Publications by authors named "Joyce H Keyak"

26 Publications

  • Page 1 of 1

Effect of cortical bone micro-structure in fragility fracture patients on lamellar stress.

J Biomech 2020 02 24;100:109596. Epub 2019 Dec 24.

Department of Radiological Sciences, Department of Biomedical Engineering, and Department of Mechanical and Aerospace Engineering, University of California, Irvine, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jbiomech.2019.109596DOI Listing
February 2020

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

J Bone Miner Res 2020 04 30;35(4):681-690. Epub 2019 Dec 30.

Department of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, IN, USA.

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.
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http://dx.doi.org/10.1002/jbmr.3939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145739PMC
April 2020

Use of Quantitative Computed Tomography to Assess for Clinically-relevant Skeletal Effects of Prolonged Spaceflight on Astronaut Hips.

J Clin Densitom 2020 Apr - Jun;23(2):155-164. Epub 2019 Aug 26.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1016/j.jocd.2019.08.005DOI Listing
August 2019

Liquid Calibration Phantoms in Ultra-Low-Dose QCT for the Assessment of Bone Mineral Density.

J Clin Densitom 2020 Jan - Mar;23(1):108-116. Epub 2019 Feb 22.

Medical Physics Department, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

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 (KHPO) concentrations phantoms.

Methodology: Four ranges of concentrations of KHPO were made and tested with 2 exposure settings. Accuracy of the phantoms with ash gravimetry and intermediate KHPO 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 (R 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/cm) were lower than high concentration phantoms with 135 and 234 mg/cm 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 KHPO concentrations increased 25% for 50 mg/cm solution and 0.7 % for 1300 mg/cm 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.
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http://dx.doi.org/10.1016/j.jocd.2019.02.005DOI Listing
February 2019

Hip load capacity cut-points for Astronaut Skeletal Health NASA Finite Element Strength Task Group Recommendations.

NPJ Microgravity 2019 14;5. Epub 2019 Mar 14.

18Division of Biomedical Research and Environmental Sciences, NASA Lyndon B. Johnson Space Center, Houston, TX USA.

Concerns raised at a 2010 Bone Summit held for National Aeronautics and Space Administration Johnson Space Center led experts in finite element (FE) modeling for hip fracture prediction to propose including hip load capacity in the standards for astronaut skeletal health. The current standards for bone are based upon areal bone mineral density (aBMD) measurements by dual X-ray absorptiometry (DXA) and an adaptation of aBMD cut-points for fragility fractures. Task Group members recommended (i) a minimum permissible outcome limit (POL) for post-mission hip bone load capacity, (ii) use of FE hip load capacity to further screen applicants to astronaut corps, (iii) a minimum pre-flight standard for a second long-duration mission, and (iv) a method for assessing which post-mission physical activities might increase an astronaut's risk for fracture after return. QCT-FE models of eight astronaut were analyzed using nonlinear single-limb stance (NLS) and posterolateral fall (NLF) loading configurations. QCT data from the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort and the Rochester Epidemiology Project were analyzed using identical modeling procedures. The 75 percentile of NLS hip load capacity for fractured elderly males of the AGES cohort (9537N) was selected as a post-mission POL. The NLF model, in combination with a Probabilistic Risk Assessment tool, was used to assess the likelihood of exceeding the hip load capacity during post-flight activities. There was no recommendation to replace the current DXA-based standards. However, FE estimation of hip load capacity appeared more meaningful for younger, physically active astronauts and was recommended to supplement aBMD cut-points.
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http://dx.doi.org/10.1038/s41526-019-0066-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418107PMC
March 2019

Runners With Patellofemoral Pain Exhibit Greater Peak Patella Cartilage Stress Compared With Pain-Free Runners.

J Appl Biomech 2018 Aug 11;34(4):298-305. Epub 2018 Jul 11.

1 University of Southern California.

The primary purpose of this study is to determine whether recreational runners with patellofemoral pain (PFP) exhibit greater peak patella cartilage stress compared with pain-free runners. A secondary purpose was to determine the kinematic and/or kinetic predictors of peak patella cartilage stress during running. A total of 22 female recreational runners (12 with PFP and 10 pain-free controls) participated in this study. Patella cartilage stress profiles were quantified using subject-specific finite element models simulating the maximum knee flexion angle during the stance phase of running. Input parameters to the finite element model included subject-specific patellofemoral joint geometry, quadriceps muscle forces, and lower-extremity kinematics in the frontal and transverse planes. Tibiofemoral joint kinematics and kinetics were quantified to determine the best predictor of stress using stepwise regression analysis. Compared with the pain-free runners, those with PFP exhibited greater peak hydrostatic pressure (PFP vs control: 21.2 [5.6] MPa vs 16.5 [4.6] MPa) and maximum shear stress (PFP vs control: 11.3 [4.6] MPa vs 8.7 [2.3] MPa). Knee external rotation was the best predictor of peak hydrostatic pressure and peak maximum shear stress (38% and 25% of variances, respectively), followed by the knee extensor moment (21% and 25% of variances, respectively). Runners with PFP exhibit greater peak patella cartilage stress during running compared with pain-free individuals. The combination of knee external rotation and a high knee extensor moment best predicted the elevated peak stress during running.
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http://dx.doi.org/10.1123/jab.2017-0229DOI Listing
August 2018

Physical Activity for Strengthening Fracture Prone Regions of the Proximal Femur.

Curr Osteoporos Rep 2017 02;15(1):43-52

Department of Physical Therapy and Center for Translational Musculoskeletal Research, School of Health and Rehabilitation Sciences, Indiana University, 1140 W. Michigan St, Indianapolis, IN, CF-120, USA.

Purpose Of Review: Physical activity improves proximal femoral bone health; however, it remains unclear whether changes translate into a reduction in fracture risk. To enhance any fracture-protective effects of physical activity, fracture prone regions within the proximal femur need to be targeted.

Recent Findings: The proximal femur is designed to withstand forces in the weight-bearing direction, but less so forces associated with falls in a sideways direction. Sideways falls heighten femoral neck fracture risk by loading the relatively weak superolateral region of femoral neck. Recent studies exploring regional adaptation of the femoral neck to physical activity have identified heterogeneous adaptation, with adaptation principally occurring within inferomedial weight-bearing regions and little to no adaptation occurring in the superolateral femoral neck. There is a need to develop novel physical activities that better target and strengthen the superolateral femoral neck within the proximal femur. Design of these activities may be guided by subject-specific musculoskeletal modeling and finite-element modeling approaches.
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http://dx.doi.org/10.1007/s11914-017-0343-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5317179PMC
February 2017

Accelerating the pace of discovery in orthopaedic research: A vision toward team science.

J Orthop Res 2016 10 5;34(10):1673-1679. Epub 2016 Jun 5.

Orthopaedic Research Society (ORS) Advocacy Committee.

The landscape of basic science in the United States and around the world is changing, and the field of orthopaedic research is positioned to lead by embracing a culture of collaborative, team science that reflects our field's interdisciplinary nature. In this article we hope to address some of the cultural challenges and programmatic barriers that impede a team science approach in the US and suggest opportunities for change. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1673-1679, 2016.
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http://dx.doi.org/10.1002/jor.23307DOI Listing
October 2016

Automatic multi-parametric quantification of the proximal femur with quantitative computed tomography.

Quant Imaging Med Surg 2015 Aug;5(4):552-68

1 Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA ; 2 Department of Endocrinology, Creighton University, Omaha, NE, USA ; 3 Department of Radiological Sciences, Department of Mechanical and Aerospace Engineering, Department of Biomedical Engineering, and Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA, USA ; 4 Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA ; 5 Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Internal Medicine, College of Medicine, Mayo Clinic, Rochester, MN, USA.

Background: Quantitative computed tomography (QCT) imaging is the basis for multiple assessments of bone quality in the proximal femur, including volumetric bone mineral density (vBMD), tissue volume, estimation of bone strength using finite element modeling (FEM), cortical bone thickness, and computational-anatomy-based morphometry assessments.

Methods: Here, we present an automatic framework to perform a multi-parametric QCT quantification of the proximal femur. In this framework, the proximal femur is cropped from the bilateral hip scans, segmented using a multi-atlas based segmentation approach, and then assigned volumes of interest through the registration of a proximal femoral template. The proximal femur is then subjected to compartmental vBMD, compartmental tissue volume, FEM bone strength, compartmental surface-based cortical bone thickness, compartmental surface-based vBMD, local surface-based cortical bone thickness, and local surface-based cortical vBMD computations. Consequently, the template registrations together with vBMD and surface-based cortical bone parametric maps enable computational anatomy studies. The accuracy of the segmentation was validated against manual segmentations of 80 scans from two clinical facilities, while the multi-parametric reproducibility was evaluated using repeat scans with repositioning from 22 subjects obtained on CT imaging systems from two manufacturers.

Results: Accuracy results yielded a mean dice similarity coefficient of 0.976±0.006, and a modified Haussdorf distance of 0.219±0.071 mm. Reproducibility of QCT-derived parameters yielded root mean square coefficients of variation (CVRMS) between 0.89-1.66% for compartmental vBMD; 0.20-1.82% for compartmental tissue volume; 3.51-3.59% for FEM bone strength; 1.89-2.69% for compartmental surface-based cortical bone thickness; and 1.08-2.19% for compartmental surface-based cortical vBMD. For local surface-based assessments, mean CVRMS were between 3.45-3.91% and 2.74-3.15% for cortical bone thickness and vBMD, respectively.

Conclusions: The automatic framework presented here enables accurate and reproducible QCT multi-parametric analyses of the proximal femur. Our subjects were elderly, with scans obtained across multiple clinical sites and manufacturers, thus documenting its value for clinical trials and other multi-site studies.
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http://dx.doi.org/10.3978/j.issn.2223-4292.2015.08.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559986PMC
August 2015

Inter-scanner differences in in vivo QCT measurements of the density and strength of the proximal femur remain after correction with anthropomorphic standardization phantoms.

Med Eng Phys 2014 Oct 4;36(10):1225-32. Epub 2014 Jul 4.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States.

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 (My) and yield force (Fy), and finite-element derived strength of the femur under stance (FEstance) and fall (FEfall) 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 My and FEfall, 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.
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http://dx.doi.org/10.1016/j.medengphy.2014.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589175PMC
October 2014

Spatial heterogeneity in the response of the proximal femur to two lower-body resistance exercise regimens.

J Bone Miner Res 2014 Jun;29(6):1337-45

Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.

Understanding the skeletal effects of resistance exercise involves delineating the spatially heterogeneous response of bone to load distributions from different muscle contractions. Bone mineral density (BMD) analyses may obscure these patterns by averaging data from tissues with variable mechanoresponse. To assess the proximal femoral response to resistance exercise, we acquired pretraining and posttraining quantitative computed tomography (QCT) images in 22 subjects (25-55 years, 9 males, 13 females) performing two resistance exercises for 16 weeks. One group (SQDL, n = 7) performed 4 sets each of squats and deadlifts, a second group (ABADD, n = 8) performed 4 sets each of standing hip abductions and adductions, and a third group (COMBO, n = 7) performed two sets each of squat/deadlift and abduction/adduction exercise. Subjects exercised three times weekly, and the load was adjusted each session to maximum effort. We used voxel-based morphometry (VBM) to visualize BMD distributions. Hip strength computations used finite element modeling (FEM) with stance and fall loading conditions. We used QCT analysis for cortical and trabecular BMD, and cortical tissue volume. For muscle size and density, we analyzed the cross-sectional area (CSA) and mean Hounsfield unit (HU) in the hip extensor, flexor, abductor, and adductor muscle groups. Whereas SQDL increased vertebral BMD, femoral neck cortical BMD and volume, and stance hip strength, ABADD increased trochanteric cortical volume. The COMBO group showed no changes in any parameter. VBM showed different effects of ABADD and SQDL exercise, with the former causing focal changes of trochanteric cortical bone, and the latter showing diffuse changes in the femoral neck and head. ABADD exercise increased adductor CSA and HU, whereas SQDL exercise increased the hip extensor CSA and HU. In conclusion, we observed different proximal femoral bone and muscle tissue responses to SQDL and ABADD exercise. This study supports VBM and volumetric QCT (vQCT) to quantify the spatially heterogeneous effects of types of muscle contractions on bone.
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http://dx.doi.org/10.1002/jbmr.2155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029859PMC
June 2014

Comparison of patella bone strain between females with and without patellofemoral pain: a finite element analysis study.

J Biomech 2014 Jan 15;47(1):230-6. Epub 2013 Oct 15.

Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jbiomech.2013.09.010DOI Listing
January 2014

Structural patterns of the proximal femur in relation to age and hip fracture risk in women.

Bone 2013 Nov 25;57(1):290-9. Epub 2013 Aug 25.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1016/j.bone.2013.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809121PMC
November 2013

Measuring bone mineral density with fat-water MRI: comparison with computed tomography.

J Magn Reson Imaging 2013 Jan 10;37(1):237-42. Epub 2012 Jul 10.

Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, California 90033, USA.

Purpose: To develop a method for measuring bone mineral density (BMD) with MRI, and to validate this method against quantitative computed tomography (QCT).

Materials And Methods: A mathematical relationship between signal intensities from proton-density-weighted in-phase images generated by multi-fat-peak T2*-IDEAL MRI and BMD was derived using a set of calibration standards constructed from various concentrations of hydroxyapatite in water. Using these standards, the relationship between hydroxyapatite concentration and MRI signal intensity was examined. A T2*-IDEAL protocol was performed on the patella of 5 volunteers and the signal model was used to compute BMD of all voxels of the patella. The BMD data were validated by obtaining QCT scans of the same patella, computing QCT BMD of all voxels, and comparing the MRI and QCT BMD data by performing linear regression analysis on a voxel-by-voxel basis.

Results: A strong linear correlation between hydroxyapatite concentration of the calibration standards and MRI signal intensities was observed (r = 0.98; P < 0.01). In the patella, BMD measurements (N = 28796 voxels) from the MRI signal model were significantly correlated with those from QCT (r = 0.82; P < 0.001; slope = 1.02; and intercept = -0.26).

Conclusion: A standardized phantom consisting of hydroxyapatite and water can be used to accurately quantify BMD in vivo using MRI.
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http://dx.doi.org/10.1002/jmri.23749DOI Listing
January 2013

Quantitative computed tomography reveals the effects of race and sex on bone size and trabecular and cortical bone density.

J Clin Densitom 2009 Jul-Sep;12(3):330-6. Epub 2009 Jul 4.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94143-0946, USA.

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 35-45 yr. 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.
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http://dx.doi.org/10.1016/j.jocd.2009.04.001DOI Listing
October 2009

Effect of an UHMWPE patellar component on stress fields in the patella: a finite element analysis.

Knee Surg Sports Traumatol Arthrosc 2009 Jan 1;17(1):71-82. Epub 2008 Oct 1.

School of Information and Mechatronics, Gwangju Institute of Science and Technology, 1 Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea.

An increased stress in the patella due to the implantation of a patellar button may also be another potential source of pain in total knee arthroplasty patients. This study assessed the location inside the patella having largest stress change after implantation of an ultra high molecular polyethylene patella button. Finite elements models of the patellae before and after implantation of patellar button were created. Experimentally determined spring constants of muscles and ligaments, and patellofemoral contacting loads were applied to the models at 30 degrees , 60 degrees , and 90 degrees of knee flexion. The Von Mises stress of the intact patella decreased with increased knee flexion, while that of implanted patella increased. Also, the stress range in the implanted patella was 3-9 times higher than in the intact one. The highly stressed region of the intact patella moved proximally with higher knee flexion angles, while that of the implanted model stayed near the central anterior patella. At 90 degrees of knee flexion, the stress in the anterodistal patella increased considerably after implantation of a patella button so that the anterodistal patella may be susceptible to be painful source after the total knee replacement.
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http://dx.doi.org/10.1007/s00167-008-0628-5DOI Listing
January 2009

Lytic lesions in the femoral neck: Importance of location and evaluation of a novel minimally invasive repair technique.

J Orthop Res 2008 Aug;26(8):1127-32

Department of Orthopaedic Surgery, B170 Medical Sciences I, University of California, Irvine, California 92697, USA.

Proximal femoral metastases can lead to pathologic fracture. The goals of this study were to improve guidelines for assessing pathologic hip fracture risk by quantifying the effect of location of femoral neck metastases on hip strength under single-limb stance loading and to evaluate the effectiveness of a proposed minimally invasive surgical repair technique for restoring hip strength. Twelve matched pairs of human cadaveric proximal femora were used to create a total of 564 finite element models before and after introduction and repair of simulated lytic defects, modeled as spherical voids, at various locations within the femoral neck. Defect site greatly affected hip strength (p < 0.001). Defects in the inferomedial aspect of the neck and in the dense trabecular bone near the base of the femoral head had the greatest effect, with hip strengths 23% to 72% and 43% to 64% that of the intact strength, respectively, for 20-mm diameter defects. Even so, the proposed percutaneous repair technique restored static strength of femora with defects at all of the studied locations. These findings may lead to a reduction in the number of patients who suffer a preventable pathologic fracture, a decreased likelihood of unnecessary surgery, and a less invasive prophylactic surgical procedure.
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http://dx.doi.org/10.1002/jor.20555DOI Listing
August 2008

The effect of simulated metastatic lytic lesions on proximal femoral strength.

Clin Orthop Relat Res 2007 Jun;459:139-45

Department of Orthopaedic Surgery, University of California, Irvine, CA 92868-5382, USA.

Metastatic lesions in the proximal femur can reduce hip strength and lead to pathologic fracture. However, current methods for identifying patients at risk of pathologic fracture are inadequate. We hypothesized the percentage of intact proximal femoral strength remaining after formation of a simulated lytic defect within the femoral neck or at the level of the lesser trochanter depends on defect location within the respective region. Computed tomography scan-based finite element models of 12 cadaveric proximal femora were used to evaluate the effect of 20-mm-diameter spherical voids at various locations in the neck and at the level of the lesser trochanter. In both regions, the percentage of intact strength remaining depended on defect location (p < 0.001). In the neck, the strength of specimens with inferomedial defects (median, 50.4% of intact; range, 27.8-71.7%) was less than the strength of specimens with defects located in the center of the neck, superolaterally, or anteriorly (p < 0.05). Near the lesser trochanter, anteromedial defects resulted in the lowest strength (median, 66.6% of intact; range, 49.2-73.8%). Other defects at the level of the lesser trochanter had a markedly smaller effect. These findings may be helpful for evaluating pathologic fracture risk.
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http://dx.doi.org/10.1097/BLO.0b013e3180514caaDOI Listing
June 2007

Feasibility of a percutaneous technique for repairing proximal femora with simulated metastatic lesions.

Med Eng Phys 2007 Jun 1;29(5):594-601. Epub 2006 Sep 1.

Department of Orthopaedic Surgery, University of California, Irvine, B170 Medical Sciences I, Irvine, CA 92697, USA.

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.
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http://dx.doi.org/10.1016/j.medengphy.2006.06.008DOI Listing
June 2007

Predicting the strength of femoral shafts with and without metastatic lesions.

Clin Orthop Relat Res 2005 Oct;439:161-70

Department of Orthopaedic Surgery, University of California, Irvine, CA, USA.

To evaluate a potential tool for assessing the risk of a pathologic fracture of the femoral shaft, we examined whether fracture loads computed by our computed tomography scan-based finite element models are predictive of measured fracture loads. We also evaluated whether the precision of the computed fracture loads for shafts with metastases is altered if models are generated using mechanical property-density relationships for bone without metastases. We investigated whether femoral shafts with a hemispheric defect and shafts with metastases have qualitatively similar structural behavior. Using identical four-point bending loading conditions, we computed and measured fracture loads of femoral shafts with and without metastases and with a burred hemispheric defect to simulate a tumor. Finite element model fracture loads were strongly predictive of the measured fracture loads (range, 0.92-0.98) even when the models of bones with metastases used mechanical property relationships for bone without metastases. Specimens with hemispheric defects behaved structurally differently than specimens with metastases, indicating that these defects do not accurately simulate the effects of metastases. Results of our study show that these computed tomography scan-based finite element models can be used to estimate the strength of femoral shafts with and without metastases. These models may be useful for assessing the risk of pathologic fractures of femoral shafts.
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http://dx.doi.org/10.1097/01.blo.0000174736.50964.3bDOI Listing
October 2005

Predicting proximal femoral strength using structural engineering models.

Clin Orthop Relat Res 2005 Aug(437):219-28

Department of Orthopaedic Surgery, University of California, Irvine, 92868, USA.

Hip fracture related to osteoporosis and metastatic disease is a major cause of morbidity and mortality. An accurate and precise method of predicting proximal femoral strength and fracture location would be useful for research and clinical studies of hip fracture. The goals of this study were to develop a structural modeling technique that accurately predicts proximal femoral strength; to evaluate the accuracy and precision of this predicted strength on an independent data set; and to evaluate the ability of this technique to predict fracture location. Fresh human cadaveric proximal femora with and without metastatic lesions were studied using computed tomography scan-based three-dimensional structural models and mechanical testing to failure under single-limb stance-type loading. The models understated proximal femoral strength by an average of 444 N, and the precision of the predicted strength was +/- 1900 N. Therefore, the ability to predict hip strength in an individual subject is limited primarily by the level of precision, rather than accuracy. This level of precision is likely to be sufficient for many studies of hip strength. Finally, these models predict fractures involving the subcapital and cervical regions, consistent with most fractures produced experimentally under single-limb stance-type loading.
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http://dx.doi.org/10.1097/01.blo.0000164400.37905.22DOI Listing
August 2005

Differences in hip quantitative computed tomography (QCT) measurements of bone mineral density and bone strength between glucocorticoid-treated and glucocorticoid-naive postmenopausal women.

Osteoporos Int 2005 Jun 28;16(6):642-50. Epub 2004 Sep 28.

Department of Medicine and Radiology, University of California-San Francisco, San Francisco, CA 94143, USA.

Unlabelled: Chronic treatment with glucocorticoids (GCs) leads to significant bone loss and increased risk of fractures. In chronically GC-treated patients, hip fracture risk is nearly 50%. The purpose of this investigation was to determine if there are differences in the quantities of trabecular and cortical bone and bone strength of the hip between GC-treated osteoporotic patients and controls.

Methods: Study subjects were GC-treated osteoporotic postmenopausal women, and controls were postmenopausal women, recruited for separate clinical trials. Quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) of the hip were obtained from all subjects. QCT outcome variables measured included total, cortical, and trabecular BMD of hip subregions (femoral neck and trochanter) and total hip. In addition, finite element modeling (FEM) was performed on a subset of 19 cases and 38 controls, matched on age (+/- 5 years), weight (+/- 5 kg), and history of hormone replacement (> 1 year use) to assess failure load in stance and fall loading conditions. Generalized linear models were used to adjust the QCT variables for covariates between groups. Multiple regression was performed to identify independent predictors of bone strength from the QCT variables.

Results: Compared with controls, GC-treated subjects were significantly (p < 0.05) younger, weighed less, and had more years of hormone replacement. QCT of the hip in GC-treated subjects for total femoral integral, cortical, and trabecular BMD averaged 4.9-23.2% (p < 0.002) less than controls, and similar results were seen by hip subregion including the trochanter and femoral neck. DXA of the total hip was 17% lower in GC subjects than controls (p < 0.05). Compared with controls, FEM failure load in GC subjects was 15% (p<0.05) and 16% (p = 0.07) lower for stance and fall loading conditions, respectively. Multiple regression analysis demonstrated that a combination of QCT measures was correlated with bone strength as measured by FEM.

Conclusions: Chronic GC treatment in postmenopausal women resulted in significantly decreased BMD of the hip, measured by QCT, with loss of both trabecular and cortical bone. In addition, GC treatment decreased bone strength as determined by FEM. The reduced cortical and trabecular bone mass in the hip may contribute to the disproportionately high hip fracture rates observed in GC-treated subjects.
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http://dx.doi.org/10.1007/s00198-004-1736-9DOI Listing
June 2005

Mechanical properties, density and quantitative CT scan data of trabecular bone with and without metastases.

J Biomech 2004 Apr;37(4):523-30

Department of Orthopaedic Surgery, University of California, Irvine, CA 92868-5382, USA.

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, 15x15x15-mm cubes of trabecular bone were cut. QCT density (rho(QCT)), compressive elastic modulus (E), compressive yield and ultimate strengths (S(y) and S(u)), and ash density (rho(ash)) of each cube were determined. Regression analysis was performed between rho(ash) and E, S(y), S(u) and rho(QCT), and analysis of covariance was used to identify differences between groups. Power relationships that did not depend on group (p >/= 0.1) were found between E and rho(ash) (0.74 /= 0.94; p<0.001). rho(ash) was strongly related to rho(QCT) (r >/= 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 rho(ash) that can be used to estimate mechanical properties of trabecular bone with and without metastases.
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http://dx.doi.org/10.1016/j.jbiomech.2003.08.010DOI Listing
April 2004

Comparison of in situ and in vitro CT scan-based finite element model predictions of proximal femoral fracture load.

Med Eng Phys 2003 Nov;25(9):781-7

Department of Orthopaedic Surgery, University of California, Irvine, CA 92697, USA.

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 (F(FE)) was the maximum femoral head reaction force. F(FE) 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.
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http://dx.doi.org/10.1016/s1350-4533(03)00081-xDOI Listing
November 2003

Relationships between material properties and CT scan data of cortical bone with and without metastatic lesions.

Med Eng Phys 2003 Jul;25(6):445-54

Department of Orthopaedic Surgery, University of California, Irvine, CA 92697, USA.

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 (rhoQCT), longitudinal mechanical properties, and ash density (rhoAsh) 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 rhoQCT and elastic modulus, strength, and rhoAsh were found for bone with metastases (0.73
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http://dx.doi.org/10.1016/s1350-4533(03)00030-4DOI Listing
July 2003

Computed tomographic osteoabsorptiometry of the elbow joint in clinically normal dogs.

Am J Vet Res 2002 Aug;63(8):1159-66

Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis 95616, USA.

Objective: To evaluate subchondral bone density patterns in elbow joints of clinically normal dogs by use of computed tomographic (CT) osteoabsorptiometry.

Sample Population: 20 cadaver forelimbs from 10 clinically normal dogs.

Procedure: Each elbow joint was imaged in parasagittal and transverse planes of 1.5-mm thickness. Slice data were converted to dipotassium phosphate equivalent density (PPED) values. Sagittal, parasagittal, and transverse medial coronoid process topographic maps were constructed. Defined zones were created for each of the 3 CT planes, and confluence and peak PPED values were determined.

Results: The lowest PPED value was 340 mg/ml (articular and subchondral confluence), and the highest was 1780 mg/ml (peak subchondral density). Detectable effects of joint laterality were not found in the confluence or peak PPED measurements or in the peak-to-confluence PPED ratio for all 3 CT planes. Significant differences were found among zones in all 3 planes for confluence and peak PPED measurements and between sagittal and transverse planes for peak-to-confluence PPED ratios. Subjectively, the pattern of density distribution among dogs was fairly consistent for the sagittal and parasagittal slices. Three specific patterns of density distribution were apparent on the transverse topographic maps of the medial coronoid process that corresponded to conformational differences.

Conclusions And Clinical Relevance: The use of CT osteoabsorptiometry provides a repeatable technique that can be used to noninvasively examine bone density and the effects of stress acting on joints in vivo. Variability in density values for any of the CT planes was not identified among clinically normal dogs.
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http://dx.doi.org/10.2460/ajvr.2002.63.1159DOI Listing
August 2002