Ossifying Fibroma of Non-odontogenic Origin: A Fibro-osseous Lesion in the Craniofacial Skeleton to be (Re-)considered

In the cranio-facial skeleton, a heterogeneous group of well characterized fibro-osseous lesions can be distinguished. Whereas fibrous dysplasia can affect any skeletal bone, ossifying fibroma and cemento-osseous dysplasia exclusively develop in the cranio-facial region, with most subtypes restricted to the tooth bearing areas of the jaws. Herein we present a series of 20 fibro-osseous lesions that developed mostly in the frontal bone and in the mandible, presenting as expansile intramedullary tumors with a unique histologic appearance and an indolent clinical course. We provide evidence that these tumors are distinct from the categories included in the WHO classification and are therefore currently unclassifiable. The definition of cemento-ossifying fibroma as an odontogenic neoplasm developing only in close proximity to teeth should be re-considered and incorporate also extragnathic lesions as shown here.

Case Report: Two Monochorionic Twins With a Critically Different Course of Progressive Osseus Heteroplasia

Progressive osseous heteroplasia (POH; OMIM 166350) is a rare autosomal-dominant genetic disorder in which extra-skeletal bone forms within skin and muscle tissue. POH is one of the clinical manifestations of an inactivating mutation in the GNAS gene. GNAS gene alterations are difficult matter to address, as GNAS alleles show genetic imprinting and produce several transcript products, and the same mutation may lead to strikingly different phenotypes. Also, most of the publications concerning POH patients are either clinical depictions of a case (or a case series), descriptions of their genetic background, or a tentative correlation of both clinical and molecular findings. Treatment for POH is rarely addressed, and POH still lacks therapeutic options. We describe a unique case of POH in two monochorionic twins, who presented an almost asymptomatic vs. the severe clinical course, despite sharing the same mutation and genetic background. We also report the results of the therapeutic interventions currently available for heterotopic ossification in the patient with the severe course. This article not only critically supports the assumption that the POH course is strongly influenced by factors beyond genetic background but also remarks the lack of options for patients suffering an orphan disease, even after testing drugs with promising in vitro results.

THE IMPACT OF THE SPINAL DEFICIENCIES PROPHYLAXIS UPON THE 6-7 YEAROLD PRESCHOOL CHILDREN PHYSICAL DEVELOPMENT LEVEL

The problem of prophylaxis of various deficiencies of the skeletal bone of preschool children and first of all of the spine, as a basic pillar in their development, was and remains in the sights of specialists in the field of physical education and sports. It has been shown experimentally that the means of physical education can and must be a basic support in terms of spinal deficiencies prophylaxis, especially in children of preschool age, in this case the age of 6-7 years. It is at this age that the first symptoms occur related to the appearance of one or another spine deficiency. If no direct action is taken, with the application of specific means to eliminate or reduce the occurrence of these deficiencies, the situation may become much more serious and much more difficult to resolve. In this case, a series of means of physical education are proposed in the form of complex exercises and dynamic games, which have been used successfully in the training process of preschoolers aged 6-7. At the same time, the influence of the prophylaxis process of spinal deficiencies on the level of physical development of the contingent given by children was researched.

Region-specific effects of blocking estrogen receptors on longitudinal bone growth

Estrogen receptors (ERs) regulate the development of the growth plate (GP) by binding to estrogen, a phenomenon that determines the growth of skeletal bone. However, the exact mechanisms underlying the regulatory effects of ERs on axial and appendicular growth plates during puberty remain unclear. In the present study, the strategy of ERβ blocking resulted in increased longitudinal elongation of the appendicular bone (P<0.01), whereas ERα blocking suppressed appendicular elongation (P<0.05). Blocking both ERs did not have opposite effects on axial longitudinal growth. The expression of chondrocyte proliferation genes including collagen II, aggrecan, and Sox9 and hypertrophic marker genes including collagen X, MMP13, and Runx2 was significantly increased in the growth plate of female mice treated with ERβ antagonist compared with that in the GP of control mice (P<0.05). There were no significant differences in local insulin-like growth factor 1 (IGF-1) expression among these groups (P>0.05), and Indian hedgehog protein (Ihh) and parathyroid related protein (PTHrP) expression differed among these groups (P<0.05). ERs appeared not to affect axial bone growth during puberty in female mice (P<0.05). Our data show that the blocking of different ER subtypes might have a region-specific influence on longitudinal appendicular and axial growth.

Intelligent Bone Age Assessment: An Automated System to Detect a Bone Growth Problem Using Convolutional Neural Networks with Attention Mechanism

Skeletal bone age assessment using X-ray images is a standard clinical procedure to detect any anomaly in bone growth among kids and babies. The assessed bone age indicates the actual level of growth, whereby a large discrepancy between the assessed and chronological age might point to a growth disorder. Hence, skeletal bone age assessment is used to screen the possibility of growth abnormalities, genetic problems, and endocrine disorders. Usually, the manual screening is assessed through X-ray images of the non-dominant hand using the Greulich–Pyle (GP) or Tanner–Whitehouse (TW) approach. The GP uses a standard hand atlas, which will be the reference point to predict the bone age of a patient, while the TW uses a scoring mechanism to assess the bone age using several regions of interest information. However, both approaches are heavily dependent on individual domain knowledge and expertise, which is prone to high bias in inter and intra-observer results. Hence, an automated bone age assessment system, which is referred to as Attention-Xception Network (AXNet) is proposed to automatically predict the bone age accurately. The proposed AXNet consists of two parts, which are image normalization and bone age regression modules. The image normalization module will transform each X-ray image into a standardized form so that the regressor network can be trained using better input images. This module will first extract the hand region from the background, which is then rotated to an upright position using the angle calculated from the four key-points of interest. Then, the masked and rotated hand image will be aligned such that it will be positioned in the middle of the image. Both of the masked and rotated images will be obtained through existing state-of-the-art deep learning methods. The last module will then predict the bone age through the Attention-Xception network that incorporates multiple layers of spatial-attention mechanism to emphasize the important features for more accurate bone age prediction. From the experimental results, the proposed AXNet achieves the lowest mean absolute error and mean squared error of 7.699 months and 108.869 months2, respectively. Therefore, the proposed AXNet has demonstrated its potential for practical clinical use with an error of less than one year to assist the experts or radiologists in evaluating the bone age objectively.

RARE SARCOMA OF BREAST- PRIMARY OSTEOSARCOMA

Extraskeletal osteosarcomas are malignant and arise from soft tissue that produce osteoid, without any continuity to skeletal bone. Primary osteosarcoma of breast is a rare clinical entity. Although reported previously, there are no available guidelines for their management. A 52- year old lady who presented with rapidly growing tumor in breast was managed surgically. We discuss the diagnostic challenges and role of adjuvant therapy in our report

Microarchitecture of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva: An HR-pQCT Case Series

It is challenging to study heterotopic ossification (HO) in patients with fibrodysplasia ossificans progressiva (FOP) due to the contraindication of invasive techniques (i.e., bone biopsies), which can trigger flare-ups. The aim of this case study was to assess mature HO at the microarchitectural level non-invasively with high-resolution peripheral quantitative computed tomography (HR-pQCT). Depending on the patient’s mobility, HR-pQCT scans were acquired of peripherally located HO and standard distal radius and tibia regions in two FOP patients, a 33-year-old woman and a 23-year-old man, with the classical mutation (p.R206H). HO was located around the halluces, the ankles, and in the Achilles tendon. Standard HR-pQCT analyses were performed of the distal radius, tibia, and HO to quantify bone mineral density (BMD) and bone microarchitecture. Micro-finite element analysis was used to estimate failure load (FL). The outcomes were compared between HO and neighboring skeletal bone and with an age- and gender-matched normative dataset from literature. The bone parameters of the radius were within the interquartile range (IQR) of normative data. In contrast, in the tibiae of both patients, total and trabecular BMD were below the IQR, as were trabecular bone volume fraction, number, and thickness, cortical thickness, and FL. Trabecular separation and heterogeneity were above the IQR. Isolated HO in the Achilles tendon had a lower total, trabecular, and cortical BMD, trabecular bone volume fraction, and cortical thickness than the normative tibia data. Trabecular microarchitecture was within the IQR, and FL was approximately 10% higher than that of the neighboring tibia after accounting for areal differences. Other scanned HO could only be qualitatively assessed, which revealed coalescence with the neighboring skeletal bone, development of a neo-cortex, and partial replacement of the original skeletal cortex with trabeculae. To conclude, isolated HO seemed microarchitecturally more comparable to reference tibia data than the peripheral skeleton of the FOP patients. HO and skeleton also appear to be able to become one entity when contiguous.

Minocycline Hydrochloride as a Potential Adjuvant to Improve Osteoconductive and Osteoinductive Properties of Bone Substitutes in an Extra-Skeletal Bone Augmentation Model: Preliminary Observations in Rats

Objectives The present study was performed to determine if minocycline HCl could influence the behavior of deproteinized bovine bone mineral (DBBM) and bioactive glass (BG) particles when used as filler material for new bone generation in a guided bone augmentation model. Materials and Methods Two occlusive titanium caps were placed on the rat calvaria. One filled with BG particles, the second with DBBM particles, both previously mixed with blood (control). In minocycline HCl loaded groups (experimental), grafts were additionally placed into a minocycline solution. Samples were harvested after 4, 8, and 16 weeks. Half of the samples were embedded in methylmethacrylate for undecalcified histology and the other half was fixed, decalcified, and embedded in paraffin for classical histologic analysis. Results The control groups highlighted osteoconductive and osteoinductive responses associated to BG particles, as well as an osteoconductive reaction, in DBBM sections. The addition of minocycline HCl to BG particles had no measurable influence on the result. In minocycline HCl loaded DBBM sections; however, areas of spontaneous ossification could be observed after 8 and 16 weeks. Conclusion Our observations suggest that minocycline HCl may add some osteoinductive properties to DBBM within the limitations of this study design. Further investigations are needed to refine the present results.