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

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.

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

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.

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

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.

Proximal femoral density distribution and structure in relation to age and hip fracture risk in women.

Hip fracture risk rises exponentially with age, but there is little knowledge about how fracture-related alterations in hip structure differ from those of aging. We employed computed tomography (CT) imaging to visualize the three-dimensional (3D) spatial distribution of bone mineral density (BMD) in the hip in relation to age and incident hip fracture. We used intersubject image registration to integrate 3D hip CT images into a statistical atlas comprising women aged 21 to 97 years (n = 349) and a group of women with (n = 74) and without (n = 148) incident hip fracture 4 to 7 years after their imaging session. Voxel-based morphometry was used to generate Student's t test statistical maps from the atlas, which indicated regions that were significantly associated with age or with incident hip fracture. Scaling factors derived from intersubject image registration were employed as measures of bone size. BMD comparisons of young, middle-aged, and older American women showed preservation of load-bearing cortical and trabecular structures with aging, whereas extensive bone loss was observed in other trabecular and cortical regions. In contrast, comparisons of older Icelandic fracture women with age-matched controls showed that hip fracture was associated with a global cortical bone deficit, including both the superior cortical margin and the load-bearing inferior cortex. Bone size comparisons showed larger dimensions in older compared to younger American women and in older Icelandic fracture women compared to controls. The results indicate that older Icelandic women who sustain incident hip fracture have a structural phenotype that cannot be described as an accelerated pattern of normal age-related loss. The fracture-related cortical deficit noted in this study may provide a biomarker of increased hip fracture risk that may be translatable to dual-energy X-ray absorptiometry (DXA) and other clinical images.