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Cluster Analysis of Finite Element Analysis and Bone Microarchitectural Parameters Identifies Phenotypes with High Fracture Risk.

ABSTRACT: High-resolution peripheral quantitative computed tomography (HRpQCT) is increasingly used for exploring associations between bone microarchitectural and finite element analysis (FEA) parameters and fracture. We hypothesised that combining bone microarchitectural parameters, geometry, BMD and FEA estimates of bone strength from HRpQCT may improve discrimination of fragility fractures. The analysis sample comprised of 359 participants (aged 72-81 years) from the Hertfordshire Cohort Study. Fracture history was determined by self-report and vertebral fracture assessment. Participants underwent HRpQCT scans of the distal radius and DXA scans of the proximal femur and lateral spine. Poisson regression with robust variance estimation was used to derive relative risks for the relationship between individual bone microarchitectural and FEA parameters and previous fracture. Cluster analysis of these parameters was then performed to identify phenotypes associated with fracture prevalence. Receiver operating characteristic analysis suggested that bone microarchitectural parameters improved fracture discrimination compared to aBMD alone, whereas further inclusion of FEA parameters resulted in minimal improvements. Cluster analysis (k-means) identified four clusters. The first had lower Young modulus, cortical thickness, cortical volumetric density and Von Mises stresses compared to the wider sample; fracture rates were only significantly greater among women (relative risk [95%CI] compared to lowest risk cluster: 2.55 [1.28, 5.07], p?=?0.008). The second cluster in women had greater trabecular separation, lower trabecular volumetric density and lower trabecular load with an increase in fracture rate compared to lowest risk cluster (1.93 [0.98, 3.78], p?=?0.057). These findings may help inform intervention strategies for the prevention and management of osteoporosis.

SUBMITTER: Westbury LD

PROVIDER: S-EPMC6694037 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Cluster Analysis of Finite Element Analysis and Bone Microarchitectural Parameters Identifies Phenotypes with High Fracture Risk.

Westbury Leo D LD Shere Clare C Edwards Mark H MH Cooper Cyrus C Dennison Elaine M EM Ward Kate A KA

Calcified tissue international 20190611 3

High-resolution peripheral quantitative computed tomography (HRpQCT) is increasingly used for exploring associations between bone microarchitectural and finite element analysis (FEA) parameters and fracture. We hypothesised that combining bone microarchitectural parameters, geometry, BMD and FEA estimates of bone strength from HRpQCT may improve discrimination of fragility fractures. The analysis sample comprised of 359 participants (aged 72-81 years) from the Hertfordshire Cohort Study. Fractur ...[more]

PMID: 31187198

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Project description:BackgroundOsteoporosis is characterised by a reduction of bone mineral density (BMD) and predisposition to fracture. Bone microarchitecture, measured by high resolution peripheral quantitative computed tomography (HR-pQCT), has been related to fragility fractures and BMD and has been the subject of large-scale genome-wide analysis. We investigated whether fracture was related to baseline values and longitudinal changes in bone microarchitecture and whether bone microarchitecture was associated with established BMD loci.Methods115 males and 99 females (aged 72-81 at baseline) from the Hertfordshire Cohort Study (HCS) were analysed. Fracture history was determined in 2011-2012 by self-report and vertebral fracture assessment. Participants underwent HR-pQCT scans of the distal radius and tibia in 2011-2012 and 2017. Previous fracture in relation to baseline values and changes in tibial HR-pQCT parameters was examined using sex-adjusted logistic regression with and without adjustment for age, sociodemographic, lifestyle and clinical characteristics; baseline values and changes in parameters associated with previous fracture were then examined in relation to four established BMD loci after adjustment for sex and age.ResultsPrevious fracture was related to: higher trabecular area (fully-adjusted odds ratio [95% CI] per SD greater baseline value: 2.18 [1.27,3.73], p = 0.005); lower total volumetric BMD (0.53 [0.34,0.84], p = 0.007), cortical area (0.53 [0.30,0.95], p = 0.032), cortical BMD (0.56 [0.36,0.88], p = 0.011) and cortical thickness (0.45 [0.27,0.77], p = 0.004); and greater declines in trabecular BMD (p = 0.001). Associations were robust in sex- and fully-adjusted analysis. Relationships between BMD loci and these HR-pQCT parameters were weak: rs3801387 (WNT16) was related to decline in trabecular BMD (p = 0.011) but no other associations were significant (p > 0.05).ConclusionBaseline values of HR-pQCT parameters and greater decline in trabecular BMD were associated with fracture. Change in trabecular BMD was associated with WNT16 which has been demonstrated to influence bone health in murine models and human genome-wide association studies (GWAS).

Project description:Prior studies show vertebral strength from computed tomography-based finite element analysis may be associated with vertebral fracture risk. We found vertebral strength had a strong association with new vertebral fractures, suggesting that vertebral strength measures identify those at risk for vertebral fracture and may be a useful clinical tool.IntroductionWe aimed to determine the association between vertebral strength by quantitative computed tomography (CT)-based finite element analysis (FEA) and incident vertebral fracture (VF). In addition, we examined sensitivity and specificity of previously proposed diagnostic thresholds for fragile bone strength and low BMD in predicting VF.MethodsIn a case-control study, 26 incident VF cases (13 men, 13 women) and 62 age- and sex-matched controls aged 50 to 85 years were selected from the Framingham multi-detector computed tomography cohort. Vertebral compressive strength, integral vBMD, trabecular vBMD, CT-based BMC, and CT-based aBMD were measured from CT scans of the lumbar spine.ResultsLower vertebral strength at baseline was associated with an increased risk of new or worsening VF after adjusting for age, BMI, and prevalent VF status (odds ratio (OR) = 5.2 per 1 SD decrease, 95% CI 1.3-19.8). Area under receiver operating characteristic (ROC) curve comparisons revealed that vertebral strength better predicted incident VF than CT-based aBMD (AUC = 0.804 vs. 0.715, p = 0.05) but was not better than integral vBMD (AUC = 0.815) or CT-based BMC (AUC = 0.794). Additionally, proposed fragile bone strength thresholds trended toward better sensitivity for identifying VF than that of aBMD-classified osteoporosis (0.46 vs. 0.23, p = 0.09).ConclusionThis study shows an association between vertebral strength measures and incident vertebral fracture in men and women. Though limited by a small sample size, our findings also suggest that bone strength estimates by CT-based FEA provide equivalent or better ability to predict incident vertebral fracture compared to CT-based aBMD. Our study confirms that CT-based estimates of vertebral strength from FEA are useful for identifying patients who are at high risk for vertebral fracture.

Project description:BackgroundIn the follow-up after internal fixation of thoracolumbar fractures, the imaging of some patients shows "crater-like" collapse of the superior endplate of the injured vertebra, with variable collapse area and depth, even involving the anterior edge of the vertebral body. Though many papers had described the phenomenon, but nearly no one did biomechanical research about this. So we did this research in a creative way by using finite element model.MethodsA healthy male volunteer was selected. The 64-slice thin-section spiral computed tomography images at the level of T11-L3 were collected. Data were imported into Mimics 15.0 medical image processing software to establish three-dimensional finite element skeletal models of T11 to L3 containing only three-dimensional surface elements without entities. The model was assigned values and verified. Then the pedicle screw-rod system was added to this model, and five models containing the screw-rod system with different defect sizes as well as five models that simulated the removal of the screw-rod system were derived at the same time (the defect volume was 1/5, 2/5, 3/5, 4/5, or 5/5 of the anterior vertebral column, respectively). Biomechanical analysis was then performed on this basis.ResultsAfter the removal of the internal fixator, as defect volume increased, the stress difference between the 4/5 defect group and the 5/5 defect group had the greatest magnitude of combined stress under the seven working conditions. When the volume of the collapse defect reached 4/5 of the anterior column of the vertebral body, the concentration of stress increased significantly, suggesting that the risk of continued compression or even refracture of the injured vertebra increased if the internal fixator was removed at that time.ConclusionsWhen the volume of the defect in the superior endplate of the injured vertebra reaches 4/5 of the anterior column, the removal of the internal fixator should be carefully considered to avoid refracture of the anterior column of the injured vertebra.

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Cluster Analysis of Finite Element Analysis and Bone Microarchitectural Parameters Identifies Phenotypes with High Fracture Risk.

Publications

Cluster Analysis of Finite Element Analysis and Bone Microarchitectural Parameters Identifies Phenotypes with High Fracture Risk.

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