Head Bone Research Articles

Screening for Mutations in Isolated Central Hypothyroidism Reveals a Novel Mutation in Insulin Receptor Substrate 4.

BackgroundCentral hypothyroidism (CeH) is a rare condition affecting approximately 1:16 000- 100 000 individuals. Congenital forms can harm normal development if not detected and treated promptly. Clinical and biochemical diagnosis, especially of isolated CeH, can be challenging. Cases are not usually detected in neonatal screening, which, in most countries, is focused on detection of the more prevalent primary hypothyroidism. Until now, five genetic causes for isolated CeH have been identified. Here we aimed to identify the genetic cause in two brothers with impaired growth diagnosed with CeH at the age of 5 years. We further evaluated the candidate gene variants in a large genetic database.MethodsClinical and biochemical characterization together with targeted next-generation sequencing (NGS) was used to identify the genetic cause in a family of two brothers presenting with CeH. Screening of insulin receptor substrate 4 (IRS4) variants was carried out in the FinnGen database.ResultsA novel monoallelic frameshift mutation c.1712_1713insT, p.Gly572Trp fs*32 in the X-linked IRS4 gene was identified by NGS analysis in both affected males and confirmed using Sanger sequencing. Their mother was an unaffected carrier. In addition to the declined growth at presentation, central hypothyroidism and blunted TRH test, no other phenotypic alterations were found. Diagnostic tests included head MRI, thyroid imaging, bone age, and laboratory tests for thyroid autoantibodies, glucose, insulin and glycosylated hemoglobin levels. Examination of the IRS4 locus in FinnGen (R5) database revealed the strongest associations to a rare Finnish haplotype associated with thyroid disorders (p = 1.3e-7) and hypothyroidism (p = 8.3e-7).ConclusionsHere, we identified a novel frameshift mutation in an X-linked IRS4 gene in two brothers with isolated CeH. Furthermore, we demonstrate an association of IRS4 gene locus to a general thyroid disease risk in the FinnGen database. Our findings confirm the role of IRS4 in isolated central hypothyroidism.

The cytokine interleukin-11 crucially links bone formation, remodeling and resorption

Bone development is a complex process that requires the activity of several different signaling pathways and cell types. It involves the coordinated action of osteoclasts (cells that are capable of resorbing bone), osteoblasts (cells that are able to form bone), osteocytes (cells that form a syncytial network within the bone), skeletal muscle cells and the bone marrow. In recent years, the cytokine interleukin-11 (IL-11), a member of the IL-6 family of cytokines, has emerged as an important regulatory protein for bone formation, remodeling and resorption. Furthermore, coding missense mutations in the IL11RA gene, which encodes the IL-11 receptor (IL-11R), have recently been linked to craniosynostosis, a human disease in which the sutures that line the head bones close prematurely. This review summarizes current knowledge about IL-11 and highlights its role in bone development and homeostasis. It further discusses the specificity and redundancy provided by the other members of the IL-6 cytokine family and how they facilitate signaling and cross-talk between skeletal muscle cells, bone cells and the bone marrow. We describe their actions in physiological and in pathological states and discuss how this knowledge could be translated into therapy.

Factors related to large bone defects of bipolar lesions and a high number of instability episodes with anterior glenohumeral instability

BackgroundSignificant bone defects are associated with poor clinical results after surgical stabilization in cases of glenohumeral instability. Although multiple factors are thought to adversely affect enlargement of bipolar bone loss and increased shoulder instability, these factors have not been sufficiently evaluated. The purpose of this study was to identify the factors related to greater bone defects and a higher number of instability episodes in patients with glenohumeral instability.MethodsA total of 120 consecutive patients with symptomatic unilateral instability of the glenohumeral joint were retrospectively reviewed. Three-dimensional surface-rendered/registered models of bilateral glenoids and proximal humeri from computed tomography data were matched by software, and the volumes of bone defects identified in the glenoid and humeral head were assessed. After relationships between objective variables and explanatory variables were evaluated using bivariate analyses, factors related to large bone defects in the glenoid and humeral head and a high number of total instability episodes and self-irreducible dislocations greater than the respective 75th percentiles were evaluated using logistic regression analyses with significant variables on bivariate analyses.ResultsLarger humeral head defects (P < .001) and a higher number of total instability episodes (P = .032) were found to be factors related to large glenoid defects. On the other hand, male sex (P = .014), larger glenoid defects (P = .015), and larger number of self-irreducible dislocations (P = .027) were related to large humeral head bone defects. An increased number of total instability episodes was related to longer symptom duration (P = .001) and larger glenoid defects (P = .002), and an increased number of self-irreducible dislocations was related to larger humeral head defects (P = .007).ConclusionsWhereas this study showed that bipolar lesions affect the amount of bone defects reciprocally, factors related to greater bone defects differed between the glenoid and the humeral head. Glenoid defects were related to the number of total instability episodes, whereas humeral head defects were related to the number of self-irreducible dislocations.

Portentosoceros, the new genus for the Neogene fish Pentaceros sakhaliniсus Gretchina (Perciformes, Percoidei) from the western Pacific and its taxonomic position

ABSTRACT The Miocene fossil fish †Pentaceros sakhaliniсus Gretchina, 1975, (Perciformes, Pentacerotidae) is redescribed based on the holotype and numerous additional materials collected on Sakhalin Island (western Pacific, Russian Far East) at the end of the 20th century. The general appearance and body proportions, as well as the presence of multiple (more than three) anal-fin spines, make the Miocene taxon similar to members of the family Pentacerotidae, whereas generalized morphological characters such as the presence of three supraneurals and the absence of rugosity of the superficial head bones differentiate this species greatly from any known pentacerotid genus. Thus, the new genus †Portentosoceros is erected for this fish, which was considered the only known fossil member of the family. Due to the fact that this fish lacks the main synapomorphic characters of the Pentacerotidae, †Portentosoceros gen. nov. is left incertae sedis within the Percoidei, though probably related to Recent armorheads. The observed variability in the number of anal-fin spines (from four to six) in †Portentosoceros sakhalinicus is extremely unusual.

Emerging Entities and New Diagnostic Markers for Head and Neck Soft Tissue and Bone Tumors.

Bone and soft tissue tumors of the head and neck are relatively uncommon tumors that often represent a diagnostic challenge because of the wide range of entities that must be considered in the differential diagnosis. Over the past few years, classification of bone and soft tissue tumors has evolved primarily because of substantial contributions from molecular genetics, with the identification of new markers that are increasingly used to complement histopathologic findings in the routine diagnostic workup. This review focuses on the recently described mesenchymal tumors that preferentially involve the head and neck region, with a focus on the most relevant novel immunohistochemical and molecular findings, including gene fusions and mutations, that can help in the diagnosis and in the assessment of clinical behavior.

Bone mass and vertebral fractures in South African children on prolonged oral glucocorticoids for chronic non-malignant illnesses

IntroductionWe hypothesized that the prevalence of vertebral fractures would be low and that bone mineral density (BMD) would be less severely affected in a black South African (SA) population treated with glucocorticoids (GCs) than that reported in mainly white populations. MethodsAll children aged 5–17.9 years with chronic non-malignant illnesses who were on GCs (intravenous or oral) for greater than 3 months duration were evaluated. DXA scans were performed using a Hologic Discovery machine (Software version Apex 4.0.2) and the Hologic paediatric reference database. Whole body less head (WBLH) and lumbar spine (LS) bone mineral content (BMC) and density (BMD) Z-scores unadjusted and adjusted for height were calculated using the Zemel equation calculator. ResultsSeventy-two patients (49% with renal, 24% with rheumatic, 14% with neurological, 11% with hepatic and 3% with respiratory conditions; mean age 11.6 ± 3.3 years, 57% boys, 92% SA black) were enrolled. The mean duration of GC treatment was 34.1 (±25.1) months. Mean WBLH and LS height adjusted BMD Z-scores were −1.2 ± 1.5 and −0.9 ± 1.0 respectively. Eleven percent of patients had a LS height adjusted BMD Z-score ≤ −2. The prevalence of vertebral fractures on lateral vertebral fracture assessment (VFA) was 15% (11 of 72 patients). ConclusionThe prevalence of vertebral fractures (15%) in predominantly black children on GCs with chronic non-malignant illnesses is similar to that reported from North America suggesting that routine yearly DXA scans including VFA are warranted in this highly at-risk population.

Investigation of Mechanical, Material, and Compositional Determinants of Human Trabecular Bone Quality in Type 2 Diabetes.

Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time, reports on alterations in bone tissue's material properties obtained from individuals with diabetes and known fragility fracture status. To investigate the role of T2D in altering biomechanical, microstructural, and compositional properties of bone in individuals with fragility fracture. Femoral head bone tissue specimens were collected from patients who underwent replacement surgery for fragility hip fracture. Trabecular bone quality parameters were compared in samples of 2 groups, nondiabetic (n = 40) and diabetic (n = 30), with a mean duration of disease 7.5 ± 2.8 years. No significant difference was observed in aBMD between the groups. Bone volume fraction (BV/TV) was lower in the diabetic group due to fewer and thinner trabeculae. The apparent-level toughness and postyield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in the diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications-higher total fluorescent advanced glycation end-products (fAGEs), higher nonenzymatic cross-link ratio (NE-xLR), and altered secondary structure (amide bands). There was a strong inverse correlation between NE-xLR and postyield strain, fAGEs and postyield energy, and fAGEs and toughness. The current study is novel in examining bone tissue in T2D following first hip fragility fracture. Our findings provide evidence of hyperglycemia's detrimental effects on trabecular bone quality at multiple scales leading to lower energy absorption and toughness indicative of increased propensity to bone fragility.

Craniomandibular Osteopathy in Mixed Breed Dogs

Background: Craniomandibular osteopathy (CMO) is a degenerative, osteopetrotic, and self-limiting bone disease that is rare in the canine species. The most affected bones and joints are the branches of the mandible, tympanic bulla, and temporomandibular joint (TMJ) with generalized thickening of the bone trabeculae, increased lines of bone cementation, and bone proliferation. The aim of the present study was to evaluate 2 cases of CMO in mixed-breed dogs belonging to the same litter sent to the Laboratório Regional de Diagnóstico, Faculdade de Veterinária, Universidade Federal de Pelotas (LRD / FV / UFPel).Cases: Three canines (mixed-breed, 2 female and 1 male) belonging to the same litter presented at eight months of age with increases in volume and pain in the face, difficulties in moving the jaw, anorexia, and sialorrhea. The 2 female dogs were euthanized and sent to LRD / FV / UFPel for necropsy. The animals underwent radiography of the left and right lateral and dorsoventral lateral projections in the imaging sector of the Hospital de Clínicas Veterinária (HCV) at UFPel. During the necropsy, fragments of organs from the abdominal and thoracic cavities, as well as the central nervous system and head bones, were collected and fixed in 10% buffered formalin. The tissue samples were cleaved, processed routinely, embedded in paraffin, cut into sections of 3 µm thickness, and stained using hematoxylin and eosin (HE). The bone fragments were decalcified in a 50/50 solution of 8% hydrochloric acid and 8% formic acid and subsequently cleaved and stained with HE. The head and jaw of one of the animals was dissected and subjected to maceration in water at room temperature. Radiographic examination of the two remaining animals showed irregular and exuberant bone proliferation in the mandible and temporomandibular region. In the tympanic bullae, occipital bone, and zygomatic process, thickening of the structures was observed with increased opacity. On necropsy, the animals were cachectic with marked muscle atrophy and increased volume of the mandibular branches and head bones, in addition to marked edema in the adjacent subcutaneous tissue. The regional lymph nodes were enlarged, and in one of the animals, bilateral lesions in the femurs were also observed. In the head subjected to biological maceration, areas of bone proliferation and rarefaction were observed, with increased volume and destruction of the TMJ. On histopathological evaluation of the ventral portion of the mandibular bodies, a network of bony trabeculae was observed, composed of a chondroid matrix with different degrees of mineralization. The cortical portion of the bones exhibited loss of lamellar compactness, with greater spread of the bone trabeculae. The bone trabeculae were perpendicular to the long axis of the cortical of the mandible and were distributed in the medullary spaces, presenting some dense foci of inflammatory infiltrates composed predominantly of neutrophils, lymphocytes, and plasma cells.Discussion: The breeds most predisposed to developing CMO are the West Highland White Terrier and Scottish Terrier; however, the disease has also been described in other non-Terriers. Nevertheless, there are no descriptions in the literature of mixed-breed animals (SRD), with this report being the first of CMO in SRD dogs. The bones most frequently affected in CMO are those of the head. In Terrier dogs, the TMJ is also affected. In the cases of this study, severe CMO occurred, affecting both the head bones and TMJ, and in 1 of the animals, it also affected the femurs. Although CMO has not previously been reported in SRD dogs, the condition can seriously affect these animals, and differential diagnosis should always be made.Keywords: degenerative bone disease, bone proliferation, lion jaw, TMJ.Título: Osteopatia craniomandibular em cães sem raça definidaDescritores: doença óssea degenerativa, proliferação óssea, mandíbula de leão, ATM.

Učestalost anomalija skeleta u fetalnim i neonatalnim obdukcijama

Introduction: Skeletal anomalies are a heterogeneous group of disorders including changes in bone shape, size, and density that cause abnormalities of the extremities, trunk, and head. They rank second in Europe in the frequency of all congenital anomalies. The most common skeletal anomalies include head, face and limb anomalies. Aim: The aim of this study was to determine the frequency of skeletal anomalies and their association with anomalies of internal organs, as well as to show the age of the mother and the gestational week of the fetus with established skeletal anomalies. Material and methods: All fetal and neonatal autopsies in the period from January 1, 2018 to December 31, 2020 at the Institute of Pathology "Djordje Joannovic" of the Faculty of Medicine University of Belgrade were analyzed. In the mentioned period, 580 fetal and neonatal autopsies were performed. Clinical data were obtained from the Gynecology and Obstetrics Clinic "Narodni Front" on the basis of completed requests for clinical autopsy. Descriptive statistics methods were used (data are presented as absolute numbers and percentage frequencies). Results: The most common skeletal anomalies are divided into seven groups: spina bifida (20; 33.34%), limb anomalies (16; 26.67%), head and face bone anomalies (15; 25%), joint anomalies (2; 3.33%), achondroplasia (3; 5%), osteogenesis imperfecta (2; 3.33%) and other anomalies (2; 3.33%). The most common associated anomalies were central nervous system (CNS) abnormalities, followed by heart and kidney abnormalities. The youngest mother was 15 years old, and the oldest was 47 years old. The mean age of the mothers was 30 years. Conclusion: In our study, the most common anomaly was spina bifida, while limb anomalies and craniofacial anomalies are next in frequency. Skeletal anomalies were often associated with anomalies of the heart, kidneys, and CNS. They were mostly diagnosed between the 22nd and 27th gestational week. Our results showed that skeletal anomalies are more common in fetuses or neonates of mothers older than 30 years.

Imaging Analysis of Hill-Sachs Lesions: A Systematic Review

To perform a systematic review of the current literature on the accuracy and reliability of different imaging modalities used to assess the presence and various parameters for Hill-Sachs Lesions in patients with anterior shoulder instability. A systematic review was performed according to the PRISMA guidelines. Inclusion criteria were clinical trials or cadaver studies that assessed the accuracy of humeral head bone loss imaging or reliability and clinical relevance in anterior shoulder instability, and were in the English language. Exclusion criteria were animal studies, imaging studies without measures of accuracy, reliability, or clinical predictive power, shoulder injuries without humeral head bone loss, editorial articles, abstracts, presentations, reviews case reports, and surveys. The systematic review identified 40 studies (2,560 shoulders) after inclusion and exclusion criteria application. For diagnosing the presence of a Hill-Sachs lesion, CTA was found to have the highest accuracy (median = 91%, range = 66-100%), followed by MRA (median = 90.6%, range = 81-93%) and MRI (median = 88%, range = 79-94%). For the same assessment, CTA was also found to have the greatest sensitivity (median = 94%, range = 50-100%), followed by MRA (median = 91%, range = 69-100%) and ultrasound (median = 91%, range = 74-95.6%), and lastly MRI (median = 78%, range = 60-97%). For the quantification of Hill-Sachs lesion parameters, intraobserver reliabilities were reported for 3D CT (ICC range = 0.916-0.999), 2D CT (ICC range = 0.858-0.861), MRI (ICC range = 0.28-0.97), MRA (Kappa = 0.86; ICC = 0.87), and radiographs (Kappa range = 0.464-0.528). For the same quantification parameters, interobserver reliabilities were reported for 3D CT (Kappa range = 0.823-0.975; ICC range = 0.772-0.996), 2D CT (ICC range = 0.721-0.879), MRI (Kappa range = 0.444-0.700), MRA (ICC range = 0.830-0.904), and radiographs (Kappa range = 0.278-0.336). Intraobserver reliabilities for determining if a lesion was “on-” or “off-track” were only reported for 3D CT (Kappa range = 0.730-1.00; ICC range = 0.803-0.901) and MRI (ICC range = 0.770-0.790). This study demonstrates that there is verity of different imaging modalities that provides clinically acceptable accuracy in diagnosing Hill-Sachs Lesions, with CTA being the most reliable. Furthermore, this systematic review also solidifies that 3D CT has the greatest potential in quantifying and determining if a Hill-Sachs lesion will cause persistent anterior shoulder instability.

Comparison of Condylar Bone Density in Cone-Beam Computed Tomographic Images of Patients with and without Temporomandibular Joint Disorders

Introduction: Temporomandibular disorders (TMDs) are the main source of orofacial pain of nondental origin. Density changes in mandibular condyles of patients with TMD have not been well documented. The aim of this study was to compare condylar head bone density values in patient with and without TMD in cone-beam computed tomographic (CBCT) images. Materials and Methods: CBCT images of 70 patients with TMD and 70 age- and sex-controlled individuals were studied. Density of the cancellous bone in the left and right condylar heads was measured on a CBCT slice with the widest mediolateral dimension. Moreover, absence of at least one maxillary or mandibular posterior tooth (except for third molars) was recorded. Interclass correlation, t test, and Chi-squared test were used for statistical analysis. Results: Bone density in the condylar head significantly increased in patients with TMD compared with the non-TMD group (P &lt; 0.001). The difference between males and females in each group was not significant (P = 0.182). Condylar head bone density in patients with TMD with posterior missing teeth was significantly less than individuals without missing teeth (P = 0.002). Conclusion: Increased density of condylar head must be regarded as a potential diagnostic tool for TMD when interpreting CBCT images of the joints.

Comparative analysis and study on the rehabilitation of cruciate ligaments before and after treatment with nano-biomaterials

This paper uses porous silicon carbide as a stent, and applies chemical vapour deposition technology to prepare a new type of porous tantalum metal material and conduct preliminary biological evaluation. An experimental study on the repair of anterior and posterior cruciate ligament composite of porous tantalum metal material is carried out, and it is used in clinical practice. To treat patients with anterior cruciate ligament injury, comprehensively evaluate the biological characteristics of new porous tantalum metal and its clinical effect in the treatment of anteroposterior cruciate ligament injury, and apply a new porous tantalum rod combined with anterior cruciate ligament combined with vascular pedicle iliac flap transfer. Young and strong patients with anterior and posterior cruciate ligament injury were treated with ligament-preserving surgery. Under the condition that it was clear that bone marrow stromal cells had a bone-promoting effect, and porous tantalum metal rods could induce bone growth and biomechanical support, and vascularised iliac bone flap metastasis was studied. Young and middle-aged patients with anterior and posterior cruciate ligament injuries were treated with satisfactory results. The research results found that a new porous tantalum rod combined with anterior and posterior cruciate ligament combined with vascular pedicle iliac flap transfer effectively removed the femoral head. Internal necrosis bone promotes the new femoral head bone regeneration and provides a reliable blood supply and biomechanical support. Prevention of further collapse occurred, to assist front and rear cruciate ligament rehabilitation, and did not increase surgical complications.

Limited Predictive Value of the Instability Severity Index Score: Evaluation of 217 Consecutive Cases of Recurrent Anterior Shoulder Instability

To review the existing variables and their ability to predict recurrence of shoulder instability as it relates to the Instability Severity Index Score (ISIS), as well as evaluate any other pertinent imaging and patient history variables that may impact risk of recurrent anterior instability after arthroscopic Bankart repair. All consecutive patients with recurrent anterior shoulder instability and who had arthroscopic instability repair were identified. Exclusion criteria were prior surgery on the shoulder, posterior or multidirectional instability, instability caused by seizure disorder, or a rotator cuff tear. All ISIS variables were recorded (age <20 years, sport type and level, hyperlaxity, Hill-Sachs on anteroposterior external rotation radiograph, loss of glenoid contour on anteroposterior radiograph), as well as additional variables: (1) number of instability events; (2) total time of instability; (3) glenoid bone loss (GBL) percent; and (4) Hill-Sachs measures (H/L/W/D/Volume). Postoperative outcomes were assessed based on the Western Ontario Shoulder Instability Index (WOSI), Single Assessment Numeric Evaluation (SANE) scores, and American Shoulder and Elbow Surgeons (ASES) scores, and recurrent anterior instability. Regression analysis was used to determine preoperative variables that predicted outcomes and failures. There were 217 consecutive patients (209 male patients [96.5%], 8 female patients [3.5%]) who met the inclusion criteria and were all treated with a primary arthroscopic shoulder stabilization during a 3.5-year period (2007-2011), with a mean follow-up time of 42 months (range, 26-58). The mean age at first instability event was 23.9 years (range, 16-48 years) and the mean cumulative ISIS score for the overall group was 3.6 (range, 1-6). Outcomes were improved from mean preoperative (WOSI= 1,050/2,100; ASES= 61.0; SANE= 52.5) to postoperative (WOSI= 305/2,100; ASES= 93.5; SANE= 95.5). A total of 11.5% (25/217) of patients had evidence of recurrent instability (subluxation or dislocation). Additionally, all 25 patients who failed postoperatively also had consistently inferior ASES, SANE, and WOSI outcome scores when compared with successfully treated patients. Factors associated with failure were GBL greater than 14.5% (P < .001), total time of instability symptoms greater than 3 months (P= .03), Hill-Sachs volume greater than 1.3 cm3 (P= .02), contact sports participation (P= .05), and age 20 years or younger (P < .01). There was no correlation in outcomes with Hill-Sachs on presence of glenoid contour loss on radiograph (P= .07), participation sports, or ISIS (mean= 3.4 success vs 3.9 failure, P > .05). At a mean follow-up of 42 months was an 11.5% failure rate after arthroscopic Bankart stabilization surgery. This study shows no correlation between treatment outcome and the ISIS measure, given a mean score of 3.4 for the overall cohort with little difference identified in those who failed. However, several important parameters previously unidentified were detected including, GBL greater than 14.5%, Hill-Sachs volume greater than 1.3 cm3, and duration of instability symptoms (>3 months). The ISIS may need to be redesigned to incorporate variables that more accurately portray the actual risk of failure after arthroscopic stabilization, including quantification of both glenoid and humeral head bone loss. III (Retrospective Case Series).

Retrieving, Curating and Depositing Skulls at Pitted Ware culture Sites

At many Middle Neolithic sites in south-central Scandinavia associated with the hunter-gatherer complex known as the Pitted Ware culture, the skulls of humans and animals seem to have been treated differently from other skeletal elements. This is evident, for example, in inhumation graves lacking crania or entire skulls as well as numerous finds of cranial and mandibular fragments scattered in cultural layers or deposited in hearths and pits. Despite parallels in overall treatment and find contexts, the selective handling of human skulls has generally been regarded as a mortuary practice and thus qualitatively different from the handling of animal skulls. Focusing primarily on the head bones themselves and relating their treatment to the wider use of skeletal remains allows us to consider a more complex system of retrieving, modifying, curating and depositing crania and mandibles. Drawing on the overlapping general treatment of human and animal remains, it is suggested that head bones from both humans and animals were efficacious objects that could be used in depositional acts.

Associations Between Late Pregnancy Dietary Inflammatory Index (DII) and Offspring Bone Mass: A Meta-Analysis of the Southampton Women's Survey (SWS) and the Avon Longitudinal Study of Parents and Children (ALSPAC).

ABSTRACTSystemic inflammation is associated with reduced bone mineral density and may be influenced by pro‐inflammatory diets. We undertook an observational analysis of associations between late pregnancy energy‐adjusted dietary inflammatory index (E‐DII) scores and offspring bone outcomes in childhood. E‐DII scores (higher scores indicating pro‐inflammatory diets) were derived from food frequency questionnaires in late pregnancy in two prospective mother‐offspring cohorts: the Southampton Women's Survey (SWS) and the Avon Longitudinal Study of Parents and Children (ALSPAC). The mean (SD) offspring age at dual‐energy X‐ray absorptiometry (DXA) scanning was 9.2 (0.2) years. Linear regression was used to assess associations between E‐DII and bone outcomes, adjusting for offspring sex and age at DXA and maternal age at childbirth, educational level, pre‐pregnancy body mass index (BMI), parity, physical activity level, and smoking in pregnancy. Associations were synthesized using fixed‐effect meta‐analysis. Beta coefficients represent the association per unit E‐DII increment. In fully adjusted models (total n = 5910) late pregnancy E‐DII was negatively associated with offspring whole body minus head bone area (BA: β = −3.68 [95% confidence interval −6.09, −1.27] cm2/unit), bone mineral content (BMC: β = −4.16 [95% CI −6.70, −1.62] g/unit), and areal bone mineral density (aBMD: β = −0.0012 [95% CI −0.0020, −0.0004] g.cm−2/unit), but there was only a weak association with BMC adjusted for BA (β = −0.48 [95% CI −1.11, 0.15] g/unit) at 9 years. Adjustment for child height partly or, for weight, fully attenuated the associations. Higher late pregnancy E‐DII scores (representing a more pro‐inflammatory diet) are negatively associated with offspring bone measures, supporting the importance of maternal and childhood diet on longitudinal offspring bone health. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Convolutional neural network for automatically segmenting magnetic resonance images of the shoulder joint

BackgroundMagnetic resonance imaging (MRI) has been known to replace computed tomography (CT) for bone and skeletal joint examination. The accurate automatic segmentation of bone structure in shoulder MRI is important for the measurement and diagnosis of bone injury and disease. Existing bone segmentation algorithms cannot achieve automatic segmentation without any prior knowledge, and their versatility and accuracy are relatively low. Therefore, an automatic segmentation combining pulse coupled neural network (PCNN) and full convolutional neural networks (FCN) is proposed. MethodologyBy constructing the block-based AlexNet segmentation model and U-Net-based bone segmentation module, we implemented the humeral segmentation model, articular bone segmentation model, humeral head and articular bone segmentation model synthesis model. We use this four kinds of segmentation models to obtain candidate bone regions, and accurately detect the positions of humerus and articular bone by voting. Finally, we perform an AlexNet segmentation model in the detected bone area in one step to segment accuracy at the pixel level. ResultsThe experimental data came from 8 groups of patients in Shengjing Hospital affiliated to China Medical University. The scanning volume of each group is approximately 100 images. Five fold cross-validations and for training were recorded, and five sets of data were carefully separated. After using our technique in the three groups of patients tested, the positive predictive value of dice coefficient (PPV) and the average accuracy of sensitivity were very significant, which reached 0.96±0.02, 0.97±0.02 and 0.94±0.03, respectively. ConclusionThe method used in the experiment in this paper is based on a small amount of patient sample data. The deep learning required for the experiment needs to be performed through 2D medical images. The shoulder segmentation data obtained in this way can be very accurate.

Regional differences in the three-dimensional bone microstructure of the radial head: implications for observed fracture patterns.

A characterization of the internal bone microstructure of the radial head could provide a better understanding of commonly occurring fracture patterns frequently involving the (antero)lateral quadrant, for which a clear explanation is still lacking. The aim of this study is to describe the radial head bone microstructure using micro-computed tomography (micro-CT) and to relate it to gross morphology, function and possible fracture patterns. Dry cadaveric human radii were scanned by micro-CT (17μm/pixel, isotropic). The trabecular bone microstructure was quantified on axial image stacks in four quadrants: the anterolateral (AL), posterolateral (PL), posteromedial (PM) and anteromedial (AM) quadrant. The AL and PL quadrants displayed the significantly lowest bone volume fraction and trabecular number (BV/TV range 12.3-25.1%, Tb.N range 0.73-1.16mm-1) and highest trabecular separation (Tb.Sp range 0.59-0.82mm), compared to the PM and AM quadrants (BV/TV range 19.9-36.9%, Tb.N range 0.96-1.61mm-1, Tb.Sp range 0.45-0.74mm) (p = 0.03). Our microstructural results suggest that the lateral side is the "weaker side", exhibiting lower bone volume faction, less trabeculae and higher trabecular separation, compared to the medial side. As the forearm is pronated during most falls, the underlying bone microstructure could explain commonly observed fracture patterns of the radial head, particularly more often involving the AL quadrant. If screw fixation in radial head fractures is considered, surgeons should take advantage of the "stronger" bone microstructure of the medial side of the radial head, should the fracture line allow this.

Osteoblasts/Osteocytes sirtuin6 Is Vital to Preventing Ischemic Osteonecrosis Through Targeting VDR-RANKL Signaling.

Ischemic osteonecrosis (ION) can produce permanent deformity and osteoarthritis in the femoral head and other joints. No biologic treatment has been established, and the molecular mechanisms involved in the pathogenesis of ION have not been elucidated. In this work, we found that treatment with sirtuin6 (Sirt6) suppressed inflammatory cytokines, bone resorption, progression of osteoarthritis, and reduced bone deformity in an ION mouse model. We used a deacetylase mutant adenovirus to confirm that those effects were caused by the deacetylase function of Sirt6. Among the osteoclastogenic factors of osteoblasts, only the receptor activator of NF-κb ligand (RANKL) level changed in response to Sirt6 knockout in primary osteoblasts. In particular, the vitamin D receptor physically interacted with Sirt6 and induced recruitment of Sirt6 around RANKL promoters. Finally, Tg mice overexpressing Sirt6 resisted osteocyte death, bone resorption, and progression of osteoarthritis after ischemic surgery, whereas osteoblast/osteocyte-specific Sirt6 knockout mice showed aggravated bone loss and severe deformity. Our findings demonstrate that administration of Sirt6 prevents bone loss and osteoarthritis in ischemic conditions. Activation of Sirt6 in osteoblasts/osteocytes could be a new therapeutic approach to treating ION of the femoral head and other bone regions. © 2020 American Society for Bone and Mineral Research (ASBMR).

Assessing and coping with the financial burden of computed tomography utilization in Limbe, Cameroon: a sequential explanatory mixed-methods study

BackgroundThere has been a significant increase in computed tomography (CT) utilization over the past two decades with the major challenges being a high exposure to ionizing radiation and rising cost. In this study we assess the risk of financial hardship after CT utilization and elaborate on how users adapt and cope in a sub-Saharan context with user fee for services and no national health insurance policy.MethodsWe carried out a sequential explanatory mixed methods study with a quantitative hospital-based survey of CT users followed by in-depth interviews of some purposively selected participants who reported risk of financial hardship after CT utilization. Data was summarized using frequencies, percentages and 95% confidence intervals. Logistic regression was used in multivariable analysis to determine predictors of risk of financial hardship. Identified themes from in-depth interviews were categorized. Quantitative and qualitative findings were integrated.ResultsA total of 372 participants were surveyed with a male to female sex ratio of 1:1.2. The mean age (standard deviation) was 52(17) years. CT scans of the head and facial bones accounted for 63% (95%CI: 59–68%) and the top three indications were suspected stroke (27% [95%CI: 22–32%]), trauma (14% [95%CI: 10–18%]) and persistent headaches (14% [95%CI: 10–18%]). Seventy-two percent (95%CI: 67–76%) of the respondents reported being at risk of financial hardship after CT utilization and predictors in the multivariable analysis were a low socioeconomic status (aOR: 0.19 [95%CI: 0.10–0.38]; p < 0.001), being unemployed or retired (aOR: 11.75 [95%CI: 2.59–53.18]; p = 0.001) and not having any form of health insurance (aOR: 3.59 [95%CI: 1.31–9.85]; p = 0.013). Coping strategies included getting financial support from family and friends, borrowing money and obtaining discounts from the hospital administration and staff.ConclusionNo health insurance ownership, being unemployed or retired and a low socioeconomic status are associated with financial hardship after CT utilization. Diverse coping strategies are utilized to lessen the financial burden, some with negative consequences. Minimizing out-of-pocket payments and/or the direct cost of CT can reduce this financial burden and improve CT access.

Assessment of First Metatarsal Head Bone Density for Optimal Screw Placement in Minimally-Invasive Hallux Valgus Surgery

Category:Bunion; Basic Sciences/BiologicsIntroduction/Purpose:Minimally-invasive surgery (MIS) for hallux valgus correction has become increasingly common. This technique involves an osteotomy of the first metatarsal, followed by fixation with two cannulated screws. Since screws are typically not bicortical, they rely upon bone quality within the metatarsal head for fixation strength. However, bone mineral density (BMD) within different regions of the metatarsal head is unknown. Measuring the BMD in the target region may predict the strength of the bone-screw fixation. Similar to previous work which determined the optimal position for lag screw placement in the femoral head during hip fracture fixation, this study aimed to determine average BMD within four quadrants of the metatarsal head using CT and thus predict the optimal trajectories for cannulated screws during the MIS bunion procedure.Methods:All patients between 18-75 years of age scheduled to undergo MIS hallux valgus correction by one of two surgeons experienced in the MIS technique were eligible to participate. Patients were excluded if they had a prior first metatarsal surgery, pre-existing hardware, previous first metatarsal fracture, or a history of osteoporosis treatment. Patients were enrolled prospectively, and a weight-bearing CT scan of the affected foot was obtained pre-operatively. Demographic factors including age, sex, laterality, body mass index (BMI), comorbidities, and smoking status as well as standard three-view weight-bearing radiographs were collected for all patients.Using the coronal CT slice at maximal metatarsal head diameter, each head was divided into equal quadrants. Hounsfield units (HU) within each quadrant were measured independently by three study investigators using our hospital’s radiology viewing software (Merge PACS; IBM Corporation, Armonk, NY), and these density measurements were averaged. Statistical analysis was conducted using ANOVA and Student’s t-test.Results:Fifteen patients were included for preliminary analysis. All patients were female. The average age was 45.7 years. 9 of the 15 included feet were right feet. Average BMI was 28.0. One patient reported active smoking prior to surgery. Comorbidities included obesity in three patients; none were diabetic. One had a history of diplegic cerebral palsy. The average HVA on a weight- bearing AP foot x-ray was 28.2°, and the average IMA was 12.6°. The BMD within the metatarsal head varied by quadrant, with the two combined dorsal quadrants having higher average BMD than the two combined plantar quadrants (122 vs 85 HU; p<0.001). The dorsal lateral quadrant had the highest average BMD of any quadrant (132 HU, p<0.001; Table 1).Conclusion:The density of the metatarsal head did vary by region within the head. The highest BMD was found in the dorsal lateral quadrant, and the lowest in the plantar lateral and plantar medial quadrants, which did not differ significantly from each other. Because strength of screw fixation is predicated upon screw design as well as bone density, these results suggest that surgeons may wish to direct screws toward the dorsolateral region of the metatarsal head in order to achieve optimal fixation. Further work is needed to determine whether this varies with patient age, gender, or hallux valgus angle.