Validation of High-Resolution peripheral Quantitative Computed Tomography-Derived Achilles Tendon Properties Against Diagnostic Ultrasound.

OBJECTIVES: 1) To assess the precision of high resolution peripheral quantitative computed tomography (HR-pQCT)-derived Achilles tendon (AT) cross-sectional area (HR AT-CSA) and density, and 2) to validate HR AT-CSA against ultrasound-derived AT-CSA (US AT-CSA). METHODS: Women and men (≥50 years) had HR-pQCT (0.082mm isotropic) and US scans (B-mode) performed on the non-dominant ankle. Linear regression and Bland-Altman analyses assessed systematic differences between HR-pQCT and US-derived AT-CSA. Precision measured by % root mean square coefficients of variation (%RMSCV) and agreement by type 2,1 intraclass correlation coefficients (ICC2,1), were determined for test-retest US AT-CSA scans, and analysis-reanalysis of 30 HR-pQCT and US images. RESULTS: Among 44 participants, HR and US AT-CSA were strongly correlated (R2=0.84, p<0.01, B=1.05[0.90-1.19]), with no differences between modalities (p=0.37). Bland-Altman analysis revealed minimal systematic bias (-0.7mm2[-10.7-9.3]; 1.3%) between HR-pQCT and US-derived AT-CSA with smaller AT-CSA values showing larger inter-modality differences (R2=0.098, B=-0.137 [-0.268--0.008], p=0.039). US AT-CSA demonstrated excellent test-retest precision (ICC2,1=0.998, %RMSCV=1.04%). Analysis-reanalysis of HR-pQCT AT-density and both HR-pQCT and US AT-CSA displayed ICC2,1 above 0.95 and %RMSCV within 3%. CONCLUSION: HR-pQCT can examine AT-morphometry with acceptable analytical precision. Future studies should explore these metrics' association with functional outcomes and ankle-bone structural and mechanical properties.

Adverse effects of hydroxychloroquine and azithromycin on contractility and arrhythmogenicity revealed by human engineered cardiac tissues.

The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic as declared by World Health Organization (WHO). In the absence of an effective treatment, different drugs with unknown effectiveness, including antimalarial hydroxychloroquine (HCQ), with or without concurrent administration with azithromycin (AZM), have been tested for treating COVID-19 patients with developed pneumonia. However, the efficacy and safety of HCQ and/or AZM have been questioned by recent clinical reports. Direct effects of these drugs on the human heart remain very poorly defined. To better understand the mechanisms of action of HCQ +/- AZM, we employed bioengineered human ventricular cardiac tissue strip (hvCTS) and anisotropic sheet (hvCAS) assays, made with human pluripotent stem cell (hPSC)-derived ventricular cardiomyocytes (hvCMs), which have been designed for measuring cardiac contractility and electrophysiology, respectively. Our hvCTS experiments showed that AZM induced a dose-dependent negative inotropic effect which could be aggravated by HCQ; electrophysiologically, as revealed by the hvCAS platform, AZM prolonged action potentials and induced spiral wave formations. Collectively, our data were consistent with reported clinical risks of HCQ and AZM on QTc prolongation/ventricular arrhythmias and development of heart failure. In conclusion, our study exposed the risks of HCQ/AZM administration while providing mechanistic insights for their toxicity. Our bioengineered human cardiac tissue constructs therefore provide a useful platform for screening cardiac safety and efficacy when developing therapeutics against COVID-19.

Thermolabile Cross-Linkers for Templating Precise Multicomponent Metal-Organic Framework Pores.

While a number of approaches toward multicomponent metal-organic frameworks have been reported, new strategies affording greater structural versatility and molecular precision are needed to replicate the sophisticated active sites found in enzymes. Here, we outline a general method for templating functional groups within framework pores using thermolabile ligand cross-linkers. We show that tertiary ester-based cross-linkers can be used to install well-defined carboxylic acid pairs at precise relative distances and orientations. The tertiary ester linkages remain intact during framework formation but are readily cleaved to reveal free carboxylic acids upon microwave heating. Successful cross-linker synthesis, framework incorporation, and thermolysis is demonstrated using the mesoporous, terphenyl expanded analogues of MOF-74. When short cross-linkers are used, modeling studies show that the carboxylic acids are installed in a single configuration down the pore channels, spaced ∼7 Šapart. These precisely positioned acid pairs can be used as synthetic handles to build up more complex cooperative active sites.

Drone phenotyping and machine learning enable discovery of loci regulating daily floral opening in lettuce.

Flower opening and closure are traits of reproductive importance in all angiosperms because they determine the success of self- and cross-pollination. The temporal nature of this phenotype rendered it a difficult target for genetic studies. Cultivated and wild lettuce, Lactuca spp., have composite inflorescences that open only once. An L. serriola×L. sativa F6 recombinant inbred line (RIL) population differed markedly for daily floral opening time. This population was used to map the genetic determinants of this trait; the floral opening time of 236 RILs was scored using time-course image series obtained by drone-based phenotyping on two occasions. Floral pixels were identified from the images using a support vector machine with an accuracy >99%. A Bayesian inference method was developed to extract the peak floral opening time for individual genotypes from the time-stamped image data. Two independent quantitative trait loci (QTLs; Daily Floral Opening 2.1 and qDFO8.1) explaining >30% of the phenotypic variation in floral opening time were discovered. Candidate genes with non-synonymous polymorphisms in coding sequences were identified within the QTLs. This study demonstrates the power of combining remote sensing, machine learning, Bayesian statistics, and genome-wide marker data for studying the genetics of recalcitrant phenotypes.

Patient Care During the COVID-19 Pandemic: Use of Virtual Care.

Virtual care, the use of videoconferencing technology to connect with patients, has become critical in providing continuing care for patients during the current COVID-19 pandemic. Virtual care has now been adopted by health care providers across the spectrum, including physicians, residents, nurse practitioners, nurses, and allied health care professionals. Virtual care is novel and nuanced compared to in-person care. Most of the health care providers who are delivering or expected to deliver virtual care have little to no prior experience with it. The nuances of virtual care involve regulatory standards, platforms, technology and troubleshooting, patient selection, etiquette, and workflow, all of which comprise critical points in the provision of health care. It is important to consistently deliver high-quality, equitable, and professional virtual care to inspire patients with the trust they need to continue follow-up of their care in these difficult times. We have been adopting virtual care in our clinical practice for over two years. In partnership with Canada Health Infoway, we have assembled a primer for virtual care that can serve as a guide for any health care provider in Canada and globally, with the goal of providing seamless transitions between in-person and virtual care.

Vertebral Fractures: Which Radiological Criteria Are Better Associated With the Clinical Course of Osteoporosis?

STUDY PURPOSE: Morphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing OVF. We used data from both sexes in the Canadian Multicentre Osteoporosis Study (CaMos) to compare the 2 methods in identifying OVF at baseline and during 10 years of follow-up. MATERIALS AND METHODS: We obtained lateral thoracic and lumbar spinal radiographs (T4-L4) 3 times, at 5-year intervals, in 828 participants of the population-based CaMos. Logistic regressions were used to study the association of 10-year changes in bone mineral density (BMD) with incident fractures. RESULTS: At baseline, 161 participants had grade 1 and 32 had grade 2 GSQ OVF; over the next 10 years, only 9 of these participants had sustained incident GSQ OVF. Contrastingly, 21 participants at baseline had grade 1 and 48 grade 2 mABQ events; over the next 10 years, 79 subjects experienced incident grade 1 or grade 2 mABQ events. Thus, incident grades 1 and 2 morphologic fractures were 8 times more common than morphometric deformities alone. Each 10-year decrease of 0.01 g/cm2 in total hip BMD was associated with a 4.1% (95% CI: 0.7-7.3) higher odds of having an incident vertebral fracture. CONCLUSIONS: This analysis further suggests that morphometric deformities and morphologic fractures constitute distinct entities; morphologic fractures conform more closely to the expected epidemiology of OVF.

A Comparison of Peripheral Imaging Technologies for Bone and Muscle Quantification: A Review of Segmentation Techniques.

Musculoskeletal science has developed many overlapping branches, necessitating specialists from 1 area of focus to often require the expertise in others. In terms of imaging, this means obtaining a comprehensive illustration of bone, muscle, and fat tissues. There is currently a lack of a reliable resource for end users to learn about these tissues' imaging and quantification techniques together. An improved understanding of these tissues has been an important progression toward better prediction of disease outcomes and better elucidation of their interaction with frailty, aging, and metabolic disorders. Over the last decade, there have been major advances into the image acquisition and segmentation of bone, muscle, and fat features using computed tomography (CT), magnetic resonance imaging (MRI), and peripheral modules of these systems. Dedicated peripheral quantitative musculoskeletal imaging systems have paved the way for mobile research units, lower cost clinical research facilities, and improved resolution per unit cost paid. The purpose of this review was to detail the segmentation techniques available for each of these peripheral CT and MRI modalities and to describe advances in segmentation methods as applied to study longitudinal changes and treatment-related dynamics. Although the peripheral CT units described herein have established feasible standardized protocols that users have adopted globally, there remain challenges in standardizing MRI protocols for bone and muscle imaging.

A Valid and Precise Semiautomated Method for Quantifying Intermuscular Fat Intramuscular Fat in Lower Leg Magnetic Resonance Images.

The accumulation of INTERmuscular fat and INTRAmuscular fat (IMF) has been a hallmark of individuals with diabetes, those with mobility impairments such as spinal cord injuries and is known to increase with aging. An elevated amount of IMF has been associated with fractures and frailty, but the imprecision of IMF measurement has so far limited the ability to observe more consistent clinical associations. Magnetic resonance imaging has been recognized as the gold standard for portraying these features, yet reliable methods for quantifying IMF on magnetic resonance imaging is far from standardized. Previous investigators used manual segmentation guided by histogram-based region-growing, but these techniques are subjective and have not demonstrated reliability. Others applied fuzzy classification, machine learning, and atlas-based segmentation methods, but each is limited by the complexity of implementation or by the need for a learning set, which must be established each time a new disease cohort is examined. In this paper, a simple convergent iterative threshold-optimizing algorithm was explored. The goal of the algorithm is to enable IMF quantification from plain fast spin echo (FSE) T1-weighted MR images or from water-saturated images. The algorithm can be programmed into Matlab easily, and is semiautomated, thus minimizing the subjectivity of threshold-selection. In 110 participants from 3 cohort studies, IMF area measurement demonstrated a high degree of reproducibility with errors well within the 5% benchmark for intraobserver, interobserver, and test-retest analyses; in contrast to manual segmentation which already yielded over 20% error for intraobserver analysis. This algorithm showed validity against manual segmentations (r > 0.85). The simplicity of this technique lends itself to be applied to fast spin echo images commonly ordered as part of standard of care and does not require more advanced fat-water separated images.

Human ISL1+ Ventricular Progenitors Self-Assemble into an In Vivo Functional Heart Patch and Preserve Cardiac Function Post Infarction.

The generation of human pluripotent stem cell (hPSC)-derived ventricular progenitors and their assembly into a 3-dimensional in vivo functional ventricular heart patch has remained an elusive goal. Herein, we report the generation of an enriched pool of hPSC-derived ventricular progenitors (HVPs), which can expand, differentiate, self-assemble, and mature into a functional ventricular patch in vivo without the aid of any gel or matrix. We documented a specific temporal window, in which the HVPs will engraft in vivo. On day 6 of differentiation, HVPs were enriched by depleting cells positive for pluripotency marker TRA-1-60 with magnetic-activated cell sorting (MACS), and 3 million sorted cells were sub-capsularly transplanted onto kidneys of NSG mice where, after 2 months, they formed a 7 mm × 3 mm × 4 mm myocardial patch resembling the ventricular wall. The graft acquired several features of maturation: expression of ventricular marker (MLC2v), desmosomes, appearance of T-tubule-like structures, and electrophysiological action potential signature consistent with maturation, all this in a non-cardiac environment. We further demonstrated that HVPs transplanted into un-injured hearts of NSG mice remain viable for up to 8 months. Moreover, transplantation of 2 million HVPs largely preserved myocardial contractile function following myocardial infarction. Taken together, our study reaffirms the promising idea of using progenitor cells for regenerative therapy.

Investigating the Effects of Motion Streaks on pQCT-Derived Leg Muscle Density and Its Association With Fractures.

Lower peripheral quantitative computed tomography (pQCT)-derived leg muscle density has been associated with fragility fractures in postmenopausal women. Limb movement during image acquisition may result in motion streaks in muscle that could dilute this relationship. This cross-sectional study examined a subset of women from the Canadian Multicentre Osteoporosis Study. pQCT leg scans were qualitatively graded (1-5) for motion severity. Muscle and motion streak were segmented using semi-automated (watershed) and fully automated (threshold-based) methods, computing area, and density. Binary logistic regression evaluated odds ratios (ORs) for fragility or all-cause fractures related to each of these measures with covariate adjustment. Among the 223 women examined (mean age: 72.7 ± 7.1 years, body mass index: 26.30 ± 4.97 kg/m2), muscle density was significantly lower after removing motion (p < 0.001) for both methods. Motion streak areas segmented using the semi-automated method correlated better with visual motion grades (rho = 0.90, p < 0.01) compared to the fully automated method (rho = 0.65, p < 0.01). Although the analysis-reanalysis precision of motion streak area segmentation using the semi-automated method is above 5% error (6.44%), motion-corrected muscle density measures remained well within 2% analytical error. The effect of motion-correction on strengthening the association between muscle density and fragility fractures was significant when motion grade was ≥3 (p interaction <0.05). This observation was most dramatic for the semi-automated algorithm (OR: 1.62 [0.82,3.17] before to 2.19 [1.05,4.59] after correction). Although muscle density showed an overall association with all-cause fractures (OR: 1.49 [1.05,2.12]), the effect of motion-correction was again, most impactful within individuals with scans showing grade 3 or above motion. Correcting for motion in pQCT leg scans strengthened the relationship between muscle density and fragility fractures, particularly in scans with motion grades of 3 or above. Motion streaks are not confounders to the relationship between pQCT-derived leg muscle density and fractures, but may introduce heterogeneity in muscle density measurements, rendering associations with fractures to be weaker.

Measuring Marrow Density and Area Using Peripheral Quantitative Computed Tomography at the Tibia: Precision in Young and Older Adults and Individuals With Spinal Cord Injury.

The objective of this study was to compare the test-retest precision error for peripheral quantitative computed tomography (pQCT)-derived marrow density and marrow area segmentation at the tibia using 3 software packages. A secondary analysis of pQCT data in young adults (n = 18, mean ± standard deviation 25.4 ± 3.2 yr), older adults (n = 47, 71.8 ± 8.2 yr), and individuals with spinal cord injury (C1-T12 American Spinal Injury Association Impairment Scale, classes A-C; n = 19, 43.5 ± 8.6 yr) was conducted. Repeat scans of the tibial shaft (66%) were performed using pQCT (Stratec XCT2000). Test-retest precision errors (root mean square standard deviation and root mean square coefficient of variation [RMSCV%]) for marrow density (mg/cm3) and marrow area (mm2) were reported for the watershed-guided manual segmentation method (SliceOmatic version 4.3 [Sliceo-WS]) and the 2 threshold-based edge detection methods (Stratec version 6.0 [Stratec-TB] and BoneJ version 1.3.14 [BoneJ-TB]). Bland-Altman plots and 95% limits of agreement were computed to evaluate test-retest discrepancies within and between methods of analysis and subgroups. RMSCV% for marrow density segmentation was >5% for all methods across subgroups (Stratec-TB: 12.2%-28.5%, BoneJ-TB: 14.5%-25.2%, and Sliceo-WS: 10.9%-23.0%). RMSCV% for marrow area segmentation was within 5% for all methods across subgroups (Stratec-TB: 1.9%-4.4%, BoneJ-TB: 2.6%-5.1%, and Sliceo-WS: 2.4%-4.5%), except using BoneJ-TB in older adults. Intermethod discrepancies in marrow density appeared to be present across the range of marrow density values and did not differ by subgroup. Intermethod discrepancies varied to a greater extent for marrow area and were found to be more frequently at mid- to higher-range values for those with spinal cord injury. Precision error for pQCT-derived marrow density segmentation exceeded 5% for all methods of analysis across a range of bone mineral densities and fat infiltration, whereas precision error for marrow area segmentation ranged from 2% to 5%. Further investigation is necessary to determine alternative acquisition and analysis methods for pQCT-derived marrow segmentation.

Osteoporotic fractures and obesity affect frailty progression: a longitudinal analysis of the Canadian multicentre osteoporosis study.

BACKGROUND: Despite knowing better how to screen older adults, understanding how frailty progression might be modified is unclear. We explored effects of modifiable and non-modifiable factors on changes in frailty in community-dwelling adults aged 50+ years who participated in the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: Rates of change in frailty over 10 years were examined using the 30-item CaMos Frailty Index (CFI). Incident and prevalent low-trauma fractures were categorized by fracture site into hip, clinical vertebral and non-hip-non-vertebral fractures. Multivariable generalized estimating equation models accounted for the time of frailty assessment (baseline, 5 and 10 years), sex, age, body mass index (BMI, kg/m2), physical activity, bone mineral density, antiresorptive therapy, health-related quality of life (HRQL), cognitive status, and other factors for frailty or fractures. Multiple imputation and scenario analyses addressed bias due to attrition or missing data. RESULTS: The cohort included 5566 women (mean ± standard deviation: 66.8 ± 9.3 years) and 2187 men (66.3 ± 9.5 years) with the mean baseline CFI scores of 0.15 ± 0.11 and 0.12 ± 0.10, respectively. Incident fractures and obesity most strongly predicted frailty progression in multivariable analyses. The impact of fractures differed between the sexes. With each incident hip fracture, the adjusted mean CFI accelerated per 5 years by 0.07 in women (95% confidence interval [CI]: 0.03 to 0.11) and by 0.12 in men (95% CI: 0.08 to 0.16). An incident vertebral fracture increased frailty in women (0.05, 95% CI: 0.02 to 0.08) but not in men (0.01, 95% CI: -0.07 to 0.09). Irrespective of sex and prevalent fractures, baseline obesity was associated with faster frailty progression: a 5-year increase in the adjusted mean CFI ranged from 0.01 in overweight (BMI: 25.0 to 29.9 kg/m2) to 0.10 in obese individuals (BMI: ≥ 40 kg/m2). Greater physical activity and better HRQL decreased frailty over time. The results remained robust in scenario analyses. CONCLUSIONS: Older women and men with new vertebral fractures, hip fractures or obesity represent high-risk groups that should be considered for frailty interventions.

Heavy snow: IR spectroscopy of isotope mixed crystalline water ice.

Mid-infrared spectra have been measured for crystalline water ice aerosols of widely varied H/D isotopic composition. Particles with diameters ranging from 10-200 nm were generated via rapid collisional cooling with a cold buffer gas over a range of temperatures from 7-200 K. In near isotopically pure ices, the νL band position is slightly red-shifted with increasing temperature whilst in the ν2 region apparently anomalous shifts in peak maxima are explained by the contribution of a broad 2νL band of H2O and a 3νL band of D2O together with ν2 intensity that is particularly weak in low temperature crystalline ice. The hydrogen bonded OH (or OD) oscillator bands of near pure H2O (or D2O) ices are blue-shifted with temperature, with a gradient very similar to that of the corresponding band in isotope diluted samples, HOD in D2O (or H2O). It implies that this observed temperature trend is predominantly due to the intrinsic change in local hydride stretch potential energy, rather than to changes in intermolecular coupling. However, it is also observed that the narrow hydride stretch bands of an isotope diluted sample rapidly develop sub-band structure as the oscillator concentration increases, evidence of strong intermolecular coupling and a high degree of delocalisation. Anomalous blue-shifts in the OD stretch profile as D2O concentration grows is attributable to Fermi resonance with 2ν2 of D2O, in much closer proximity than the corresponding H2O levels. Theoretical results from a mixed quantum/classical approach are used to validate these findings in the hydride stretching region. Theory qualitatively reproduces the experimental trends as a function of temperature and isotopic variance.

A Comparison of Peripheral Imaging Technologies for Bone and Muscle Quantification: a Mixed Methods Clinical Review.

PURPOSE OF REVIEW: Bone and muscle peripheral imaging technologies are reviewed for their association with fractures and frailty. A narrative systematized review was conducted for bone and muscle parameters from each imaging technique. In addition, meta-analyses were performed across all bone quality parameters. RECENT FINDINGS: The current body of evidence for bone quality's association with fractures is strong for (high-resolution) peripheral quantitative computed tomography (pQCT), with trabecular separation (Tb.Sp) and integral volumetric bone mineral density (vBMD) reporting consistently large associations with various fracture types across studies. Muscle has recently been linked to fractures and frailty, but the quality of evidence remains weaker from studies of small sample sizes. It is increasingly apparent that musculoskeletal tissues have a complex relationship with interrelated clinical endpoints such as fractures and frailty. Future studies must concurrently address these relationships in order to decipher the relative importance of one causal pathway from another.

Improving reliability of pQCT-derived muscle area and density measures using a watershed algorithm for muscle and fat segmentation.

In peripheral quantitative computed tomography scans of the calf muscles, segmentation of muscles from subcutaneous fat is challenged by muscle fat infiltration. Threshold-based edge detection segmentation by manufacturer software fails when muscle boundaries are not smooth. This study compared the test-retest precision error for muscle-fat segmentation using the threshold-based edge detection method vs manual segmentation guided by the watershed algorithm. Three clinical populations were investigated: younger adults, older adults, and adults with spinal cord injury (SCI). The watershed segmentation method yielded lower precision error (1.18%-2.01%) and higher (p<0.001) muscle density values (70.2±9.2 mg/cm3) compared with threshold-based edge detection segmentation (1.77%-4.06% error, 67.4±10.3 mg/cm3). This was particularly true for adults with SCI (precision error improved by 1.56% and 2.64% for muscle area and density, respectively). However, both methods still provided acceptable precision with error well under 5%. Bland-Altman analyses showed that the major discrepancies between the segmentation methods were found mostly among participants with SCI where more muscle fat infiltration was present. When examining a population where fatty infiltration into muscle is expected, the watershed algorithm is recommended for muscle density and area measurement to enable the detection of smaller change effect sizes.

A trimodality comparison of volumetric bone imaging technologies. Part I: Short-term precision and validity.

In vivo peripheral quantitative computed tomography (pQCT) and peripheral magnetic resonance imaging (pMRI) modalities can measure apparent bone microstructure at resolutions 200 µm or higher. However, validity and in vivo test-retest reproducibility of apparent bone microstructure have yet to be determined on 1.0 T pMRI (196 µm) and pQCT (200 µm). This study examined 67 women with a mean age of 74±9 yr and body mass index of 27.65±5.74 kg/m2, demonstrating validity for trabecular separation from pMRI, cortical thickness, and bone volume fraction from pQCT images compared with high-resolution pQCT (hr-pQCT), with slopes close to unity. However, because of partial volume effects, cortical and trabecular thickness of bone derived from pMRI and pQCT images matched hr-pQCT more only when values were small. Short-term reproducibility of bone outcomes was highest for bone volume fraction (BV/TV) and densitometric variables and lowest for trabecular outcomes measuring microstructure. Measurements at the tibia for pQCT images were more precise than at the radius. In part I of this 3-part series focused on trimodality comparisons of precision and validity, it is shown that pQCT images can yield valid and reproducible apparent bone structural outcomes, but because of longer scan time and potential for more motion, the pMRI protocol examined here remains limited in achieving reliable values.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part II: 1-Yr Change, Long-Term Precision, and Least Significant Change.

The previous article in this 3-part series demonstrated short-term precision and validity for volumetric bone outcome quantification using in vivo peripheral (p) quantitative computed tomography (pQCT) and magnetic resonance imaging (MRI) modalities at resolutions 200 µm or higher. However, 1-yr precision error and clinically significant references are yet to be reported for these modalities. This study examined 59 women with mean age of 75 ± 9 yr and body mass index of 26.84 ± 4.77 kg/m², demonstrating the lowest 1-yr precision error, standard errors of the estimate, and least significant change values for high-resolution (hr) pQCT followed by pQCT, and 1.0-T pMRI for all volumetric bone outcomes except trabecular number. Like short-term precision, 1-yr statistics for trabecular separation were similar across modalities. Excluding individuals with a previous history of fragility fractures, or who were current users of antiresorptives reduced 1-yr change for bone outcomes derived from pQCT and pMR images, but not hr-pQCT images. In Part II of this 3-part series focused on trimodality comparisons of 1-yr changes, hr-pQCT was recommended to be the prime candidate for quantifying change where smaller effect sizes are expected, but pQCT was identified as a feasible alternative for studies expecting larger changes.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part III: SD, SEE, LSC Association With Fragility Fractures.

Part II of this 3-part series demonstrated 1-yr precision, standard error of the estimate, and 1-yr least significant change for volumetric bone outcomes determined using peripheral (p) quantitative computed tomography (QCT) and peripheral magnetic resonance imaging (pMRI) modalities in vivo. However, no clinically relevant outcomes have been linked to these measures of change. This study examined 97 women with mean age of 75 ± 9 yr and body mass index of 26.84 ± 4.77 kg/m(2), demonstrating a lack of association between fragility fractures and standard deviation, least significant change and standard error of the estimate-based unit differences in volumetric bone outcomes derived from both pMRI and pQCT. Only cortical volumetric bone mineral density and cortical thickness derived from high-resolution pQCT images were associated with an increased odds for fractures. The same measures obtained by pQCT erred toward significance. Despite the smaller 1-yr and short-term precision error for measures at the tibia vs the radius, the associations with fractures observed at the radius were larger than at the tibia for high-resolution pQCT. Unit differences in cortical thickness and cortical volumetric bone mineral density able to yield a 50% increase in odds for fractures were quantified here and suggested as a reference for future power computations.