Diaphysis Of Long Bones Research Articles

A probable case of infantile cortical hyperostosis in 2nd–4th centuries AD Romania

ObjectiveThis study aims to discuss the differential diagnosis for the pathological alterations displayed on an infant skeleton from Romania. MaterialsOne infant skeleton retrieved form the bathhouse of an abandoned Roman fort and dated between the 2nd and the 4th centuries AD. MethodsAll available skeletal elements were analyzed macroscopically. In addition, the isotopic signatures (δ13C and δ15N) and the control region of the human mitochondrial genome for this archaeological sample were analyzed. ResultsBased on dental development and long bone length, the skeleton was aged between birth and 2 months of age. Pathological lesions were noted on the mandible and diaphyses of long bones, but spared the metaphyses. ConclusionsThe perinatal age of the individual, along with lesion morphology and location, suggests a diagnosis of infantile cortical hyperostosis. LimitationsThe analysis would benefit from further stable isotope and mitochondrial genome analyses, which was limited due to the absence of comparative human and faunal remains from the site. Suggestions for further researchFurther multidisciplinary research on human archaeological remains from Romania would provide a clearer image of past disease and life histories in this geographic area.

MON-511 Erdheim-Chester Disease: A Challenging Diagnosis in a Patient with Ataxia, Osteosclerotic Bone Lesions, and a Long-Standing History of Central Diabetes Insipidus

Background: Erdheim- Chester Disease (ECD) is a rare hematopoietic neoplasm characterized by multi-organ infiltration with CD-68 -positive, CD1a-/S100-negative foamy histiocytes causing xantho-granulomatous inflammation. ECD most commonly involves the skeleton. CNS, pulmonary and CV involvement are also reported. Clinical Case: A 47-year-old male with a prior history of central Diabetes Insipidus (DI) presented with bone pain and ataxia. He was initially referred in 1993 for evaluation of DI. It was concluded that he had lymphocytic infundibulitis (LI), based on the finding of a thickened pituitary stalk on MRI while CSF revealed no evidence of infection or neoplasm. His DI was controlled with DDAVP. He had no other anterior pituitary hormone deficiencies. Although subsequent MRI showed resolution of the pituitary stalk thickening, his DI persisted. In 2012, he developed progressive gait instability, slurred speech and impaired motor coordination. On exam, he exhibited horizontal nystagmus, dysarthria, and truncal ataxia greater than limb ataxia. A brain MRI revealed absence of the posterior pituitary bright spot, enhancement along the proximal 7th and 8th nerve complex, disproportionate cerebellar atrophy and enhancement along the bilateral cerebellar folia. He complained of progressive, chronic leg pain since 2005. In 2018, he underwent tibial bone biopsy for an osteosclerotic lesion with diagnosis of Paget’s disease (PD). His Ca, Phos, 25OH- D, PTH, and Alk Phos were normal. Subsequent X-rays noted lesions of the pedicle of the left shoulder and pelvis, medullary sclerosis in the humeral diaphysis, and symmetrical lesions in the distal femur and tibia, bilaterally. Bone scan and FDG-Pet scan showed increased activity in the lesions. A repeat tibial biopsy revealed the marrow was infiltrated with histiocytes, fibrosis and sclerosis of trabecular bone. The histiocytes were highlighted by CD163, CD68, CD14, factor XIIIa and fascin A few scattered histiocytes were BRAF V600E immuno-stain positive, consistent with a diagnosis of ECD. His symptoms improved on Vemurafenib. Conclusion: We report a male with ECD who initially presented with isolated DI and a clinical course that mimicked LI. DI is a feature that occurs early in the disease process in 25% of patients. More than 10 years later, he developed ataxia and multifocal osteosclerotic bone lesions. His bone lesions were misdiagnosed as PD, but a repeat bone biopsy led to the correct diagnosis. In contrast to PD, the bone lesions in ECD are bilateral and symmetric and affect the diaphysis of long bones, specifically. As in our case, some patients with ECD can be asymptomatic for decades. For symptomatic patients who are BRAFV600E +, the B-Raf enzyme inhibitor, Vemurafenib, is recommended. His diagnosis was challenging, because ECD is rare (500 cases) and has features that overlap with other more common medical conditions.

Primary Vnutrikostnyj Osteosynthesis Diaphysis of Tibia Counter Pins

The author developed and introduced into clinical practice method intraosseous osteosynthesis counter pins diaphysis of long bones. He applied his 185 victims with fractures of the diaphysis of tibia. Of these, 101 (54.6%) operation was a primary character, is performed during the first 6:00 since the injury, with 50 (27%) It was open. The method resulted in complete stillness fragments while maintaining joint mobility of a limb. Describes monitoring almost complete detachment of the tibia, which managed to restore its function.

Ewing's Sarcoma and Primary Osseous Lymphoma: Spectrum of Imaging Appearances.

Ewing's sarcoma (ES) is a rare, highly malignant anaplastic stem cell tumor. Histologically, the tumor consists of uniform densely packed small monomorphic cells with round nuclei. The typical appearance at hematoxylin and eosin (H&E) staining is small blue round cells without any matrix formation. On conventional radiography, ES typically presents as a permeative lesion in the diaphysis of a long bone in a child. A large soft tissue component is another characteristic feature, best depicted by magnetic resonance imaging.Primary osseous lymphomas are most commonly highly malignant B-cell lymphomas. At H&E histologic staining, the tumor stroma consists of diffuse round-cell infiltrates that resembles the appearance of ES. Although there is no typical imaging appearance of an osseous lymphoma, it should be considered in an adult presenting with a Lodwick grade II or III lesion in the metaphysis or diaphysis of a large long bone, the pelvis, or the vertebral column. Histologic confirmation is mandatory.

Architecture of the femoral and tibial diaphyses in relation to body mass and composition: Research from whole-body CT scans of adult humans.

Recent investigations have evaluated the influence of body composition on long bones in order to overcome the limits of body mass (BM) estimation methods and eventually lead to studying nutrition in past populations. Knowing how fat mass (FM) and fat-free mass (FFM) impact the skeleton would also enhance the understanding of mobility, activity, and locomotion derived from bone architecture. We investigated the relationship between BM and composition, and the architecture of the entire tibial and femoral diaphyses in an adult sample representative of a wide range of variation in age, BM, and composition. Body composition was measured directly from 78 whole-body CT scans for which the age, sex, BM, and stature were recorded. The entire diaphyseal thickness, volume, curvature, and cross-sectional geometry parameters of both the femur and tibia were numerically extracted. FM correlates with large portions of the femoral thickness in females only. FFM correlates with the femoral diaphysis in males but not in females. FFM correlates with the tibia architecture in both sexes, while FM is correlated in males exclusively. BM and body components influence the architecture of the diaphysis of lower limb long bones in sex-specific patterns that are mostly reflected in their thickness and can be recorded, in some cases, for their strength, rigidity, and volume. Our results suggest that (1) long bone diaphyses should be thoroughly studied, as a whole, when possible; and (2) BM and body components should be accounted for when deriving activity, mobility, or locomotion patterns from cortical bone.

Ewing’s Sarcoma: imaging findings of a patient with primary tumor in the femur and mandibular metastasis

ABSTRACT Ewing’s Sarcoma, a common primary bone malignancy that usually occurs in childhood and young adults, has a predilection for males and occurs mostly in the diaphysis of long bones and pelvis. This tumor rarely affects the head and neck. Histologically, this neoplasm is a small round cell tumor and there is evidence of a neuroectodermal origin. Radiographic findings of ES show an osteolytic lesion, that is not a pathognomonic feature for this neoplasm. The association of conventional imaging methods such radiography, Computed Tomograph (CT), magnetic resonance imaging (MRI), combined with scintigraphy or Positron Emission Tomography/ Computed tomography PET /CT), is essential for a correct diagnosis and treatment. Therefore, the aim of this report was to present image findings of a patient who presented with ES in the femur, and a metastasis in the mandible after eighteen months, and discuss the importance of imaging methods for a correct diagnosis, treatment and consequently, prognosis.

Signalling Alterations in Bones of Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Gene Deficient Mice.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with diverse developmental roles, including differentiation of skeletal elements. It is a positive regulatory factor of chondrogenesis and osteogenic differentiation in vitro, but little is known about its in vivo role in bone formation. In our experiments, diaphyses of long bones from hind limbs of PACAP gene-deficient mice showed changes in thickness and increased staining intensity. Our main goal was to perform a detailed morphological and molecular biological analysis of femurs from PACAP knockout (KO) and wild type (WT) mice. Transverse diameter and anterior cortical bone thickness of KO femurs showed significant alterations with disturbed Ca2+ accumulation and collagen type I expression. Higher expression and activity of alkaline phosphatase were also observed, accompanied by increased fragility PACAP KO femurs. Increased expression of the elements of bone morphogenic protein (BMP) and hedgehog signalling was also observed, and are possibly responsible for the compensation mechanism accounting for the slight morphological changes. In summary, our results show that lack of PACAP influences molecular and biomechanical properties of bone matrix, activating various signalling cascade changes in a compensatory fashion. The increased fragility of PACAP KO femur further supports the role of endogenous PACAP in in vivo bone formation.

Targeting Osteogenesis-Angiogenesis Coupling for Bone Repair.

An estimated 6 million long bone fractures occur in the United States each year,1 and up to 10% of these fractures result in delayed union or nonunion.2 Although volumetric bone loss and/or inadequate progenitor cell numbers are common causes of nonunion, the most common defining feature of nonunion is impaired vascularization.3 The current standard of care for fracture nonunion consists of bone grafting and/or distraction osteogenesis; however, limited availability of graft material, pain with graft harvest and distraction, and poor angiogenesis represent significant limitations of these treatment options. Thus, strategies to enhance angiogenesis and subsequent osteogenesis in these most severe cases are urgently needed. Here we discuss osteoprogenitor-endothelial cell crosstalk in bone healing and outline strategies for targeting osteogenesis-angiogenesis coupling for the prevention and management of delayed healing and fracture nonunion. Osteoprogenitor–Endothelial Cell Crosstalk During development and in adulthood, osteoprogenitor cells (OPCs) co-localize with endothelial cells (ECs) in the perivascular niche.4,5 During fracture repair, OPCs invade the injury site with newly forming vasculature,6 which suggests the existence of a functional codependency between OPCs and ECs via cell-cell contact and paracrine signaling. ECs exert control over osteogenesis by expressing a variety of factors that regulate OPC survival, proliferation, and differentiation, including bone morphogenetic protein (BMP)-2 and -4, Wnt5a, and Notch signaling.7 Early committed osteoblasts are primarily associated with vessels that highly express CD31 and endomucin; these vessels, which are also referred to as type H vessels, are predominantly located below the growth plate and adjacent to the endosteum in the diaphysis of long bone.5 The number of type H vessels decreases with age, with a corresponding reduction in OPCs,8 which may partially explain the reduced healing capacity of aged bone. Although these data suggest that the vascular niche has a role in nurturing osteogenic cells, osteolineage cells at all stages of differentiation express pro-angiogenic factors, including hypoxia-inducible factor-α,9 vascular endothelial growth factor,10 BMP-2,11 and C-X-C motif chemokine ligand 12 (CXCL12),12 a chemokine involved in stem cell recruitment and differentiation. Our work shows that osteoprogenitor cells regulate EC migration, angiogenic sprouting, and tubule formation,13 and our unpublished data suggest that release of CXCL12 from osteolineage cells regulates angiogenesis during fracture repair. Ongoing clinical trials are investigating the effects of targeting CXCL12 signaling in conditions such as diabetes and cardiovascular disease, but none has yet focused on bone regeneration. Targeting Osteogenesis-Angiogenesis Coupling In animal studies, exogenous vascular endothelial growth factor (VEGF) treatment has been shown to enhance osteogenesis at low doses14 and to disrupt osteogenesis at high doses as the result of abnormal angiogenesis and vascular structure.15 Delivery of CXCL12 and VEGF enhanced recruitment of endothelial progenitors in a hindlimb ischemia model,16 and fat grafts expressing CXCL12 and BMP-2 enhanced mesenchymal stem cell recruitment to a critical-sized femoral defect in a murine model.17 More recent delivery strategies have focused on sustained release of osteogenic and angiogenic factors at physiologic levels. For example, fibrin matrices with highly tunable release of VEGF164 showed significant functional improvement of hindlimb ischemia (P < 0.01).18 In another approach, three-dimensional–printed β-tricalcium phosphate/calcium silicate scaffolds pre-seeded with human umbilical cord vein endothelial cells and human bone marrow stromal cells stimulated robust angiogenesis and osteogenesis in an ectopic bone formation model.19 Most recently, collagen-based scaffolds with host cell BMP-2 and VEGF transfection capabilities showed significantly enhanced vessel formation and repair of critical-sized calvarial defects (P < 0.001).20 Mechanical loading is a robust modulator of bone repair,21,22 and there is evidence that its effects are exerted, in part, through regulation of angiogenesis.13,23,24 Exogenous mechanical loading during the bone matrix formation phase results in increased bone volume and induces vascular remodeling, resulting in decreased vessel number and connectivity and increased vessel thickness. This effect may be mediated through the release of mechanosensitive paracrine factors from ECs, neighboring cells,25 and the hematoma.26 Summary The concurrent induction of osteogenesis and angiogenesis using three-dimensional constructs with gene activation capabilities, controlled microarchitecture, and highly tunable protein release profiles is being validated in preclinical animal models. Many of these approaches target endothelial and osteogenic cell coupling through regulation of VEGF, BMP, and CXCL12 signaling. Osteogenesis and angiogenesis are both highly sensitive to mechanical signals, and new approaches must also take into account the mechanical environment at both the macro level (in the form of tissue deformation) and the micro level (in terms of scaffold stiffness).27 Typically, intramedullary fixation is chosen for reconstruction of critical-sized defects because it allows early weight bearing and increased callus formation. However, additional studies are needed to reveal how mechanical signals regulate osteogenesis-angiogenesis coupling at the cellular and molecular levels.

Dimensions around the nutrient foramina of the tibia and fibula in the estimation of sex

Sex estimation from skeletal remains is one of the key components in establishing a biological profile and consequent identification of an individual in a forensic and medico-legal practice. The use of dimensions around the nutrient foramen in instances where long bones may be fragmented and damaged is of benefit due to the fact that the nutrient foramen is easily identifiable and may be preserved on the shaft of long bones. This study is an investigation of the usefulness of various measurements around the nutrient foramen of the tibia and fibula of South Africans in an attempt to develop osteometric standards for sex estimation. The sample included 206 tibiae and 204 fibulae of South African Africans (SAA) and South African whites (SAW) procured from the Raymond A. Dart Collection of Human Skeletons based at the University of the Witwatersrand. Sex was correctly classified for the tibia with an accuracy ranging between 79–82% in SAA and 84–88% in SAW, with the circumference at the level of the nutrient foramen as the single best predictor of sex in both populations. An accuracy ranging from 69 to 74% in SAA and 70–77% in SAW was observed for the combined measurements on the fibula. The current study confirms the usefulness of measurements around the nutrient foramen of the tibia in the assignment of sex. However functions of the fibula generally performed poorly and should be used with caution.

Active muscle response contributes to increased injury risk of lower extremity in occupant–knee airbag interaction

ABSTRACTObjective: Recent field data analysis has demonstrated that knee airbags (KABs) can reduce occupant femur and pelvis injuries but may be insufficient to decrease leg injuries in motor vehicle crashes. An enhanced understanding of the associated injury mechanisms requires accurate assessment of physiological-based occupant parameters, some of which are difficult or impossible to obtain from experiments. This study sought to explore how active muscle response can influence the injury risk of lower extremities during KAB deployment using computational biomechanical analysis.Methods: A full-factorial matrix, consisting of 48 finite element simulations of a 50th percentile occupant human model in a simplified vehicle interior, was designed. The matrix included 32 new cases in combination with 16 previously reported cases. The following influencing factors were taken into account: muscle activation, KAB use, KAB design, pre-impact seating position, and crash mode. Responses of 32 lower extremity muscles during emergency braking were replicated using one-dimensional elements of a Hill-type constitutive model, with the activation level determined from inverse dynamics and validated by existing volunteer tests. Dynamics of unfolding and inflating of the KABs were represented using the state-of-the-art corpuscular particle method. Abbreviated Injury Scale (AIS) 2+ injury risks of the knee–thigh–hip (KTH) complex and the tibia were assessed using axial force and resultant bending moments. With all simulation cases being taken together, a general linear model was used to assess factor significance (P <.05).Results: As estimated by the regression model across all simulation cases, use of KABs significantly reduced axial femur forces by 4.74 ± 0.43 kN and AIS 2+ injury risk of KTH by 47 ± 6% (P <.05) but did not provide substantial change to injury risk of leg fractures. Muscle activation significantly increased axial force and bending moment of the femur (3.87 ± 0.38 kN and 64.3 ± 5.9 Nm), the tibia (1.49 ± 0.12 kN and 43.0 ± 6.4 Nm), and the resultant probability of AIS 2+ tibia injuries by 36 ± 6% regardless of KAB use and crash scenario. Specifically, when counting on a relative scale, muscle activation exhibited more prominent elevation of injury risk for in-position occupants than out-of-position occupants. In a representative crash scenario—that is, using a bottom-deployed KAB in a nearside oblique impact—muscle bracing of the right leg may lead to 2.6 times higher tibia fracture risk than being relaxed for an out-of-position occupant and 5.4 times higher for an in-position occupant.Discussion and Conclusions: The mechanism of higher leg injuries in the presence of KAB deployment in real-world crashes can be interpreted by the increased effective body mass, axial compression along the shafts of long bones, and altered pre-impact posture due to muscle contraction. The present analysis suggests that active muscle response can increase the risk of lower extremity injury during occupant–KAB interaction. This study demonstrated the feasibility of advanced human models to investigate the influence of physiologically based parameters on injury outcomes evidenced in field study and insight from computational examination on human variability for development of future restraint systems. Future efforts are recommended on realistic vehicle and restraint environment and advanced modeling strategies toward a full understanding of KAB efficacy.

439 Extraosseous ewing’s sarcoma presenting as a scrotal mass

Case reportEwing’s sarcoma is a highly malignant, poorly differentiated bone tumour of childhood and adolescence primarily involving diaphysis of long bones; femur, tibia, fibula, and humerus and may also occur in other bony structures and cartilage tissue. It is a very clinically aggressive tumour

Histomorphometric analysis of bone lacunae in human and pig: Can it be useful for species discrimination?

In recent years, several studies have focused on species identification of bone fragments by the assessment of the histomorphological appearance of bone tissue as well as the quantification of histological structures such as Haversian systems. According to literature, the most consistent distinguishing features are Haversian canal and Haversian system areas. Nonetheless, there is a consistent overlap between human and non-human secondary osteon dimensions. One of the structure that has never been analyzed for the purpose of species discrimination is the bone lacuna, a small oblong cavity in which the osteocyte is locked in. The aim of this study is to verify whether there are significant quantitative differences between human and pig lacunae within secondary osteons with similar areas. Study sample comprises the diaphysis of long bones of a medieval human adult and a subadult pig. A total of 68 secondary osteons with similar areas have been selected for each individual. Each osteon was analyzed with a light microscope and the following measurements were taken at 200X magnification using IScapture® software: 1) total number of lacunae within the osteon, 2) minimum and maximum diameter, area and perimeter of nine lacunae divided between inner, intermediate and outer lacunae. T-test was employed to compare the mean values for the two individuals. The mean number of lacunae per osteon does not seem to be significantly different between human (48.9) and pig (46.9). However, human lacunae seem generally bigger when compared with pig lacunae with a mean area respectively of 45.06 (±17.42) μm2 and 39.6 (± 15.52) μm2. Nonetheless, there is a significant overlap between human and pig. Concerning the differences between inner, intermediate and outer lacunae, the ones close to the cement line (outer lacunae) are clearly bigger when compared with lacunae which are close to the Haversian canal (inner lacunae). Statistical analysis showed a significant difference in the maximum diameter, perimeter and area of the lacunae between human and pig. Though results seem promising, this exploratory study need further research on a bigger sample including individuals of different ages and different species in order to verify its potential for species discrimination.

WNT-activated bone grafts repair osteonecrotic lesions in aged animals

The Wnt pathway is a new target in bone therapeutic space. WNT proteins are potent stem cell activators and pro-osteogenic agents. Here, we gained insights into the molecular and cellular mechanisms responsible for liposome-reconstituted recombinant human WNT3A protein (L-WNT3A) efficacy to treat osteonecrotic defects. Skeletal injuries were coupled with cryoablation to create non-healing osteonecrotic defects in the diaphysis of the murine long bones. To replicate clinical therapy, osteonecrotic defects were treated with autologous bone graft, which were simulated by using bone graft material from syngeneic ACTB-eGFP-expressing mice. Control osteonecrotic defects received autografts alone; test sites received autografts treated ex vivo with L-WNT3A. In vivo µCT monitored healing over time and immunohistochemistry were used to track the fate of donor cells and assess their capacity to repair osteonecrotic defects according to age and WNT activation status. Collectively, analyses demonstrated that cells from the autograft directly contributed to repair of an osteonecrotic lesion, but this contribution diminished as the age of the donor increased. Pre-treating autografts from aged animals with L-WNT3A restored osteogenic capacity to autografts back to levels observed in autografts from young animals. A WNT therapeutic approach may therefore have utility in the treatment of osteonecrosis, especially in aged patients.

Combined fixation of modular tumor proximal humeral endoprosthesis (experimental and clinical study)

Objective: to substantiate, develop and implement a more reliable combined endoprosthesis fixation system for replacement of postresectional defects of the proximal humerus, reduction in the number of complications from the endoprosthesis and improvement of the results of tumor joint replacement.Methods: finite element models of the «endoprosthesis – humerus» system with different fixation methods (combined and intramedullary only) have been developed, investigated for tension, bending and twisting. In an experiment on 20 white rats, the situation was modeled after tumor resection of the long-bone diaphysis and replacement of the defect with a modular endoprosthesis. The animals were divided into two groups: in the experimental, an endoprosthesis was installed with a combined fixation system, in the control one — with intramedullary. Twelve patients with tumor lesion of the proximal humerus were operated: in 3 an endoprosthesis with intramedullary fixation was implanted, in 9 patients with a combined implant. The observation period is up to 7 years.Results: on mathematical models it is determined that the use of an additional fixation system can significantly reduce the load on the «critical zone» due to its redistribution to extracortical plates. In vivo experiment, the stability of fixation and a significant reduction in the number of complications with the use of combined fixation was demonstrated. On the basis of the theoretical and experimental data obtained, the proximal humeral endoprosthesis with a combined fixation system was developed and implemented into practice. In patients operated on with the proposed fixation system, complications associated with the endoprosthesis were not revealed.Conclusions: the use of the developed endoprosthesis with extra-cortical fixation to replace the post-exposure defects of the proximal humerus makes it possible to reduce the risk of complications associated with the implant.

Epiphyseal bone formation occurs via thyroid hormone regulation of chondrocyte to osteoblast transdifferentiation

Endochondral ossification in the diaphysis of long bones has been studied in-depth during fetal development but not postnatally in the epiphysis. Immunohistochemical studies revealed that Sox9 and Col2 expressing immature chondrocytes in the epiphysis transition into prehypertrophic and hypetrophic chondrocytes and finally into osteoblasts expressing Col1 and BSP during postnatal day 7–10, when serum levels of thyroid hormone (TH) rise. Lineage tracing using Rosa-td tomatoCol2-Cre-ERT2 mice treated with tamoxifen indicated that the same Col2 expressing chondrocytes expressed prehypertrophic, hypertrophic, and subsequently bone formation markers in a sequential manner in euthyroid but not hypothyroid mice, thus providing evidence that chondrocyte to osteoblast transdifferentiation is TH-dependent. Vascular invasion was apparent at the time of bone formation but not earlier. In vitro studies revealed that TH acting via TRα1 promoted expression of SHH while TRβ1 activation increased IHH but inhibited SHH expression. SHH promoted expression of markers of immature chondrocytes but inhibited chondrocyte hypertrophy while IHH promoted chondrocyte hypertrophy. Based on our data, we propose a model in which TH acting through TRα1 and TRβ1, respectively, fine tune levels of SHH and IHH and, thereby control the transit of proliferating immature chondrocytes into mature hypertrophic chondrocytes to become osteoblasts at the epiphysis.

Primary intracranial dural-based Ewing sarcoma/peripheral primitive neuroectodermal tumor mimicking a meningioma: A rare tumor with review of literature.

Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) is a malignant small, round cell tumor arising from bone and soft tissue in children and young adults. It can occur at osseous and extraosseous sites. Its usual locations are diaphysis of long bones followed by pelvis, ribs, vertebrae, and rarely skull. We reviewed the literature and PubMed advanced search on ES/pPNET occurring at extraosseous sites, mainly involving the central nervous system (CNS). We reported a case of a 22-year-old male presenting with seizure finally diagnosed as a case of ES/pPNET. The challenges in management of this rare CNS tumor and its differential diagnosis are highlighted. We found that most cases of ES involving CNS represent secondary metastases from extracranial sites of ES/pPNET and there are rare case reports of primary intracranial ES-pPNET. Furthermore, among these intracranial tumors, most common tumors occupy an intraaxial location and only a handful of cases of dural-based or extraaxial tumors mimicking meningioma are reported. Differentiation of pPNET from central PNET (cPNET) is important as it has definitive therapeutic and prognostic implications. Awareness of this entity of ES/pPNET, its rare dural presentation, and differentiation from the more common cPNET is needed for appropriate patient management. Meningeal ES/pPNET has to be kept in mind in the differential diagnosis of meningeal tumors eroding bone.

Muscle-Bone Interactions in Pediatric Bone Diseases.

Here, we review the skeletal effects of pediatric muscle disorders as well as muscle impairment in pediatric bone disorders. When starting in utero, muscle disorders can lead to congenital multiple contractures. Pediatric-onset muscle weakness such as cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, or spina bifida typically are associated with small diameter of long-bone shafts, low density of metaphyseal bone, and increased fracture incidence in the lower extremities, in particular, the distal femur. Primary bone diseases can affect muscles through generic mechanisms, such as decreased physical activity or in disease-specific ways. For example, the collagen defect underlying the bone fragility of osteogenesis imperfecta may also affect muscle force generation or transmission. Transforming growth factor beta released from bone in Camurati Engelman disease may decrease muscle function. Considering muscle-bone interactions does not only contribute to the understanding of musculoskeletal disorders but also can identify new targets for therapeutic interventions.

Osteopatia hipertrófica secundária a osteossarcoma condroblástico extraesquelético em um cão

Background: hypertrophic osteopathy is a periosteum disturb characterized by diffuse new bone formation which leads to significant thickening and deformity of members. Secondary in nature, it usually follows large pulmonary lesions such as abscesses and neoplasms. Extraskeletal osteosarcomas are rare and extremely malignant mesenchymal neoplasms. They comprise approximately 1% of all domestic animals’ osteosarcomas and develop in the absence of a primary bone lesion. The aim of this paper was to describe a case of hypertrophic osteopathy, involving joints and upper limbs bones including ilium, secondary to a mediastinal chondroblastic osteosarcoma with pulmonary metastasis.Case: A 10-year-old spayed female mixed breed dog, weighing 9 kg, was presented with painful limbs, lameness, hind limbs swelling and a four-month history of weight loss. Radiographic examination revealed bilateral and asymmetric periosteal reactions on diaphyseal and/or epiphyseal areas of all proximal phalanges; metacarpal, metatarsal, carpal and tarsal bones; radius; ulna; tibia; fibula; humerus; femur and right ilium. An increased soft tissue radiopacity was noted on the lateral side of the right knee joint. Thoracic radiographies and ultrasonography suggested the presence of a 5-cm neoplasm or abscess in the left caudal lung lobe. At necropsy, the lobe showed a firm and solid, oval white mass measuring 5.2 x 2.9 cm. Another mass was found in the caudal mediastinum, near the diaphragm, with same color and more irregular aspect, measuring 3.3 cm of diameter. Intense periosteal new-bone formation was seen in the entire length of the four limbs bones, characterized by thickening of the bone surface and formation of irregular trabeculae perpendicular to the cortex. Significant swelling and thickening of the joint capsule was noted in the right knee. There was no microbial growth on aerobic or anaerobic cultures from the masses samples sent to culture. Histopathological examination showed areas of chondroid differentiation, osteoidtissue formation and cell morphology suggestive of chondroblastic osteosarcoma in mediastinal region, with invasion and involvement of the diaphragm and lungs. The analyzed bone fragment had large foci of tissue compaction, peritrabecular bleeding and mineralization of osteoid tissue, permeated by plasma cells and typical lymphocytes.Discussion: Although hypertrophic osteopathy is often characterized as a disease which affects the diaphysis of distal long bones, this case presented a proximal progression of the disease. There was an unusual involvement of joints and ilium, which reinforces the importance of radiographic evaluation of these regions. Further studies on the pathogenesis of the syndrome are required, as its exact mechanisms remain obscure. It is suggested that the term hypertrophic osteoarthropathy should not be consider a misnomer since joint involvement is not exclusive of human form of the disease. Mediastinal masses are important cause of hypertrophic osteopathy. However, this is the first paper the authors are aware of that reports the occurrence of hypertrophic osteopathy secondary to mediastinal osteosarcoma. Finally, although rare, extra skeletal osteosarcoma should be considered in the differential diagnosis of intrathoracic masses in dogs with hypertrophic osteopathy. Timely diagnosis of hypertrophic osteopathy, whose signs of lameness and painful limbs draw the owner’s attention, may favor the diagnosis of severe concomitant diseases.

Benign or Malignant: A Case Report of Multifocal Epithelioid Hemangioma of Fibula

Case Presentations: A 63-year-old female with no significant prior trauma and relevant past medical history presented with a 2-month history of severe, persistent, gradually worsening, sharp and non-radiating pain over her left distal fibula. Physical examination revealed extreme tenderness to palpation over the lateral distal fibula. There was soft tissue prominence over the mid to lower third of the fibula. Results: Left lower leg radiographs depicted two ill-defined osteolytic destructive lesions measuring 29 and 37 mm in length in the fibular diaphysis. A pathologic fracture was present through the distal lesion. A laboratory test, including serum protein electrophoresis, alkaline phosphatase and basic metabolic profile, was ordered to evaluate for multiple myeloma. CT scans of the chest and abdomen were obtained to evaluate for primary malignancy or any evidence of metastatic disease. The results of these tests were unremarkable. Image-guided biopsy of the lesions was performed and revealed epithelioid hemangioma (EH). The patient was initially managed with a walker boot. At the 2-month follow-up, an additional third smaller lesion was detected along with an interval increase in size of the two previously seen lesions. The patient proceed with preoperative embolization followed by surgical curettage and open reduction and internal fixation. Angiogram was done and tumor feeding artery was identified but tumor embolization was unsuccessful. The patient underwent fibular bone lesion curettage, PRO-DENSE bone grafting and open reduction and internal fixation with the left fibular diaphyseal plate. Radiographs revealed continued healing with bone graft incorporation at 1.5-, 3- and 7-month follow-ups. The patient was permitted to return to all activities without restriction 1.5 months after the surgery. Conclusions: EH is an uncommon, slow-growing vascular tumor that generally presents on the skin and the subcutaneous soft tissues of the head, with osseous EHs being rare. Although osseous EHs can present as multifocal lesions, the majority of bony EHs are solitary and arise in the diaphysis or metaphysis of long tubular bones, with a predilection for the lower extremity. Radiographically, EH may present as well-defined lytic lesions with sclerotic margins or mixed lytic and sclerotic lesions. These lesions are often located eccentrically and may demonstrate a disrupted or intact cortex.

Orthopedic Manifestations of Type I Camurati-Engelmann Disease.

BackgroundCamurati-Engelmann disease (CED) is a rare genetic skeletal disorder characterized by limb pain, muscle emaciation and weakness, and cortical thickening of the diaphysis of long bones. It is caused by mutations in the transforming growth factor beta 1 (TGFB1) (type I) or other unknown gene(s) (type II). We present 8 consecutive patients with type I CED.MethodsWe retrospectively reviewed medical records and radiographs of type I CED patients with special reference to the mode of presentation, process of diagnostic work-up, and disease course. They were 4 sporadic patients, and two pairs of mother and son.ResultsWe categorized the mode of presentation into three groups. Group I had 4 patients who mainly presented with motor disturbances in young age. They drew medical attention for waddling gait, awkward ambulation or running, difficulty in going upstairs, or a positive Gower's sign at age 4 to 6 years. Subsequent development of limb pain and radiographic abnormality led to the diagnosis of CED at age 6 to 29 years. Group II had 3 patients who mainly presented with limb pain at age 15, 20, and 54 years, respectively. Radiographic evaluation and molecular genetic test led to the diagnosis of CED. The remaining 1 patient (group III) was asymptomatic until age 9 years when bony lesions at the tibiae were found incidentally. For the last 10 years, he intermittently complained of leg pain in the morning or after sports activities, which did not interfere with daily life. All the patients in group I showed a body mass index in the underweight range (< 18.4 kg/m2). At the latest follow-up, 4 patients in groups I and II required medication for the limb pain.ConclusionsCED presents with a wide range of severity. Awareness of this rare disease entity may be the key to timely correct diagnosis. This disease entity should be considered in the differential diagnosis of limb pain or motor disturbance in children to avoid unnecessary diagnostic work-up.