Fjola Johannesdottir

Distribution of cortical bone in the femoral neck and hip fracture: a prospective case-control analysis of 143 incident hip fractures; the AGES-REYKJAVIK Study.

In this prospective nested case-control study we analyzed the circumferential differences in estimated cortical thickness (Est CTh) of the mid femoral neck as a risk factor for osteoporotic hip fractures in elderly women and men. Segmental QCT analysis of the mid femoral neck was applied to assess cortical thickness in anatomical quadrants. The superior region of the femoral neck was a stronger predictor for hip fracture than the inferior region, particularly in men. There were significant gender differences in Est CTh measurements in the control group but not in the case group. In multivariable analysis for risk of femoral neck (FN) fracture, Est CTh in the supero-anterior (SA) quadrant was significant in both women and men, and remained a significant predictor after adjustment for FN areal BMD (aBMD, dimensions g/cm², DXA-like), (p=0.05 and p<0.0001, respectively). In conclusion, Est CTh in the SA quadrant best discriminated cases (n=143) from controls (n=298), especially in men. Cortical thinning superiorly in the hip might be of importance in determining resistance to fracture.

Similarities and differences between sexes in regional loss of cortical and trabecular bone in the mid‐femoral neck: The AGES‐Reykjavik longitudinal study

The risk of hip fracture rises rapidly with age, and is notably higher in women. After falls and prior fragility fractures, the main clinically recognized risk factor for hip fracture is reduced bone density. To better understand the extent to which femoral neck density and structure change with age in each sex, we carried out a longitudinal study in subjects not treated with agents known to influence bone mineral density (BMD), to investigate changes in regional cortical thickness, as well as cortical and trabecular BMD at the mid‐femoral neck. Segmental quantitative computed tomography (QCT) analysis was used to assess bone measurements in two anatomic subregions, the superolateral (superior) and inferomedial (inferior). A total of 400 older individuals (100 men and 300 women, aged 66–90 years) who were participants in the Age Gene/Environment Susceptibility‐Reykjavik Study (AGES‐Reykjavik), were studied. Participants had two QCT scans of the hip over a median follow‐up of 5.1 years (mean baseline age 74 years). Changes in bone values during follow‐up were estimated from mixed effects regression models. At baseline women had lower bone values in the superior region than men. At follow‐up all bone values were lower in women, except cortical volumetric bone mineral density (vBMD) inferiorly. The relative losses in all bone values estimated in the superior region were substantially (about threefold) and significantly greater compared to those estimated in the inferior region in both sexes. Women lost cortical thickness and cortical vBMD more rapidly than men in both regions; and this was only weakly reflected in total femoral neck dual‐energy X‐ray absorptiometry (DXA)‐like results. The higher rate of bone loss in women at critical locations may contribute materially to the greater femoral neck fracture incidence among women than men.

Focal osteoporosis defects play a key role in hip fracture.

Background Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation. Methods The sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location (‘femoral neck’ or ‘trochanteric’) to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases. Results Hip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than aBMD parameters. CBM measures however improved only minimally on aBMD for predicting any hip fracture and depended on the inclusion of trabecular bone measures alongside cortical regions. Focal osteoporosis was confirmed on biopsy as reduced sub-cortical trabecular bone volume. Conclusion Using 3D imaging methods and targeted bone biopsy, we discovered focal osteoporosis affecting trabecular and cortical bone of the proximal femur, among men and women with hip fracture.

Cortical bone assessed with clinical computed tomography at the proximal femur.

Hip fractures are the most serious of all fragility fractures in older people of both sexes. Trips, stumbles, and falls result in fractures of the femoral neck or trochanter, and the incidence of these two common fractures is increasing worldwide as populations age. Although clinical risk factors and chance are important in causation, the ability of a femur to resist fracture also depends on the size and spatial distribution of the bone, its intrinsic material properties, and the loads applied. Over the past two decades, clinical quantitative computed tomography (QCT) studies of living volunteers have provided insight into how the femur changes with advancing age to leave older men and women at increased risk of hip fractures. In this review, we focus on patterns of cortical bone loss associated with hip fracture, age‐related changes in cortical bone, and the effects of drugs used to treat osteoporosis. There are several methodologies available to measure cortical bone in vivo using QCT. Most techniques quantify bone density (g/cm3), mass (g), and thickness (mm) in selected, predefined or “traditional” regions of interest such as the “femoral neck” or “total hip” region. A recent alternative approach termed “computational anatomy,” uses parametric methods to identify systematic differences, before displaying statistically significant regions as color‐scaled maps of density, mass, or thickness on or within a representative femur model. This review will highlight discoveries made using both traditional and computational anatomy methods, focusing on cortical bone of the proximal femur.

Comparison of non-invasive assessments of strength of the proximal femur

It is not clear which non-invasive method is most effective for predicting strength of the proximal femur in those at highest risk of fracture. The primary aim of this study was to compare the abilities of dual energy X-ray absorptiometry (DXA)-derived aBMD, quantitative computed tomography (QCT)-derived density and volume measures, and finite element analysis (FEA)-estimated strength to predict femoral failure load. We also evaluated the contribution of cortical and trabecular bone measurements to proximal femur strength. We obtained 76 human cadaveric proximal femurs (50 women and 26 men; age 74±8.8years), performed imaging with DXA and QCT, and mechanically tested the femurs to failure in a sideways fall configuration at a high loading rate. Linear regression analysis was used to construct the predictive model between imaging outcomes and experimentally-measured femoral strength for each method. To compare the performance of each method we used 3-fold cross validation repeated 10 times. The bone strength estimated by QCT-based FEA predicted femoral failure load (R2adj=0.78, 95%CI 0.76-0.80; RMSE=896N, 95%CI 830-961) significantly better than femoral neck aBMD by DXA (R2adj=0.69, 95%CI 0.66-0.72; RMSE=1011N, 95%CI 952-1069) and the QCT-based model (R2adj=0.73, 95%CI 0.71-0.75; RMSE=932N, 95%CI 879-985). Both cortical and trabecular bone contribute to femoral strength, the contribution of cortical bone being higher in femurs with lower trabecular bone density. These findings have implications for optimizing clinical approaches to assess hip fracture risk. In addition, our findings provide new insights that will assist in interpretation of the effects of osteoporosis treatments that preferentially impact cortical versus trabecular bone.

Bone Structure and Biomechanics

Bone is a composite, living tissue made primarily of type I collagen fibers impregnated with crystals of calcium phosphate. Bone is dynamic, continuously undergoing repair, and remodeling. Specialized cells carry out these functions under the control of systemic and local signals. The surface of bone is completely covered by live cells. Bone is also filled with cells that communicate with each other, with the bone surface and with the circulation via a network of cell extensions. The structure of bone reveals its history of growth and development. The shape and microarchitecture of bones are exquisitely designed for mechanical support and metabolic functions.

Correction to: Characterization of trabecular bone microstructure in premenopausal women with distal radius fractures

Owing to an oversight by the corresponding author, the name of the third author of this article was rendered wrongly. His correct name is Kempland C. Walley.

Chapter 12 – Overview of Bone Structure and Strength

Many individuals who fracture do not have bone mineral density values in the osteoporotic range, suggesting that a better understanding of the factors that influence bone strength and fracture risk may improve identification of those at the highest risk for fracture. This chapter outlines the key determinants of bone strength, focusing on age-related changes and the contribution of bone morphology and microarchitecture to bone strength and fracture risk.

Fracture Prediction by Computed Tomography and Finite Element Analysis: Current and Future Perspectives

Purpose of ReviewThis review critiques the ability of CT-based methods to predict incident hip and vertebral fractures.Recent FindingsCT-based techniques with concurrent calibration all show strong associations with incident hip and vertebral fracture, predicting hip and vertebral fractures as well as, and sometimes better than, dual-energy X-ray absorptiometry areal biomass density (DXA aBMD). There is growing evidence for use of routine CT scans for bone health assessment.SummaryCT-based techniques provide a robust approach for osteoporosis diagnosis and fracture prediction. It remains to be seen if further technical advances will improve fracture prediction compared to DXA aBMD. Future work should include more standardization in CT analyses, establishment of treatment intervention thresholds, and more studies to determine whether routine CT scans can be efficiently used to expand the number of individuals who undergo evaluation for fracture risk.