J.S. Gregory

A method for assessment of the shape of the proximal femur and its relationship to osteoporotic hip fracture

The shape of the proximal femur has been demonstrated to be important in the occurrence of fractures of the femoral neck. Unfortunately, multiple geometric measurements frequently used to describe this shape are highly correlated. A new method, active shape modeling (ASM) has been developed to quantify the morphology of the femur. This describes the shape in terms of orthogonal modes of variation that, consequently, are all independent. To test this method, digitized standard pelvic radiographs were obtained from 26 women who had suffered a hip fracture and compared with images from 24 age-matched controls with no fracture. All subjects also had their bone mineral density (BMD) measured at five sites using dual-energy X-ray absorptiometry. An ASM was developed and principal components analysis used to identify the modes which best described the shape. Discriminant analysis was used to determine which variable, or combination of variables, was best able to discriminate between the groups. ASM alone correctly identified 74% of the individuals and placed them in the appropriate group. Only one of the BMD values (Ward’s triangle) achieved a higher value (82%). A combination of Ward’s triangle BMD and ASM improved the accuracy to 90%. Geometric variables used in this study were weaker, correctly classifying less than 60% of the study group. Logistic regression showed that after adjustment for age, body mass index, and BMD, the ASM data was still independently associated with hip fracture (odds ratio (OR)=1.83, 95% confidence interval 1.08 to 3.11). The odds ratio was calculated relative to a 10% increase in the probability of belonging to the fracture group. Though these initial results were obtained from a limited data set, this study shows that ASM may be a powerful method to help identify individuals at risk of a hip fracture in the future.

Femoral geometry as a risk factor for osteoporotic hip fracture in men and women

Osteoporotic hip fracture is associated with high mortality and morbidity and often results in a loss of mobility and independence. Osteoporosis is diagnosed by measuring Bone Mineral Density (BMD), a measure of the amount of mineral in a bone. Although BMD continues to serve well it does not fully account for bone strength and only partially accounts for the risk of hip fracture. The shape and structure of the proximal femur also help to determine how forces act in the hip in a fall and their measurement can aid the prediction of hip fracture. This review examines the link between simple geometrical measures of the proximal femur and hip fracture, or bone strength. It will explore how they relate to each other and to anthropometric factors such as sex, height, weight and age. Limitations in these measures will be identified and new methods of analysis reviewed that encompass many different aspects of the shape of the femur. These new methods show great promise for improving the prediction of fracture risk in the future.

Identification of hip fracture patients from radiographs using Fourier analysis of the trabecular structure: a cross-sectional study

BackgroundThis study presents an analysis of trabecular bone structure in standard radiographs using Fourier transforms and principal components analysis (PCA) to identify contributions to hip fracture risk.MethodsRadiographs were obtained from 26 hip fracture patients and 24 controls. They were digitised and five regions of interest (ROI) were identified from the femoral head and neck for analysis. The power spectrum was obtained from the Fourier transform of each region and three profiles were produced; a circular profile and profiles parallel and perpendicular to the preferred orientation of the trabeculae. PCA was used to generate a score from each profile, which we hypothesised could be used to discriminate between the fracture and control groups. The fractal dimension was also calculated for comparison. The area under the receiver operating characteristic curve (Az) discriminating the hip fracture cases from controls was calculated for each analysis.ResultsTexture analysis of standard radiographs using the fast Fourier transform yielded variables that were significantly associated with fracture and not significantly correlated with age, body mass index or femoral neck bone mineral density. The anisotropy of the trabecular structure was important; both the perpendicular and circular profiles were significantly better than the parallel-profile (P < 0.05). No significant differences resulted from using the various ROI within the proximal femur. For the best three groupings of profile (circular, parallel or perpendicular), method (PCA or fractal) and ROI (Az= 0.84 – 0.93), there were no significant correlations with femoral neck bone mineral density, age, or body mass index. PCA analysis was found to perform better than fractal analysis (P = 0.019).ConclusionsBoth PCA and fractal analysis of the FFT data could discriminate successfully between the fracture and control groups, although PCA was significantly stronger than fractal dimension. This method appears to provide a powerful tool for the assessment of bone structure in vivo with advantages over standard fractal methods.

Bone shape, structure, and density as determinants of osteoporotic hip fracture: a pilot study investigating the combination of risk factors.

Objectives:This article compares and combines methods for examining the external shape and the internal structure of the proximal femur with bone mineral density (BMD) to provide a classifier for hip fracture. Materials and Methods:Fifty standard pelvic radiographs were available from age-matched fracture and control groups of postmenopausal women. Femoral shape was measured using an active shape model, the trabecular structure by means of a Fourier transform. Results:Both the shape and various structure measures were independent of BMD (P = 0.16 and >0.50, respectively). Calculating the area under the receiver operator characteristic (ROC) curve (Az), each of shape (Az = 0.81), the best structure measure (Az = 0.79–0.93), and BMD (Az = 0.79), could partially classify the fracture and control groups. However, the combination achieved almost perfect separation (Az = 0.99). Conclusions:This pilot study shows how bone shape and structure can complement BMD measurements for investigations of fracture risk.

Predicting OA progression to total hip replacement: can we do better than risk factors alone using active shape modelling as an imaging biomarker?

OBJECTIVE Previously, active shape modelling (ASM) of the proximal femur was shown to identify those individuals at highest risk of developing radiographic OA. Here we determine whether ASM predicts the need for total hip replacement (THR) independent of Kellgren-Lawrence grade (KLG) and other known risk factors. METHODS A retrospective cohort study of 141 subjects consulting primary care with new hip pain was conducted. Pelvic radiographs taken on recruitment were assessed for KLG, centre-edge angle, acetabular depth and femoral head migration. Clinical factors (duration of pain, use of a stick and physical function) were collected by self-completed questionnaires. ASM differences between shape mode scores at baseline for individuals who underwent THR during the 5-year follow-up (n = 27) and those whose OA did not progress radiographically (n = 75) were compared. RESULTS A 1 s.d. reduction in baseline ASM mode 2 score was associated with an 81% reduction in odds of THR (OR = 0.19, 95% CI 0.52, 0.70) after adjustment for KLG, radiographic and clinical factors. A similar reduction in odds of THR was associated with a 1 s.d. reduction in mode 3 (OR = 0.45, 95% CI 0.28, 0.71) and a 1 s.d. increase in mode 4 score (OR = 2.8, 95% CI 1.7, 4.7), although these associations were no longer significant after adjustment for KLG and clinical factors. CONCLUSION ASM of the hip joint is a reliable early biomarker of radiographic OA severity, which can improve the ability to identify patients at higher risk of rapid progression and poor outcome even when KLG and clinical risk factors are taken into account.

The intrinsic shape of the human lumbar spine in the supine, standing and sitting postures: characterization using an active shape model

The shape of the lumbar spine in the sagittal plane varies between individuals and as a result of postural changes but it is not known how the shape in different postures is related. Sagittal images of the lumbar spines of 24 male volunteers were acquired using a positional magnetic resonance scanner. The subjects were imaged lying supine, standing and sitting. An active shape model was used to characterize shape in terms of independent modes of variation. Two modes were identified that described the total (mode 1) and distribution (mode 2) of the curvature. The spinal shape was found to be intercorrelated between the three postures for both modes, suggesting that the lumbar spine has an element of shape that is partially maintained despite postural alterations. Mode 1 values indicated that the spine was straightest when standing and curviest when sitting. Mode 2 values indicated that the distribution in the curvature was most even when sitting and least even when lying supine. Systematic differences in the behaviour of the spine, when changing posture, were found that suggest that the shape of the spine may affect its biomechanics.

Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing

Two bottlenecks impeding the genetic analysis of complex traits in rodents are access to mapping populations able to deliver gene-level mapping resolution and the need for population-specific genotyping arrays and haplotype reference panels. Here we combine low-coverage (0.15×) sequencing with a new method to impute the ancestral haplotype space in 1,887 commercially available outbred mice. We mapped 156 unique quantitative trait loci for 92 phenotypes at a 5% false discovery rate. Gene-level mapping resolution was achieved at about one-fifth of the loci, implicating Unc13c and Pgc1a at loci for the quality of sleep, Adarb2 for home cage activity, Rtkn2 for intensity of reaction to startle, Bmp2 for wound healing, Il15 and Id2 for several T cell measures and Prkca for bone mineral content. These findings have implications for diverse areas of mammalian biology and demonstrate how genome-wide association studies can be extended via low-coverage sequencing to species with highly recombinant outbred populations.

Characterizing the shape of the lumbar spine using an active shape model: reliability and precision of the method.

Study Design. Analysis of positional magnetic resonance images of normal volunteers. Objective. To compare the reliability and precision of an active shape model to that of conventional lordosis measurements. Summary of Background Data. Characterization of lumbar lordosis commonly relies on measurement of angles; these have been found to have errors of around 10°. Methods. T2 weighted sagittal images of the lumbar spines of 24 male volunteers in the standing posture were acquired using a positional magnetic resonance scanner. An active shape model of the vertebral bodies from S1 to L1 was created. Lumbar lordosis was also determined by measuring the angles of the superior endplates. All measurements were performed twice by one observer and once by a second observer. Results. The shape model identified 2 modes of variation to describe the shape of the lumbar spine (mode 1 described curvature and mode 2 described evenness of curvature). Significant correlations were found between mode 1 and total lordosis (R = 0.97, P < 0.001) and between mode 2 and mean absolute deviation of segmental lordosis (R = 0.80, P < 0.001). Intra- and interobserver reliability was higher for the shape model (intraclass correlation coefficients, 0.98–1.00) than for the lordosis angle measurements (intraclass correlation coefficients, 0.68–0.99). The relative error of the shape model (mode 1 = 4%; mode 2 = 9%) was lower than the conventional measurements (total lordosis = 10%). Conclusion. The shape of the lumbar spine in the sagittal plane can be comprehensively characterized using a shape model. The results are more reliable and precise than measurements of lordosis calculated from endplate angles.

Can we improve the prediction of hip fracture by assessing bone structure using shape and appearance modelling

PURPOSE There is a continuing need to improve the prediction of hip fractures to identify those at highest risk, enabling cost-effective use of preventative therapies. METHODS The aim of this work was to validate an innovative imaging biomarker for hip fracture by modelling the shape and texture of the proximal femur assessed from dual energy X-ray absorptiometry (DXA) scans. Scans used were acquired at baseline from elderly patients participating in a prospective, placebo-controlled fracture prevention study of the bisphosphonate, clodronate. 182 subjects who subsequently suffered a hip fracture were age, weight and height matched with two controls who did not suffer a fracture during a median 4-year follow-up period. Logistic regression was used to test if variables were good predictors of fracture and adjust for bone mineral density (BMD). RESULTS Shape mode 2, reflecting variability in neck-shaft angle, neck width and the size of both trochanters (0.81 (OR), 0.68-0.97 (CI), 0.024 (P)), and appearance mode 6, recording grey-level contrast (1.33, 1.11-1.59, 0.002), were significant predictors of hip fracture and remained so after adjustment for BMD (shape mode 2 (0.77, 0.64-0.93, 0.006), appearance mode 6 (1.32, 1.10-1.59, 0.003)). Receiver Operating Curve analysis showed the combination of shape mode 2, appearance mode 6 and BMD was 3% better than any single predictor. CONCLUSION Variables derived from shape and appearance models gave a prediction of fracture comparable to BMD and in combination with BMD gave an improvement in the prediction of hip fracture that could predict an additional 2000 hip fracture cases per year in the UK, potentially saving more than £20 million per year and 10,000 cases in the US.

How many different types of femora are there in primary hip osteoarthritis? An active shape modeling study.

We assessed the variation in proximal femoral canal shape and its association with geometric and demographic parameters in primary hip OA. In a retrospective cohort study, the joint geometry of the proximal femur was evaluated on radiographs and corresponding CT scans of 345 consecutive patients with end‐stage hip OA. Active shape modeling (ASM) was performed to assess the variation in endosteal shape of the proximal femur. To identify natural groupings of patients, hierarchical cluster analysis of the shape modes was used. ASM identified 10 independent shape modes accounting for >96% of the variation in proximal femoral canal shape within the dataset. Cluster analysis revealed 10 specific shape clusters. Significant differences in geometric and demographic parameters between the clusters were observed. ASM and subsequent cluster analysis have the potential to identify specific morphological patterns of the proximal femur despite the variability in proximal femoral anatomy. The study identified patterns of proximal femoral canal shape in hip OA that allow a comprehensive classification of variation in shape and its association with joint geometry. Our data may improve future stem designs that will optimize stem fit and simultaneously allow individual restoration of hip biomechanics.