Dual-energy X-ray Absorptiometry Images Research Articles

Decreased trabecular bone score in patients affected by Fabry disease.

Fabry disease (FD) is an inherited X-linked lysosomal storage disease characterized by increased risk of osteoporosis and fractures. The impact of FD on clinical measures of bone quality is unknown. This considered, aim of our study was to evaluate whether trabecular bone microarchitecture, measured by trabecular bone score (TBS), is altered in patients with FD compared to control subjects. This retrospective monocentric study enrolled 14 patients (M/F 1/1, median age 46 [37-63] years, range 31-72 years) newly diagnosed with FD between January 2016 and July 2023 who underwent dual-energy X-ray absorptiometry (DXA) image at the time of diagnosis and 42 matched controls. In all subjects, data about bone mineral density (BMD) and lumbar spine TBS were collected and total calcium, parathyroid hormone (PTH), 25(OH) vitamin D, alkaline phosphatase (ALP), creatinine and estimated glomerular filtration rate (eGFR) were evaluated. In subjects with FD, globotriaosylsphingosine (lyso-Gb3), 24-hour proteinuria and albumin-creatinine ratio were also assessed. Patients with FD presented significantly lower lumbar spine TBS (1.29 [1.22-1.38] vs. 1.42 [1.39-1.47], p < 0.001) and lower lumbar spine BMD (0.916 ± 0.166 vs. 1.031 ± 0.125g/cm2, p = 0.008) compared to controls; moreover, FD was shown to be an independent risk factor for both low lumbar spine TBS (β = -0.118, p < 0.001) and BMD (β = -0.115, p = 0.009). No differences were found in serum calcium, ALP, 25(OH) vitamin D and eGFR in both groups, but FD patients had significantly higher PTH levels compared to controls (p = 0.016). Finally, 8 patients with FD presented either moderately or severely increased albuminuria and only 2 patients presented normal lyso-Gb3 levels. Patients affected by FD present significantly lower lumbar spine TBS and BMD compared to controls. Our findings strongly support the importance of carrying out a thorough evaluation of bone status in all patients affected by FD at baseline.

Valid inference for machine learning-assisted genome-wide association studies.

Machine learning (ML) has become increasingly popular in almost all scientific disciplines, including human genetics. Owing to challenges related to sample collection and precise phenotyping, ML-assisted genome-wide association study (GWAS), which uses sophisticated ML techniques to impute phenotypes and then performs GWAS on the imputed outcomes, have become increasingly common in complex trait genetics research. However, the validity of ML-assisted GWAS associations has not been carefully evaluated. Here, we report pervasive risks for false-positive associations in ML-assisted GWAS and introduce Post-Prediction GWAS (POP-GWAS), a statistical framework that redesigns GWAS on ML-imputed outcomes. POP-GWAS ensures valid and powerful statistical inference irrespective of imputation quality and choice of algorithm, requiring only GWAS summary statistics as input. We employed POP-GWAS to perform a GWAS of bone mineral density derived from dual-energy X-ray absorptiometry imaging at 14 skeletal sites, identifying 89 new loci and revealing skeletal site-specific genetic architecture. Our framework offers a robust analytic solution for future ML-assisted GWAS.

Sex-specific association of chronic proton pump inhibitor use with reduced bone density and quality.

Chronic use of proton pump inhibitors (PPIs) has been associated with an increase in bone fragility. However, evidence on the effect of chronic PPI use on bone density is conflicting, and data on bone microarchitectural quality are scarce. The primary aim of this study was to evaluate whether trabecular bone microarchitecture, assessed by trabecular bone score (TBS), is altered in chronic PPI users. The association between PPI use and bone density was also evaluated as a secondary endpoint. We extracted individual patient data from the 2005-2008 cycles of the population-based National Health and Nutrition Examination Survey (NHANES), in which lumbar spine dual-energy X-ray absorptiometry (DXA) scans were acquired. TBS values were calculated from DXA images using a dedicated software. Multivariable linear regression analyses stratified by sex were performed to evaluate the association of chronic PPI use with TBS and bone mineral density (BMD), adjusting for relevant confounders. A total of 7478 subjects were included (3961 men, 3517 women). After adjustment for relevant confounders, chronic PPI use was associated with a worse bone health profile in men, with lower TBS (-0.039, 95%CI:[-0.058, -0.020], p<0.001), lumbar spine T-score (-0.27, 95%CI:[-0.49, -0.05], p=0.018), total hip T-score (-0.20, 95%CI:[-0.39, -0.01], p=0.038), and femoral neck T-score (-0.21, 95%CI:[-0.42, -0.01], p=0.045). Notably, the association between chronic PPI use and degraded TBS remained statistically significant even after further adjustment for BMD at lumbar spine and femoral neck (-0.026, 95%CI:[-0.039, -0.012], p=0.001). In contrast, no significant association was observed between chronic PPI use and either TBS or BMD in women. Chronic PPI use is associated with degraded trabecular bone quality in men, even after adjustment for BMD. No association was observed in women.

Improved cut weight predictions from DEXA scans of lamb carcasses enables more accurate allocation of cuts to processing plans

The value of precise dual energy X-ray absorptiometry (DEXA) cut weight predictions to lamb allocation to cut plans is unknown. Lambs (n = 191) varying in carcase weight (HSCW) and GR (tissue depth over the 12th rib) were DEXA scanned and boned out to weigh retail cuts. Cut weights were predicted using HSCW; HSCW + GR; HSCW + DEXA and HSCW + DEXA image components in GLM models. DEXA improved cut weight predictions in most cuts (P < 0.05). A dataset of 10,000 carcases was then simulated using the associations between HSCW, GR and cut weights, before being truncated to 4500 lambs representing onel day's HSCW distribution. A lamb Carcase Optimisation Tool scenario was developed with 2–3 cut options per carcase section and cut weight thresholds applied to several cuts. Processing costs, market values and actual cut weights were input into the Optimiser to determine carcase allocation to cut options for optimised profits. This scenario was repeated using the predicted cut weights to determine the cut misallocations caused. DEXA-predicted cut weights produced 16.7% and 8.0% less misallocations than HSCW and GR. DEXA produced 20.8% and 14.3% less misallocations than HSCW and GR in shortloins, and 25.5% and 12.9% less in hindquarters. While cut misallocations have little direct impact on total profits, as product is over and under-valued when misallocated, reducing cut misallocations will improve processor compliance when sorting carcases into cut plans- reducing their need to retrim, downgrade and repackage product or the erosion of customer confidence caused by supplying product not meeting market specifications.

Potential non-invasive detection of lesions in broiler femur heads: application of the DXA imaging system.

Leg health is a significant economic and welfare concern for the poultry industry. Current methods of detection rely on visual assessment of the legs and gait scores and bone scoring during necropsy for full characterization. Additionally, the current scoring of femurs only examines the external surface of the femoral head. Through the use of the dual-energy X-ray absorptiometry (DXA) imaging system, we show the presence of a necrotic region in the femurs that would otherwise be considered healthy based on the current evaluation procedures. Importantly, these lesions were present in almost 60% (22 of 37) of femurs that scored normal for femoral head necrosis (FHN). Additionally, these femurs showed greater bone mineral content (BMC) relative to weight compared to their counterparts with no lucent lesions (6.95% ± 0.20% vs. 6.26% ± 0.25; p = 0.038). Identification of these lesions presents both a challenge and an opportunity. These subclinical lesions are likely to be missed in routine scoring procedures for FHN and can inadvertently impact the characterization of the disease and genetic selection programs. Furthermore, this imaging system can be used for in vivo, ex vivo, and embryonic (egg) studies and, therefore, constitutes a potential non-invasive method for early detection of bone lesions in chickens and other avian species.

Synthetic phantoms enable calibration between abattoir based dual energy X-ray absorptiometers used for prediction of lamb carcass composition

Dual energy x-ray absorptiometry (DXA) devices were installed at two Australian abattoirs to predict computed tomography (CT) determined fat % and lean % of lamb carcasses. This study tested three algorithms developed for these devices, termed β1, β2 and β3, and assessed their accuracy and precision in predicting CT composition. Algorithm β3 included the use of a plastic phantom calibration block scanned by both DXA devices to adjust prediction equations, resulting in superior accuracy to the algorithms without phantom calibration (β1 and β2). When compared to the gold-standard CT composition, the bias of the DXA predictions was lowest when using algorithm β3 at the two sites (−1.17%, −0.49% for fat %, 0.11%, −0.37% for lean %). The difference of DXA composition predictions between sites was lowest when using algorithm β3, which demonstrated between site differences of 0.59 CT fat %, and 0.46 CT lean%. In contrast, algorithm β1 and β2 produced differences of 23.7% and 30.8% for CT fat, and 17.3% and 21.9% for CT lean between the two DXA devices. There was a small difference of 0.78% between the fat predictions of the first DXA image compared to the second DXA image for each carcass. The precision of predictions improved slightly using algorithm β3. This work demonstrates that the in-line DXA systems can produce comparable results across sites.

Automated radiographic hip morphology measurements: An open-access method

ObjectiveThe aim of this study is to present a newly developed automated method to determine radiographic measurements of hip morphology on dual-energy x-ray absorptiometry (DXA) images. The secondary aim was to compare the performance of the automated and manual measurements. Design30 DXA scans from 13-year-olds of the prospective population-based cohort study Generation R were randomly selected. The hip shape was outlined automatically using radiographic landmarks from which the acetabular depth-width ratio (ADR), acetabular index (AI), alpha angle (AA), Wiberg and lateral center edge angle (WCEA) (LCEA), extrusion index (EI), neck-shaft angle (NSA), and the triangular index (TI) were determined. Manual assessments were performed twice by two orthopedic surgeons. The agreement within and between observers and methods was visualized using Bland-Altman plots, and the reliability was studied using the intraclass correlation coefficient (ICC) with 95 % confidence intervals (CI). ResultsThe automated method was able to perform all radiographic hip morphology measurements. The intermethod reliability between the automated and manual measurements ranged from 0.57 to 0.96 and was comparable to or better than the manual interobserver reliability, except for the AI. ConclusionThis open-access, automated method allows fast and reproducible calculation of radiographic measurements of hip morphology on right hip DXA images. It is a promising tool for performing automated radiographic measurements of hip morphology in large population studies and clinical practice.

Computed Tomography and Dual-Energy X-Ray Asorptiometry body composition parameter harmonisation to universalise adipose tissue measurements in a population-based cross-sectional study.

To harmonise computed tomography (CT) and dual-energy x-ray absorptiometry (DXA) body composition measurements allowing easy conversion in longitudinal assessments and across cohorts to assess cardiometabolic risk and disease. Retrospective cross-sectional observational study from 1996 to 2008 included participants in the Pennington Center Longitudinal Study (PCLS) (N = 1967; 571 African American/1396 White). Anthropometrics, whole-body DXA and abdominal CT images were obtained. Multi-layer segmentation techniques (Analyze; Rochester, MN) quantified visceral adipose tissue (VAT). Clinical biomarkers were obtained from routine blood samples. Linear models were used to predict CT-VAT from DXA-VAT and examine the effects of traditional biomarkers on cross-sectional-VAT. Predicted CT-VAT was highly associated with measured CT-VAT using ordinary least square linear regression analysis and random forest models (R2 = 0.84; 0.94, respectively, p < .0001). Model stratification effects showed low variability between races and sexes. Overall, associations between measured CT-VAT and DXA-predicted CT-VAT were good (R2 > 0.7) or excellent (R2 > 0.8) and improved for all stratification groups except African American men using random forest models. The clinical effects on measured CT-VAT and DXA-VAT showed no significant clinical difference in the measured adipose tissue areas (mean difference = 0.22 cm2). Random forest modelling seamlessly predicts CT-VAT from measured DXA-VAT to a degree of accuracy that falls within the bounds of universally accepted standard error.

Leukocyte telomere length is associated with MRI-thigh fat-free muscle volume: data from 16 356 UK Biobank adults.

Telomere attrition may share common biological mechanisms with bone and muscle loss with aging. Here, we investigated the association between these hallmarks of aging using data from UK Biobank, a large observational study. Leukocyte telomere length (LTL as T/S ratio) was measured using a multiplex qPCR assay at baseline (2006-2010). Bone mineral density (whole body and regional; via dual-energy X-ray absorptiometry), trabecular bone score (via lumbar-spine dual-energy X-ray absorptiometry images), fat-free muscle volume (thighs; via magnetic resonance imaging), and muscle fat infiltration (thighs; via magnetic resonance imaging) were measured during the imaging visit (2014-2018). Regression models were used to model LTL against a muscle or bone outcome, unadjusted and adjusted for covariates. A total of 16356 adults (mean age: 62.8±7.5years, 50.5% women) were included. In the fully adjusted model, thigh fat-free muscle volume was associated with LTL in the overall sample (adjusted standardized β (aβ)=0.017, 95% CI 0.009 to 0.026, P<0.001, per SD increase in LTL), with stronger associations in men (aβ=0.022, 95% CI 0.010 to 0.034, P<0.001) than in women (aβ=0.013, 95% CI 0.000 to 0.025, P=0.041) (sex-LTL P=0.028). The adjusted odds ratio (aOR) for low thigh fat-free muscle volume (body mass index-adjusted, sex-specific bottom 20%) was 0.93 per SD increase in LTL (95% CI 0.89 to 0.96, P<0.001) in the overall sample, with stronger associations in men (aOR=0.92, 95% CI 0.87 to 0.99, P=0.008) than women (aOR=0.93, 95% CI 0.88 to 0.98, P=0.009), although the sex difference was not statistically significant in this model (sex-LTL P=0.37). LTL was not associated with bone mineral density, trabecular bone score, or muscle fat infiltration in the overall or subgroup analyses (P>0.05). LTL was consistently associated with thigh fat-free muscle volume in men and women. Future research should investigate moderating effects of lifestyle factors (e.g., physical activity, nutrition, or chronic diseases) in the association between LTL and muscle volume.

Body composition in early pubescent children with obesity: effects following 1 year of nonintervention.

Little is known about whether body composition changes differently between children with and without obesity following 1 year of nonintervention. Therefore, we investigated body composition in early pubescent children (8-12 yr) with and without obesity before and after a period of 1 year of nonintervention. Early pubescent children (8-12 yr; Tanner stage ≤ 3) with (body mass index, BMI ≥ 95th percentile) and without obesity (15th < BMI < 85th percentile) were recruited. At baseline, 88 children (n = 25 without obesity) completed dual-energy X-ray absorptiometry imaging (DXA) for body composition measurements [%body fat, fat mass, fat-free mass (FFM)]. One year later, 47 participants (n = 15 without obesity) returned for repeat testing. The children without obesity were older (11.0 ± 1.0 vs. 10.0 ± 1.2 yr; means ± SD) (P = 0.013). There was no group difference in height, and both groups increased in height similarly after 1 year (147.7 ± 8.9 to 154.5 ± 9.2 cm without vs. 145.6 ± 5.8 to 152.5 ± 5.9 cm with obesity) (P < 0.001). Weight was greater (P < 0.001) in children with obesity at baseline as was the increase in weight after 1 yr (9.25 vs. 5.82 kg) (interaction, P = 0.005). Fat mass increased by 4.4 kg in children with obesity and by 1.1 kg in children without obesity (interaction, P < 0.001). However, there was no difference in fat-free mass between those with and without obesity at baseline (29.9 ± 5.9 vs. 31.6 ± 4.8 kg) (P = 0.206) with both groups increasing similarly over 1 year (gain of 4.87 vs. 4.85 kg with and without obesity, respectively). Without intervention, the increase in fat mass is four times greater in children with obesity after 1 year as compared with children without obesity.NEW & NOTEWORTHY Little is known about changes in body composition in children with and without obesity following 1 year of nonintervention. We report that without intervention, fat mass gain is significantly greater in children with obesity after 1 year compared with those without obesity. Body mass index (BMI) and %body fat measurements after 1 year yielded no significant increase suggesting that BMI and %fat alone are not suitable measures for tracking changes in adiposity among children.

A CNN-based strategy to automate contour detection of the hip and proximal femur using DXA hip images from longitudinal databases (CLSA and CaMos)

ABSTRACT Hip fractures contribute significantly to mortality in older adults. New methods to identify those at risk use dual-energy X-ray absorptiometry (DXA) images and advanced image processing. However, DXA images have an overlapping femur and pelvis and may contain boundary lines, making automation challenging. Herein, a 5-layer U-net convolutional neural network (CNN) was developed to segment the femur from hip DXA images. Images were used from the Canadian Longitudinal Study on Aging (CLSA, N=104) and Canadian Multicentre Osteoporosis Study (CaMos, N=105) databases for training, with manual contour drawing defining the ‘true output’ of each image. An algorithm was then developed to mask each hip image, and trained to predict subsequent masks. The CNN was tested with 44 additional CLSA images and 42 CaMos images. This proposed approach had an accuracy and intersection over union (IoU) of 97% and 0.57, and 93% and 0.51, for CaMos and CLSA scans, respectively. Furthermore, a series of augmentation techniques was applied to increase the data size, with accuracies of 96% and 94%, and IoU of 0.53 and 0.50. Overall, our strategy automatically determined the contour of the proximal femur using various clinical DXA images, a key step to automate fracture risk assessment in clinical practice.

Femora of women with premature ovarian insufficiency exhibit reduced strength and misalignment with the transmitted vertical forces from the upper body.

Women with premature ovarian insufficiency (POI) lack oestrogen, which is a key determinant of bone growth, epiphyseal closure, and bone tissue organisation. Although dual-energy X-ray absorptiometry (DXA)-derived areal bone mineral density (BMD) remains the gold standard for fracture risk evaluation, it does not fully characterise the skeletal abnormalities present in these women. Hence, we aimed to assess hip/femur anatomy, strength, and geometry and femoral alignment using advanced hip analysis (AHA). We conducted a cross-sectional, case-control study including 89 women with spontaneous normal karyotype POI (s-POI) or iatrogenic POI (i-POI), aged 20-50 years compared with 89 age- and body mass index (BMI)-matched population-based female controls. Hip anatomy, strength, geometrical parameters, and femur alignment were measured using hip DXA images and Lunar AHA software. Femoral orientation angle (FOA) was quantified as the overall orientation of the femur with respect to the axis of the forces transmitted from the upper body. The median age of POI diagnosis was 35 (18-40) years; the mean POI duration at the time of DXA was 2.07 (range 0-13) years, and 84% of POI women received oestrogen therapy. Areal BMD at all sites was significantly lower in the POI group (all P < .05). Indices of compressive and bending strength were lower in women with POI compared with controls, specifically the cross-sectional area (CSA, mm2) and section modulus (SM, mm3) (139.30 ± 29.08 vs 157.29 ± 22.26, P < .001 and 665.21 ± 129.54 vs 575.53 ± 150.88, P < .001, respectively). The FOA was smaller (124.99 ± 3.18) in women with POI as compared with controls (128.04 ± 3.80; P < .001) at baseline and after adjusting for height and femoral neck BMD. Alongside lower BMD at multiple sites, the femora of women with POI demonstrate reduced strength and a misalignment with forces transmitted from the upper body. Further research is needed to establish the role of these newly identified features and their role in fracture risk prediction in this population.

Clinical Use of Trabecular Bone Score: The 2023 ISCD Official Positions

Osteoporosis can currently be diagnosed by applying the WHO classification to bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry (DXA). However, skeletal factors other than BMD contribute to bone strength and fracture risk. Lumbar spine TBS, a grey-level texture measure which is derived from DXA images has been extensively studied, enhances fracture prediction independent of BMD and can be used to adjust fracture probability from FRAX® to improve risk stratification. The purpose of this International Society for Clinical Densitometry task force was to review the existing evidence and develop recommendations to assist clinicians regarding when and how to perform, report and utilize TBS. Our review concluded that TBS is most likely to alter clinical management in patients aged ≥ 40 years who are close to the pharmacologic intervention threshold by FRAX. The TBS value from L1-L4 vertebral levels, without vertebral exclusions, should be used to calculate adjusted FRAX probabilities. L1-L4 vertebral levels can be used in the presence of degenerative changes and lumbar compression fractures. It is recommended not to report TBS if extreme structural or pathological artifacts are present. Monitoring and reporting TBS change is unlikely to be helpful with the current version of the TBS algorithm. The next version of TBS software will include an adjustment based upon directly measured tissue thickness. This is expected to improve performance and address some of the technical factors that affect the current algorithm which may require modifications to these Official Positions as experience is acquired with this new algorithm.

Using magnetic resonance imaging to measure head muscles: An innovative method to opportunistically determine muscle mass and detect sarcopenia.

Sarcopenia is associated with multiple adverse outcomes. Traditional methods to determine low muscle mass for the diagnosis of sarcopenia are mainly based on dual-energy X-ray absorptiometry (DXA), whole-body magnetic resonance imaging (MRI) and bioelectrical impedance analysis. These tests are not always available and are rather time consuming and expensive. However, many brain and head diseases require a head MRI. In this study, we aim to provide a more accessible way to detect sarcopenia by comparing the traditional method of DXA lean mass estimation versus the tongue and masseter muscle mass assessed in a standard brain MRI. The H70 study is a longitudinal study of older people living in Gothenburg, Sweden. In this cross-sectional analysis, from 1203 participants aged 70years at baseline, we included 495 with clinical data and MRI images available. We used the appendicular lean soft tissue index (ALSTI) in DXA images as our reference measure of lean mass. Images from the masseter and tongue were analysed and segmented using 3D Slicer. For the statistical analysis, the Spearman correlation coefficient was used, and concordance was estimated with the Kappa coefficient. The final sample consisted of 495 participants, of which 52.3% were females. We found a significant correlation coefficient between both tongue (0.26) and masseter (0.33) with ALSTI (P<0.001). The sarcopenia prevalence confirmed using the alternative muscle measure in MRI was calculated using the ALSTI (tongue=2.0%, masseter=2.2%, ALSTI=2.4%). Concordance between sarcopenia with masseter and tongue versus sarcopenia with ALSTI as reference has a Kappa of 0.989 (P<0.001) for masseter and a Kappa of 1 for the tongue muscle (P<0.001). Comorbidities evaluated with the Cumulative Illness Rating Scale were significantly associated with all the muscle measurements: ALSTI (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.07-1.26, P<0.001), masseter (OR 1.16, 95% CI 1.07-1.26, P<0.001) and tongue (OR 1.13, 95% CI 1.04-1.22, P=0.002); the higher the comorbidities, the higher the probability of having abnormal muscle mass. ALSTI was significantly correlated with tongue and masseter muscle mass. When performing the sarcopenia diagnostic algorithm, the prevalence of sarcopenia calculated with head muscles did not differ from sarcopenia calculated using DXA, and almost all participants were correctly classified using both methods.

A Brief Review of the Literature for Published Dual-Energy X-Ray Absorptiometry Protocols for Athletes.

Dual-energy x-ray absorptiometry (DXA) is widely known for its utility in diagnosing a patient with osteopenia or osteoporosis; however, its utility in evaluation of body composition and potential athletic performance was previously routinely overlooked. In recent years, athletic programs have begun employing this equipment during athlete screening. However, it is currently unknown how athletic programs are utilizing this information to guide an athlete's training and health. To explore the literature to identify what is known regarding sports performance and athlete health based on body composition recordings. PubMed and Google Scholar databases were searched for this brief review. A focus was placed on articles within the past 10 years that discussed DXA protocols within athletic populations; 14 articles were included in this brief literature review. Brief literature review. Level 5. One member of the research team searched the literature and retrieved articles with the purpose of analyzing and/or explaining DXA imaging in body composition analysis of active persons (primarily athletes). Quality assurance scans with a phantom calibration block as well as athlete prescreening condition and activity standardization was routinely recommended. However, only 1 study reported a specific DXA protocol for athletes, and only 1 study described guidelines for how to report DXA results in athletic populations, suggesting it is plausible yet difficult due to the small changes detectable. Due to the limited literature as well as a lack of reference values for specific athletic populations, the authors of this review recommend using the current Nana et al (Int J Sport Nutr Exerc Metab 2015;25:198-215) DXA protocol for performing DXA scans in the athletic population as well as current Hind et al (J Clin Densitom 2018;21:429-443) guidelines for distributing the information.

Classification of Fracture Risk in Fallers Using Dual-Energy X-Ray Absorptiometry (DXA) Images and Deep Learning-Based Feature Extraction.

Dual-energy X-ray absorptiometry (DXA) scans are one of the most frequently used imaging techniques for calculating bone mineral density, yet calculating fracture risk using DXA image features is rarely performed. The objective of this study was to combine deep neural networks, together with DXA images and patient clinical information, to evaluate fracture risk in a cohort of adults with at least one known fall and age-matched healthy controls. DXA images of the entire body as, well as isolated images of the hip, forearm, and spine (1488 total), were obtained from 478 fallers and 48 non-faller controls. A modeling pipeline was developed for fracture risk prediction using the DXA images and clinical data. First, self-supervised pretraining of feature extractors was performed using a small vision transformer (ViT-S) and a convolutional neural network model (VGG-16 and Resnet-50). After pretraining, the feature extractors were then paired with a multilayer perceptron model, which was used for fracture risk classification. Classification was achieved with an average area under the receiver-operating characteristic curve (AUROC) score of 74.3%. This study demonstrates ViT-S as a promising neural network technique for fracture risk classification using DXA scans. The findings have future application as a fracture risk screening tool for older adults at risk of falls. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

SAT236 Pharmacokinetics (PK) And Pharmacodynamics (PD) Of The Parathyroid Hormone Analog PTH (1-34) (Teriparatide) Delivered Via An Orally Administered Robotic Pill (RT-102)

Abstract Disclosure: K. Horlen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. K. Kaminskaya: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A. Yamaguchi: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. L.C. Fung: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. H. Kennedy: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. S. Nguyen: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A. Dasari: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A. Toledo Vo: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. B. Archana: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. N. Patel: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. D. Mohan: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. B. Syed: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. A.K. Dhalla: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. M. Imran: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. M.A. Hashim: Employee; Self; Rani Therapeutics. Stock Owner; Self; Rani Therapeutics. Background: An orally administered robotic pill (RP) protects the drug from digestion during transit through the gastrointestinal tract before painlessly injecting the drug trans-enterically into the peritoneal space. Although parenteral, this unique delivery route can result in altered PK/PD profiles as drug absorption is primarily via mesenteric vasculature which drains into the portal vein. Here we report on two nonclinical studies which, 1) in awake canines, compared the PK profiles of orally delivered teriparatide via the RP (RT-102) versus subcutaneous (SC) injections; and 2) in an ovariectomized (OVX) rat model of osteoporosis, compared the PD (osteoanabolic) effect of intraperitoneal (IP) vs SC administered teriparatide on bone mineral density (BMD).Methods:PK Study: Beagle dogs (n = 43) received a single RT-102 capsule orally containing 20, 40, 80, or 160µg of teriparatide or a SC or intravenous (IV) injection of 20µg of the FDA-approved PTH(1-34) commercial product (Forteo®). Teriparatide concentrations in serial blood samples (collected for up to 300 minutes) were quantitated via a validated ELISA.PD Study: OVX Sprague-Dawley rats (n=50) underwent an 8-week bone depletion period followed by 6-weeks of daily treatment with teriparatide at a dose of 2, 5, or 15 µg/kg via IP injection or 5 µg/kg via SC injection (Forteo®) (n = 10 per treatment). A sham-operated control group received daily saline injections. BMD was assessed via dual-energy X-ray absorptiometry (DXA). Results:PK Study: RT-102 yielded steep increases in serum PTH concentrations followed by rapid declines to baseline levels, similar to the overall PK profile of Forteo® SC. RT-102 yielded more sustained exposures resulting in a prolonged Tmax compared to Forteo® SC (Tmax 37 to 48 vs 21 min). At 80 µg, PK curves of RT-102 tracked closely with SC, albeit with RT-102 yielding higher peak concentrations (Cmax = 3511 vs 1342 pg/mL). PD Study: DXA imaging of whole-body skeleton, femur, femur diaphysis, and lumbar vertebrae showed that intraperitoneally administered teriparatide yielded dose dependent increases in BMD in all areas examined. Animals receiving teriparatide via either IP or SC injections at equivalent doses showed no significant differences in the BMD increases between the two routes of administration. Conclusions: Orally administered RT-102 capsules to canines yielded steep rises in serum teriparatide concentrations followed by rapid elimination within three hours. When administered intraperitonially to mimic RT-102 delivery in a rodent model of osteoporosis, teriparatide was osteoanabolic similar to equivalent drug doses injected SC. These data provide the PK/PD proof-of-concept data for oral RT-102 capsules indicating their potential to replace current injection therapy for the treatment of osteoporosis. Presentation: Saturday, June 17, 2023

Computed Tomography Provides Improved Quantification of Trabecular Lumbar Spine Bone Loss Compared to Dual-Energy X-Ray Absorptiometry in Ovariectomized Sheep.

Early detection of osteoporosis using advanced imaging is imperative to the successful treatment and prevention of high morbidity fractures in aging patients. In this preclinical study, we aimed to compare dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) to quantify bone mineral density (BMD) changes in the sheep lumbar spine. We also aimed to determine the relationship of BMD to microarchitecture in the same animals as an estimate of imaging modality precision. Osteoporosis was induced in 10 ewes via laparoscopic ovariectomy and administration of high-dose corticosteroids. We performed DXA and QCT imaging to measure areal BMD (aBMD) and trabecular volumetric BMD (Tb.vBMD)/cortical vBMD (Ct.vBMD), respectively, at baseline (before ovariectomy) and at 3, 6, 9, and 12 months after ovariectomy. Iliac crest bone biopsies were collected at each time point for micro-computed tomography (microCT) analysis; bone volume fraction (BV/TV), trabecular number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp) were reported. aBMD and Tb.vBMD both decreased significantly by 3 and 6 months (p < 0.05) compared with baseline, whereas no changes to Ct.vBMD were observed. Combined (Tb. and Ct.) vBMD was significantly correlated with aBMD at all time points (all p < 0.05). Additionally, greater significant correlations were found between BV/TV and Tb.vBMD at all five time points (R 2 = 0.54, 0.57, 0.66, 0.46, and 0.56, respectively) than with aBMD values (R 2 = 0.23, 0.55, 0.41, 0.20, and 0.19, respectively). The higher correlation of microCT values with QCT than with DXA indicates that QCT provides additional detailed information regarding bone mineral density changes in preclinical settings. Because trabecular bone is susceptible to rapid density loss and structural changes during osteoporosis, QCT can capture these subtle changes more precisely than DXA in a large animal preclinical model. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

3D Finite Element Models Reconstructed From 2D Dual-Energy X-Ray Absorptiometry (DXA) Images Improve Hip Fracture Prediction Compared to Areal BMD in Osteoporotic Fractures in Men (MrOS) Sweden Cohort.

Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed a method to reconstruct the 3D hip anatomy from a 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a population-based cohort (Osteoporotic Fractures in Men [MrOS] Sweden). We defined two subcohorts: (i) hip fracture cases and controls cohort: 120 men with a hip fracture (<10 years from baseline) and two controls to each hip fracture case, matched by age, height, and body mass index; and (ii) fallers cohort: 86 men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, ΔAUROC = 0.06) and fallers (ΔAUROC = 0.22) cohorts. This is the first time that FE models outperformed aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Trabecular Bone Score as a More Sensitive Tool to Evaluate Bone Involvement in MEN1-related Primary Hyperparathyroidism.

The skeletal involvement of multiple endocrine neoplasia type 1-related primary hyperparathyroidism (MHPT) is not exactly the same as that of sporadic primary hyperparathyroidism (SHPT). Trabecular bone score (TBS) as a texture parameter has been reported to reflect trabecular bone damage. This study aimed to compare the clinical characteristics, especially the skeletal involvement, between patients with MHPT and SHPT. The clinical characteristics were retrospectively collected in 120 patients with MHPT and compared with 360 patients with SHPT in the same period. Dual-energy X-ray absorptiometry were conducted in some patients with MHPT, in whom bone mineral density (BMD) and calculated TBS derived from lumbar spine dual-energy X-ray absorptiometry images were compared with those of patients with SHPT. Although the duration of disease in the MHPT group was longer, the age at hospital visit was significantly lower than that in the SHPT group (43.5 [interquartile range, 31.5-52.0] vs 52.0 [interquartile range, 40.5-61.0], P < .001). The proportion of skeletal involvement in the MHPT group was significantly lower. However, in the subgroup of MHPT cases (n = 86) with data of BMD, there was no significant difference in skeletal involvement from SHPT cases matched for gender and age. Although the BMD and TBS in the lumbar spines of patients with MHPT were lower than those of patients with SHPT (BMD: 0.91 ± 0.18 g/cm2 vs 1.01 ± 0.17 g/cm2; TBS: 1.22 ± 0.14 vs 1.29 ± 0.11, P < .001). According to TBS, among 34 patients with MHPT with normal BMD, 15 patients had bone microstructure damage. The cancellous bone microarchitecture was more severely damaged in patients with MHPT according to TBS, which suggested that TBS could be a sensitive supplemental index in addition to BMD to identify bone-involvement risk in patients with MHPT.