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.

BackgroundHip 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.MethodsThe 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.ResultsHip 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.ConclusionUsing 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.

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Purpose: We 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. Methods: In a case-control study, 26 incident VF cases (13 men, 13 women) and 62 age and sexmatched 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.

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 have carried out a longitudinal study in subjects not treated with agents known to influence bone mineral density to investigate changes in regional cortical thickness, as well as cortical and trabecular bone mineral density at the mid-femoral neck. Segmental QCT analysis was used to assess bone measurements in two anatomic sub-regions, the supero-lateral (superior) and infero-medial (inferior). A total of 400 older individuals (100 men and 300 women, aged 66–90 years) who were participants in the AGES-Reykjavik study, were studied. Participants had two QCT scans of the hip over a median follow-up of 5.1 yr. (mean baseline age 74 yr.). 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 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 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.

In a cross-sectional study we investigated the relationship between muscle and bone parameters in mid-thigh in older people using data from a single axial computed tomography (CT) section through the mid-thigh. Additionally we studied the association of these variables with incident low trauma lower limb fractures. A total of 3762 older individuals (1838 men and 1924 women) age 66-96 years, participants in the AGES-Reykjavík Study, were studied. The total cross-sectional muscular area and knee extensor strength declined with age similarly in both sexes. Muscle parameters correlated most strongly with cortical area and total shaft area (adjusted for age, height and weight) but explained less than 10% of variability in those bone parameters. The increment in medullary area and buckling ratio with age was almost fourfold greater in women than men. The association between medullary area and muscle parameters was non-significant. One hundred-thirteen women and 66 men sustained incident lower limb fractures during median follow-up of 5.3 years. Small muscular area, low knee extensor strength, large medullary area, low cortical thickness and high buckling ratio were significantly associated with fractures in both sexes. Our results show that bone and muscle loss proceeds at different rates and with different gender patterns.

This comprehensive study of trunk muscle deficits with increasing age may have important implications for physical function, disability, pain, and risk of injury in older adults. The greater levels of mobility impairments with aging in women may in part be explained by greater proportion of intramuscular fat tissue and greater age-related fat accumulation in trunk muscles in women than in men.

CT-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. CT-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.