Magnetic resonance and computed tomographic imaging characteristics and potential molecular mechanisms of feline meningioma associated calvarial hyperostosis.

Meningiomas are the most common feline primary brain tumours, and calvarial hyperostosis (CH) is frequently documented in association with this neoplastic entity. The clinical significance of and mechanisms driving the formation of CH in cats with meningiomas are poorly understood, although tumour invasion into the skull and tumour production of cytokines and enzymes have been implicated as causes of CH in humans. This retrospective study investigated relationships between signalment, MRI or CT imaging features, histopathologic tumour characteristics, alkaline phosphatase (ALP) isoenzyme concentrations, tumour expression of matrix metalloproteinases (MMP)-2, MMP-9, and interleukin-6 (IL-6), and progression free survival times (PFS) following surgical treatment in 27 cats with meningiomas with (n = 15) or without (n = 12) evidence of CH. No significant differences in breed, age, sex, body weight, tumour grade, tumour volume, peritumoral edema burden, ALP isoenzyme concentrations, tumour Ki-67 labelling indices or MMP-2 or MMP-9 expression and activity, or PFS were noted between cats with or without CH. There was a trend towards higher serum (p = .06) and intratumoral (p = .07) concentrations of IL-6 in cats with CH, but these comparisons were not statistically significant. Histologic evidence of tumour invasion into bone was observed in 5/12 (42%) with CH and in no (0/6) cats without CH, although this was not statistically significant (p = .07). Tumour invasion into bone and tumour production of IL-6 may contribute to the formation of meningioma associated CH in cats, although larger studies are required to further substantiate these findings and determine their clinical relevance.

Porotic hyperostosis and cribra orbitalia in samples from the Late Hillfort Period sites at Detkovice - Za zahradama (district Prostejov) and Vídenská street (district Brno), Czech Republic.

Porotic hyperostosis and cribra orbitalia are pathological changes occurring on the human skull. These changes were observed and evaluated on skeletal remains from Detkovice - Za zahradama and Vídenská Street in Brno; both sites are dated back to the 10th to 12th centuries AD. A total of 605 subjects were assessed for age, sex, and the above-stated pathologies using standard methods. The influence of age and sex on the occurrence of these pathologies was examined statistically. Results indicated that at the site of Detkovice - Za zahradama, porotic hyperostosis, and cribra orbitalia do not depend on sex or age. However, at Vídenská Street in Brno, these pathologies do not depend on sex, but they depend on age so a higher incidence of pathologies in juveniles is observed. Differences between both sites could be caused by different numbers of evaluated individuals or different state of preservation of skeletal remains. The aetiology of the origin of these pathologies could not be determined by the methodology used here, but with the prevailing lower age of pathological subjects, a lack of nutrition with consequent absence of iron and developing anaemia might be the cause. Based on our statistical data, we can observe that the pathologies we studied occur more frequently in children older than newborns and younger infants. This may indicate that these studied pathologies arise only during the lifetime of the individual and do not have a prenatal occurrence.

Long-term follow-up of severe autosomal recessive SP7-related bone disorder.

The SP7 gene encodes a zinc finger transcription factor (Osterix), which is a member of the Sp subfamily of sequence-specific DNA-binding proteins, playing an important role in osteoblast differentiation and maturation. SP7 pathogenic variants have been described in association with different allelic disorders. Monoallelic or biallelic SP7 variants cause Osteogenesis imperfecta type XII (OI12), a very rare condition characterized by recurrent fractures, skeletal deformities, undertubulation of long bones, hearing loss, no dentinogenesis imperfecta, and white sclerae. Monoallelic or biallelic SP7 variants may also cause sclerotic skeletal dysplasias (SSD), partially overlapping with Juvenile Paget's disease and craniodiaphyseal dysplasia, characterized by skull hyperostosis, long bones sclerosis, large ribs and clavicles, and possible recurrent fractures. Here, we report the long-term follow-up of an 85-year-old woman presenting with a complex bone disorder including features of either OI12 (bone fragility with multiple fractures, severe deformities and short stature) or SSD (striking skull hyperostosis with optic atrophy, very large ribs and clavicles and long bones sclerosis). Exome sequencing showed previously undescribed biallelic loss of function variants in the SP7 gene: NM_001173467.2(SP7): c.359_362del, p.(Asp120Valfs*11); NM_001173467.2(SP7): c.1163_1174delinsT, p.(Pro388Leufs*33). RT-qPCR confirmed a severely reduced SP7 transcription compared to controls. Our report provides new insights into the clinical and molecular features and long-term outcome of SP7-related bone disorders (SP7-BD), suggesting a continuum phenotypic spectrum characterized by bone fragility, undertubulation of long bones, scoliosis, and very heterogeneous bone mineral density ranging from osteoporosis to osteosclerosis.

[Domestic software, medical devices and materials in surgery for hyperostotic craniofacial meningiomas]. / Primenenie otechestvennogo programmnogo obespecheniya, meditsinskikh izdelii i materialov v khirurgii giperostoticheskikh kraniofatsial'nykh meningiom. (Klinicheskii sluchai i obzor literatury).

OBJECTIVE: The modern concept of resection of hyperostotic craniofacial meningiomas involves the desire for one-stage surgery with excision of tumor and simultaneous extensive skull defect closure. MATERIAL AND METHODS: The authors present skull defect closure with an individual implant after resection of cranioorbital meningioma in a 61-year-old man. The neoplasm was accompanied by exophthalmos and eyelid edema. The patient underwent simultaneous microsurgical resection and skull reconstruction with an individual implant. At discharge (7 days after surgery), exophthalmos regressed to 3 mm. After 3 months, ophthalmologist revealed complete regression of exophthalmos. RESULTS: Domestic software and 3D printers were used for implant modeling and preparing the necessary physical models and molds. We intraoperatively used domestic polymer and titanium fixation systems for manufacturing and fixation of implant. CONCLUSION: This clinical case confirms that resection of hyperostotic craniofacial meningioma with simultaneous bone defect closure using domestic analogues of software, technical equipment, materials and methods is possible at all stages of this procedure.

Observer agreement on the morphology of porous cranial lesions: Results from a workshop at the 2019 meeting of the Paleopathology Association.

OBJECTIVE: This paper presents the results of a 2019 Paleopathology Association workshop that tested observer agreement on porous cranial lesion morphology and presence using multiple sets of existing guidelines for data collection. MATERIALS: Sixteen conference attendees of varying osteological experience served as observers. Three crania were assigned to each of four published guidelines for identifying and categorizing lesion morphology, for a total of twelve well-preserved human crania from the National Museum of Natural History Biological Anthropology Collections. METHODS: Observers assessed each cranium macroscopically according to its assigned set of guidelines. RESULTS: Observer concordance was higher using scoring guidelines with higher-quality photographs, such as the 2019 guidelines from Rinaldo and colleagues. CONCLUSIONS: Data collection guidelines with high-quality color photos may support greater reliability of researcher-generated data on macroscopic skeletal features. SIGNIFICANCE: The conclusions of any research study are only as reliable as the data on which they are based. This work highlights the need for ongoing practices of quality control in a field in which much data results from individual judgement calls. LIMITATIONS: Observer concordance is not a measure of observer accuracy. Sample size is insufficient to draw broadly generalizable conclusions on the reliability of data collected using the guidelines tested, and conference environments are not a facsimile of research settings. SUGGESTIONS FOR FURTHER RESEARCH: Iterative testing of methodological consistency using larger sample sizes and more non-pathological crania is advised to identify the factors that influence observer discordance and to improve guidelines for qualitative assessments.

Skeletal manifestations of disease experience: Length of illness and porous cranial lesion formation in a contemporary juvenile mortality sample.

OBJECTIVES: Porous lesions of the orbit (cribra orbitalia [CO]) and cranial vault (porotic hyperostosis [PH]) are used as skeletal indicators of childhood stress. Because they are understudied in contemporary populations, their relationship to disease experience is poorly understood. This paper examines the relationship between length of childhood illness and CO/PH formation in a clinically documented sample. "Turning points," which identify the window for lesion formation for CO/PH, are defined, implications for hidden heterogeneity in frailty are considered. METHODS: Data are from 333 (199 males; 134 females) pediatric postmortem computed tomography scans. Individuals died in New Mexico (2011-2019) and are 0.5 to 15.99 years (mean = 7.1). Length of illness was estimated using information from autopsy and field reports. Logistic regression was used to estimate predicted probabilities, odds ratios, and the temporal window for lesion formation. RESULTS: Illness, single bouts, or cumulative episodes lasting over 1 month is associated with higher odds of CO; individuals who were never sick have lower odds of having PH. This relationship was consistent for fatal and incidental illnesses that did not cause death. The developmental window for CO formation appears to close at 8 years. CONCLUSIONS: Those ill for over 1 month are more likely to have CO/PH than those with acute illnesses. Some individuals lived sufficiently long to form CO/PH but died of illness. Others with lesions died of circumstances unrelated to disease. This indicates hidden variation in robusticity even among ill individuals with CO/PH, which is vital in interpreting lesion frequencies in the archeological record.

Synovitis, acne, pustulosis, hyperostosis and osteitis syndrome with mandibular involvement: Would surgical operation help?

BACKGROUND: Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare autoinflammatory disease; its primary manifestation includes osteoarthropathy with skin involvement. Janus kinase (JAK) inhibitors, such as tofacitinib, were used for rheumatoid arthritis; however, due to its downregulation of immune cytokines including interleukin (IL)-6 and IL-8, it might be effective for SAPHO patients. CASE SUMMARY: We report the 1st case of mandibular-related SAPHO syndrome treated with tofacitinib. The patient underwent mandibular resection surgery twice and postoperative pathology showed "osteomyelitis". The patient developed sclerosing osteomyelitis in the left wrist 9 months after surgery and SAPHO syndrome was diagnosed. The patient was administered nonsteroidal anti-inflammatory drugs and corticosteroids therapy without much remission. A 3-month tofacitinib therapy provided remission from both systemic inflammation status and peripheral osteoarticular symptoms and no significant recurrence was observed during follow-up in this case. CONCLUSION: Mandibular involvement in SAPHO syndrome is easily misdiagnosed due to its rarity. Mandibular resection surgery should be applied carefully; after systemic treatment with tofacitinib, the patient had remission. We provide a successful experience for the treatment of mandibular-related SAPHO syndrome.

Coincidence of pachydermoperiostosis and synovitis, acne, pustulosis, hyperostosis, osteitis syndrome, a causal or casual association?

Pachydermoperiostosis (PDP) is a rare disorder characterized by skin thickening, acropachia, and periostosis. Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome is also an orphan disease featured by different dermatological and osteoarthritic manifestations. Herein, we report the first case of an adolescent male diagnosed with both PDP and SAPHO syndrome, presenting with digital clubbing, polyarthralgia, ostealgia, pachydermia and acne on his face, chest and back. Furthermore, we distinguish the characteristics of both diseases and explore the potential pathological mechanism for this coexistence in one patient. Further investigations are needed to establish the detailed pathophysiological association of these 2 diseases.

Pro and contra: is synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) a spondyloarthritis variant?

PURPOSE OF REVIEW: The purpose of this review is to present the up-to-date evidence on the epidemiology, pathogenesis, musculoskeletal manifestations, and imaging of the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and to discuss its relationship with spondyloarthritis (SpA). RECENT FINDINGS: SAPHO is a rare inflammatory disorder of bone, joints, and skin, with a worldwide distribution that predominantly affects the middle-age adults. The hallmark of the syndrome is a constellation of sterile inflammatory osteitis, hyperostosis, and synovitis involving the anterior chest wall, associated with acneiform and neutrophilic dermatoses, such as palmoplantar pustulosis and severe acne. The axial skeleton, sacroiliac, and peripheral joints can be involved in a similar fashion to SpA. The pathogenesis of the syndrome is multifactorial. The diagnosis is mainly based on the clinical and typical radiological features. The treatment approach is based on the off-label use of antibiotics, bisphosphonates, disease-modifying antirheumatic drugs, and anticytokine biologics. SUMMARY: The SAPHO syndrome shares common features with SpA-related diseases, yet also shows some unique pathogenetic and clinical features. The nosology of SAPHO remains a subject of controversy, awaiting further research into the pathogenetic and clinical aspects of this syndrome. A better understanding of these aspects will improve the diagnostics and clinical care of patients with SAPHO.

Synovitis-acne-pustulosis-hyperostosis-osteitis Syndrome with Bilateral Pleural Effusion.

Pleural effusion is a rare manifestation in synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, which is characterized by the presence of osteoarticular lesions and dermatological involvement. We herein report a 71-year-old man with pleural effusion resulting from SAPHO syndrome. He was successfully treated using corticosteroids and has experienced no recurrence for one year. We should consider SAPHO syndrome when encountering cases of anterior chest pain and pleural fluid.

Long-term effect of bilateral anterior elevation of occlusion on the temporomandibular joints.

OBJECTIVE: Incisors tubed prosthesis with bilateral anterior elevation (BAE) relation had been reported to stimulate the proliferative response in the mandibular condylar cartilage of mice, thus the prosthetic occlusion elevation had been proposed to treat cartilage degeneration. Currently, we aimed to detect the long-term effect of BAE on temporomandibular joints (TMJs). MATERIALS AND METHODS: Twelve 6-week-old female mice were assigned to age-matched control and BAE groups (n = 6). Micro-CT images and the macro- and micro-morphology of the mandibular condyles were analyzed at 29 weeks. RESULTS: Compared with the age-matched controls, in BAE group, there were loss of subchondral cortical bone and heavy loss of the subchondral trabecular bone at the superior sites of the TMJ condyles, but hyperostosis at the inferior sites as revealed by micro-CT images and histological slices. In BAE group, cartilage thickness and matrix area were increased with upregulated expression of type II, type X collagen, and Ki67, but the expression of cleaved caspase-3 was downregulated (all, p < 0.05). CONCLUSION: In addition to cartilage thickening, long-term BAE induces loss of the subchondral cortical bone and heavy loss of the underneath subchondral trabecular bone, but hyperostosis further underneath. Using BAE as a treatment remains double-edged.

Estudio anatómico de la hiperostosis porótica en órbitas oculares: cribra orbitalia en la población arqueológica de Tutuquén, región del Maule, Chile / Anatomical study of porotic hyperostosis in the eye orbits: cribra orbitalia in the archaeological population of Tutuquén, Maule region, Chile

RESUMEN: La cribra orbitalia o hiperostosis porótica del techo orbitario es considerada una manifestación ósea microperforativa de condiciones patológicas hematológicas, especialmente la anemia ferropénica. Este hallazgo, se enmarca de manera casi exclusiva a estudios en poblaciones arqueológicas. El propósito de este estudio fue describir la expresión de cribra orbitalia en una población arqueológica de Chile central. Restos óseos de 32 individuos fueron analizados, los cuales fueron obtenidos de la población del Monumento Arqueológico Cementerio Tutuquén, los que están depositados en el Museo Regional de Rancagua. En cada una de la muestras incluidas, se evaluaron períodos de datación, sexo, rango etáreo, presencia v/s ausencia de cribra orbitalia y en los casos en que ésta estuvo presente, se determinó su intensidad mediante visión directa con lente de aumento. Un 59,38 % de los individuos presentó cribra orbitalia. De éstos, 26,32 % fueron de sexo femenino, 31,58 % de sexo masculino y 42,10 % indeterminado. De los individuos del período 10.000 AP, 33,33 % presentó cribra orbitalia; de los individuos del período 7.000 AP un 50 % y de los individuos pertenecientes al período 1.000 AP, un 68,4 %. Al clasificar la severidad de la cribra orbitalia se observó que 31,57 % de los individuos presentaron Cribra orbitalia tipo I; 36,84 % tipo II; 10,52 % tipo III; 10,52 % tipo IV y 10,52 % tipo V. Los datos aportados complementarán el conocimiento morfopatológico de la órbita ocular humana desde el estudio de poblaciones arqueológicas.

SUMMARY: The cribra orbitalia or porotic hyperostosis of the orbital roof is considered a microperforative bone manifestation of hematological pathological conditions, especially iron deficiency anemia. This finding is almost exclusively part of studies in archaeological populations. The purpose of this study was to describe the expression of cribra orbitalia in an archaeological population of central Chile. Bone remains of 32 individuals were analyzed, which were obtained from the population of the Tutuquén Cemetery Archaeological Monument, which are deposited in the Regional Museum of Rancagua. In each of the included samples, dating periods, sex, age range, presence v / s absence of cribra orbitalia were evaluated and in the cases in which it was present, its intensity was determined by direct vision with a magnifying lens. The 59.38 % of the individuals presented cribra orbitalia. Of these, 26.32 % were female, 31.58 % male, and 42.10 % undetermined. Of the individuals in the period 10,000 BP, 33.33 % presented cribra orbitalia; of the individuals of the period 7,000 AP, 50% and of the individuals belonging to the period 1,000 AP, 68.4 %. When classifying the severity of the cribra orbitalia, it was observed that 31.57 % of the individuals had type I; 36.84 % type II; 10.52 % type III; 10.52 % type IV and 10.52 % type V. The data provided will complement the morpho-pathological knowledge of the human eye orbit from the study of archaeological populations.

Identification of Compound Heterozygous Variants in LRP4 Demonstrates That a Pathogenic Variant outside the Third ß-Propeller Domain Can Cause Sclerosteosis.

Sclerosteosis is a high bone mass disorder, caused by pathogenic variants in the genes encoding sclerostin or LRP4. Both proteins form a complex that strongly inhibits canonical WNT signaling activity, a pathway of major importance in bone formation. So far, all reported disease-causing variants are located in the third ß-propeller domain of LRP4, which is essential for the interaction with sclerostin. Here, we report the identification of two compound heterozygous variants, a known p.Arg1170Gln and a novel p.Arg632His variant, in a patient with a sclerosteosis phenotype. Interestingly, the novel variant is located in the first ß-propeller domain, which is known to be indispensable for the interaction with agrin. However, using luciferase reporter assays, we demonstrated that both the p.Arg1170Gln and the p.Arg632His variant in LRP4 reduced the inhibitory capacity of sclerostin on canonical WNT signaling activity. In conclusion, this study is the first to demonstrate that a pathogenic variant in the first ß-propeller domain of LRP4 can contribute to the development of sclerosteosis, which broadens the mutational spectrum of the disorder.

Osteoblastic and hyperostotic craniofacial lesion detected by 99mTc-labeled methylene diphosphonate bone scintigraphy and single-photon emission computed tomography/computed tomography: a pictorial essay.

99mTc-bisphophonates bone scan, planar and single-photon emission computed tomography/computed tomography (SPECT/CT) modalities, is a commonly used technique that provides high sensitivity and specificity for detection of osseous metastases. However, besides bone metastases, SPECT/CT provides an accurate evaluation of the localization of the lesions and supplies anatomic information that can be valuable for diagnosis of nonmalignant bone diseases, occasionally disclosed in the skull. Reporting of craniofacial lesions detected by 99mTc-MDP (99mTc-labeled methylene diphosphonate) bone scintigraphy and SPECT/CT in the literature is limited. The aim of this pictorial review is to present the findings detected by 99mTc-MDP bone scintigraphy and SPECT/CT including cases under two broad categories: osteoblastic and hyperostosis craniofacial lesions.

The Genetic Architecture of High Bone Mass.

The phenotypic trait of high bone mass (HBM) is an excellent example of the nexus between common and rare disease genetics. HBM may arise from carriage of many 'high bone mineral density [BMD]'-associated alleles, and certainly the genetic architecture of individuals with HBM is enriched with high BMD variants identified through genome-wide association studies of BMD. HBM may also arise as a monogenic skeletal disorder, due to abnormalities in bone formation, bone resorption, and/or bone turnover. Individuals with monogenic disorders of HBM usually, though not invariably, have other skeletal abnormalities (such as mandible enlargement) and thus are best regarded as having a skeletal dysplasia rather than just isolated high BMD. A binary etiological division of HBM into polygenic vs. monogenic, however, would be excessively simplistic: the phenotype of individuals carrying rare variants of large effect can still be modified by their common variant polygenic background, and by the environment. HBM disorders-whether predominantly polygenic or monogenic in origin-are not only interesting clinically and genetically: they provide insights into bone processes that can be exploited therapeutically, with benefits both for individuals with these rare bone disorders and importantly for the many people affected by the commonest bone disease worldwide-i.e., osteoporosis. In this review we detail the genetic architecture of HBM; we provide a conceptual framework for considering HBM in the clinical context; and we discuss monogenic and polygenic causes of HBM with particular emphasis on anabolic causes of HBM.

Cribra orbitalia and porotic hyperostosis are associated with respiratory infections in a contemporary mortality sample from New Mexico.

OBJECTIVES: Cribra orbitalia (CO) and porotic hyperostosis (PH) are porous cranial lesions (PCLs) classically associated with iron-deficiency anemia in bioarchaeological contexts. However, recent studies indicate a need to reassess the interpretation of PCLs. This study addresses the potential health correlates of PCLs in a contemporary sample by examining relationships between the known cause of death (COD) and PCL presence/absence. METHODS: This study includes a sample of 461 juvenile individuals (6 months to 15 years of age) who underwent examination at the University of New Mexico's Office of the Medical Investigator between 2011 and 2019. The information available for each individual includes their sex, age at death, and their COD and manner of death. RESULTS: Odds ratio of having CO (OR = 3.92, p < .01) or PH (OR = 2.86, p = .02) lesions are increased in individuals with respiratory infections. Individuals with heart conditions have increased odds of having CO (OR = 3.52, p = .03) lesions, but not PH. CONCLUSION: Individuals with respiratory infection are more likely to have CO and/or PH. CO appears to have a greater range of health correlates than PH does, as indicated by the heart condition results. However, individuals with congenital heart defects are at higher risk for respiratory infections, so bony alterations in cases of heart conditions may be due to respiratory illness. Since respiratory infection remains a leading cause of mortality today, CO and PH in bioarchaeological contexts should be considered as potential indicators of respiratory infections in the past.

Expression Analysis of Susceptibility Genes for Ossification of the Posterior Longitudinal Ligament of the Cervical Spine in Human OPLL-related Tissues and a Spinal Hyperostotic Mouse (ttw/ttw).

STUDY DESIGN: Immunohistochemical and real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. OBJECTIVE: The aim of this study was to analyze the expression of five susceptibility genes (RSPO2, HAO1, CCDC91, RHPH9, and STK38L) for human ossification of the posterior longitudinal ligaments (OPLL) identified in a genome-wide association study. SUMMARY OF BACKGROUND DATA: Detailed expression and functional studies for the five susceptibility genes are needed to aid in clarification of the etiology and pathogenesis of OPLL. METHODS: Immunostaining, cell culture, and real-time RT-PCR were performed on ossified ligament samples collected during anterior cervical decompression for symptomatic OPLL (n = 39 patients) and on control non-OPLL samples (n = 8 patients). Immunohistochemical analysis in spinal hyperostotic mice (ttw/ttw) (n = 25) was also performed. The sample sections were stained for RSPO2, HAO1, CCDC91, RHPH9, STK38L, Runx2, Sox9, and CD90. The mRNA expression levels of the five susceptibility genes were also analyzed in cultured human OPLL and non-OPLL cells subjected to cyclic tensile strain. RESULTS: Immunoreactivity for RSPO2 and Sox9 was evident in proliferating chondrocytes in human OPLL tissues and ttw/ttw mice. Application of cyclic tensile strain to cultured human OPLL cells resulted in increases in mRNA levels for RSPO2, HAO1, and CCDC91. However, individual differences in expression in human OPLL-related samples were seen. HAO1-positive cells were detected only in 3- to 6-week-old ttw/ttw mice that did not simultaneously express RSPO2-positive samples. CONCLUSION: Among the five susceptibility genes, RSPO2, HAO1, and CCDC91 might be contributory factors in progression of OPLL. RSPO2 may be involved in endochondral ossification, especially in mixed or continuous type OPLL, HAO1 may be an initiation factor for OPLL that is rarely seen in mature human OPLL samples, and CCDC91 may be associated with progression of ossification caused by mechanical stress. These findings provide important insights into the pathogenesis and therapeutic targets for OPLL. LEVEL OF EVIDENCE: N/A.

Hyperostosing sphenoid wing meningiomas.

Some sphenoid wing meningiomas are associated with a significant hyperostotic reaction of the adjacent sphenoid ridge that may even exceed the size of the intradural mass. The decision-making process and surgical planning based on neuroanatomic knowledge are the mainstays of management of this group of lesions. Given their natural history and biologic behavior, many hyperostosing meningiomas at this location require long-term management analogous to a chronic disease. This is particularly true when making initial decisions regarding treatment and planning surgical intervention, when it is important to take into consideration the possibility of further future interventions during the patient's life span.

Anatomical similarity between the Sost-knockout mouse and sclerosteosis in humans.

Sclerosteosis, a rare autosomal recessive genetic disorder caused by a mutation of the Sost gene, manifests in the facial skeleton by gigantism, facial distortion, mandibular prognathism, cranial nerve palsy, and, in extreme cases, compression of the medulla oblongata. Mice lacking sclerostin reflect some symptoms of sclerosteosis, but this is the first report of the effect on the facial skeleton. We used geometric morphometrics (GMM) to analyze the deformations of the murine facial skeleton from the wild-type to the Sost gene knockout. Landmark coordinates were obtained by surface reconstructions from micro-computed tomography. Centroid size, principal component scores in shape space and form space, and asymmetry were computed by the standard GMM formulas, and dental and skeletal jaw lengths were examined as ratios. We show here that, compared to wild type controls, mice lacking Sost have larger centroid size (effect size, p-value: 4.59, <.001), higher mean asymmetry (1.14, .065), dental and skeletal mandibular prognathism (1.36, .010 and 5.92, <.001), a smaller foramen magnum (-1.71, .015), and calvaria that are more highly curved (form space p = 4.09, .002; shape space p = 12.82, .002). These features of mice lacking sclerostin largely correspond to the changes of the facial skeleton observed in sclerosteosis. This alignment further supports claims that the Sost gene plays a fundamental role in bony facial development in rodents and humans alike.

Hypertrophic osteopathy in a cat with cardiac interventricular septal defect.

A 3-year-old mixed-breed female cat was diagnosed with a ventricular septal defect of the heart through an echocardiogram. After a 9-month treatment, progressive and diffuse hard thickening of all limbs was observed, which on radiographic examinations, revealed a marked thickening of the long bones. The necropsy findings were limited to the appendicular skeleton and thoracic vertebrae, in addition to a severe cardiac interventricular septal defect and lung edema. The histological evaluation revealed severe replacement of the cortical bone by spongy bone in all bone fragments examined. This is the first report of hypertrophic osteopathy occurring in association with a cardiac malformation in a cat.