In vivo discrimination of hip fracture with quantitative computed tomography: Results from the prospective European Femur Fracture Study (EFFECT)

In assessing osteoporotic fractures of the proximal femur, the main objective of this in vivo case‐control study was to evaluate the performance of quantitative computed tomography (QCT) and a dedicated 3D image analysis tool [Medical Image Analysis Framework—Femur option (MIAF‐Femur)] in differentiating hip fracture and non–hip fracture subjects. One‐hundred and seven women were recruited in the study, 47 women (mean age 81.6 years) with low‐energy hip fractures and 60 female non–hip fracture control subjects (mean age 73.4 years). Bone mineral density (BMD) and geometric variables of cortical and trabecular bone in the femoral head and neck, trochanteric, and intertrochanteric regions and proximal shaft were assessed using QCT and MIAF‐Femur. Areal BMD (aBMD) was assessed using dual‐energy X‐ray absorptiometry (DXA) in 96 (37 hip fracture and 59 non–hip fracture subjects) of the 107 patients. Logistic regressions were computed to extract the best discriminates of hip fracture, and area under the receiver characteristic operating curve (AUC) was calculated. Three logistic models that discriminated the occurrence of hip fracture with QCT variables were obtained (AUC = 0.84). All three models combined one densitometric variable—a trabecular BMD (measured in the femoral head or in the trochanteric region)—and one geometric variable—a cortical thickness value (measured in the femoral neck or proximal shaft). The best discriminant using DXA variables was obtained with total femur aBMD (AUC = 0.80, p = .003). Results highlight a synergistic contribution of trabecular and cortical components in hip fracture risk and the utility of assessing QCT BMD of the femoral head for improved understanding and possible insights into prevention of hip fractures. © 2011 American Society for Bone and Mineral Research.     

Spatial Differences in the Distribution of Bone Between Femoral Neck and Trochanteric Fractures

There is little knowledge about the spatial distribution differences in volumetric bone mineral density and cortical bone structure at the proximal femur between femoral neck fractures and trochanteric fractures. In this case‐control study, a total of 93 women with fragility hip fractures, 72 with femoral neck fractures (mean ± SD age: 70.6 ± 12.7 years) and 21 with trochanteric fractures (75.6 ± 9.3 years), and 50 control subjects (63.7 ± 7.0 years) were included for the comparisons. Differences in the spatial distributions of volumetric bone mineral density, cortical bone thickness, cortical volumetric bone mineral density, and volumetric bone mineral density in a layer adjacent to the endosteal surface were investigated using voxel‐based morphometry (VBM) and surface‐based statistical parametric mapping (SPM). We compared these spatial distributions between controls and both types of fracture, and between the two types of fracture. Using VBM, we found spatially heterogeneous volumetric bone mineral density differences between control subjects and subjects with hip fracture that varied by fracture type. Interestingly, femoral neck fracture subjects, but not subjects with trochanteric fracture, showed significantly lower volumetric bone mineral density in the superior aspect of the femoral neck compared with controls. Using surface‐based SPM, we found that compared with controls, both fracture types showed thinner cortices in regions in agreement with the type of fracture. Most outcomes of cortical and endocortical volumetric bone mineral density comparisons were consistent with VBM results. Our results suggest: 1) that the spatial distribution of trabecular volumetric bone mineral density might play a significant role in hip fracture; 2) that focal cortical bone thinning might be more relevant in femoral neck fractures; and 3) that areas of reduced cortical and endocortical volumetric bone mineral density might be more relevant for trochanteric fractures in Chinese women. © 2017 American Society for Bone and Mineral Research.     

Predicting Hip Fracture Type With Cortical Bone Mapping (CBM) in the Osteoporotic Fractures in Men (MrOS) Study

Hip fracture risk is known to be related to material properties of the proximal femur, but fracture prediction studies adding richer quantitative computed tomography (QCT) measures to dual‐energy X‐ray (DXA)‐based methods have shown limited improvement. Fracture types have distinct relationships to predictors, but few studies have subdivided fracture into types, because this necessitates regional measurements and more fracture cases. This work makes use of cortical bone mapping (CBM) to accurately assess, with no prior anatomical presumptions, the distribution of properties related to fracture type. CBM uses QCT data to measure the cortical and trabecular properties, accurate even for thin cortices below the imaging resolution. The Osteoporotic Fractures in Men (MrOS) study is a predictive case‐cohort study of men over 65 years old: we analyze 99 fracture cases (44 trochanteric and 55 femoral neck) compared to a cohort of 308, randomly selected from 5994. To our knowledge, this is the largest QCT‐based predictive hip fracture study to date, and the first to incorporate CBM analysis into fracture prediction. We show that both cortical mass surface density and endocortical trabecular BMD are significantly different in fracture cases versus cohort, in regions appropriate to fracture type. We incorporate these regions into predictive models using Cox proportional hazards regression to estimate hazard ratios, and logistic regression to estimate area under the receiver operating characteristic curve (AUC). Adding CBM to DXA‐based BMD leads to a small but significant (p < 0.005) improvement in model prediction for any fracture, with AUC increasing from 0.78 to 0.79, assessed using leave‐one‐out cross‐validation. For specific fracture types, the improvement is more significant (p < 0.0001), with AUC increasing from 0.71 to 0.77 for trochanteric fractures and 0.76 to 0.82 for femoral neck fractures. In contrast, adding DXA‐based BMD to a CBM‐based predictive model does not result in any significant improvement. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.     

Simulated increases in body fat and errors in bone mineral density measurements by DXA and QCT

Major alterations in body composition, such as with obesity and weight loss, have complex effects on the measurement of bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA). The effects of altered body fat on quantitative computed tomography (QCT) measurements are unknown. We scanned a spine phantom by DXA and QCT before and after surrounding with sequential fat layers (up to 12 kg). In addition, we measured lumbar spine and proximal femur BMD by DXA and trabecular spine BMD by QCT in 13 adult volunteers before and after a simulated 7.5 kg increase in body fat. With the spine phantom, DXA BMD increased linearly with sequential fat layering at the normal (p < 0.01) and osteopenic (p < 0.01) levels, but QCT BMD did not change significantly. In humans, fat layering significantly reduced DXA spine BMD values (mean ± SD: ?2.2 ± 3.7%, p = 0.05) and increased the variability of measurements. In contrast, fat layering increased QCT spine BMD in humans (mean ± SD: 1.5 ± 2.5%, p = 0.05). Fat layering did not change mean DXA BMD of the femoral neck or total hip in humans significantly, but measurements became less precise. Associations between baseline and fat‐simulation scans were stronger for QCT of the spine (r² = 0.97) than for DXA of the spine (r² = 0.87), total hip (r² = 0.80), or femoral neck (r² = 0.75). Bland‐Altman plots revealed that fat‐associated errors were greater for DXA spine and hip BMD than for QCT trabecular spine BMD. Fat layering introduces error and decreases the reproducibility of DXA spine and hip BMD measurements in human volunteers. Although overlying fat also affects QCT BMD measurements, the error is smaller and more uniform than with DXA BMD. Caution must be used when interpreting BMD changes in humans whose body composition is changing. © 2012 American Society for Bone and Mineral Research     

Heterogeneous Spatial and Strength Adaptation of the Proximal Femur to Physical Activity: A Within-Subject Controlled Cross-Sectional Study

Physical activity (PA) enhances proximal femur bone mass, as assessed using projectional imaging techniques. However, these techniques average data over large volumes, obscuring spatially heterogeneous adaptations. The current study used quantitative computed tomography, statistical parameter mapping, and subject-specific finite element (FE) modeling to explore spatial adaptation of the proximal femur to PA. In particular, we were interested in adaptation occurring at the superior femoral neck and improving strength under loading from a fall onto the greater trochanter. High/long jump athletes (n = 16) and baseball pitchers (n = 16) were utilized as within-subject controlled models as they preferentially load their take-off leg and leg contralateral to their throwing arm, respectively. Controls (n = 15) were included but did not show any dominant-to-nondominant (D-to-ND) leg differences. Jumping athletes showed some D-to-ND leg differences but less than pitchers. Pitchers had 5.8% (95% confidence interval [CI] 3.9%–7.6%) D-to-ND leg differences in total hip volumetric bone mineral density (vBMD), with increased vBMD in the cortical compartment of the femoral neck and trochanteric cortical and trabecular compartments. Voxel-based morphometry analyses and cortical bone mapping showed pitchers had D-to-ND leg differences within the regions of the primary compressive trabeculae, inferior femoral neck, and greater trochanter but not the superior femoral neck. FE modeling revealed pitchers had 4.1% (95% CI 1.4%–6.7%) D-to-ND leg differences in ultimate strength under single-leg stance loading but no differences in ultimate strength to a fall onto the greater trochanter. These data indicate the asymmetrical loading associated with baseball pitching induces proximal femur adaptation in regions associated with weight bearing and muscle contractile forces and increases strength under single-leg stance loading. However, there were no benefits evident at the superior femoral neck and no measurable improvement in ultimate strength to common injurious loading during aging (ie, fall onto the greater trochanter), raising questions as to how to better target these variables with PA. © 2019 American Society for Bone and Mineral Research.     

Odanacatib Treatment Affects Trabecular and Cortical Bone in the Femur of Postmenopausal Women: Results of a Two‐Year Placebo‐Controlled Trial

Odanacatib, a selective cathepsin K inhibitor, increases areal bone mineral density (aBMD) at the spine and hip of postmenopausal women. To gain additional insight into the effects on trabecular and cortical bone, we analyzed quantitative computed tomography (QCT) data of postmenopausal women treated with odanacatib using Medical Image Analysis Framework (MIAF; Institute of Medical Physics, University of Erlangen, Erlangen, Germany). This international, randomized, double‐blind, placebo‐controlled, 2‐year, phase 3 trial enrolled 214 postmenopausal women (mean age 64 years) with low aBMD. Subjects were randomized to odanacatib 50 mg weekly (ODN) or placebo (PBO); all participants received calcium and vitamin D. Hip QCT scans at 24 months were available for 158 women (ODN: n = 78 women; PBO: n = 80 women). There were consistent and significant differential treatment effects (ODN‐PBO) for total hip integral (5.4%), trabecular volumetric BMD (vBMD) (12.2%), and cortical vBMD (2.5%) at 24 months. There was no significant differential treatment effect on integral bone volume. Results for bone mineral content (BMC) closely matched those for vBMD for integral and trabecular compartments. However, with small but mostly significant differential increases in cortical volume (1.0% to 1.3%) and thickness (1.4% to 1.9%), the percentage cortical BMC increases were numerically larger than those of vBMD. With a total hip BMC differential treatment effect (ODN‐PBO) of nearly 1000 mg, the proportions of BMC attributed to cortical gain were 45%, 44%, 52%, and 40% for the total, neck, trochanter, and intertrochanter subregions, respectively. In postmenopausal women treated for 2 years, odanacatib improved integral, trabecular, and cortical vBMD and BMC at all femur regions relative to placebo when assessed by MIAF. Cortical volume and thickness increased significantly in all regions except the femoral neck. The increase in cortical volume and BMC paralleled the increase in cortical vBMD, demonstrating a consistent effect of ODN on cortical bone. Approximately one‐half of the absolute BMC gain occurred in cortical bone. © 2014 American Society for Bone and Mineral Research.     

Differences in hip quantitative computed tomography (QCT) measurements of bone mineral density and bone strength between glucocorticoid-treated and glucocorticoid-naïve postmenopausal women

Chronic treatment with glucocorticoids (GCs) leads to significant bone loss and increased risk of fractures. In chronically GC-treated patients, hip fracture risk is nearly 50%. The purpose of this investigation was to determine if there are differences in the quantities of trabecular and cortical bone and bone strength of the hip between GC-treated osteoporotic patients and controls. Methods: Study subjects were GC-treated osteoporotic postmenopausal women, and controls were postmenopausal women, recruited for separate clinical trials. Quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) of the hip were obtained from all subjects. QCT outcome variables measured included total, cortical, and trabecular BMD of hip subregions (femoral neck and trochanter) and total hip. In addition, finite element modeling (FEM) was performed on a subset of 19 cases and 38 controls, matched on age (± 5 years), weight (± 5 kg), and history of hormone replacement (>1 year use) to assess failure load in stance and fall loading conditions. Generalized linear models were used to adjust the QCT variables for covariates between groups. Multiple regression was performed to identify independent predictors of bone strength from the QCT variables. Results: Compared with controls, GC-treated subjects were significantly (p<0.05) younger, weighed less, and had more years of hormone replacement. QCT of the hip in GC-treated subjects for total femoral integral, cortical, and trabecular BMD averaged 4.9–23.2% (p<0.002) less than controls, and similar results were seen by hip subregion including the trochanter and femoral neck. DXA of the total hip was 17% lower in GC subjects than controls (p<0.05). Compared with controls, FEM failure load in GC subjects was 15% (p<0.05) and 16% (p=0.07) lower for stance and fall loading conditions, respectively. Multiple regression analysis demonstrated that a combination of QCT measures was correlated with bone strength as measured by FEM. Conclusions: Chronic GC treatment in postmenopausal women resulted in significantly decreased BMD of the hip, measured by QCT, with loss of both trabecular and cortical bone. In addition, GC treatment decreased bone strength as determined by FEM. The reduced cortical and trabecular bone mass in the hip may contribute to the disproportionately high hip fracture rates observed in GC-treated subjects.This work was supported by grants from the NIH 1R01AG05407, 1R01AR40431, 1R01AR46197, the Doris Duke Clinical Research Fellowship (CRF) Program for Medical Students (#20000684) K24AR048841-02 and the Rosalind Russell Arthritis Foundation.     

基于体素的股骨近端骨密度和骨皮质厚度的测量及可重复性研究

目的研究基于定量CT(quantitative computed tomography,QCT)的股骨近段骨密度和骨皮质厚度体素化测量的可重复性,为髋部骨折研究提供技术支持。方法选择28例短时间内QCT扫描两次的髋部骨折患者,其中男性6例,女性22例。从QCT影像中手动分割出股骨近段结构。借助体素形态学分析(voxel-based morphometry,VBM)思想,选择一个形状和结构适中的股骨近段结构作为标准模板,通过三维弹性配准算法将其他股骨近段映射到标准模板上。采用最小二乘和列文伯格-马夸尔特(Levenberg-Marquardt)方法将CT值转化成体素化的骨密度和骨皮质厚度值。最后,使用统计参数图(statistical parametric mapping,SPM)方法对28例患者短时间内两次QCT扫描数据的股骨近段骨密度和骨皮质厚度进行统计分析,获取三维统计参数图。结果所选28例骨折患者短时间内两次QCT扫描数据的股骨近段骨密度和骨皮质厚度的测量结果差异无统计学意义(P0.05),一致性均较好,说明测量结果较为准确。结论股骨近段骨密度和骨皮质厚度的测量方法具有较好的可重复性,为髋部骨折风险评估提供有效手段。     

Distribution of bone density in the proximal femur and its association with hip fracture risk in older men: The osteoporotic fractures in men (MrOS) study

This prospective case‐cohort study aimed to map the distribution of bone density in the proximal femur and examine its association with hip fracture. We analyzed baseline quantitative computed tomography (QCT) scans in 250 men aged 65 years or older, which comprised a randomly‐selected subcohort of 210 men and 40 cases of first hip fracture during a mean follow‐up period of 5.5 years. We quantified cortical, trabecular, and integral volumetric bone mineral density (vBMD), and cortical thickness (CtTh) in four quadrants of cross‐sections along the length of the femoral neck (FN), intertrochanter (IT), and trochanter (TR). In most quadrants, vBMDs and CtTh were significantly (p < 0.05) lower in cases compared to the subcohort and these deficits were present across the entire proximal femur. To examine the association of QCT measurements with hip fracture, we merged the two quadrants in the medial and lateral aspects of the FN, IT, and TR. At most sites, QCT measurements were associated significantly (p < 0.001) with hip fracture, the hazard ratio (HR) adjusted for age, body mass index (BMI), and clinical site for a 1‐SD decrease ranged between 2.28 (95% confidence interval [CI], 1.44–3.63) to 6.91 (95% CI, 3.11–15.53). After additional adjustment for total hip (TH) areal BMD (aBMD), trabecular vBMDs at the FN, TR, and TH were still associated with hip fracture significantly (p < 0.001), the HRs ranged from 3.21 (95% CI, 1.65–6.24) for the superolateral FN to 6.20 (95% CI, 2.71–14.18) for medial TR. QCT measurements alone or in combination did not predict fracture significantly (p > 0.05) better than TH aBMD. With an area under the receiver operating characteristic curve (AUC) of 0.901 (95% CI, 0.852–0.950), the regression model combining TH aBMD, age, and trabecular vBMD predicted hip fracture significantly (p < 0.05) better than TH aBMD alone or TH aBMD plus age. These findings confirm that both cortical and trabecular bone contribute to hip fracture risk and highlight trabecular vBMD at the FN and TR as an independent risk factor. © 2012 American Society for Bone and Mineral Research.     

Assessment of incident spine and hip fractures in women and men using finite element analysis of CT scans

Finite element analysis of computed tomography (CT) scans provides noninvasive estimates of bone strength at the spine and hip. To further validate such estimates clinically, we performed a 5‐year case‐control study of 1110 women and men over age 65 years from the AGES‐Reykjavik cohort (case = incident spine or hip fracture; control = no incident spine or hip fracture). From the baseline CT scans, we measured femoral and vertebral strength, as well as bone mineral density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric BMD only). We found that for incident radiographically confirmed spine fractures (n = 167), the age‐adjusted odds ratio for vertebral strength was significant for women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to 3.2) and for men remained significant (p = 0.01) independent of vertebral trabecular volumetric BMD. For incident hip fractures (n = 171), the age‐adjusted odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to 6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting for femoral neck areal BMD in women and for total hip areal BMD in both sexes; fracture classification improved for women by combining femoral strength with femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine and hip fractures were similarly high at the BMD‐based interventional thresholds for osteoporosis and at corresponding preestablished thresholds for “fragile bone strength” (spine: women ≤ 4500 N, men ≤ 6500 N; hip: women ≤ 3000 N, men ≤ 3500 N). Because it is well established that individuals over age 65 years who have osteoporosis at the hip or spine by BMD criteria should be considered at high risk of fracture, these results indicate that individuals who have fragile bone strength at the hip or spine should also be considered at high risk of fracture. © 2014 American Society for Bone and Mineral Research.     

Quantitative computed tomographic assessment of the effects of 24 months of teriparatide treatment on 3D femoral neck bone distribution,geometry, and bone strength: Results from the EUROFORS study

We studied the changes in bone distribution, geometry, and bone strength based on 3D quantitative computed tomography (QCT) of the femoral neck (FN) in subjects receiving teriparatide (TPTD). Fifty‐two postmenopausal women with severe osteoporosis were analyzed. Patients were divided into three subgroups based on their prior treatment with osteoporosis drugs: treatment‐naive (Tx‐naive; n = 8), pretreated (pre‐Tx; n = 12), and pretreated showing an inadequate response to treatment (inad. pre‐Tx; n = 32). QCT scans were performed at baseline and after 6, 12, and 24 months of treatment and were analyzed with Mindways QCT‐PRO BIT software. Minimum and maximum section modulus, buckling ratio (BR), and cross‐sectional area (CSA) were calculated as measurements of bending strength, risk of buckling, and bone apposition, respectively. After 24 months of TPTD treatment, areal and volumetric FN BMD increased significantly by 4.0% and 3.0%, respectively, compared with baseline. Decreases in cortical volumetric BMD occurred in locations not adversely affecting minimum bending strength indicators. Cortical CSA increased by 4.3%, whereas total CSA remained unchanged over the study duration, indicating that endosteal but no periosteal growth was observed. Strength parameters for buckling did not change at 6 and 12 months but improved significantly at 24 months. Measures of bending strength showed a trend toward improvement. Changes tended to be larger in individuals at higher risk of buckling failure. Prior antiresorptive treatment may delay response to TPTD, but based on the small magnitude of the mostly insignificant changes at 6 months, this does not appear to lead to an interim phase of reduced bone strength. In summary, FN QCT provides a tool for detailed longitudinal investigation of bone strength indices in vivo for different loading modes, yields insight into underlying structural changes, and provides relevant mechanostructural information beyond dual‐energy X‐ray absorptiometry. Continuous TPTD treatment for 24 months improves FN bone strength parameters. © 2010 American Society for Bone and Mineral Research     

Computed tomographic measurements of thigh muscle cross‐sectional area and attenuation coefficient predict hip fracture: The health,aging, and body composition study

Fatty infiltration of muscle, myosteatosis, increases with age and results in reduced muscle strength and function and increased fall risk. However, it is unknown if increased fatty infiltration of muscle predisposes to hip fracture. We measured the mean Hounsfield unit (HU) of the lean tissue within the midthigh muscle bundle (thigh muscle HU, an indicator of intramuscular fat), its cross‐sectional area (CSA, a measure of muscle mass) by computed tomography (CT), bone mineral density (BMD) of the hip and total‐body percent fat by dual X‐ray absorptiometry (DXA), isokinetic leg extensor strength, and the Short Physical Performance Battery (SPPB) in 2941 white and black women and men aged 70 to 79 years. Sixty‐three hip fractures were validated during 6.6 years of follow‐up. Proportional hazards regression analysis was used to assess the relative risk (RR) of hip fracture across variations in thigh muscle attenuation, CSA, muscle strength, and physical function for hip fracture. In models adjusted by age, race, gender, body mass index, and percentage fat, decreased thigh muscle HU resulted in increased risk of hip fracture [RR/SD = 1.58; 95% confidence interval (CI) 1.10–1.99], an association that continued to be significant after further adjustment for BMD. In models additionally adjusted by CSA, muscle strength, and SPPB score, decreased thigh muscle HU but none of the other muscle parameters continued to be associated with an increased risk of hip fracture (RR/SD = 1.42; 95% CI 1.03–1.97). Decreased thigh muscle HU, a measure of fatty infiltration of muscle, is associated with increased risk of hip fracture and appears to account for the association between reduced muscle strength, physical performance, and muscle mass and risk of hip fracture. This characteristic captures a physical characteristic of muscle tissue that may have importance in hip fracture etiology. © 2010 American Society for Bone and Mineral Research     

An in vivo comparison of hip structure analysis (HSA) with measurements obtained by QCT

Summary  

In a population of elderly women, bone cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (Z), femoral neck axis length (FNAL), and width measured with hip structure analysis (HSA) on dual-energy x-ray absorptiometry (DXA) images in the femoral neck and trochanteric regions are highly correlated to quantitative computed tomography (QCT) measurements.     

Association of 3D Geometric Measures Derived From Quantitative Computed Tomography With Hip Fracture Risk in Older Men

We investigated the associations of 3D geometric measures and volumetric bone mineral density (vBMD) of the proximal femur assessed by quantitative computed tomography (QCT) with hip fracture risk among elderly men. This study was a prospective case‐cohort design nested within the Osteoporotic Fractures in Men Study (MrOS) cohort. QCT scans of 230 men (65 with confirmed hip fractures) were evaluated with Mindways' QCTPRO‐BIT software. Measures that are indicative of bone strength for the femoral neck (FN) and for the trochanteric region (TR) were defined. Bending strength measures were estimated by minimum section modulus, buckling strength by buckling ratio, and a local thinning index (LTI). Integral and trabecular vBMD measures were also derived. Areal BMD (aBMD) of the total proximal femur from dual‐energy X‐ray absorptiometry (DXA) is presented for comparison. Associations of skeletal measures with incident hip fracture were estimated with hazard ratios (HR) per standard deviation and their 95% confidence intervals (CI) from Cox proportional hazard regression models with adjustment for age, body mass index (BMI), site, and aBMD. Men with hip fractures were older than men without fracture (77.1 ± 6.0 years versus 73.3 ± 5.7 years, p < 0.01). Age, BMI, and site‐adjusted HRs were significant for all measures except TR_LTI. Total femural BMD by DXA (HR = 4.9, 95% CI 2.5–9.9) and QCT (HR = 5.5, 95% CI 2.5–11.7) showed the strongest association followed by QCT FN integral vBMD (HR = 3.6, 95% CI 1.8–6.9). In models that additionally included aBMD, FN buckling ratio (HR = 1.9, 95% CI 1.1–3.2) and trabecular vBMD of the TR (HR = 2.0, 95% CI 1.2–3.4) remained associated with hip fracture risk, independent of aBMD. QCT‐derived 3D geometric indices of instability of the proximal femur were significantly associated with incident hip fractures, independent of DXA aBMD. Buckling of the FN is a relevant failure mode not entirely captured by DXA. Further research to study these relationships in women is warranted. © 2016 American Society for Bone and Mineral Research.     

Longitudinal Change in Bone Density,Geometry, and Estimated Bone Strength in Older Men and Women From The Gambia: Findings From the Gambian Bone and Muscle Aging Study (GamBAS)

Musculoskeletal aging in the most resource-limited countries has not been quantified, and longitudinal data are urgently needed to inform policy. The aim of this prospective study was to describe musculoskeletal aging in Gambian adults. A total of 488 participants were recruited stratified by sex and 5-year age band (aged 40 years and older); 386 attended follow-up 1.7 years later. Outcomes were dual-energy X-ray absorptiometry (DXA) (n = 383) total hip areal bone mineral density (aBMD), bone mineral content (BMC), bone area (BA); peripheral quantitative computed tomography (pQCT) diaphyseal and epiphyseal radius and tibia (n = 313) total volumetric BMD (vBMD), trabecular vBMD, estimated bone strength indices (BSIc), cross-sectional area (CSA), BMC, and cortical vBMD. Mean annualized percentage change in bone outcomes was assessed in 10-year age bands and linear trends for age assessed. Bone turnover markers, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25(OH)D) were explored as predictors of change in bone. Bone loss was observed at all sites, with an annual loss of total hip aBMD of 1.2% in women after age 50 years and in men at age 70 years plus. Greater loss in vBMD and BSIc was found at the radius in both men and women; strength was reduced by 4% per year in women and 3% per year in men (p trend 0.02, 0.03, respectively). At cortical sites, reductions in BMC, CSA, and vBMD were observed, being greatest in BMC in women, between 1.4% and 2.0% per annum. Higher CTX and PINP predicted greater loss of trabecular vBMD in women and BMC in men at the radius, and higher 25(OH)D with less loss of tibial trabecular vBMD and CSA in women. The magnitude of bone loss was like those reported in countries where fragility fracture rates are much higher. Given the predicted rise in fracture rates in resource-poor countries such as The Gambia, these data provide important insights into musculoskeletal health in this population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Proximal Femoral Structure and the Prediction of Hip Fracture in Men: A Large Prospective Study Using QCT

The structure of the femoral neck contributes to hip strength, but the relationship of specific structural features of the hip to hip fracture risk is unclear. The objective of this study is to determine the contribution of structural features and volumetric density of both trabecular and cortical bone in the proximal femur to the prediction of hip fracture in older men. Baseline QCT scans of the hip were obtained in 3347 men ≥65 yr of age enrolled in the Osteoporotic Fractures in Men Study (MrOS). All men were followed prospectively for an average of 5.5 yr. Areal BMD (aBMD) by DXA was also assessed. We determined the associations between QCT‐derived measures of femoral neck structure, volumetric bone density, and hip fracture risk. Forty‐two men sustained incident hip fractures during follow‐up: an overall rate of 2.3/1000 person‐years. Multivariable analyses showed that, among the QCT‐derived measures, lower percent cortical volume (hazard ratio [HR] per SD decrease: 3.2; 95% CI: 2.2–4.6), smaller minimal cross‐sectional area (HR: 1.6; 95% CI: 1.2–2.1), and lower trabecular BMD (HR: 1.7; 95% CI: 1.2–2.4) were independently related to increased hip fracture risk. Femoral neck areal BMD was also strongly related to hip fracture risk (HR: 4.1; 95% CI: 2.7–6.4). In multivariable models, percent cortical volume and minimum cross‐sectional area remained significant predictors of hip fracture risk after adjustment for areal BMD, but overall prediction was not improved by adding QCT parameters to DXA. Specific structural features of the proximal femur were related to an increased risk of hip fracture. Whereas overall hip fracture prediction was not improved relative to aBMD, by adding QCT parameters, these results yield useful information concerning the causation of hip fracture, the evaluation of hip fracture risk, and potential targets for therapeutic intervention.     

Bone Loss After Bariatric Surgery: Discordant Results Between DXA and QCT Bone Density

Several studies, using dual‐energy X‐ray absorptiometry (DXA), have reported substantial bone loss after bariatric surgery. However, profound weight loss may cause artifactual changes in DXA areal bone mineral density (aBMD) results. Assessment of volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT) may be less susceptible to such artifacts. We assessed changes in BMD of the lumbar spine and proximal femur prospectively for 1 year using DXA and QCT in 30 morbidly obese adults undergoing Roux‐en‐Y gastric bypass surgery and 20 obese nonsurgical controls. At 1 year, subjects who underwent gastric bypass surgery lost 37 ± 2 kg compared with 3 ± 2 kg lost in the nonsurgical controls (p < 0.0001). Spine BMD declined more in the surgical group than in the nonsurgical group whether assessed by DXA (?3.3 versus ?1.1%, p = 0.034) or by QCT (?3.4 versus 0.2%, p = 0.010). Total hip and femoral neck aBMD declined significantly in the surgical group when assessed by DXA (?8.9 versus ?1.1%, p < 0.0001 for the total hip and ?6.1 versus ?2.0%, p = 0.002 for the femoral neck), but no changes in hip vBMD were noted using QCT. Within the surgical group, serum P1NP and CTX levels increased by 82% ± 10% and by 220% ± 22%, respectively, by 6 months and remained elevated over 12 months (p < 0.0001 for all). Serum calcium, vitamin D, and PTH levels remained stable in both groups. We conclude that moderate vertebral bone loss occurs in the first year after gastric bypass surgery. However, striking declines in DXA aBMD at the proximal femur were not confirmed with QCT vBMD measurements. These discordant results suggest that artifacts induced by large changes in body weight after bariatric surgery affect DXA and/or QCT measurements of bone, particularly at the hip. © 2014 American Society for Bone and Mineral Research.     

Volumetric DXA (VXA): A new method to extract 3D information from multiple in vivo DXA images

Three‐dimensional geometric and structural measurements of the proximal femur are of considerable interest in understanding the strength of the femur and its susceptibility to fracture. Quantitative computed tomography (QCT) with a small voxel size (≤1 mm per side) is the current “gold standard” to examine the macrostructure of the femur, but it has a high effective radiation dose (approximately 2 to 5 mSv) and cost. Volumetric dual‐energy X‐ray absorptiometry (VXA) uses a commercially available DXA system (Hologic Discovery A) to reconstruct the proximal femur from four DXA scans delivering an effective radiation dose of 0.04 mSv. VXA was compared with QCT (voxel size of 0.29 × 0.29 × 1 mm) in 41 elderly women (age 82 ± 2.4 years) at slices located at the femoral neck and trochanteric regions of interest. For parameters of shape, the femoral neck axis length (FNAL) and the cross‐sectional slice area (SA), accuracy and strong linear correlations (r = 0.84 to 0.98) were demonstrated. Similar correlations (r = 0.81 to 0.97) were observed for the density parameters, the cross‐sectional bone area (CSA) and volumetric bone mineral density (vBMD). VXA also demonstrated strong correlations (r = 0.76 to 0.99) for the engineering parameters of the minimum, maximum, and polar cross‐sectional moments of inertia (CSMIs) and the section modulus (Z). We conclude that VXA is capable of generating a variety of 3D geometric and structural measurements that are highly correlated with QCT in elderly subjects in vivo. Moreover, the VXA measurements can be made with a commercially available DXA device at a very low radiation dose. © 2010 American Society for Bone and Mineral Research.     

Effect of Low‐Magnitude Mechanical Stimuli on Bone Density and Structure in Pediatric Crohn's Disease: A Randomized Placebo‐Controlled Trial

Pediatric Crohn's Disease (CD) is associated with low trabecular bone mineral density (BMD), cortical area, and muscle mass. Low‐magnitude mechanical stimulation (LMMS) may be anabolic. We conducted a 12‐month randomized double‐blind placebo‐controlled trial of 10 minutes daily exposure to LMMS (30 Hz frequency, 0.3 g peak‐to‐peak acceleration). The primary outcomes were tibia trabecular BMD and cortical area by peripheral quantitative CT (pQCT) and vertebral trabecular BMD by QCT; additional outcomes included dual‐energy X‐ray absorptiometry (DXA) whole body, hip and spine BMD, and leg lean mass. Results were expressed as sex‐specific Z‐scores relative to age. CD participants, ages 8 to 21 years with tibia trabecular BMD <25th percentile for age, were eligible and received daily cholecalciferol (800 IU) and calcium (1000 mg). In total, 138 enrolled (48% male), and 121 (61 active, 60 placebo) completed the 12‐month trial. Median adherence measured with an electronic monitor was 79% and did not differ between arms. By intention‐to‐treat analysis, LMMS had no significant effect on pQCT or DXA outcomes. The mean change in spine QCT trabecular BMD Z‐score was +0.22 in the active arm and –0.02 in the placebo arm (difference in change 0.24 [95% CI 0.04, 0.44]; p = 0.02). Among those with >50% adherence, the effect was 0.38 (95% CI 0.17, 0.58, p < 0.0005). Within the active arm, each 10% greater adherence was associated with a 0.06 (95% CI 0.01, 1.17, p = 0.03) greater increase in spine QCT BMD Z‐score. Treatment response did not vary according to baseline body mass index (BMI) Z‐score, pubertal status, CD severity, or concurrent glucocorticoid or biologic medications. In all participants combined, height, pQCT trabecular BMD, and cortical area and DXA outcomes improved significantly. In conclusion, LMMS was associated with increases in vertebral trabecular BMD by QCT; however, no effects were observed at DXA or pQCT sites. © 2016 American Society for Bone and Mineral Research.     

Volumetric quantitative computed tomography of the proximal femur: relationships linking geometric and densitometric variables to bone strength. Role for compact bone

Introduction In assessing cervical fractures of the proximal femur, this in vitro quantitative computed tomography (QCT) study had three objectives: to compare QCT to dual-energy X-ray absorptiometry (DXA) for predicting the failure load of the proximal femur, to compare the contributions of density and geometry to bone failure load, and to compare the contributions of cortical and trabecular bone to bone failure load. A novel three-dimensional (3D) analysis tool [medical image analysis framework (MIAF-Femur)] was used to analyze QCT scans. Methods The proximal ends of 28 excised femurs were studied (1) using QCT to separately measure bone mineral density (BMD) and geometric variables of trabecular and cortical bone, (2) using mechanical tests to failure in a stance configuration, and (3) using DXA to measure BMD. The variables were described with mean, standard deviation, and range. Correlation matrix and multivariate linear models were computed. Results Among correlations, cortical thicknesses of the femoral neck were significantly correlated with femoral failure load, especially of the inferoanterior quadrant (r ²=0.41; p<0.001), as was cortical volume at the “extended neck“ (r ²=0.41; p<0.001). Femoral failure load variance was best explained by a combination of QCT variables. Combining densitometric and geometric variables measured by QCT explained 76% of femoral failure load variance compared with 69% with the DXA model. Geometric variables (measured by QCT) explained 43% of femoral failure load variance compared with 72% for densitometric variables (measured by QCT). A model including only trabecular variables explained 52% of femoral failure load variance compared with 59% for a model including only cortical variables. Conclusion The QCT-MIAF reported here provides analysis of both geometric and densitometric variables characterizing cortical and trabecular bone. Confirmation of our results in an independent sample would suggest that QCT may better explain failure load variance for cervical fracture than the gold standard DXA-provided BMD. This work was supported in part by grants from EU, contract number: QLK6-CT-2002-02440-3DQCT