High-resolution Peripheral Quantitative Computed Tomography Measurements Research Articles

Comparison of Motion Grading in 1,000 Patients by First- and Second-Generation HR-pQCT: A Propensity Score Matched Cohort Study

In-vivo bone microstructure measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) is gaining importance in research and clinical practice. Second-generation HR-pQCT (XCT2) shows improved image quality and shorter measurement duration compared to the first generation (XCT1). Predicting and understanding the occurrence of motion artifacts is crucial for clinical practice. We retrospectively analyzed data from HR-pQCT measurements at the distal radius and tibia of 1,000 patients (aged 20 to 89) evenly distributed between both generations of HR-pQCT. Motion artifacts were graded between 1 (no motion) and 5 (severe motion), with grades greater 3 considered unusable. Additionally, baseline characteristics and patients’ muscle performance and balance were measured. Various group comparisons between the two generations of HR-pQCT and regression analyses between patient characteristics and motion grading were performed. The study groups of XCT1 and XCT2 did not differ by age (XCT1: 64.9 vs. XCT2: 63.8 years, p = 0.136), sex (both 74.5% females, p > 0.999), or BMI (both 24.2 kg/m2, p = 0.911) after propensity score matching. XCT2 scans exhibited significantly lower motion grading in both extremities compared to XCT1 (Radius: p < 0.001; Tibia: p = 0.002). In XCT2 motion-corrupted scans were more than halved at the radius (XCT1: 35.3% vs. XCT2: 15.5%, p < 0.001), and at the tibia the frequency of best image quality scans was increased (XCT1: 50.2% vs. XCT2: 63.7%, p < 0.001). The strongest independent predictor for motion-corrupted images is the occurrence of high motion grading at the other scanning site during the same consultation. The association between high motion grading in one scan and a corresponding high motion grading in another scan within the same session suggests a non-resting patient. Additionally, aged, female, and patients with smaller stature tend towards higher motion grading, requiring special attention to a correct extremity fixation.

Independent changes in bone mineralized and marrow soft tissues following acute knee injury require dual-energy or high-resolution computed tomography for accurate assessment of bone mineral density and stiffness

Musculoskeletal injuries often induce local accumulation of blood and/or fluid within the bone marrow, which is detected on medical imaging as edema-like marrow signal intensities (EMSI). In addition to its biological effects on post-injury recovery, the displacement of low-attenuating, largely adipocytic marrow by EMSI may introduce errors into quantitative computed tomography (QCT) measurements of bone mineral density (vBMD) and resulting bone stiffness estimates from image-based finite element (FE) analysis. We aimed to investigate the impact of post-injury changes in marrow soft tissue composition on CT-based bone measurements by applying CT imaging at multiple spatial resolutions. To do so, dual energy QCT (DECT) material decomposition was used to detect EMSI in the tibiae of nineteen participants with a recent anterior cruciate ligament tear. We then measured bone density and FE-based apparent modulus within the EMSI region and in a matched volume in the uninjured contralateral knee. Three measurement methods were applied: 1.) standard, QCT density calibration and density-based FEM; 2.) a DECT density calibration that provides density measurements adjusted for marrow soft tissues; and 3.) high-resolution peripheral QCT (HR-pQCT) density and microFE analyses. When measured using standard, single-energy QCT, vBMD and apparent modulus were elevated in the EMSI compared to the contralateral. After adjusting for marrow soft tissue composition using DECT, these measurements were no longer different between the two regions. By allowing for high-resolution, localized density analysis, HR-pQCT indicated that trabecular tissue mineral density was 9 mgHA/cm3 lower, while density of marrow soft tissues was 18 mgHA/cm3 higher, in the EMSI than the contralateral region, suggesting that EMSI have opposite effects on the measured density of trabecular bone and the underlying soft marrow. Thus, after an acute injury, altered composition of marrow soft tissues may artificially inflate overall measurements of bone density and apparent modulus obtained using standard QCT. This can be corrected by accounting for marrow soft tissue attenuation, either by using DECT-based density calibration or HR-pQCT microFE and measurements of local density of trabeculae.

Reference microarchitectural values measured by HR-pQCT in a Franco-Swiss cohort of young adult women

High-resolution peripheral quantitative computed tomography (HR-pQCT) non-invasively measures three-dimensional bone microarchitectural parameters and volumetric bone mineral density. Previous studies established normative reference HR-pQCT datasets for several populations, but there were few data assessed in a reference group of young women with Caucasian ethnicity living in Western Europe. It is important to obtain different specific reference dataset for a valid interpretation of cortical and trabecular microarchitecture data. The aim of our study was to find the population with the most optimal bone status in order to establish a descriptive reference HR-pQCT dataset in a young and healthy normal-weight female cohort living in a European area including Geneva, Switzerland, Lyon and Saint-Etienne, France. We constituted a cross-sectional cohort of 339 women aged 19-41years with a BMI > 18 and < 30kg/m2. All participants had HR-pQCT measurements at both non-dominant distal radius and tibia sites. We observed that microarchitectural parameters begin to decline before the age of 30years. Based on a discriminant analysis, the optimal bone profile in this population was observed between the age range of 22 to 27years. Consequently, we considered 43 participants aged 22-27years to establish a reference dataset with median values and percentiles. This is the first study providing reference values of HR-pQCT measurements considering specific age bounds in a Franco-Swiss female cohort at the distal radius and tibia sites.

Association Between DXA And HR-pQCT Measurements Of BMD In Active, Recruit-aged Men And Women

Dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD) measurements are routinely employed to assess fracture risk despite the limitations of a two-dimensional, estimated projection of bone volume. Conversely, high-resolution peripheral quantitative computed tomography (HR-pQCT) provides three-dimensional volumetric BMD (vBMD) measurements of total, trabecular, and cortical bone, offering better characterization of fracture risk. It remains unclear whether regional aBMD accurately reflects vBMD of specific bone compartments in the distal tibia, a common injury site for military personnel. PURPOSE: To determine if lower limb aBMD correlates with distal total (Tt), trabecular (Tb) and cortical (Ct) vBMD in healthy, recruit-aged men and women. METHODS: Seventy-six recreationally active men (n = 43;26.4 ± 0.8 yrs.), and women (n = 33;26.2 ± 4.7 yrs.), free of any musculoskeletal conditions that could influence BMD, completed two HR-pQCT (XtremeCT; Scanco Medical) and one total body DXA (Lunar iDXA; GE Healthcare) scans. Total body DXA and non-dominant tibial HR-pQCT scans at the metaphysis (4% site) and diaphysis (30% site) were obtained. Lower leg aBMD was assessed in DXA scans with custom region of interest (ROI) analysis between the ultradistal tibia and the tibial plateau. Associations between variables were analyzed with Pearson’s correlation coefficient (r2); alpha was set at p < 0.05. RESULTS: aBMD positively correlated with Tt vBMD at the 4% site for men (r2 = 0.42; p < 0.001) and women (r2 = 0.17; p = 0.016) but only in men at the 30% site (r2 = 0.16; p = 0.008). aBMD positively correlated with Tb vBMD at the 4% site for men (r2 = 0.35; p < 0.001) and women (r2 = 0.20; p = 0.010), but not at the 30% site for either sex. aBMD was not correlated with Ct vBMD at the 4% site for either sex but was positively correlated with Ct vBMD at the 30% site in men (r2 = 0.12; p = 0.032). CONCLUSIONS: There is poor to moderate association between lower limb aBMD and tibial vBMD at both sites, with greater association in men than in women. aBMD is unlikely to provide a suitable assessment of distal tibial bone health. aBMD and tibial vBMD should, therefore, not be used interchangeably to examine the bone response to interventions or for the prediction of fracture risk. Supported by UK Ministry of Defence (WGCC 5.5.6-Task 0107).

Validation of Bone Density and Microarchitecture Measurements of the Load-Bearing Femur in the Human Knee Obtained Using In Vivo HR-pQCT Protocol

High resolution peripheral quantitative computed tomography (HR-pQCT) was designed to study bone mineral density (BMD) and microarchitecture in peripheral sites at the distal radius and tibia. With the introduction of the second generation HR-pQCT scanner (XtremeCT II, Scanco Medical) that has a larger, longer gantry it is now possible to study the human knee in vivo using HR-pQCT. Previous validation of HR-pQCT measurements at the distal radius and tibia against micro-CT is not representative of the knee because the increased cross-sectional area, greater amount of soft tissue surrounding the scan region, and different imaging protocol result in potentially increased beam hardening effects and photon scatter and different signal-to-noise ratio. The objective of this study is to determine the accuracy of density and microarchitecture measurements in the human knee measured by HR-pQCT using an in vivo protocol. Twelve fresh-frozen cadaver knees were imaged using in vivo HR-pQCT (60.7 µm) protocol. Subsequentially, distal femurs were extracted and imaged using a higher resolution (30.3 µm) ex vivo protocol, replicating micro-CT imaging. Scans were registered so that agreement of density and bone microarchitecture measurements could be determined using linear regression and Bland-Altman plots. All density and microarchitecture outcomes were highly correlated between the 2 protocols (R2 > 0.89) albeit with statistically significant differences between absolute measures based on paired t tests. All parameters showed accuracy between 4.5% and 8.7%, and errors were highly systematic, particularly for trabecular BMD and trabecular thickness (R2 > 0.93). We found that BMD and microarchitecture measurements in the distal femur obtained using an in vivo HR-pQCT knee protocol contained systematic errors, and accurately represented measurements obtained using a micro-CT equivalent imaging protocol. This work establishes the validity and limitations of using HR-pQCT to study the BMD and microarchitecture of human knees in future clinical studies.

Discriminating value of HR-pQCT for fractures in women with similar FRAX scores: A substudy of the FRISBEE cohort.

Areal bone mineral density (aBMD) has a low sensitivity to identify women at high fracture risk. The FRAX algorithm, by combining several clinical risk factors, might improve fracture prediction compared to aBMD alone. Several micro-architectural and biomechanical parameters which can be measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) are associated with fracture risk. HR-pQCT in combination or not with finite element analysis (FEA) may be used to improve bone strength prediction. Our aim was to assess whether HR-pQCT measurements (densities, cortical and trabecular microarchitecture, biomechanical proprieties assessed by FEA) had an added value in predicting fractures in a subgroup of women belonging to the Belgian FRISBEE cohort. One hundred nineteen women who sustained a fracture (aged 60 to 85years) during the initial follow-up of our cohort had a radius and tibia examination by HR-pQCT and were compared with controls matched for their FRAX score at baseline. We found that low distal radius total (OR=1.41 [1.07-1.86] per SD, p<0.05) and trabecular densities (OR=1.45 [1.10-1.90], p<0.01), trabecular number (OR=1.32 [1.01-1.72], p<0.05), intra individual distribution of separation (OR=0.73 [0.54-0.99], p<0.05) as several FEA parameters were significantly associated with fractures. At the distal tibia, impaired cortical density (OR=1.32 [1.03-1.70] per SD, p<0.05) and thickness (OR=1.29 [1.01-1.63], p<0.05) and apparent modulus (OR=1.30 [1.01-1.66], p<0.05) were significantly correlated with fractures. A low ultra distal radial aBMD (UDR) measured at the time of HR-pQCT was significantly associated with fractures (OR=1.67 [1.22-2.28], p<0.01). Women from both groups were followed further after the realization of the HR-pQCT and 46 new fractures were registered. In this second part of the study, low UDR aBMD (OR=1.66 [1.18-2.35], p<0.01), total (OR=1.48 [1.08-2.03], p<0.05), cortical (OR=1.40 [1.04-1.87], p<0.05) and trabecular (OR=1.37 [1.01-1.85], p<0.05) densities or apparent modulus (OR=1.49 [1.07-2.05], p<0.05) at the radius were associated with a significant increase of fracture risk. At the tibia, only the cortical density was significantly associated with the fracture risk (OR=1.34 [1.02-2.76], p<0.05). These results confirm the interest of HR-pQCT measurements for the evaluation of fracture risk, also in women matched for their baseline FRAX score. They also highlight that UDR aBMD contains pertinent information.

Virtual supersampling as post-processing step preserves the trabecular bone morphometry in human peripheral quantitative computed tomography scans.

In the clinical field of diagnosis and monitoring of bone diseases, high-resolution peripheral quantitative computed tomography (HR-pQCT) is an important imaging modality. It provides a resolution where quantitative bone morphometry can be extracted in vivo on patients. It is known that HR-pQCT provides slight differences in morphometric indices compared to the current standard approach micro-computed tomography (micro-CT). The most obvious reason for this is the restriction of the radiation dose and with this a lower image resolution. With advances in micro-CT evaluation techniques such as patient-specific remodeling simulations or dynamic bone morphometry, a higher image resolution would potentially also allow the application of such novel evaluation techniques to clinical HR-pQCT measurements. Virtual supersampling as post-processing step was considered to increase the image resolution of HR-pQCT scans. The hypothesis was that this technique preserves the structural bone morphometry. Supersampling from 82 μm to virtual 41 μm by trilinear interpolation of the grayscale values of 42 human cadaveric forearms resulted in strong correlations of structural parameters (R2: 0.96–1.00). BV/TV was slightly overestimated (4.3%, R2: 1.00) compared to the HR-pQCT resolution. Tb.N was overestimated (7.47%; R2: 0.99) and Tb.Th was slightly underestimated (-4.20%; R2: 0.98). The technique was reproducible with PE%CV between 1.96% (SMI) and 7.88% (Conn.D). In a clinical setting with 205 human forearms with or without fracture measured at 82 μm resolution HR-pQCT, the technique was sensitive to changes between groups in all parameters (p < 0.05) except trabecular thickness. In conclusion, we demonstrated that supersampling preserves the bone morphometry from HR-pQCT scans and is reproducible and sensitive to changes between groups. Supersampling can be used to investigate on the resolution dependency of HR-pQCT images and gain more insight into this imaging modality.

The Correction of Systematic Error due to Plaster and Fiberglass Casts on HR-pQCT Bone Parameters Measured In Vivo at the Distal Radius

Due to difficulty assessing healing of distal radius fractures using conventional radiography, there is interest in using high resolution peripheral quantitative computed tomography (HR-pQCT) to track healing at the microarchitectural level. Unfortunately, the plaster-of-Paris and fiberglass casts used to immobilize fractures affect HR-pQCT measurements due to beam hardening, and increased noise. The challenge is compounded because casts have variable thickness, and an individual patient will often have their cast changed 2–3 times during the course of treatment. This study quantifies the effect of casts within a clinically relevant range of thicknesses on measured bone parameters at the distal radius, and establishes conversion equations to correct for systematic error in due to cast presence. Eighteen nonfractured participants were scanned by HR-pQCT in three conditions: no cast, plaster-of-Paris cast, and fiberglass cast. Measured parameters were compared between the baseline scan (no cast) and each cast scan to evaluate if systematic error exists due to cast presence. A linear regression model was used to determine an appropriate conversion for parameters that were found to have systematic error. Plaster-of-Paris casts had a greater range of thicknesses (3.2–9.5 mm) than the fiberglass casts (3.0–5.4 mm), and induced a greater magnitude of systematic error overall. Key parameters of interest were bone mineral density (total, cortical, and trabecular) and trabecular bone volume fraction, all of which were found to have systematic error due to presence of either cast type. Linear correlations between baseline and cast scans for these parameters were excellent (R2 > 0.98), and appropriate conversions could be determined within a margin of error less than a ±6% for the plaster-of-Paris cast, and ±4% for the fiberglass cast. We have demonstrated the effects of cast presence on bone microarchitecture measurements, and presented a method to correct for systematic error, in support of future use of HR-pQCT to study fracture healing.

Bariatric Surgery: Weighing In on Bone Loss.

Bariatric Surgery: Weighing In on Bone Loss.

Validation of calcaneus trabecular microstructure measurements by HR-pQCT

ObjectiveAssessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against ‘gold-standard’ micro-CT measurements. MethodsTen human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82μm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Dissected portions of these bones were scanned using micro-computed tomography (micro-CT) at an isotropic 17.4μm voxel size. HR-pQCT images were rigidly registered to those obtained with micro-CT and divided into multiple 5mm sided cubes to evaluate and compare morphometric parameters between the modalities. Standard HR-pQCT measurements (derived bone volume fraction (BV/TVd); trabecular number, Tb.N; derived trabecular thickness, Tb.Thd; derived trabecular spacing, Tb.Spd) and corresponding micro-CT voxel-based measurements (BV/TV, Tb.N, Tb.Th, Tb.Sp) were compared. ResultsA total of 108 regions of interest were analysed across the 10 specimens. At all integration times HR-pQCT BV/TVd was strongly correlated with micro-CT BV/TV (r2=0.95–0.98, RMSE=1%), but BV/TVd was systematically lower than that measured by micro-CT (mean bias=5%). In contrast, HR-pQCT systematically overestimated Tb.N at all integration times; of the in situ scans, 200ms yielded the lowest mean bias and the strongest correlation with micro-CT (r2=0.61, RMSE=0.15mm−1). Regional analysis revealed greater accuracy for Tb.N in the superior regions of the calcaneus at all integration times in situ (mean bias=0.44–0.85mm−1; r2=0.70–0.88, p<0.001 versus mean bias=0.63–1.46mm−1; r2≤0.08, p≥0.21 for inferior regions). Tb.Spd was underestimated by HR-pQCT compared to micro-CT, but showed similar trends with integration time and the region evaluated as Tb.N. HR-pQCT Tb.Thd was also underestimated and moderately correlated (r2=0.53–0.59) with micro-CT Tb.Th, independently from the integration time. Stronger correlations, smaller biases and error were found in the scans of the calcaneus ex vivo compared to in situ. ConclusionCalcaneus trabecular BV/TVd and trabecular microstructure, particularly in the superior region of the calcaneus, can be assessed by HR-pQCT. The highest integration time examined, 200ms, compared best with micro-CT. Weaker correlations for microstructure at inferior regions, and also with lower integration times, might limit the use of the proposed protocol, which warrants further investigation in vivo.

High-resolution peripheral quantitative computed tomography (HR-pQCT) to detect compartmental bone loss on androgen deprivation therapy (ADT): A feasibility study.

209 Background: ADT causes bone loss, yet standard bone density (DXA) measurements do not distinguish cortical vs. trabecular bone loss and are falsely elevated in patients (pts) with sclerotic metastases, potentially underestimating fracture risk. HR-pQCT of the tibia and radius is a validated method to assess compartmental bone density and architecture that may overcome these limitations. Methods: Cross-sectional study of prostate cancer pts who underwent HR-pQCT (Scanco XtremeCT) of the radius and tibia and DXA scans within 6 months of initiating ADT. The relationship between HR-pQCT and relevant clinical variables was assessed using Spearman’s rank correlation method. Results: 22 pts were enrolled. Median baseline characteristics included: age = 64.5 (range 53-90), serum testosterone (T) level = 17 ng/dL (6-978), and interval between ADT start and HR-pQCT = 1.6 months (0-5.7). 5 pts (23%) were osteopenic as assessed by DXA. The correlation between HR-pQCT and clinical variables in shown in the Table. Of 12 pts with bone metastases, 7 (58%) had DXA L-spine and/or hip t-scores &gt; 2 standard deviations above mean for 30 year-old male. In contrast, all 7 pts had HR-pQCT measurements within the expected range based on age, sex, and serum T. Conclusions: HR-pQCT to assess bone loss in prostate cancer pts on ADT is feasible. Radial trabecular bone volume and density are correlated with relevant clinical variables including ADT duration and serum T. In pts with bone metastases, HR-pQCT may provide more accurate means to estimate BMD and determine fracture risk. Longitudinal studies in pts on ADT with paired HR-pQCT scans are ongoing. Clinical trial information: NCT02168062. [Table: see text]

Multiscale and multimodality computed tomography for cortical bone analysis

In clinical studies, high resolution peripheral quantitative computed tomography (HR-pQCT) is used to separately evaluate cortical bone and trabecular bone with an isotropic voxel of 82 µm3, and typical cortical parameters are cortical density (D.comp), thickness (Ct.Th), and porosity (Ct.Po).In vitro, micro-computed tomography (micro-CT) is used to explore the internal cortical bone micro-structure with isotropic voxels and high resolution synchrotron radiation (SR); micro-CT is considered the ‘gold standard’.In 16 tibias and 8 femurs, HR-pQCT measurements were compared to conventional micro-CT measurements. To test modality effects, conventional micro-CT measurements were compared to SR micro-CT measurements at 7.5 µm3; SR micro-CT measurements were also tested at different voxel sizes for the femurs, specifically, 7.5 µm3 versus 2.8 µm3.D.comp (r = −0.88, p < 10−3) was the parameter best correlated with porosity (Po.V/TV). The correlation was not affected by the removal of pores under 130 µm. Ct.Th was also significantly highly correlated (r = −0.89 p < 10−3), while Ct.Po was correlated with its counterpart Po.V/TV (r = 0.74, p < 10−3).From SR micro-CT and conventional micro-CT at 7.5 µm3 in matching areas, Po.V/TV and pore diameter were underestimated in conventional micro-CT with mean ± standard deviation (SD) biases of −2.5 ± 1.9% and −0.08 ± 0.08 mm, respectively. In contrast, pore number (Po.N) and pore separation (Po.Sp) were overestimated with mean ± SD biases of +0.03 ± 0.04 mm−1 and +0.02 ± 0.04 mm, respectively. The results from the tibia and femur were similar when the results of SR micro-CT at 7.5 µm3 and 2.8 µm3 were compared. Po.V/TV, specific surface of pores (Po.S/Po.V), and Po.N were underestimated with mean biases of −1.7 ± 0.9%, −4.6 ± 4.4 mm−1, and −0.26 ± 0.15 mm−1, respectively. In contrast, pore spacing was overestimated at 7.5 µm3 compared to 2.8 µm3 with mean biases of 0.05 ± 0.03 mm.Cortical bone measurements from HR-pQCT images provided consistent results compared to those obtained using conventional micro-CT at the distal tibia. D.comp was highly correlated to Po.V/TV because it considers both the micro-porosity (Haversian systems) and macro-porosity (resorption lacunae) of cortical bone. The complexity of canal organization, (including shape, connectivity, and surface) are not fully considered in conventional micro-CT in relation to beam hardening and cone beam reconstruction artifacts. With the exception of Po.V/TV measurements, morphological and topological measurements depend on the characteristics of the x-ray beam, and to a lesser extent, on image resolution.

A Critical Comparison Between Two Scanning Protocols of High-Resolution Peripheral Quantitative Computed Tomography at the Distal Radius in Adolescents

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a unique technology for assessing bone mineral density and bone microarchitecture. Currently, no universally accepted protocol for selecting the region of interest (ROI) at the distal radius has been established for growing subjects. This study aimed (1) to investigate the differences in HR-pQCT measurements of 2 different ROI protocols applied to the distal radius of healthy adolescents and (2) to identify the least common area of ROI (the least common ROI) between the protocols. Twenty-six boys and 26 girls aged between 13 and 16 yr old were recruited. Nondominant distal radius was scanned by 2 HR-pQCT protocols, namely, the “5-mm protocol,” where the distal end of ROI started at 5 mm proximal to a reference line, and the “4% protocol,” where the ROI started at 4% of the ulnar length proximal to another reference line. The least common ROI between the 2 protocols was identified and the slice numbering within the common ROI was determined. Bland–Altman plots were used to check the agreement of the least common ROIs between the 2 protocols. Paired t-test and Wilcoxon signed-rank test were used for analysis. In boys, significant differences between protocols were found in most parameters with the maximum difference observed in the cortical area (25.0%, p < 0.001). In girls, differences were observed only for total volumetric bone mineral density (3.6%, p = 0.032). The number of slices in the least common ROI was 66 (60.0%) and 57 (51.8%) in boys and girls, respectively. Good agreements on all HR-pQCT parameters from the least common ROI between the 2 protocols were found. Significant differences in bone parameters were noted between the 2 protocols. When comparing the 2 protocols, observed gender differences could reflect the differences in skeletal growth at the peripubertal period between genders. Least common ROI could be useful for cross-center comparisons and when merging datasets from different centers.

Effect of a Cast on Short-Term Reproducibility and Bone Parameters Obtained from HR-pQCT Measurements at the Distal End of the Radius

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a promising tool to assess the fracture-healing process at the microscale in vivo. Since casts are often used during fracture treatment, they might affect the assessment of bone density, microarchitectural, and biomechanical parameters and the short-term reproducibility of those parameters, e.g., as a result of beam-hardening. The aim of this study was to assess the effect of a plaster-of-Paris and/or fiberglass cast on bone parameters and on the short-term reproducibility of the HR-pQCT measurements of those parameters. The effects of a cast on HR-pQCT-derived bone parameters were evaluated by comparing HR-pQCT scans of fifteen human cadaveric distal radial specimens from one male and fourteen female donors (median age, eighty-four years [range, sixty-two to ninety years] at the time of death) in three conditions: with a plaster-of-Paris cast, with a fiberglass cast, or without a cast. Short-term reproducibility was assessed using duplicate scans of the distal end of the radius in sixteen healthy volunteers without a fracture (nine men and seven women with a median age of twenty-six years; range, twenty-two to thirty-nine years) while wearing and not wearing a fiberglass cast. Compared with measurements made with no cast, the plaster-of-Paris cast introduced a systematic error in the bone parameters ranging from -2.6% in trabecular separation to -9.8% in cortical thickness. Bone parameters were affected only marginally by fiberglass, with errors between -0.6% and -1.6% in trabecular separation and cortical thickness, respectively. Short-term reproducibility with a fiberglass cast was similar to that with no cast: approximately 1% for bone density parameters, 4% to 5% for microarchitectural parameters, and 3% to 4% for biomechanical parameters. A plaster-of-Paris cast has a considerable effect on HR-pQCT measurements. A fiberglass cast only marginally affects the bone parameters, and the short-term reproducibility of HR-pQCT measurements in patients with a fiberglass cast is comparable with that in patients without a cast. In studies on fracture-healing using HR-pQCT, a fiberglass cast is desirable if immobilization is indicated. The use of a plaster-of-Paris cast should be avoided if possible; however, if not avoidable, corrections after the scan are desirable to adjust for the error introduced in the bone parameters.

Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood.

Obesity is associated with greater areal BMD (aBMD) and is considered protective against hip and vertebral fracture. Despite this, there is a higher prevalence of lower leg and proximal humerus fracture in obesity. We aimed to determine if there are site-specific differences in BMD, bone structure, or bone strength between obese and normal-weight adults. We studied 100 individually-matched pairs of normal (body mass index [BMI] 18.5 to 24.9 kg/m2) and obese (BMI >30 kg/m2) men and women, aged 25 to 40 years or 55 to 75 years. We assessed aBMD at the whole body (WB), hip (TH), and lumbar spine (LS) with dual-energy X-ray absorptiometry (DXA), LS trabecular volumetric BMD (Tb.vBMD) by quantitative computed tomography (QCT), and vBMD and microarchitecture and strength at the distal radius and tibia with high-resolution peripheral QCT (HR-pQCT) and micro-finite element analysis. Serum type 1 procollagen N-terminal peptide (P1NP) and collagen type 1 C-telopeptide (CTX) were measured by automated electrochemiluminescent immunoassay (ECLIA). Obese adults had greater WB, LS, and TH aBMD than normal adults. The effect of obesity on LS and WB aBMD was greater in older than younger adults (p < 0.01). Obese adults had greater vBMD than normal adults at the tibia (p < 0.001 both ages) and radius (p < 0.001 older group), thicker cortices, higher cortical BMD and tissue mineral density, lower cortical porosity, higher trabecular BMD, and higher trabecular number than normal adults. There was no difference in bone size between obese and normal adults. Obese adults had greater estimated failure load at the radius (p < 0.05) and tibia (p < 0.01). Differences in HR-pQCT measurements between obese and normal adults were seen more consistently in the older than the younger group. Bone turnover markers were lower in obese than in normal adults. Greater BMD in obesity is not an artifact of DXA measurement. Obese adults have higher BMD, thicker and denser cortices, and higher trabecular number than normal adults. Greater differences between obese and normal adults in the older group suggest that obesity may protect against age-related bone loss and may increase peak bone mass.

Microstructural Parameters of Bone Evaluated Using HR-pQCT Correlate with the DXA-Derived Cortical Index and the Trabecular Bone Score in a Cohort of Randomly Selected Premenopausal Women

Background Areal bone mineral density is predictive for fracture risk. Microstructural bone parameters evaluated at the appendicular skeleton by high-resolution peripheral quantitative computed tomography (HR-pQCT) display differences between healthy patients and fracture patients. With the simple geometry of the cortex at the distal tibial diaphysis, a cortical index of the tibia combining material and mechanical properties correlated highly with bone strength ex vivo. The trabecular bone score derived from the scan of the lumbar spine by dual-energy X-ray absorptiometry (DXA) correlated ex vivo with the micro architectural parameters. It is unknown if these microstructural correlations could be made in healthy premenopausal women. Methods Randomly selected women between 20–40 years of age were examined by DXA and HR-pQCT at the standard regions of interest and at customized sub regions to focus on cortical and trabecular parameters of strength separately. For cortical strength, at the distal tibia the volumetric cortical index was calculated directly from HR-pQCT and the areal cortical index was derived from the DXA scan using a Canny threshold-based tool. For trabecular strength, the trabecular bone score was calculated based on the DXA scan of the lumbar spine and was compared with the corresponding parameters derived from the HR-pQCT measurements at radius and tibia. Results Seventy-two healthy women were included (average age 33.8 years, average BMI 23.2 kg/m2). The areal cortical index correlated highly with the volumetric cortical index at the distal tibia (R = 0.798). The trabecular bone score correlated moderately with the microstructural parameters of the trabecular bone. Conclusion This study in randomly selected premenopausal women demonstrated that microstructural parameters of the bone evaluated by HR-pQCT correlated with the DXA derived parameters of skeletal regions containing predominantly cortical or cancellous bone. Whether these indexes are suitable for better predictions of the fracture risk deserves further investigation.

Lean mass as a predictor of bone density and microarchitecture in adult obese individuals with metabolic syndrome

The effects of obesity and metabolic syndrome (MS) on bone health are controversial. Furthermore, the relationship between body composition and bone quality has not yet been determined in this context. The aim of this study was to investigate the correlations between body composition and bone mineral density (BMD) and bone microstructure in obese individuals with MS. This cross-sectional study assessed 50 obese individuals with MS with respect to their body composition and BMD, both assessed using dual X-ray absorptiometry, and bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia and radius. Several HR-pQCT measurements exhibited statistically significant correlations with lean mass. Lean mass was positively correlated with parameters of better bone quality (r: 0.316–0.470) and negatively correlated with parameters of greater bone fragility (r: −0.460 to −0.310). Positive correlations were also observed between lean mass and BMD of the total femur and radius 33%. Fat mass was not significantly correlated with BMD or any HR-pQCT measurements. Our data suggest that lean mass might be a predictor of bone health in obese individuals with MS.

Reproducibility for linear and nonlinear micro-finite element simulations with density derived material properties of the human radius

Finite element (FE) simulations based on high-resolution peripheral quantitative computed-tomography (HRpQCT) measurements provide an elegant and direct way to estimate bone strength. Parallel solvers for nonlinear FE simulations allow the assessment not only of the initial linear elastic behavior of the bone but also materially and geometrically nonlinear effects. The reproducibility of HRpQCT measurements, as well as their analysis of microarchitecture using linear-elastic FE simulations with a homogeneous elastic modulus has been investigated before. However, it is not clear to which extent density-derived and nonlinear FE simulations are reproducible. In this study, we introduced new mechanical indices derived from nonlinear FE simulations that describe the onset of yielding and the behavior at maximal load. Using 14 embalmed forearms that were imaged three times, we found that in general the in vitro reproducibility of the nonlinear FE simulations is as good as the reproducibility of linear FE. For the nonlinear simulations precision errors (PEs) ranged between 0.4 and 3.2% and intraclass correlation coefficients were above 0.9. In conclusion, nonlinear FE simulations with density derived material properties contain important additional information that is independent from the results of the linear simulations.

Precision of High-Resolution Peripheral Quantitative Computed Tomography Measurement Variables: Influence of Gender, Examination Site, and Age

High-resolution peripheral quantitative computed tomography (HR-pQCT) is increasingly being used in the research setting to assess the effects of osteoporosis treatments and disease on trabecular and cortical bone compartments. Further in-depth study of HR-pQCT measurement variables is essential to ensure study strength and statistical confidence when designing large multicenter studies. Duplicate HR-pQCT examinations of the distal radius and tibia were performed in 180 healthy men and women ages 16-18, 30-32, and >70 years. HR-pQCT images were processed using standard and extended cortical bone analysis techniques. Biomechanical properties of bone were assessed using finite element analysis. Percent root mean square coefficient of variation (RMSCV) was calculated for each measurement variable. Age, site, and gender influences on measurement variability were investigated using variance ratio tests. Smaller precision errors were observed for densitometric (0.2-5.5%) than for microstructural (1.2-7.0%), extended cortical bone (3.4-20.3%), and biomechanical (0.3-9.9%) measures at both the radius and tibia. Tibial measurements (RMSCVs = 0.2-7.4%) tended to be more precise than radial measurements (RMSCVs = 0.7-20.3%). Variability was influenced by age, site, and gender (all p < 0.05). HR-pQCT measurements for the tibia were more precise than those for the radius, and this may be explained by the larger bone volumes examined and the reduced likelihood of movement artifact. The greater measurement variability observed for older volunteers may be due to the loss of bone density and microstructural integrity with age.

Sa1256 High-Resolution Peripheral Quantitative Computerized Tomography Demonstrates Characteristics of Bone Fragility in Active Celiac Disease Patients

Backgrounds: Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk for bone fractures. Cole's fracture is the most common event in CD patients (54%). Assessment of patients' risk using bone mineral densitometry (BMD) is recommended by CD guidelines. However, BMD does not always represent a precise indicator of damage and a reliable predictor of bone fracture. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new in vivo imaging technique for assessing 3D microstructure of cortical and trabecular bone and for giving inside to factors involved in bone fragility. To our knowledge, no studies have investigated microstructural quality of bones in CD patients. Aims: To determine the structure characteristics of peripheral bones in a consecutive cohort of adult pre-menopausal females with active CD assessed at the time of diagnosis by using HR-pQCT. Methods: We prospectively enrolled 30 consecutive female patients with newly diagnosed CD. Parameters of patients were compared with 30 healthy, age-matched females with normal BMD measurements (lumbar spine, femoral neck and ultradistal radius). HR-pQCT bone volumetric and structural measurements were determined at the ultradistal non-dominant radius and tibia. Results: CD patients and healthy controls were comparable in terms of age, height, weight and body mass index (pNS). Lumbar spine, femoral neck and ultradistal radius BMD of CD patients were significantly lower than those values determined for healthy controls (p,0.01; p,0.04, p,0.001; respectively). However, while mean lumbar spine and femoral neck BMD values for CD patients remained in the normal range, ultradistal radius BMD mean z-score value for patients (-1.9±1.2) was borderline the lower end of the range expected for age. Structural damage in patients measured by using HR-pQCT was considerably higher in the ultradistal radius compared with tibia. Compared with controls, CD patients were significantly affected in the total volumetric density (p,0.006), trabecular density (p,0.001), bone volume/trabecular volume ratio (p,0.001), number of trabecules/mm (p,0.001) and trabecular thickness (p,0.004). Cortical bone was not significantly affected in any of the areas assessed. Conclusions: HR-pQCT was able to identify significant bone trabecular deterioration that may be responsible for the increased fragility and fracture prevalence in active CD. This affected quality of the trabecular bone was characterized by a lower number and a reduced thickness of trabecules, both producing a lower trabecular density. These changes were more pronounced in the ultradistal radius. Notably, cortical bone was preserved. Whether these women are able to recover trabecular bone density and structure after gluten-free diet is not known and will be assess in future results of this longitudinal study.