European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (2) intraoperative imaging.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of intraoperative and postoperative complications. So far, only limited data regarding the best radiological approach to monitor children during liver transplantation is available. OBJECTIVE: To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra- and postoperative phase. This paper reports the responses related to intraoperative imaging. MATERIALS AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. RESULTS: Intraoperative ultrasound (US) is used by all sites to assess the quality of the vascular anastomosis in order to ensure optimal perfusion of the liver transplant. Vessel depiction is commonly achieved using color Doppler (95.3%). Additional US-based techniques are employed by fewer centers (power angio mode, 28.6%; B-flow, 19%; contrast-enhanced US, 14.3%). Most centers prefer a collaborative approach, with surgeons responsible for probe handling, while radiologists operate the US machine (47.6%). Less commonly, the intraoperative US is performed by the surgeon alone (28.6%) or by the radiologist alone (23.8%). Timing of US, imaging frequency, and documentation practices vary among centers. CONCLUSION: Intraoperative US is consistently utilized across all sites during pediatric liver transplantation. However, considerable variations were observed in terms of the US setup, technique preferences, timing of controls, and documentation practices. These differences provide valuable insights for future optimization and harmonization studies.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (3) postoperative imaging.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of postoperative complications. So far, limited data is available regarding the best radiologic approach to monitor children after liver transplantation. OBJECTIVE: To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phases. This paper reports the responses related to postoperative imaging. MATERIALS AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. RESULTS: All sites commence ultrasound (US) monitoring within 24 h after liver transplantation. Monitoring frequency varies across sites, ranging from every 8 h to 72 h in early, and from daily to sporadic use in late postoperative phases. Predefined US protocols are used by 73% of sites. This commonly includes gray scale, color Doppler, and quantitative flow assessment. Alternative flow imaging techniques, contrast-enhanced US, and elastography are applied at 31.8%, 18.2%, and 63.6% of sites, respectively. Computed tomography is performed at 86.4% of sites when clarification is needed. Magnetic resonance imaging is used for selected cases at 36.4% of sites, mainly for assessment of biliary abnormalities or when blood tests are abnormal. CONCLUSION: Diagnostic imaging is extensively used for postoperative surveillance of children after liver transplantation. While US is generally prioritized, substantial differences were noted in US protocol, timing, and monitoring frequency. The study highlights potential areas for future optimization and standardization of imaging, essential for conducting multicenter studies.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (1) pre-transplant evaluation.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment in end-stage liver disease. Imaging is a key element for successful organ-transplantation to assist surgical planning. So far, only limited data regarding the best radiological approach to prepare children for liver transplantation is available. OBJECTIVES: In an attempt to harmonize imaging surrounding pediatric liver transplantation, the European Society of Pediatric Radiology (ESPR) Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phase. This paper reports the responses on preoperative imaging. MATERIAL AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted and 22 institutions from 11 countries returned the survey. From 2018 to 2020, the participating centers collectively conducted 1,524 transplantations, with a median of 20 transplantations per center per annum (range, 8-60). RESULTS: Most sites (64%) consider ultrasound their preferred modality to define anatomy and to plan surgery in children before liver transplantation, and additional cross-sectional imaging is only used to answer specific questions (computed tomography [CT], 90.9%; magnetic resonance imaging [MRI], 54.5%). One-third of centers (31.8%) rely primarily on CT for pre-transplant evaluation. Imaging protocols differed substantially regarding applied CT scan ranges, number of contrast phases (range 1-4 phases), and applied MRI techniques. CONCLUSION: Diagnostic imaging is generally used in the work-up of children before liver transplantation. Substantial differences were noted regarding choice of modalities and protocols. We have identified starting points for future optimization and harmonization of the imaging approach to multicenter studies.

Finding the most suitable puncture site for intraosseous access in term and preterm neonates: an ultrasound-based anatomical pilot study.

The purpose of this prospective ultrasound-based pilot study was to identify the most suitable tibial puncture site for intraosseous (IO) access in term and preterm neonates, describe tibial dimensions at this site, and provide anatomical landmarks for rapid localization. We measured the tibial dimensions and distances to anatomical landmarks at puncture sites A (proximal: 10 mm distal to the tibial tuberosity; distal: 10 mm proximal to the malleolus medialis) and B (chosen by palpation of the pediatrician), in 40 newborns in four weight groups (< 1000 g; 1000-2000 g, 2000-3000 g, and 3000-4000 g). Sites were rejected if they fell short of the assumed safety distance to the tibial growth plate of 10 mm. If both A and B were rejected, puncture site C was determined sonographically at the maximum tibial diameter while maintaining the safety distance. Puncture site A violated the safety distance in 53% and 85% (proximally and distally, respectively) and puncture site B in 38% and 33%. In newborns weighing 3000-4000 g, at median (IQR), the most suitable puncture site at the proximal tibia was 13.0 mm (12.0-15.8) distal to the tuberosity and 6.0 mm (4.0-8.0) medial to the anterior rim of the tibia. The median (IQR) diameters at this site were 8.3 mm (7.9-9.1) (transverse) and 9.2 mm (8.9-9.8) (anterior-posterior). The diameters increased significantly with increasing weight.  Conclusion: This study adds concise, practical information on the implementation of IO access in neonatal patients: the tibial dimensions in newborns in four different weight groups and initial data on anatomical landmarks to easily locate the IO puncture site. The results may help implement IO access in newborns more safely. What is Known: • Intraosseous access is a feasible option for emergency administration of vital drugs and fluids in newborns undergoing resuscitation when an umbilical venous catheter is impossible to place. • Severe complications of IO access due to malpositioned IO needles have been reported in neonates. What is New: • This study reports the most suitable tibial puncture sites for IO access and the tibial dimensions, in newborns of four weight groups. • The results can help to implement safe IO access in newborns.

Low muscle volume of the anal sphincter complex: A novel prognostic factor in children with anorectal malformations?

BACKGROUND/PURPOSE: The anal sphincter complex (ASC) plays a key role in continence and is often dysfunctional in infants born with anorectal malformations (ARM). The ASC is well depicted by magnetic resonance (MR) imaging but volumetric reference data are lacking in infants. Thus, we tested the feasibility of MR based ASC volumetry, collected reference data, and compared them with cases of favorableprognosis and unfavorable prognosis (as defined by the type of ARM). METHODS: We determined ASC volume on T2 weighted MR images of seventy six infants (ARM n = 33; controls n = 43) by manual segmentation. Inter operator agreement was assessed by intraclass correlation coefficient. Linear regression was used to establish weight dependent reference data. Observed to expected ASC volumes of patients with unfavorable and favorable prognosis were compared (unpaired t test). RESULTS: ASC volumetry was feasible in all cases. Patients with ARM had low 'observed to expected' ASC volume ( 18.1%; p = 0.006). 'Observed to expected' ASC volume differed significantly between patients with favorableand unfavorable prognosis (p < 0.001). CONCLUSION: We confirmed the feasibility of MRI based ASC volumetry and provided initial reference data for infants. Although ASC volumes were lowest in infants with ARM of unfavorable prognosis for fecal continence, the value of ASC volume as prognostic parameter remains to be determined.

Is There an Association Between Bone Microarchitecture and Fracture in Patients who were Treated for High-grade Osteosarcoma? A Controlled Study at Long-term Follow-up Using High-resolution Peripheral Quantitative CT.

BACKGROUND: Neoadjuvant chemotherapy in patients with primary osteosarcoma improves survival rates, but it also causes side effects in various organs including bone. Low bone mineral density (BMD) can occur owing partly to chemotherapy or limited mobility. This can cause a higher risk of fractures compared with those who do not receive such treatment. Changes in BMD alone cannot explain the propensity of fractures. Studying microarchitectural changes of bone might help to understand the effect. QUESTIONS/PURPOSES: (1) Do patients who were treated for osteosarcoma (more than 20 years previously) have low BMD? (2) Do these patients experience more fractures than controls who do not have osteosarcoma? (3) What differences in bone microarchitecture are present between patients treated for high-grade osteosarcoma and individuals who have never had osteosarcoma? METHODS: We contacted 48 patients who were treated for osteosarcoma and who participated in an earlier study. These patients underwent multimodal treatment including chemotherapy more than 20 years ago. Of the original patient group, 60% (29 of 48) were missing, leaving 40% (19 of 48) available for inclusion in this study; all 19 agreed to participate. There were nine men and 10 women with a mean age of 46 ± 4 years and a mean time from surgery to examination of 28 ± 3 years. BMD was measured by dual-energy x-ray absorptiometry, and any fracture history was assessed using a questionnaire. Additionally, high-resolution peripheral quantitative CT was performed to compare the groups in terms of microarchitectural changes, such as cortical and trabecular area, cortical and trabecular thickness, cortical porosity, and endocortical perimeter. Participants in the control group were selected from a cohort consisting of a population-based random sample of 499 healthy adult women and men. Osteoporosis or low BMD was not an exclusion criterion for entering this study; however, the patients in the control group were selected based on a normal BMD (that is, T score > -1.0 at both the spine and hip). Also, the participants were matched based on age and sex. Differences between patients and controls were assessed using the Wilcoxon rank sum test for continuous variables and a chi-square test for categorical variables. A multiple regression analysis was performed. Model assumptions were checked using histograms and quantile-quantile plots of residuals. RESULTS: Twelve of 19 patients who were treated for osteosarcoma had either osteopenia (eight patients) or osteoporosis (four patients). More patients with osteosarcoma reported sustaining fractures (11 of 19 patients) than did control patients (2 of 19 controls; p < 0.001). Among all microarchitectural parameters, only the endocortical perimeter was increased in patients compared with the control group (75 ± 15 mm versus 62 ± 18 mm; p = 0.04); we found no differences between the groups in terms of cortical and trabecular area, cortical and trabecular thickness, or cortical porosity. CONCLUSION: Although patients who were treated for osteosarcoma had osteopenic or osteoporotic BMD and a higher proportion of patients experienced fractures than did patients in the control group, we could not confirm differences in microarchitectural parameters using high-resolution peripheral quantitative CT. Therefore, it seems that bone geometry and microstructural parameters are not likely the cause of the increased proportion of fractures observed in our patients who were treated for osteosarcoma. Until we learn more about the bone changes associated with chemotherapy in patients with osteosarcoma, we recommend that patients undergo regular BMD testing, and we recommend that physicians consider osteoporosis treatment in patients with low BMD. These data might provide the impetus for future multicenter prospective studies examining the association between chemotherapy and bone microarchitecture. LEVEL OF EVIDENCE: Level III, therapeutic study.

Imaging of pediatric bone and growth disorders: Of diagnostic workhorses and new horizons.

Children and adolescents with bone and growth disorders require interdisciplinary care from various specialists including pediatric radiologists with a focus on musculoskeletal disorders. This article covers routine topics, differential diagnoses, and selected research imaging in children with osteogenesis imperfecta (OI), X­linked hypophosphatemic rickets (XLH), achondroplasia, and other bone and growth disorders from the standpoint of a tertiary referral center.

Assessment of sacral ratio in patients with anorectal malformations: Can magnetic resonance imaging replace conventional radiograph?

INTRODUCTION: In patients with anorectal malformations (ARM), the sacral ratio (SR) serves as an established predictive marker for functional prognosis and is derived from conventional radiographs. More recently, magnetic resonance imaging (MRI) has emerged as a diagnostic alternative for preoperative/baseline assessment of patients with ARM. With this study we aimed to evaluate if the SR could be reliable be measured from MRI images and if it correlated to SR measurements obtained from radiographs. METHODS: Two raters analyzed MRI data and conventional radiographs from thirty-one subjects (n = 17 with ARM; n = 14 controls). We calculated intra-class correlation coefficients (ICCs) to test inter-rater reliability and applied paired t-tests to examine if SR parameters from MRI were comparable with those from pelvic radiograph. We further computed Pearson's correlation coefficients to test the linear relationship between SR calculated from MRI and conventional radiographs. RESULTS: The ARM and control groups did not statistically differ in their age and weight on the day of the MRI scan. Reliability analysis revealed an excellent inter-rater agreement for SR from radiograph parameters with an intraclass correlation coefficient (ICC) of 0.94, respectively of 0.86 for MRI (frontal plane), and of 0.84 for MRI (sagittal plane). The correlation coefficient between SR calculated from the sagittal MRI and SR calculated from radiograph images was significant and high (r = 0.80, P < 0.001). The SRs from MRI images did not significantly differ from SRs from radiographs, but were also not statistically equivalent. CONCLUSION: Our results demonstrate that the SR can be derived from MRI images with good inter-rater reliability. The SR value is marginal higher when calculated on MRI, presumably due to inclusion of cartilaginous yet unossified structures.

Decreased Compressional Sound Velocity Is an Indicator for Compromised Bone Stiffness in X-Linked Hypophosphatemic Rickets (XLH).

Objectives: To assess the diagnostic potential of bidirectional axial transmission (BDAT) ultrasound, and high-resolution peripheral quantitative computed tomography (HR-pQCT) in X-linked hypophosphatemia (XLH, OMIM #307800), a rare genetic disorder of phosphate metabolism caused by mutations in the PHEX gene. Methods: BDAT bone ultrasound was performed at the non-dominant distal radius (33% relative to distal head) and the central left tibia (50%) in eight XLH patients aged between 4.2 and 20.8 years and compared to twenty-nine healthy controls aged between 5.8 and 22.4 years. In eighteen controls, only radius measurements were performed. Four patients and four controls opted to participate in HR-pQCT scanning of the ultradistal radius and tibia. Results: Bone ultrasound was feasible in patients and controls as young as 4 years of age. The velocity of the first arriving signal (νFAS) in BDAT ultrasound was significantly lower in XLH patients compared to healthy controls: In the radius, mean νFAS of XLH patients and controls was 3599 ± 106 and 3866 ± 142 m/s, respectively (-6.9%; p < 0.001). In the tibia, it was 3578 ± 129 and 3762 ± 124 m/s, respectively (-4.9%; p = 0.006). HR-pQCT showed a higher trabecular thickness in the tibia of XLH patients (+16.7%; p = 0.021). Conclusions: Quantitative bone ultrasound revealed significant differences in cortical bone quality of young XLH patients as compared to controls. Regular monitoring of XLH patients by a radiation-free technology such as BDAT might provide valuable information on bone quality and contribute to the optimization of treatment. Further studies are needed to establish this affordable and time efficient method in the XLH patients.

Intestinal bacterial indicator phylotypes associate with impaired DNA double-stranded break sensors but augmented skeletal bone micro-structure.

Intestinal microbiota are considered a sensor for molecular pathways, which orchestrate energy balance, immune responses, and cell regeneration. We previously reported that microbiota restriction promoted higher levels of systemic radiation-induced genotoxicity, proliferative lymphocyte activation, and apoptotic polarization of metabolic pathways. Restricted intestinal microbiota (RM) that harbors increased abundance of Lactobacillus johnsonii (LBJ) has been investigated for bacterial communities that correlated radiation-induced genotoxicity. Indicator phylotypes were more abundant in RM mice and increased in prevalence after whole body irradiation in conventional microbiota (CM) mice, while none of the same ten most abundant phylotypes were different in abundance between CM mice before and after heavy ion irradiation. Muribaculum intestinale was detected highest in female small intestines in RM mice, which were lacking Ureaplasma felinum compared with males, and thus these bacteria could be contributing to the differential amounts of radiation-induced systemic genotoxicity between the CM and RM groups. Helicobacter rodentium and M.intestinale were found in colons in the radiation-resistant CM phenotype. While the expression of interferon-γ was elevated in the small intestine, and lower in blood in CM mice, high-linear energy transfer radiation reduced transforming growth factor-ß with peripheral interleukin (IL)-17 in RM mice, particularly in females. We found that female RM mice showed improved micro-architectural bone structure and anti-inflammatory radiation response compared with CM mice at a delayed phase 6 weeks postexposure to particle radiation. However, microbiota restriction reduced inflammatory markers of tumor necrosis factor in marrow, when IL-17 was reduced by intraperitoneal injection of IL-17 neutralizing antibody.

Microvessel ultrasound of neonatal brain parenchyma: feasibility, reproducibility, and normal imaging features by superb microvascular imaging (SMI).

OBJECTIVES: To evaluate the feasibility and reproducibility of superb microvascular imaging (SMI) of the neonatal brain and to describe normal imaging features. METHODS: We performed transcranial ultrasound with SMI in 19 healthy term-born neonates. SMI was done according to a structured examination protocol, using two linear 18 MHz and 14 MHz transducers. Superficial and deep scans were acquired in the coronal and sagittal planes, using the left and right superior frontal gyri as anatomical landmarks. All SMI views were imaged by monochrome and colour SMI and evaluated with respect to visibility of extrastriatal (i.e. cortical and medullary) and striatal microvessels. RESULTS: We have described normal morphologic features of intraparenchymal brain microvasculature as "short parallel" cortical vessels, "smoothly curved" medullary vessels, and deep striatal vessels. In general, SMI performance was better on coronal views than on sagittal views. On superficial coronal scans, cortical microvessels were identifiable in 90-100%, medullary microvessels in 95-100%. On deep scans, cortical and medullary microvessels were visible in all cases, while striatal microvessels were identifiable in 71% of cases. CONCLUSIONS: Cerebral SMI ultrasound is feasible and well-reproducible and provides a novel non-invasive imaging tool for the assessment of intraparenchymal brain microvasculature (extrastriatal and striatal microvessels) in neonates without the use of contrast. KEY POINTS: • Superb microvascular imaging (SMI) of the neonatal brain is feasible and reproducible. • SMI depicts extrastriatal and striatal microvessels. • SMI detects two types of extrastriatal microvessels: cortical and medullary.

The role of the subchondral layer in osteonecrosis of the femoral head: analysis based on HR-QCT in comparison to MRI findings.

BACKGROUND: Non-traumatic avascular osteonecrosis of the femoral head (ONFH) is a severe disease causing destruction of the hip joint, often necessitating total hip arthroplasty (THA) even in young patients. Magnetic resonance imaging (MRI) is commonly used for diagnosis of ONFH, but provides limited insight into the subchondral bone microstructure. PURPOSE: To analyze routine MRI findings in comparison to high-resolution quantitative computed tomography (HR-QCT) with a special focus on the subchondral layer and to estimate the importance of differences determining the indication for THA. MATERIAL AND METHODS: Twelve patients with ONFH were included before THA. Preoperative MRI and HR-QCT of the retrieved femoral heads were aligned using a registration algorithm. Pathological findings and trabecular bone parameters in matched areas were analyzed by two readers. McNemar, marginal homogeneity test, and Pearson's correlation coefficient were used for comparison. RESULTS: Subchondral delamination was found in nine cases on HR-QCT, but missed or underestimated in all but one case on MRI ( P = 0.016). Chondral discontinuity was found in all cases on HR-QCT and in two cases on MRI ( P = 0.016). Areas of complete bone resorption on HR-QCT were linked to high signal intensity on 3D gradient-echo MRI sequences with water-selective excitation, while there was no correlation between trabecular bone parameters and MRI signal intensities in other areas ( P = 0.304). CONCLUSION: Subchondral delamination, subchondral resorption, and chondral discontinuity are found frequently in advanced stages of ONFH. These lesions tend to be underestimated on conventional MRI. Our results support the importance of CT imaging in the evaluation of ONFH.

How accurate are prenatal tractography results? A postnatal in vivo follow-up study using diffusion tensor imaging.

Prenatal detection of abnormal white matter tracts might serve as a structural marker for altered neurodevelopment. As a result of many technical and patient-related challenges, the accuracy of prenatal tractography remains unknown. We hypothesized that characteristics of prenatal tractography of the corpus callosum and corticospinal tracts derived from fetal diffusion tensor imaging (DTI) data are accurate and predictive of the integrity of these tracts postnatally. We compared callosal and corticospinal tracts of 12 subjects with paired prenatal (age: 23-35 gestational weeks) and postnatal (age: 1 day to 2 years) DTI examinations (b values of 0 s/mm2 and 700 s/mm2, 16 gradient encoding directions) using deterministic tractography. Evaluation for the presence of callosal segments and corticospinal tracts showed moderate degrees of accuracy (67-75%) for the four segments of the corpus callosum and moderate to high degrees of accuracy (75-92%) for the corticospinal tracts. Positive predictive values for segments of the corpus callosum ranged from 50% to 100% and for the corticospinal tracts, 89% to 100%. Negative predictive values for segments of the corpus callosum ranged from 25% to 80% and for the corticospinal tracts, 33% to 50%. The results suggest that when the tracts are not well characterized on the fetal MR, predictions about the postnatal tracts are difficult to make. However, accounting for brain maturation, prenatal visualization of the main projection and commissural tracts can be clinically used as an important predictive tool in the context of image interpretation for the assessment of fetal brain malformations.

Similarities in trabecular hypertrophy with site-specific differences in cortical morphology between men and women with type 2 diabetes mellitus.

The goal of our study was to investigate interactions between sex and type 2 diabetes mellitus (T2DM) with regard to morphology of the peripheral skeleton. We recruited 85 subjects (mean age, 57±11.4 years): women with and without T2DM (n = 17; n = 16); and men with and without T2DM (n = 26; n = 26). All patients underwent high-resolution, peripheral, quantitative, computed tomography (HR-pQCT) imaging of the ultradistal radius (UR) and tibia (UT). Local bone geometry, bone mineral density (BMD), and bone microarchitecture were obtained by quantitative analysis of HR-pQCT images. To reduce the amount of data and avoid multi-collinearity, we performed a factor-analysis of HR-pQCT parameters. Based on factor weight, trabecular BMD, trabecular number, cortical thickness, cortical BMD, and total area were chosen for post-hoc analyses. At the radius and tibia, diabetic men and women exhibited trabecular hypertrophy, with a significant positive main effect of T2DM on trabecular number. At the radius, cortical thickness was higher in diabetic subjects (+20.1%, p = 0.003). Interestingly, there was a statistical trend that suggested attenuation of tibial cortical hypertrophy in diabetic men (cortical thickness, pinteraction = 0.052). Moreover, we found an expected sexual dichotomy, with higher trabecular BMD, Tb.N, cortical BMD, Ct.Th, and total area in men than in women (p≤ 0.003) at both measurement sites. Our results suggest that skeletal hypertrophy associated with T2DM is present in men and women, but appears attenuated at the tibial cortex in men.

Cortical porosity not superior to conventional densitometry in identifying hemodialysis patients with fragility fracture.

Hemodialysis (HD) patients face increased fracture risk, which is further associated with elevated risk of hospitalization and mortality. High-resolution peripheral computed tomography (HR-pQCT) has advanced our understanding of bone disease in chronic kidney disease by characterizing distinct changes in both the cortical and trabecular compartments. Increased cortical porosity (Ct.Po) has been shown to be associated with fracture in patients with osteopenia or in postmenopausal diabetic women. We tested whether the degree of Ct.Po identifies hemodialysis patients with prevalent fragility fractures in comparison to bone mineral density (BMD) assessed by dual X-ray absorptiometry (DXA). We performed a post-hoc analysis of a cross-sectional study in 76 prevalent hemodialysis patients. Markers of mineral metabolism, coronary calcification score, DXA-, and HR-pQCT-data were analyzed, and Ct.Po determined at radius and tibia. Ct.Po was significantly higher in patients with fracture but association was lost after adjusting for age and gender (tibia p = 0.228, radius p = 0.5). Instead, femoral (F) BMD neck area (p = 0.03), F T-score neck area (p = 0.03), radius (R) BMD (p = 0.03), R T-score (p = 0.03), and cortical HR-pQCT indices such as cortical area (Ct.Ar) (tibia: p = 0.01; radius: p = 0.02) and cortical thickness (Ct.Th) (tibia: p = 0.03; radius: p = 0.02) correctly classified patients with fragility fractures. Area under receiver operating characteristic curves (AUC) for Ct.Po (tibia AUC: 0.711; p = 0.01; radius AUC: 0.666; p = 0.04), Ct.Ar (tibia AUC: 0.832; p<0.001; radius AUC: 0.796; p<0.001), and F neck BMD (AUC: 0.758; p = 0.002) did not differ significantly among each other. In conclusion, measuring Ct.Po is not superior to BMD determined by DXA for identification of HD patients with fragility fracture.

Effect of simulated metastatic lesions on the biomechanical behavior of the proximal femur.

Pathologic fractures of femora in patients with metastatic cancer are associated with high morbidity and mortality. Prediction of impending fractures is based on unspecific clinical criteria or past clinician's experience, which leads to underestimation or overtreatment. The aim of this study was to investigate the effect of the site of metastatic lesions on biomechanical behavior of the proximal femur. Sixteen pairs of human femora were scanned with quantitative computed tomography (QCT) to asses bone mineral density. One femur of each pair remained intact while a defined lesion was reamed out in either the superolateral or inferomedial portion of the femoral neck of the contralateral femur. All femora were loaded in a mechanical test setup mimicking one-legged stance and stiffness, failure load, and fracture location were determined. In the biomechanical experiments the superolateral lesion and the inferomedial lesion caused a stiffness reduction of 19% and 66%, respectively. The average failure load was 40% and 75% lower for specimens with the superolateral (4.53 ± 1.56 kN) and inferomedial (1.89 ± 1.73 kN) lesions, respectively, compared to intact specimens (7.66 ± 3.34 kN). Lesions in the femoral neck led to reduction in both stiffness and failure load of the proximal femur. Furthermore, the site of the lesion had a large effect on the magnitude of the reduction in biomechanical properties. The presented data emphasize the importance of differentiating between locations of the lesion in pathologic fracture prediction of the metastatic femur and underline the insufficient accuracy of current predictive guidelines. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2407-2414, 2017.

A Pediatric Patient with a CYP24A1 Mutation: Four Years of Clinical, Biochemical, and Imaging Follow-Up.

BACKGROUND: A female infant was admitted to hospital due to failure to thrive. She presented hypercalcemia (4.09 mmol/L, normal range: 2.2-2.65 mmol/L), high 25-hydroxyvitamin D (283 nmol/L, normal range: 75-250 nmol/L), 1,25-dihydroxyvitamin D in the upper normal range, and low parathyroid hormone. Vitamin D intoxication was suspected. The patient had received routine rickets prophylaxis. METHODS: Williams-Beuren syndrome was genetically excluded. Sequencing of CYP24A1 showed 2 mutations: c.443T>C and c.1186C>T. RESULTS: The patient's clinical status improved after intravenous rehydration, cessation of supplementation, and on a low-calcium diet. 25-Hydroxyvitamin D concentrations normalized within days, while 1,25-dihydroxyvitamin D remained in the upper normal range. We also investigated our patient's bone health. CONCLUSION: The patient was hospitalized initially on suspicion of vitamin D intoxication but proved to be a case of compound heterozygosity. Data on the long-term clinical and biochemical evolution of patients with idiopathic infantile hypercalcemia are sparse. Our follow-up showed seasonal variations of vitamin D and calcium parameters, with no influence on kidney function or bone health for the investigated period.

Diabetes and Bone.

Skeletal fragility has been recognized as an important feature of diabetes mellitus type 1 (T1D) and type 2 (T2D). While patients with DM1 typically display low bone mineral density (BMD) and concomitant increases in fracture risk, T2D bone disease is more complex and less understood. Although BMD is often normal or even slightly elevated, the risk of fragility fractures is disproportionally high. Alterations in bone quality (i.e., bone microstructure and matrix properties) have been reported by independent groups of researchers. Cortical porosity and the deposition of advanced glycation end-products appear to play key roles. Paired with low bone turnover, another distinct feature of T2D bone disease, secondary complications (including nephropathy, neuropathy, and angiopathy) are adding up to form a complex entity distinct from postmenopausal and age-related osteoporosis. This article offers an overview of current concepts in pathophysiology, clinical features, and imaging features of diabetic bone disease.