smaller in total cross-sectional area than average-sized male ribs by between 20% and 36% across the rib cage, with the greatest differences seen in the central portions of rib 6. This trend persisted although to smaller differences of 14%-29% when comparing females and males of equal intermediate weight and stature. Cortical bone cross-sectional areas were up to 18% smaller in females than males of equivalent height and weight but also reached parity in certain regions of the rib cage. Increased age from 25 to 80 years was associated with reductions in cortical bone cross-sectional area (up to 37% in females and 26% in males at mid-rib levels). Total cross-sectional area was also seen to reduce with age in females but to a lesser degree (of up to 17% in mid-rib regions). Similar regions saw marginal increases in total cross-sectional area for male ribs, indicating age affects rib cortex thickness moreso than overall rib cross-sectional size. Increased subject height was associated with increased rib total and cortical bone cross-sectional areas by approximately 25% and 15% increases, respectively, in mid-rib sections for a given 30 cm increase in height, although the magnitudes of these associations varied by sex and rib location. Increased weight was associated with approximately equal changes in both cortical bone and total cross-sectional areas in males. These effects were most prominent (around 25% increases for an addition of 50 kg) toward lower ribs in the rib cage and had only modest effects (less than 12% change) in ribs 2-4. Females saw greater increases with weight in total rib area compared to cortical bone area, of up to 21% at the eighth rib level. Results from this study show the expected shapes of rib cross-sections across the adult rib cage and across a broad range of demographics. This detailed geometry can be used to produce accurate rib models representing widely varying populations.

Cortical and trabecular bone deficit in middle-aged men living with HIV.

A significant increase in risk of hip fracture was observed in middle-aged men living with human immunodeficiency virus (MLWH), almost a decade earlier than those without infection. Data regarding cortical and trabecular bone deficit of hip, an important determinant of bone strength, in MLWH are limited. Quantitative computed tomography was performed in consecutive MLWH aged ≥30 years between November 2017 and October 2018 at Severance Hospital, Seoul, Korea. Volumetric bone mineral density (vBMD) and cortical bone mapping parameters of hip (cortical thickness, CTh; cortical bone vBMD, CBMD; cortical mass surface density, CMSD; endocortical trabecular density, ECTD) were compared to age- and body mass index (BMI)-matched controls (1:2), using a community-based healthy adults' cohort. Among 83 MLWH and 166 controls (mean age: 47.2 years; BMI: 23.6 kg/m2 ), MLWH had lower total hip vBMD (280 ± 41 vs. 296 ± 41 mg/cm3 ), CMSD (155 vs. 160 mg/cm2 ), and ECTD (158 vs. 175 mg/cm3 ) than controls that remained robust after adjustment for covariates (adjusted β: total hip vBMD, -18.8; CMSD, -7.3; ECTD, -18.0; p < 0.05 for all). Cortical bone mapping revealed localized deficit of CTh, CBMD, and CMSD in anterolateral trochanteric region and femoral neck in MLWH compared to controls, with more extensive ECTD deficit. In MLWH, lower CD4 T cell count (/100 cells/mm3 decrement) and protease inhibitor (PI)-based regimen (versus non-PI regimen) at the time of antiretroviral treatment initiation were associated with lower total hip vBMD (adjusted β -7.5 for lower CD4 count; -28.3 for PI-based regimen) and CMSD (adjusted β -2.6 for lower CD4 count; -12.7 for PI-based regimen; p < 0.05 for all) after adjustment for covariates including age, BMI, smoking, alcohol use, HCV co-infection, tenofovir exposure, and CT scanners types. MLWH had lower hip bone density with cortical and trabecular bone deficit compared to community-dwelling controls. This article is protected by copyright. All rights reserved.

Applying a homogeneous pressure distribution to the upper vertebral endplate: Validation of a new loading system, pilot application to human vertebral bodies, and finite element predictions of DIC measured displacements and strains

Image-based personalized Finite Element Models (pFEM) could detect alterations in physiological deformation of human vertebral bodies, but their accuracy has been seldom reported. Meaningful validation experiments should allow vertebral endplate deformability and ensure well-controlled boundary conditions. This study aimed to (i) validate a new loading system to apply a homogeneous pressure on the vertebral endplate during vertebral body compression regardless of endplate deformation; (ii) perform a pilot study on human vertebral bodies measuring surface displacements and strains with Digital Image Correlation (DIC); (iii) determine the accuracy of pFEM of the vertebral bodies.Homogeneous pressure application was achieved by pressurizing a fluid silicone encased in a rubber silicone film acting on the cranial endplate. The loading system was validated by comparing DIC-measured longitudinal strains and lower-end contact pressures, measured on three homogeneous pseudovertebrae of constant transversal section at 2.0 kN, against theoretically calculated values. Longitudinal strains and contact pressures were rather homogeneous, and their mean values close to theoretical calculations (5% underestimation).DIC measurements of surface longitudinal and circumferential displacements and strains were obtained on three human vertebral bodies at 2.0 kN. Complete displacement and strain maps were achieved for anterolateral aspects with random errors ≤0.2 μm and ≤30 μstrain, respectively. Venous plexus and double curvatures limited the completeness and accuracy of DIC data in posterior aspects.pFEM of vertebral bodies, including cortical bone mapping, were built from computed tomography images. In anterolateral aspects, pFEM accuracy of the three vertebrae was: (i) comparable to literature in terms of longitudinal displacements (R2>0.8); (ii) extended to circumferential displacements (pooled data: R2>0.9) and longitudinal strains (zero median error, 95% error: <27%). Circumferential strains were overestimated (median error: 39%).The new methods presented may permit to study how physiological and pathologic conditions influence the ability of vertebral endplates/bodies to sustain loads.

Intrinsic Cortical Property Analysis of the Medial Column of Proximal Humerus.

Adequate mechanical support of the medial column is paramount to maintain fracture reduction in locking plating of proximal humerus fractures. However, intrinsic cortical properties of the medial column are rarely discussed. The purpose of the study is to describe regional variation of cortex in the medial column. A total of 147 healthy participants were eligible for enrollment between December 2016 and December 2018. Subjects were divided into three groups: group A (20-39 years), group B (40-59 years), and group C (>60 years). For each individual, a color 3D thickness map for proximal humerus was created by cortical bone mapping (CBM) technique after bilateral shoulders were imaged by computed tomography. Measurement Indices including the cortical thickness (CTh), cortical mass surface density (CM) and the endocortical trabecular density (ECTD) were determined, after six regions of interest (ROI) were defined in metaphyseal region. Regional parameter variations were analyzed by one-way ANOVA. The CTh, CM and ECTD values were approximately equivalent between genders in the proximal part of the medial column across all ages (P> 0.05).The greatest difference between sexes was found in CTh and CM values of middle and distal part (P< 0.05). The CTh and CM within medial column were negatively associated with age (P< 0.05). The proximal cortical bone of the medial column was thicker and more dense, compared to the lateral column (P< 0.05). Significant regional variation was found in all measured parameters in group A, but not in groups B and C. Our finding proved that regional differences in the distribution of cortical bone in the medial column The attenuation of cortical bone heterogeneity in the medial column was found after the age of 40 years.

Rib cortical bone thickness variation in adults by age and sex.

Rib fractures are a common and serious outcome of blunt thoracic trauma and their likelihood is greater in older individuals. Osteoporotic bone loss is a well-documented aging phenomenon with sex-specific characteristics, but within rib bones, neither baseline maps of regional thickness nor the rates of bone thinning with age have been quantified across whole ribs. This study presents such data from 4014 ribs of 240 adult subjects aged 20-90. A validated cortical bone mapping technique was applied to clinical computed tomography scans to obtain local rib cortical bone thickness measurements over the surfaces of ribs 2 through 11. Regression models to age and sex gave rates of cortex thinning in local zones and aggregated across whole ribs. The statistical parametric mapping provided these relationships regionally as a function of rib surface location. All models showed significant reductions in bone thickness with age (p < 0.01). Average whole-rib thinning occurred at between 0.011 to 0.032 mm/decade (males) and 0.035 to 0.043 mm/decade (females), with sex and age accounting for up to 37% of population variability (R2 ). Rates of thinning differed regionally and by rib, with the highest bone loss of up to 0.074 mm/decade occurring in mid-rib cutaneous and superior regions of ribs 2-6. Rates were consistently higher in females than males (significantly so across whole ribs but not all local regions) and were more pronounced in cutaneous, superior, and inferior rib aspects (average 0.025 mm/decade difference in ribs 4-8) compared to pleural aspects which had the thickest cortices but saw only minor differences in thinning rates by sex (0.045 mm/decade for females and 0.040 mm/decade for males). Regional analysis showed male and female bone thickness differences that were not statistically significant at 20 years of age (p > 0.05 across practically all regions) but subsequent cortex thinning meant that substantial pleural and cutaneous regions were thinner (p < 0.05) in females than males by 55 years of age. The techniques and results from this study can be applied to assess rib bone content loss in clinical settings across wide populations. Additionally, average cortex thickness results can be mapped directly to finite element models of the thorax, and regression results are used to modify such models to represent the ribs of men and women across their full adult lifespan.

Menopause-related cortical loss of the humeral head region mainly occurred in the greater tuberosity.

AimsProximal humerus fractures are commonly observed in postmenopausal women. The goal of this study was to investigate menopause-related changes in cortical structure of the humeral head.Materials and methodsClinical computed tomography (CT) scans of 75 healthy women spanning a wide range of ages (20–72 years) were analyzed. For each subject, cortical bone mapping (CBM) was applied to create a color three-dimensional (3D) thickness map for the proximal humerus. Nine regions of interest (ROIs) were defined in three walls of the humeral head. Cortical parameters, including the cortical thickness (CTh), cortical mass surface density (CM), and the endocortical trabecular density (ECTD), were measured.ResultsCompared to premenopausal women, postmenopausal women were characterized by a significantly lower CTh and CM value in the lateral part of the greater tuberosity. Similar changes were only found in ROI 4, but not in ROIs 5–6 in the lesser tuberosity. Linear regression analysis revealed that the CTh and CM value of ROIs 1, 3, and 4 were negatively associated with age. These results showed that menopause-related loss in CTh and CM was mainly in the greater tuberosity besides the proximal part of the lesser tuberosity. Trabecular bone variable measured as ECTD showed a notably lower value in ROIs 1–9 in postmenopausal vs. premenopausal group. Inverse linear associations for ECTD and age were found in ROIs 2, 3, 5, 6, 7, and 9, indicating no site-specific differences of endocortical trabecular bone loss between the greater and lesser tuberosity.ConclusionsMenopause-related cortical loss of the humeral head mainly occurred in the lateral part of the greater tuberosity. The increased rate of humeral bone loss in the greater tuberosity may contribute materially to complex proximal humerus fractures.

Morphological characteristics of the surgical neck region in the proximal humerus at different ages

BackgroundThe objective of the study was to demonstrate the cortical thickness character in the humeral surgical neck region using 3D cortical bone mapping technique and try to illustrate its morphological changes with age.Material and methodsNormal individuals, including 11 volunteers younger than 18 years, 87 adult men and 46 adult women, were enrolled. The cortical thickness and height of the surgical neck region was measured with Mimic and 3 Matic software. The height of the region was compared and measured. People with an age of 18–30 years was identified as Group I, people in 31–40 years as Group II, people in 41–50 years as Group III, people in 51–60 years as Group IV, and Group V including people ≥ 61 years.ResultsCompared with the baseline Group I, cortical thickness was significantly decreased by 0.52 mm (P = 0.006) in Group III, by 0.76 mm (P < 0.001) in Group IV, and by 0.77 mm (P < 0.001) in Group V. Age moderately predicted cortical thickness with r = −0.5481. The height of the cortical change region was significantly decreased by 2.25 mm (P = 0.007) in Group II, by 2.98 mm (P < 0.001) in Group III, and by 2.07 mm (P = 0.02) in Group IV. However, no significant decrease was illustrated in Group V (0.57 mm) (P = 0.891). The relation between age and the height of the cortical thickness change region was nonlinear.ConclusionsThis study identified an obvious decrease in cortical thickness with aging, and the height was curve fitted with aging in surgical neck region.

Multiparametric 3-D analysis of bone and joint space width at the knee from weight bearing computed tomography.

Computed tomography (CT) can deliver multiple parameters relevant to osteoarthritis. In this study we demonstrate that a 3-D multiparametric approach at the weight bearing knee with cone beam CT is feasible, can include multiple parameters from across the joint space, and can reveal stronger relationships with disease status in combination. 33 participants with knee weight bearing CT (WBCT) were analysed with joint space mapping and cortical bone mapping to deliver joint space width (JSW), subchondral bone plate thickness, endocortical thickness, and trabecular attenuation at both sides of the joint. All data were co-localised to the same canonical surface. Statistical parametric mapping (SPM) was applied in uni- and multivariate models to demonstrate significant dependence of parameters on Kellgren & Lawrence grade (KLG). Correlation between JSW and bony parameters and 2-week test-retest repeatability were also calculated. SPM revealed that the central-to-posterior medial tibiofemoral joint space was significantly narrowed by up to 0.5 mm with significantly higher tibial trabecular attenuation up to 50 units for each increment in KLG as single features, and in a wider distribution when combined (p<0.05). These were also more strongly correlated with worsening KLG grade category. Test-retest repeatability was subvoxel (0.37 mm) for nearly all thickness parameters. 3-D JSW and tibial trabecular attenuation are repeatable and significantly dependent on radiographic disease severity at the weight bearing knee joint not just alone, but more strongly in combination. A quantitative multiparametric approach with WBCT may have potential for more sensitive investigation of disease progression in osteoarthritis.

Prediction of femoral strength of elderly men based on quantitative computed tomography images using machine learning.

Hip fracture is the most common complication of osteoporosis, and its major contributor is compromised femoral strength. This study aimed to develop practical machine learning models based on clinical quantitative computed tomography (QCT) images for predicting proximal femoral strength. Eighty subjects with entire QCT data of the right hip region were randomly selected from the full MrOS cohorts, and their proximal femoral strengths were calculated by QCT-based finite element analysis (QCT/FEA). A total of 50 parameters of each femur were extracted from QCT images as the candidate predictors of femoral strength, including grayscale distribution, regional cortical bone mapping (CBM) measurements, and geometric parameters. These parameters were simplified by using feature selection and dimensionality reduction. Support vector regression (SVR) was used as the machine learning algorithm to develop the prediction models, and the performance of each SVR model was quantified by the mean squared error (MSE), the coefficient of determination (R2 ), the mean bias, and the SD of bias. For feature selection, the best prediction performance of SVR models was achieved by integrating the grayscale value of 30% percentile and specific regional CBM measurements (MSE ≤ 0.016, R2 ≥ 0.93); and for dimensionality reduction, the best prediction performance of SVR models was achieved by extracting principal components with eigenvalues greater than 1.0 (MSE ≤ 0.014, R2 ≥ 0.93). The femoral strengths predicted from the well-trained SVR models were in good agreement with those derived from QCT/FEA. This study provided effective machine learning models for femoral strength prediction, and they may have great potential in clinical bone health assessments.

Can neck fractures in proximal humeri be predicted by CT-based FEA?

Background:Proximal humeri fractures at anatomical and surgical neck (∼5% and ∼50% incidence respectively) are frequent in elderly population. Yet, neither in-vitro experiments nor CT-based finite element analyses (CTFEA) have investigated these in depth. Herein we enhance (Dahan et al., 2019) (addressing anatomical neck fractures) by more experiments and specimens, accounting for surgical neck fractures and explore CTFEA’s prediction of humeri mechanical response and yield force. Methods:Four fresh frozen human humeri were tested in a new experimental configuration inducing surgical neck fractures. Digital image correlation (DIC) provided strains and displacements on humeri surfaces and used to validate CTFEA predictions. CTFEA were enhanced herein to improve the accuracy at the proximal neck: A cortical bone mapping (CBM) algorithm was implemented to overcome insufficient scanning resolution, and a new trabecular material mapping was investigated. Results:The new experimental setting induced impacted surgical neck fractures in all humeri. Excellent DIC to CTFEA correlation in strains was obtained at the shaft (slope 0.984, R2=0.99) and a fair agreement (slope 0.807, R2=0.73) at the neck. CBM algorithm had worsened the correlation, whereas the new material mapping had a negligible influence. Yield loads predictions improved considerably when trabecular yielding (maximum principal strain criterion) was considered instead of surface cortical yielding. Discussion:CTFEA well predicts strains on the shaft and reasonably well on the neck. This enhances former conclusions by past studies conducted using SGs, now also evident by DIC. Yield load prediction for surgical neck fractures (involving crushing of trabecular bone) is predicted better by trabecular failure laws rather than cortex ones. Further FEA studies using trabecular orthotropic constitutive models and failure laws are warrant.

LATERAL TIBIOFEMORAL 3‐D JOINT SPACE WIDTH AND BONE PARAMETERS IN COMBINATION ARE SIGNIFICANTLY RELATED TO PROGRESSION OF LATERAL AND MEDIAL COMPARTMENT JOINT SPACE NARROWING: A MULTICENTER OSTEOARTHRITIS STUDY INVESTIGATION

An important development in osteoarthritis imaging has been the ability to assess joint space width (JSW) from weight bearing CT (WBCT). The value of combining JSW with subchondral bone parameters in disease assessment is less well understood, particularly with respect to disease phenotype. To investigate associations of worsening medial and lateral tibiofemoral compartment structural disease over 2 years with a multivariate combination of baseline 3-D JSW and bony parameters from WBCT. WBCT knee imaging was acquired at the 144-month visit of the Multicenter Osteoarthritis Study along with same-visit and 2-year follow-up medial and lateral OARSI joint space narrowing (JSN) grade. After semi-automatic segmentation of 663 available knees, joint space mapping delivered 3-D JSW maps. Cortical bone mapping was performed to measure trabecular attenuation (TA), endocortical thickness (ET), and subchondral thickness (ST) at the femoral (f) and tibial (t) surfaces. A template was registered to each individual joint surface, a 3-D statistical shape model created, and all 7 spatially co-located parameters transferred to the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of JSW plus each bone parameter in turn on the experimental variables of 2-year medial and lateral OARSI JSN worsening. One knee per participant was used, selecting the side with greater JSN worsening, randomly if equal. 10 knees did not have radiographic grading, so the analysis used single knees from 394 individuals. 218 were female, mean ± SD age was 63.5 ± 9.6 years, mass 82.7 ± 17.7 kg, height 170 ± 9 cm, and BMI 28.5 ± 5.0 kg/m 2 . SPM results (figs 1-4 below) revealed significant parameter ROIs in the lateral tibiofemoral compartment that were associated with worsening of medial and lateral OARSI JSN grade at 2 years. Baseline lateral compartment JSW was significantly wider by up to ∼1 mm (unmasked lateral compartment blue zone in fig. 1) in combination with lower baseline tTA by up to ∼25 attenuation units (AU) (unmasked lateral compartment red zone in fig. 2) for each increment in future medial JSN over 2 years. The reverse was demonstrated for future lateral JSN with narrower baseline lateral JSW by up to ∼1 mm (unmasked lateral compartment red zone in fig. 3) in combination with higher baseline tTA by up to ∼25 AU (unmasked lateral compartment blue zone in fig. 4) for each grade of future lateral JSN over 2 years. Baseline JSW was significantly narrower at the lateral margin of the lateral compartment by up to ∼1 mm in combination with thicker tST and fST by up to ∼0.2 mm for each grade of future lateral JSN (not shown). Baseline medial 3-D JSW did not relate to any substantial significant future narrowing for any JSW-bone parameter combination for future medial or lateral JSN. ET results (with JSW) were very similar to those for ST at both sides of the joint. 3-D JSW analysed in combination with bone parameters at the lateral (but not medial) tibiofemoral compartment are significantly related to future medial and lateral OARSI JSN grade. Lower lateral compartment tTA (with higher JSW) is related to future medial JSN and may be an effect of trabecular remodelling from reduced lateral loading, while greater thickness of subchondral and endocortical bone in the lateral compartment (alongside lower JSW) can be explained by subchondral sclerosis. These results suggest the lateral compartment warrants closer attention for following both medial and lateral compartmental progression. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa. (U01AG18832), University of California-San Francisco (U01AG19069), Boston University (U01AG018820). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: tom@turmezei.com .

3-D DISTRIBUTION OF BONE PARAMETERS ACROSS THE DISTAL FEMUR FROM WEIGHT BEARING CT FOLLOWS PATTERNS ACCORDING TO JOINT SPACE NARROWING PHENOTYPE: A MULTICENTER OSTEOARTHRITIS STUDY INVESTIGATION

Weight bearing CT (WBCT) technology has been increasingly used in imaging of knee osteoarthritis in recent years because of its ability to assess the weight bearing joint space. However, relatively little is known regarding the extent to which this cone beam technology can provide useful information on peri-articular bone beyond the subchondral regions. To explore relationships between WBCT-derived 3-D cortical bone thickness and trabecular bone attenuation at the distal femur with concurrent joint space narrowing phenotypes. WBCT imaging was obtained ancillary to the Multicenter Osteoarthritis Study at the 144-month visit. After semi-automatic segmentation, femoral cortical thickness (fCT) and trabecular attenuation (fTA) maps were created for each of 663 available distal femurs using cortical bone mapping. A template was registered to each individual distal femur and a 3-D statistical shape model created, followed by transfer of fCT and fTA distribution maps onto the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of fCT and fTA in turn on the experimental variables of concurrent radiographic medial and lateral OARSI joint space narrowing (JSN) grade. One knee from each participant was selected for inclusion, taking the side with worse compartmental baseline JSN grade or randomly if equal. 16 knees were excluded due to unachievable registration, with a final study set of a single knee from 386 individuals. 219 were female, mean ± SD age was 63.6 ± 9.6 yrs, mass 82.3 ± 17.7 kg, height 169 ± 9 cm, and BMI 28.5 ± 5.0 kg/m 2 . SPM significance ROIs according to baseline medial (left, figs 1 & 2) and lateral (right, figs 3 & 4) JSN phenotypes are shown for fCT (top row, figs 1 & 3) and fTA (bottom row, figs 2 & 4). SPM revealed significantly greater fCT by up to ∼0.1mm and fTA by up to ∼40 attenuation units (AU) for each increment in baseline JSN grade along the outer margin of the respective compartments (unmasked blue zones in each figure). Significantly greater fCT by up to ∼0.1mm for each increment in medial JSN grade also spread across the anterior aspect of the medial femoral condyle suggesting a wider regional relationship. 3-D distribution of fCT and fTA follow distinct patterns according to OARSI JSN phenotype, relating to recognised distributions of marginal osteophytosis and subchondral sclerosis. These results indicate that cone beam WBCT can quantify cardinal bony structural features of osteoarthritis and that their distribution is related to specific osteoarthritis OARSI JSN phenotypes. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa. (U01AG18832), University of California-San Francisco (U01AG19069), Boston University (U01AG018820). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: tom@turmezei.com

Protective effect of bisphosphonate on the cortical bone at key locations of the femur in aromatase inhibitor-associated bone loss: A three-dimensional cortical bone mapping study

Aromatase inhibitor treatment in breast cancer is associated with accelerated bone loss and an increased risk of fracture. Bisphosphonates (BPs) are the mainstay treatment of aromatase inhibitor-associated bone loss (AIBL), which might improve femoral bone at key locations prone to fracture. To test this hypothesis, we performed three-dimensional cortical bone mapping based on quantitative computed tomography (QCT) scans in postmenopausal women with early breast cancer who were receiving aromatase inhibitors. Data of subjects who had both baseline and at least one follow-up QCT at Severance Hospital (South Korea) between 2005 and 2015 were analyzed (BP users, n = 93; BP non-users, n = 203). After exclusion of BP users with low medication persistence (proportion of days covered: <50%), BP users and non-users were 1:1 matched (n = 54 for each group) in terms of age, lumbar spine volumetric bone mineral density (LSvBMD), femoral neck areal BMD (FNaBMD), and total hip areal BMD (THaBMD). During a median follow-up of 2.1 years, BP use attenuated bone loss in LSvBMD (+7.2% vs. −3.8%, p < 0.001), FNaBMD (+1.3% vs. −2.7%, p < 0.001), and THaBMD (-0.3% vs. −2.5%, p = 0.024). BP had a protective effect on cortical parameters of femoral bone: estimated cortical thickness (CTh) (+3.3% vs. + 0.1%, p = 0.007) and cortical mass surface density (CMSD, cortical mass per unit surface area was calculated by multiplying cortical BMD with CTh) (+3.4% vs. −0.3%, p < 0.001). CMSD increased by up to 15% at key locations such as the superior part of the femoral neck and greater trochanter. BP prevented the thinning of average CTh of the femoral neck (-1.4% vs. −6.1%, p < 0.001), particularly at the superior anterior quadrant of femoral neck (absolute difference: +12.8% point vs. non-users). Compared to BP non-users, BP users had improved cross-sectional moment of inertia (+4.4% vs. −0.7%, p = 0.001) and less increase in buckling ratio (+1.3% vs. + 7.5%, p < 0.001). In summary, BP use prevented cortical bone deficits observed in AIBL at key locations of the proximal femur.

Spatial distribution of hip cortical thickness in postmenopausal women with different osteoporotic fractures.

Cortical bone is critical for bone strength. Hip cortical thickness is reported to be closely associated with the incidence of hip fractures, but its relationship with nonhip fractures is rarely studied. As the hip is a major site for fracture risk assessment, it would be of great benefit to investigate the association between hip cortical thickness and different osteoporotic fractures. One hundred age-matched postmenopausal women were equally assigned to 4 osteoporotic fracture groups (trochanteric, femoral neck, vertebral, and peripheral fractures) and a nonfracture group. Each subject had a clinical quantitative computed tomography scan of the bilateral hips and the lumbar spine. A cortical bone mapping algorithm was adopted to calculate hip cortical thickness. Hip and lumbar trabecular density and the hip cortical thickness distribution were compared among the groups. All the fracture groups presented lower lumbar trabecular density. Compared with nonfracture controls, patients with hip or vertebral fractures but not peripheral fractures showed decreased cortical thickness and trabecular density of the hip. Fracture-specific distributions of cortical thickness were revealed, including zonal defects on the neck-intertrochanter junction, greater trochanter, and the periphery of the lesser trochanter for trochanteric fractures, a focal defect on the anterosuperior neck for femoral neck fractures, a moderate and average distribution for vertebral fractures, and focally thicker cortices on the anterosuperior greater trochanter and the periphery of the lesser trochanter for peripheral fractures. The spatial distribution of hip cortical thickness was different for each type of osteoporotic fracture, and patients with centrally located fractures demonstrated more severe cortical deterioration. This finding needs to be validated in a larger sample.

Physical activity induced adaptation can increase proximal femur strength under loading from a fall onto the greater trochanter.

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.

Cortical bone mapping improves finite element strain prediction accuracy at the proximal femur.

Despite evidence of the biomechanical role of cortical bone, current state of the art finite element models of the proximal femur built from clinical CT data lack a subject-specific representation of the bone cortex. Our main research hypothesis is that the subject-specific modelling of cortical bone layer from CT images, through a deconvolution procedure known as Cortical Bone Mapping (CBM, validated for cortical thickness and density estimates) can improve the accuracy of CT-based FE models of the proximal femur, currently limited by partial volume artefacts. Our secondary hypothesis is that a careful choice of cortical-specific density-elasticity relationship may improve model accuracy. We therefore: (i) implemented a procedure to include subject-specific CBM estimates of both cortical thickness and density in CT-based FE models. (ii) defined alternative models that included CBM estimates and featured a cortical-specific or an independently optimised density-elasticity relationship. (iii) tested our hypotheses in terms of elastic strain estimates and failure load and location prediction, by comparing with a published cohort of 14 femurs, where strain and strength in stance and fall loading configuration were experimentally measured, and estimated through reference FE models that did not explicitly model the cortical compartment. Our findings support the main hypothesis: an explicit modelling of the proximal femur cortical bone layer including CBM estimates of cortical bone thickness and density increased the FE strains prediction, mostly by reducing peak errors (average error reduced by 30%, maximum error and 95th percentile of error distribution halved) and especially when focusing on the femoral neck locations (all error metrics at least halved). We instead rejected the secondary hypothesis: changes in cortical density-elasticity relationship could not improve validation performances. From these improved baseline strain estimates, further work is needed to achieve accurate strength predictions, as models incorporating cortical thickness and density produced worse estimates of failure load and equivalent estimates of failure location when compared to reference models. In summary, we recommend including local estimates of cortical thickness and density in FE models to estimate bone strains in physiological conditions, and especially when designing exercise studies to promote bone strength.

Heterogeneous Spatial and Strength Adaptation of the Proximal Femur to Physical Activity: A Within-Subject Controlled Cross-Sectional Study.

Physical activity (PA) enhances proximal femur bone mass, as assessed using projectional imaging techniques. However, these techniques average data over large volumes, obscuring spatially heterogeneous adaptations. The current study used quantitative computed tomography, statistical parameter mapping, and subject-specific finite element (FE) modeling to explore spatial adaptation of the proximal femur to PA. In particular, we were interested in adaptation occurring at the superior femoral neck and improving strength under loading from a fall onto the greater trochanter. High/long jump athletes (n = 16) and baseball pitchers (n = 16) were utilized as within-subject controlled models as they preferentially load their take-off leg and leg contralateral to their throwing arm, respectively. Controls (n = 15) were included but did not show any dominant-to-nondominant (D-to-ND) leg differences. Jumping athletes showed some D-to-ND leg differences but less than pitchers. Pitchers had 5.8% (95% confidence interval [CI] 3.9%-7.6%) D-to-ND leg differences in total hip volumetric bone mineral density (vBMD), with increased vBMD in the cortical compartment of the femoral neck and trochanteric cortical and trabecular compartments. Voxel-based morphometry analyses and cortical bone mapping showed pitchers had D-to-ND leg differences within the regions of the primary compressive trabeculae, inferior femoral neck, and greater trochanter but not the superior femoral neck. FE modeling revealed pitchers had 4.1% (95% CI 1.4%-6.7%) D-to-ND leg differences in ultimate strength under single-leg stance loading but no differences in ultimate strength to a fall onto the greater trochanter. These data indicate the asymmetrical loading associated with baseball pitching induces proximal femur adaptation in regions associated with weight bearing and muscle contractile forces and increases strength under single-leg stance loading. However, there were no benefits evident at the superior femoral neck and no measurable improvement in ultimate strength to common injurious loading during aging (ie, fall onto the greater trochanter), raising questions as to how to better target these variables with PA. © 2019 American Society for Bone and Mineral Research.

Detailed subject-specific FE rib modeling for fracture prediction

Objective: The current state of the art human body models (HBMs) underpredict the number of fractured ribs. Also, it has not been shown that the models can predict the fracture locations. Efforts have been made to create subject specific rib models for fracture prediction, with mixed results. The aim of this study is to evaluate if subject-specific finite element (FE) rib models, based on state-of-the-art clinical CT data combined with subject-specific material data, can predict rib stiffness and fracture location in anterior-posterior rib bending.Method: High resolution clinical CT data was used to generate detailed subject-specific geometry for twelve FE models of the sixth rib. The cortical bone periosteal and endosteal surfaces were estimated based on a previously calibrated cortical bone mapping algorithm. The cortical and the trabecular bone were modeled using a hexa-block algorithm. The isotropic material model for the cortical bone in each rib model was assigned subject-specific material data based on tension coupon tests. Two different modeling strategies were used for the trabecular bone.The capability of the FE model to predict fracture location was carried out by modeling physical dynamic anterior-posterior rib bending tests. The rib model predictions were directly compared to the results from the tests. The predicted force-displacement time history, strain measurements at four locations, and rotation of the rib ends were compared to the results from the physical tests by means of CORA analysis. Rib fracture location in the FE model was estimated as the position for the element with the highest first principle strain at the time corresponding to rib fracture in the physical test.Results: Seven out of the twelve rib models predicted the fracture locations (at least for one of the trabecular modeling strategies) and had a force-displacement CORA score above 0.65. The other five rib models, had either a poor force-displacement CORA response or a poor fracture location prediction. It was observed that the stress-strain response for the coupon test for these five ribs showed significantly lower Young’s modulus, yield stress, and elongation at fracture compared to the other seven ribs.Conclusion: This study indicates that rib fracture location can be predicted for subject specific rib models based on high resolution CT, when loaded in anterior-posterior bending, as long as the rib’s cortical cortex is of sufficient thickness and has limited porosity. This study provides guidelines for further enhancements of rib modeling for fracture location prediction with HBMs.

Regional maps of rib cortical bone thickness and cross-sectional geometry.

Here we present detailed regional bone thickness and cross-sectional measurements from full adult ribs using high resolution CT scans processed with a cortical bone mapping technique. Sixth ribs from 33 subjects ranging from 24 to 99years of age were used to produce average cortical bone thickness maps and to provide average±1SD corridors for expected cross-section properties (cross-sectional areas and inertial moments) as a function of rib length. Results obtained from CT data were validated at specific rib locations using direct measurements from cut sections. Individual thickness measurements from CT had an accuracy (mean error) and precision (SD error) of -0.013±0.167mm (R2 coefficient of determination of 0.84). CT-based measurement errors for rib cross-sectional geometry were -0.1±13.1% (cortical bone cross-sectional area) and 4.7±1.8% (total cross-sectional area). Rib cortical bone thickness maps show the expected regional variation across a typical rib's surface. The local mid-rib maxima in cortical thickness along the pleural rib aspect ranged from range 0.9 to 2.6mm across the study population with an average map maximum of 1.4mm. Along the cutaneous aspect, rib cortical bone thickness ranged from 0.7 to 1.9mm with an average map thickness of 0.9mm. Average cross-sectional properties show a steady reduction in total cortical bone area from 10% along the rib's length through to the sternal end, whereas overall cross-sectional area remains relatively constant along the majority of the rib's length before rising steeply towards the sternal end. On average, male ribs contained more cortical bone within a given cross-section than was seen for female ribs. Importantly, however, this difference was driven by male ribs having larger overall cross-sectional areas, rather than by sex differences in the bone thickness observed at specific local cortex sites. The cortical bone thickness results here can be used directly to improve the accuracy of current human body and rib models. Furthermore, the measurement corridors obtained from adult subjects across a wide age range can be used to validate future measurements from more widely available image sources such as clinical CT where gold standard reference measures (e.g. such as direct measurements obtained from cut sections) are otherwise unobtainable.

Regional characteristics of cortical bone quality in the proximal humerus of postmenopausal women: a preliminary study

Proximal humeral fractures represent the third most common fragility fracture treated in osteoporotic populations, after hip and distal radial fractures. The purpose of this study was to characterize the spatial variability in cortical geometry in the proximal humerus in postmenopausal women. The proximal humeri in 43 healthy postmenopausal women were imaged by computed tomography. Cortical bone mapping was applied to create color 3-dimensional thickness maps for each proximal humerus. Cortical parameters, including the cortical thickness (CTh), cortical mass surface density (CM), and endocortical trabecular density, were measured over the humeral head and metaphyseal region after 15 regions of interest (ROIs) were defined. In the humeral head region, significant differences in CTh and CM values were detected between the anterior, lateral, and posterior walls (P < .05). The highest CTh and CM were found in the anterior wall in each plane (P < .05). Regarding the endocortical trabecular density, no significant findings were noted in the 3 planes (P > .05). In the metaphyseal region, the cortical structure in the medial column had higher CTh and CM values in ROI 10 compared with the lateral column (P < .05). The highest CTh and CM values of compact bone were seen in ROI 10 of the medial column (ROIs 10-12) (P < .05). Our results showed significant regional variation of cortical bone in the humeral head region in postmenopausal women. Similar conditions were seen in the medial column in the metaphyseal region. This finding provides discriminatory information for stronger fixation of implants.