Search

Parasinusal osteoma complicated by intracranial and orbit extension, cranial vault hyperostosis, intracranial mucocele, and inflammatory pseudotumor is exceptional. A 68-year-old man presented with a long history of progressive proptosis and recurrent episodes of keratoconjunctivitis in the left eye, with restriction in upward gaze. Contrast-enhanced magnetic resonance imaging revealed a frontal sinus lesion extending to the left anterior fossa and orbit, featuring an intracranial cystic component and heterogeneous contrast enhancement. Head computed tomography confirmed the double calcific-cystic nature of the lesion. A left supraorbital-pterional approach allowed complete resection of mucocele and drilling of intracranial and orbital osteoma, including the intrasinusal component. The frontal sinus was cranialized, and a flap of pericranium, reinforced by Gelfoam sponge, was reflected on the anterior cranial base/orbital roof. The postoperative course was uneventful; magnetic resonance imaging depicted resolution of proptosis. Histological examination favored parasinusal osteoma associated with intracranial mucocele, frontal bone hyperostosis, and inflammatory pseudotumor., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2024 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Marine teleost species of commercial interest are often reported with hyperostosis, an osteological condition that results in bone thickening. Various specimens of Atlantic Spadefish Chaetodipterus faber (n = 86) obtained from artisanal fishermen in Rio de Janeiro, Brazil, were radiographed and assessed to detect the occurrence of hyperostosis across four different size classes. Of the examined individuals, 58.62% displayed signs of hyperostosis, which manifested in eight skeletal regions, notably in the supraoccipital crest, cleithrum and supraneural areas. In the vertebral column, hyperostosis was more frequently observed in haemal spines than in neural spines, predominantly between the sixth and eighth caudal vertebrae. The smallest size class (<200 mm total length) showed a low frequency of hyperostosis at 7.89%. This frequency escalated for larger classes, reaching 94.12% in individuals measuring 200-300 mm in total length and was observed in all individuals exceeding 300 mm. Hyperostosis exhibited an ontogenetic development pattern, where both the occurrence frequencies and the sizes of the affected bones expanded in proportion to the fish size. This is the first description of the hyperostosis pattern of development for the species, an important commercial resource., (© 2023 John Wiley & Sons Ltd.)

Purpose: This study aimed to explore the imaging value of 68 Ga-FAPI-04 PET/CT in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and compare it with that of 99m Tc-MDP bone scan., Methods: Nineteen participants with SAPHO syndrome underwent 68 Ga-FAPI-04 PET/CT and 99m Tc-MDP bone scan. Demographic data and clinical features were recorded, SAPHO imaging features were analyzed, and the osteoarticular lesion detection rate in both methods was calculated., Results: This prospective study recruited 4 men and 15 women aged 52.4 ± 8.6 years. The anterior chest wall was involved in all participants (100%). Palmoplantar pustulosis was the most common (36.8%) skin symptom. 99m Tc-MDP bone scan and 68 Ga-FAPI-04 PET/CT together detected 84 osteoarticular lesions, of which 91.7% (77/84) were detected by the former and 96.4% (81/84) by the latter. Furthermore, 68 Ga-FAPI-04 PET/CT detected 5 cases of knee and hip joint synovitis., Conclusions: 68 Ga-FAPI-04 PET/CT was more sensitive than 99m Tc-MDP bone scan when evaluating osteoarticular lesions in SAPHO syndrome and could also evaluate synovial lesions. 68 Ga-FAPI-04 PET/CT could be a good imaging method for SAPHO syndrome but requires further verification in a more extensive research cohort., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no competing interests. This work was supported by the school-level scientific research project of the Southwest Medical University (grant 2021ZKQN066) and Luzhou Science and Technology Plan Project (2022-JYJ-118)., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Reactive hyperostosis of spheno-orbital meningiomas (SOMs) often occurred in the sphenoid wing, while osteolytic SOMs (O-SOMs) were rarely discussed. This study preliminarily evaluated the clinical characteristics of O-SOMs and analyzed prognostic factors affecting the recurrence of SOMs. We retrospectively analyzed the medical records of consecutive patients who underwent surgery for a SOM between 2015 and 2020. According to the bone changes of sphenoid wing, SOMs were divided into O-SOMs and hyperostosis SOMs (H-SOMs). A total of 31 procedures were performed in 28 patients. All cases were treated by pterional-orbital approach. It was confirmed that 8 cases were O-SOMs and the other 20 cases were H-SOMs. Total tumor resection was performed in 21 cases. There were 19 cases with Ki 67 ≥3%. The patients were followed up for 3 to 87 months. Proptosis improved in all patients. All O-SOMs had no visual deterioration, while 4 H-SOMs cases had visual deterioration. There was no significant difference in clinical outcomes between the two types of SOM. The recurrence of SOM was related to the degree of resection, but not to the type of bone lesions, invasion of cavernous sinus and Ki 67., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Background: Hereditary cranial hyperostosis is a rare disease never described in Italy, so the neurological manifestations in patients and carriers of the disease have been little studied., Methods: We describe the neurological and neuroimaging features of patients and carriers of the gene from a large Italian family with sclerosteosis., Results: In this family, genetic testing detected the homozygous p.Gln24X (c.70C > T) mutation of the SOST gene in the proband and a heterozygous mutation in 9 siblings. In homozygous adults, severe craniofacial hyperostosis was manifested by cranial neuropathy in childhood, chronic headache secondary to intracranial hypertension, and an obstructive sleep apnea syndrome in adults. In one of the adult patients, there was a compressible subcutaneous swelling in the occipital region caused by transosseous intracranial-extracranial occipital venous drainage, a compensation mechanism of obstructed venous drainage secondary to cranial hyperostosis. Mild cranial hyperostosis causing frequent headache and snoring was evident in the nine heterozygous subjects., Conclusions: Multiple cranial neuropathies and headache in children, while severe chronic headache and sleep disturbances in adults, are the neurological manifestations of the first Italian family with osteosclerosis. It is reasonable to extend neurological and neuroimaging evaluation to gene carriers as well., (© 2022. Fondazione Società Italiana di Neurologia.)

Background and Purpose: Diagnosing spontaneous intracranial hypotension and associated CSF leaks can be challenging, and additional supportive imaging findings would be useful to direct further evaluation. This retrospective study evaluated whether there was a difference in the prevalence of calvarial hyperostosis in a cohort of patients with spontaneous intracranial hypotension compared with an age- and sex-matched control population., Materials and Methods: Cross-sectional imaging (CT of the head or brain MR imaging examinations) for 166 patients with spontaneous intracranial hypotension and 321 matched controls was assessed by neuroradiologists blinded to the patient's clinical status. The readers qualitatively evaluated the presence of diffuse or layered calvarial hyperostosis and measured calvarial thickness in the axial and coronal planes., Results: A significant difference in the frequency of layered hyperostosis (31.9%, 53/166 subjects versus 5.0%, 16/321 controls, P  < .001, OR = 11.58) as well as the frequency of overall (layered and diffuse) hyperostosis (38.6%, 64/166 subjects versus 13.2%, 42/321 controls, P  < .001, OR = 4.66) was observed between groups. There was no significant difference in the frequency of diffuse hyperostosis between groups (6.6%, 11/166 subjects versus 8.2%, 26/321 controls, P = .465). A significant difference was also found between groups for calvarial thickness measured in the axial ( P  < .001) and coronal ( P  < .001) planes., Conclusions: Layered calvarial hyperostosis is more prevalent in spontaneous intracranial hypotension compared with the general population and can be used as an additional noninvasive brain imaging marker of spontaneous intracranial hypotension and an underlying spinal CSF leak., (© 2022 by American Journal of Neuroradiology.)

Competing Interests: Declaration of interests This research was made possible by the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, Genentech, the American Association for Dental Research, and the Colgate-Palmolive Company. This research is funded by Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

Purpose: As sphenoid wing meningiomas (SWMs) are associated with varying degrees of bony involvement, we sought to understand potential relationships between genomic subgroup and this feature., Methods: Patients treated at Yale-New Haven Hospital for SWM were reviewed. Genomic subgroup was determined via whole exome sequencing, while the extent of bony involvement was radiographically classified as no bone invasion (Type I), hyperostosis only (Type II), tumor invasion only (Type III), or both hyperostosis and tumor invasion (Type IV). Among additional clinical variables collected, a subset of tumors was identified as spheno-orbital meningiomas (SOMs). Machine-learning approaches were used to predict genomic subgroups based on pre-operative clinical features., Results: Among 64 SWMs, 53% had Type-II, 9% had Type-III, and 14% had Type-IV bone involvement; nine SOMs were identified. Tumors with invasion (i.e., Type III or IV) were more likely to be WHO grade II (p: 0.028). Additionally, tumors with invasion were nearly 30 times more likely to harbor NF2 mutations (OR 27.6; p: 0.004), while hyperostosis only were over 4 times more likely to have a TRAF7 mutation (OR 4.5; p: 0.023). SOMs were a significant predictor of underlying TRAF7 mutation (OR 10.21; p: 0.004)., Conclusions: SWMs with invasion into bone tend to be higher grade and are more likely to be NF2 mutated, while SOMs and those with hyperostosis are associated with TRAF7 variants. Pre-operative prediction of molecular subtypes based on radiographic bony characteristics may have significant biological and clinical implications based on known recurrence patterns associated with genomic drivers and grade., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Diagnosis of spontaneous intracranial hypotension (SIH) may be delayed due to nonspecific symptoms and variable imaging findings. Cases of hyperostosis in children who are overshunted, a process that may be physiologically analogous to adults with SIH, have been reported by others and observed in our practice. The purpose of this retrospective study was to assess the frequency and pattern of calvarial hyperostosis in patients with SIH., Methods: We retrospectively reviewed computed tomography and magnetic resonance imaging examinations from consecutive patients who underwent myelography for the evaluation of SIH to assess for the presence of generalized calvarial thickening or development of a secondary layer of bone. Patients with typical benign hyperostosis frontalis were excluded. Patient demographics and clinical factors were evaluated for association with hyperostosis., Results: Among 285 patients with SIH, 40 (14.0%) demonstrated diffuse calvarial hyperostosis on imaging. Most of these patients (32/40; 80.0%) demonstrated a distinct circumferentially layered appearance to the skull, whereas 8 of 40 (20.0%) had generalized calvarial thickening without layering., Conclusions: Diffuse calvarial hyperostosis, particularly the concentrically layered form that we term "layer cake skull," is a relatively common imaging feature in patients with SIH. In the appropriate clinical context, this finding will allow the possibility of SIH to be raised based on computed tomography imaging, which is otherwise of limited utility in the initial diagnosis of this condition., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (© 2020 Wiley Periodicals LLC.)

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., (© 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.)

Objective: Sphenoid wing meningiomas (SWMs) can be treated with complete surgical resection and the recently introduced endoscopic transorbital approach (ETOA) offers a minimally invasive alternative. In this study, the surgical outcome of ETOA and the extended mini-pterional approach (eMPTA) for SWMs with osseous involvement is compared., Methods: From October 2015 to May 2019, 24 patients underwent surgery for SWMs with osseous involvement. Among them, tumor resection was performed by ETOA for 11 patients (45.8%) and eMPTA for 13 patients (54.2%). The tumor characteristics, surgical outcome and morbidity, and approach-related aesthetic outcome were analyzed and compared retrospectively between ETOA and eMPTA based on SWM classification., Results: The location of SWMs was mostly the middle sphenoid ridge (group III) (45.8%), followed by the greater sphenoid wing (group IV) (29.2%). Simpson resection grades I/II were achieved in 9 of 11 patients (81.8%) with ETOA and 11 of 13 patients (84.6%) with eMPTA. There were no differences in tumor characteristics between the 2 approaches. Surgery time, surgical bleeding, and hospital length of stay were significantly shorter with ETOA. Three patients had transient surgical morbidities such as diplopia (n = 1), ptosis (n = 1), and cerebrospinal fluid leak (n = 1) after ETOA. No differences could be seen in surgical morbidities between ETOA and eMPTA., Conclusions: ETOA can provide direct access to the sphenoid bone and resectability with a more rapid and minimally invasive exposure than does eMPTA. Maximal subtotal resection with extensive sphenoid bone decompression for tumors with cavernous sinus infiltration is the key to a good clinical outcome, regardless of the surgical approach., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Bone infiltration of the tumour is common in meningioma surgery. This may also affect patients without indicative signs of bone infiltration on preoperative imaging. Unrecognized bone invasion may lead to higher recurrence rates. 5-ALA fluorescence-guided resection (5-ALA-fg) could be a promising tool to help recognize possible bone invasion and/or tumour remnants. However, there is still little data about 5-ALA-fg resection in bone and soft tissue infiltrating meningiomas., Methods: We performed a retrospective study of 11 patients who were operated with the aid of 5-ALA due to bone and soft tissue infiltrating meningiomas at the University Hospital of St. Poelten between 2013 and 2019., Results: Strong and homogeneous fluorescence of the meningioma was observed in 9 cases (81.8%) and vague and heterogeneous fluorescence in 2 cases (18.2%). Hyperostosis on computerized tomography was evident in 3 of 6 cases (50%) and bone infiltration was visible in preoperative magnetic resonance imaging in 7 of 11 patients (63.6%). All eleven patients showed positive fluorescence of the bone infiltrating part. In all 7 cases where tissue could be collected, histopathological testing verified tumour infiltration (100%). There was also fluorescence of the periosteum in 3 cases and histopathological testing verified tumour infiltration in 100%., Conclusion: There is growing evidence that 5-ALA-fg resection can help to identify bone infiltration in meningioma surgery. Therefore, it may help to improve extent of resection. However, further studies are necessary to investigate the rate of false-negative fluorescence and its effect on progression free survival. If 5-ALA-fg resection of meningioma is performed, the attending surgeon should also consider investigating the adjacent periosteum under blue light for detection of possible fluorescence.

As the initial part in the development of osteoarthritis (OA), subchondral bone sclerosis has been considered to be initiated by excess mechanical loading and proven to be correlated to other pathological changes. Sclerostin, which is an essential mechanical stress response protein, is encoded by the SOST gene. It is expressed in osteocytes and mature chondrocytes and has been proven to be closely correlated to OA. However, the relationship and mechanism between the SOST gene and the development of OA remain unclear. The aim of the present study was to investigate the role of the SOST gene in OA pathogenesis in the subchondral bone. A knee anterior cruciate ligament transection (ACLT) mouse osteoarthritis (OA) model on SOST-knockout (SOST KO) and wild-type (WT) mice was established. The pathogenic and phenotypic changes in the subchondral bone were investigated by histology, micro-CT, immunohistochemistry, TRAP staining, Masson staining, and Toluidine blue staining. It was found that sclerostin expression decreased in both the calcified cartilage and mineralized subchondral structures during the development of OA. Joint instability induced a severe cartilage degradation phenotype, with higher OARSI scores in SOST KO mice, when compared to WT mice. SOST KO mice with OA exhibited a higher BMD and BV/TV ratio, as well as a higher rate of bone remodeling and TRAP-positive cell number, when compared to the WT counterparts, but the difference was not significant between the sham-operation groups. It was concluded that loss of sclerostin aggravates knee OA in mice by promoting subchondral bone sclerosis and increasing catabolic activity of cartilage., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Jingyu Li et al.)

Objective: Meningioma-related skull magnetic resonance imaging findings other than hyperostosis are not widely recognized. We evaluated the novel findings of the skull adjacent to meningiomas., Methods: Records from patients with meningiomas located adjacent to the skull on magnetic resonance imaging (n = 32) were included. Three skull findings (intramedullary prominent vessel, intramedullary enhancement, intramedullary T2-hyperintensity) and the widely known hyperostosis were retrospectively visually assessed. The frequency of these 3 findings and the relevance to each other, and their relationships with hyperostosis, size, length adjacent to the skull, and relative signal intensity of the meningioma were examined., Results: The incidence of the three findings was 46.88%, 53.13%, and 62.5%, respectively, and that of hyperostosis was 46.88%. Each association involving the findings was strong, and they were significantly related to the size and length., Conclusions: Intramedullary prominent vessel, intramedullary enhancement, and intramedullary T2-hyperintensity may be novel characteristic skull findings associated with meningioma.

Background: An increased occurrence of cortical hypertrophy (CH) was observed 1-2 years after implanting short curved Fitmore hip stems. There are no published data about either the clinical relevance or the progression of CH over the long term., Methods: Ninety-six primary total hip arthroplasties were performed between 2008 and 2010 using the Fitmore hip stem. Clinical and radiological parameters were recorded preoperatively and at 1, 2, 3, and 5 year follow-up., Results: CH appeared mainly on antero-posterior radiographs in Gruen Zones 2, 3, 5, and 6. After 1 year, the diameter was 10 ± 2 mm and remained constant thereafter. The CH rate after 1 year was 69% and after 5 years 71%. Subsidence after 1 year was 1.6 ± 1.55 mm and 1.93 ± 1.72 mm after 5 years. Cortical thinning was 46% after 1 year and 56% after 5 years, mainly in Gruen Zones 7 and 8. In the first year radiolucencies were found in 51% in all Gruen Zones, and in 20% after 5 years. Patient, implant, and surgical factors did not correlate with radiological outcomes except that larger stems had more CH. After 5 years, the Harris Hip Score had improved from 59 to 94 and the Oxford Hip Score from 22 to 41. Radiographic parameters, notably CH, were not associated with clinical outcomes except that cortical thinning correlated with lower outcome scores., Conclusions: CH correlated neither with clinical outcome nor with patient, surgical or implant factors, except for a positive correlation with stem size. The Fitmore hip stems settled within the first year to a stable fixation and then remained almost unchanged. However, cortical thinning is common in Gruen Zone 7 and 8 meaning that there is stress-shielding.

Background: Hydrocephalus is an international disease process that is commonly treated surgically with a ventriculoperitoneal shunt. This device may be prone to malfunction, most commonly from obstruction, disconnection, or infection., Case Description: A 35-year-old female with hydrocephalus and a ventriculoperitoneal shunt presented with altered mental status and imaging concerning for a shunt malfunction. Intraoperatively, she was found to have bone growing over and compressing the proximal occluder of the shunt valve, causing a mechanical obstruction. Removal of the bone allowed for egress of cerebrospinal fluid and return of proper shunt function. The patient did well postoperatively., Conclusion: Hydrocephalus, ventriculoperitoneal shunts, and shunt revisions represent a significant health burden and cost. Here we present an unusual cause of a shunt malfunction caused by bony overgrowth., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Sclerosteosis (SOST) refers to two extremely rare yet similar skeletal dysplasias featuring a diffusely radiodense skeleton together with congenital syndactyly. SOST1 is transmitted as an autosomal recessive (AR) trait and to date caused by ten homozygous loss-of-function mutations within the gene SOST that encodes the inhibitor of Wnt-mediated bone formation, sclerostin. SOST2 is transmitted as an autosomal dominant (AD) or AR trait and to date caused by one heterozygous or two homozygous loss-of-function mutation(s), respectively, within the gene LRP4 that encodes the sclerostin interaction protein, low-density lipoprotein receptor-related protein 4 (LRP4). Herein, we investigated two teenagers and one middle-aged man with SOST in three families living in the state of Tamil Nadu in southern India. Next generation sequencing of their genomic DNA using our high bone density gene panel revealed SOST1 in the teenagers caused by a unique homozygous nonsense SOST mutation (c.129C > G, p.Tyr43X) and SOST2 in the man caused by homozygosity for one of the two known homozygous missense LRP4 mutations (c.3508C > T, p.Arg1170Trp). He becomes the fourth individual and the first non-European recognized with SOST2. His clinical course was milder than the life-threatening SOST1 demonstrated by the teenagers who suffered blindness, deafness, and raised intracranial pressure, yet his congenital syndactyly was more striking by featuring bony fusion of digits. All three patients were from consanguineous families and heterozygosity for the SOST mutation was documented in the mothers of both teenagers. Thus, on the endogamous genetic background of Indian Tamils, SOST1 from sclerostin deficiency compared to SOST2 from LRP4 deactivation is a more severe and life-threatening disorder featuring complications due to osteosclerosis of especially the skull. In contrast, the syndactyly of SOST2 is particularly striking by involving bony fusion of some digits. Both the SOST and LRP4 mutations in this ethnic population likely reflect genetic founders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Several hypotheses have been proposed regarding the mechanisms underlying meningioma-related hyperostosis. In this study, we investigated the role of osteoprotegerin (OPG), insulin-like growth factor 1 (IGF-1), endothelin 1 (ET-1), and bone morphogenetic protein (BMP) 2 and 4., Methods: A total of 149 patients (39 males and 110 females; mean age, 62 years) who underwent surgery were included. Depending on the relationship with the bone, meningiomas were classified as hyperostotic, osteolytic, infiltrative, or unrelated. Expression of OPG, and IGF-1, ET-1, BMP-2, and BMP-4 was evaluated by tissue microarray analysis of surgical samples., Results: Our series comprised 132 cases of grade I, 14 cases of grade II, and 3 cases of grade III meningiomas, according to the World Health Organization classification. Based on preoperative computed tomography scan, the cases were classified as follows: hyperostotic, n = 11; osteolytic, n = 11; infiltrative, n = 15; unrelated to the bone, n = 108. Four cases were excluded from the statistical analysis. Using receiver operating characteristic curve analysis, we identified a 2% cutoff for the mean value of IGF-1 that discriminated between osteolytic and osteoblastic lesions; cases with a mean IGF-1 expression of <2% were classified as osteolytic (P = 0.0046), whereas those with a mean OPG expression of <10% were classified as osteolytic (P = 0.048). No other significant relationships were found., Conclusions: Expression of OPG and expression of IGF-1 were found to be associated with the development of hyperostosis. Preliminary findings suggest that hyperostosis can be caused by an overexpression of osteogenic molecules that influence osteoblast/osteoclast activity. Based on our results, further studies on hyperostotic bony tissue in meningiomas are needed to better understand how meningiomas influence bone overproduction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The WNT pathway has become an attractive target for skeletal therapies. High-bone-mass phenotypes in patients with loss-of-function mutations in the LRP5/6 inhibitor Sost (sclerosteosis), or in its downstream enhancer region (van Buchem disease), highlight the utility of targeting Sost/sclerostin to improve bone properties. Sclerostin-neutralizing antibody is highly osteoanabolic in animal models and in human clinical trials, but antibody-based inhibition of another potent LRP5/6 antagonist, Dkk1, is largely inefficacious for building bone in the unperturbed adult skeleton. Here, we show that conditional deletion of Dkk1 from bone also has negligible effects on bone mass. Dkk1 inhibition increases Sost expression, suggesting a potential compensatory mechanism that might explain why Dkk1 suppression lacks anabolic action. To test this concept, we deleted Sost from osteocytes in, or administered sclerostin neutralizing antibody to, mice with a Dkk1-deficient skeleton. A robust anabolic response to Dkk1 deletion was manifest only when Sost/sclerostin was impaired. Whole-body DXA scans, μCT measurements of the femur and spine, histomorphometric measures of femoral bone formation rates, and biomechanical properties of whole bones confirmed the anabolic potential of Dkk1 inhibition in the absence of sclerostin. Further, combined administration of sclerostin and Dkk1 antibody in WT mice produced a synergistic effect on bone gain that greatly exceeded individual or additive effects of the therapies, confirming the therapeutic potential of inhibiting multiple WNT antagonists for skeletal health. In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue.

A 77-year-old woman with Parkinson's disease presented with left chest pain. Physical examination revealed tenderness at her second left sternocostal joint. There was no skin rash. Chest CT revealed hyperostosis of the sternocostal joint, and cervical MRI showed vertebral osteosclerosis and osteolysis. 99mTc-MDP bone scintigraphy showed an increased activity in the sternocostal joint and vertebral column. The patient was diagnosed with SAHPO syndrome according to the diagnostic criteria. Her chest pain was relieved after oral administration of nonsteroidal anti-inflammatory drugs. Although pain is a common non-motor symptom of Parkinson's disease, chest pain is relatively rare, according to a previous reports. When patients with Parkinson's disease complain of chest pain, physicians should make an appropriate differential diagnosis after excluding emergent cardiovascular disease. To the best of our knowledge, this is the first report of Parkinson's disease associated with SAPHO syndrome. The relationship between the two diseases is unclear. However, peripheral inflammation is known to exacerbate ongoing neuronal damage in neurodegenerative diseases, such as Parkinson's disease. Therefore, systemic inflammation of SAPHO syndrome may affect the disease course of Parkinson's disease.

Objectives: Porotic hyperostosis (PH), characterized by porotic lesions on the cranial vault, and cribra orbitalia (CO), a localized appearance of porotic lesions on the roof of the orbits, are relatively common osteological conditions. Their etiology has been the focus of several studies, and an association with anemia has long been suggested. Anemia often causes bone marrow hypertrophy or hyperplasia, leading to the expansion in trabecular or cranial diploic bone as a result of increased hematopoiesis. Hypertrophy and/or hyperplasia is often coupled with a disruption of the remodeling process of outer cortical bone, cranially and/or postcranially, leading to the externally visible porotic lesions reported in osteological remains. In this article, we investigate whether individuals with CO have increased thickness of the diploë, the common morphological direct effect of increased hematopoiesis, and thus test the relationship between the two conditions, as well as explore the type of anemia that underlie it., Methods: An analysis of medical CT scans of a worldwide sample of 98 complete, young to middle-aged adult dry skulls from the Duckworth Collection was conducted on male and female cribrotic individuals (n = 23) and noncribrotic individuals (n = 75), all of whom lacked any evidence of porotic lesions on the vault. Measurements of total and partial cranial thickness were obtained by virtual landmark placement, using the Amira 5.4 software; all analyses were conducted in IBM SPSS 21., Results: Cribriotic individuals have significantly thinner diploic bone and thicker outer and inner tables than noncribriotic individuals, contrary to the expected diploic expansion that would result from anemic conditions associated to bone marrow hypertrophy or hyperplasia. Additionally, individuals without CO and those with the condition have distinctive cranial thickness at particular locations across the skull and the severity to which CO is expressed also differentiates between those with mild and those with a moderate to severe form of the condition., Conclusions: Our results suggest a complex pattern of causality in relation to the pathologies that may lead to the formation of porotic lesions on the vault and the roof of the orbits. A form of anemia may be behind the osteological changes observed in PH and CO, but it is unlikely to be the same type of anemic condition that underlies both types of osteological lesions. We suggest that CO may be associated to anemias that lead to diploic bone hypocellularity and hypoplasia, such as those caused by anemia of chronic disease and, to a lesser extent, of renal failure, aplastic anemia, protein deficiency, and anemia of endocrine disorders, and not those that lead to bone marrow hypercellularity and hyperplasia and potential PH. This leads us to the conclusion that the terms PH and CO should be used to reflect different underlying conditions., (© 2017 Wiley Periodicals, Inc.)

Objective and Importance: Camurati-Engelmann disease (CED) is a rare, autosomal-dominant genetic disorder resulting in hyperostosis of the long bones and skull. Patients often develop cranial nerve dysfunction and increased intracranial pressure secondary to stenosis of nerve foramina and hyperostosis. Surgical decompression may provide symptomatic relief in select patients; however, a small number of reports document the recurrence of symptoms due to bony regrowth. We present a patient who had been treated previously with bilateral frontal and parietal craniotomy who experienced recurrence of symptoms due to reossification of her cranial bones. This report underscores the progressive nature of CED and its influence on surgical management. Furthermore, we propose a novel surgical approach with multiple craniectomies and titanium mesh cranioplasties that could potentially offer long-term symptomatic relief., Clinical Presentation: A 46-year-old female patient with CED who was treated with ventriculoperitoneal shunting, posterior fossa decompression, and multiple craniotomies 2 decades prior presented with signs and symptoms of increased intracranial pressure. Studies of the skull at presentation demonstrated rethickening of cranial bones that resulted in severely decreased intracranial volume., Intervention: A radical craniectomy, requiring 4 separate bone flaps made up of bilateral frontal and parietal bones, was performed. The remaining coronal and sagittal bony struts were drilled to approximately 1 cm thick. Cranioplasties with 4 separate titanium meshes were performed to preserve the natural contour of the patient's skull., Conclusions: Although surgical decompression could provide some patients with CED symptomatic relief, clinicians should consider managing CED as a chronic condition. To the authors' knowledge, this is one of few case reports documenting the recurrence of symptoms in a patient with CED treated by surgical intervention. Furthermore, we propose that multiple craniectomies with titanium mesh cranioplasties confer more permanent symptomatic control, and, more importantly, lower the risk of recurrence secondary to cranial hyperostosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Temporomandibular joint (TMJ) ankylosis is a situation in which the mandibular condyle is fused to the glenoid fossa by bone or fibrous tissue. The management of TMJ ankylosis has a complicated chore, and it is challenging for the maxillofacial surgeon because of technical hitches and high rate of reankylosis. Costochondral graft (CCG) is a common treatment modality for TMJ ankylosis. One of disadvantages of CCG is unpredictability of growth pattern and risk of overgrowth. This report illustrates the fate of CCG used in the TMJ reconstruction and also the management of patients with CCG overgrowth., Materials and Methods: A retrospective evaluation of 14 patients presented with unilateral TMJ ankylosis reconstructed using CCG treated in our hospital from 2000 to 2013 was done. Only patients with unilateral ankylosis treated by CCG with at least 2-year follow-up and complete case records with clinical and radiographic details were included in the study. Patients with bilateral ankylosis, reankylosis, missing details, and the patients with <2-year follow-up were excluded from the study. The patients were selected based on the specified inclusion/exclusion criteria. All the patients were analyzed clinically and radiographically. Facial appearance, jaw motion, occlusion, contour, and linear growth changes were documented preoperatively, immediately postoperatively, and long term (>2 years)., Results: Totally 14 unilateral temporomandibular ankylosis cases were reconstructed using CCG from the period of 2000-2013. The mean age of the patients is 5.2 years with the standard deviation of 1.48 ranging from 3 to 9 years. Follow-up of the patients ranges from 2 to 6 years with mean follow-up of 3 years. Out of 14 patients, 2 patients had normal growth of CCG after the mean follow-up of 3 years, whereas 5 patients presented with moderate growth, 4 patients with CCG overgrowth, and 3 patients presented with no growth of CCG following surgery. Overgrown CCG was treated with condylar shaving, and orthodontic elastic was maintained to stabilize the occlusion. Moderately grown and nongrowing CCG was treated by internal distractor for the management of facial symmetry. Facial asymmetry and malocclusion were successfully corrected in all patients with altered growth pattern., Conclusion: The growth pattern of the CCG is extremely unpredictable, which can be in the form of no growth at all or excessive growth, and mandibular overgrowth on the grafted site can actually be more troublesome than the lack of growth. Care should also be taken to ensure proper postoperative functional therapy and to examine the role of cartilage thickness on future growth in young patients.

Sclerosteosis and van Buchem disease are two rare bone sclerosing dysplasias caused by genetic defects in the synthesis of sclerostin. In this article we review the demographic, clinical, biochemical, radiological, and histological characteristics of patients with sclerosteosis and van Buchem disease that led to a better understanding of the role of sclerostin in bone metabolism in humans and we discuss the relevance of these findings for the development of new therapeutics for the treatment of patients with osteoporosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Sclerosteosis, characterized by the hyperostosis of cranial and tubular bones, is a rare autosomal recessive hereditary disorder caused by mutation of SOST gene. Four nonsense mutations of SOST have been identified worldwide. Here, we report two affected siblings who carried a novel nonsense mutation of SOST in a consanguineous family from China. The proband manifested typical symptoms of sclerosteosis, whereas the symptoms were absent in another affected sibling. Two nucleotide substitutions in exon 2 of SOST were identified, c.444&#95;445TC>AA, resulting in a premature stop codon, p.Cys148→Stop. This truncated mutation loses 66 amino acid residues which contain 3 cysteine residues of the cysteine-knot motif, leading to loss of function of SOST. The symptoms of sclerosteosis may be clinically heterogeneous in some patients, even with the same mutation. Our results support the notion that founder effects from the ancestors contribute to the disease onset., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report a case of severe anterior cervical hyperostosis presenting with dysphagia.

We report a 4-year-old boy with sclerosteosis associated with severe digital dysostosis. The initial medical consultation was prompted by bilateral, asymmetrical syndactyly of the index and middle fingers. The left index finger had complicated phalangeal anomalies: hyperphalangy (supernumerary phalanx distal to the middle phalanx) and hypoplasia with bracket epiphyses of the proximal and middle phalanges. Development of facial nerve palsy, hearing impairment and generalized osteosclerosis had occurred between 3 years and 4 years of age, with the subsequent identification of a homozygous SOST mutation. Bilateral second and third fingers syndactyly associated with abnormal patterning of the same fingers should be considered prodromal signs of sclerosteosis.

Rounded, sessile, hyperattenuating structures detected in computed tomography (CT) studies of canine tympanic bullae have been termed "otoliths." These have been proposed to represent dystrophic mineralizations or heterotopic bone formations in the middle ear that are potentially related to chronic otitis media. Aims of the current study were to describe the prevalence, macroscopic, and histological features of structures consistent with "otoliths" in the canine tympanic cavity. Tympanic bullae from 50 routinely necropsied dogs and 139 retrospectively retrieved CT scans of canine clinical cases were examined. Small tympanic bone spicules with pointed or clubbed tips essentially arising from the free margin of the septum bullae were bilaterally present in the tympanic cavities of all 50 of the necropsied dogs. In 48% of the dogs, "otolith"-like CT-detectable bone spicules carrying drumstick-like hyperostoses that were 1-6 mm in diameter were also present. In the retrospective survey of bulla CT scans of 139 cases, the prevalence of hyperostotic tympanic bone spicules (HTBS) was 20%. Findings from the current study indicated that the presence of small tympanic bone spicules in adult dogs is most likely due to physiological bone growth in the septum bullae and that HTBS represent osseous proliferations of small tympanic bone spicules. However, the factors inducing formation of hyperostotic spicules from small tympanic bone spicules remain unknown. The high prevalence of HTBS displaying a similar appearance in bulla CT scans in dogs suggests that these spicules should be included in a differential diagnosis list for "otoliths.", (© 2014 American College of Veterinary Radiology.)

Sclerosteosis is a rare autosomal recessive condition characterized by increased bone density. Mutations in SOST gene coding for sclerostin are linked to sclerosteosis. Two Egyptian brothers with sclerosteosis and their apparently normal consanguineous parents were included in this study. Clinical evaluation and genomic sequencing of the SOST gene were performed followed by in silico analysis of the resulting variation. A novel homozygous frameshift mutation in the SOST gene, characterized as one nucleotide cytosine insertion that led to premature stop codon and loss of functional sclerostin, was identified in the two affected brothers. Their parents were heterozygous for the same mutation. To our knowledge this is the first Egyptian study of sclerosteosis and SOST gene causing mutation.

We report a case of hyperplastic callus mimicking osteosarcoma in the fibula of a patient with osteogenesis imperfecta type V. Among the various imaging modalities, computed tomography was the most useful in distinguishing this rare process from a malignant entity. In addition, simple radiographs demonstrated the presence of characteristic "zebra lines", a manifestation of cyclic bisphosphonate therapy during childhood.

Little is known about wombat diseases in general, and about their congenital diseases in particular. In the current study, the skeleton of a common wombat (Vombatus ursinus) that exhibited generalized hyperostosis is analyzed, and possible diagnoses are reviewed. Macromorphological analyses revealed that the diaphyses of the long bones manifested an increased diameter with extensive diaphyseal new-bone formation (periosteal and endosteal). Cross-sections of the diaphyses showed that the cortical-medullary demarcation was indistinct. The calvarial bones were thickened. Radiographs showed uniform sclerosis of the long bones with loss of trabecular pattern. Microradiography showed extensive bone remodeling, a hyper-vascularized lamellated layer of bone and numerous linear formation defects. Possible causes for the lesions, including sclerosing bone dysplasia disorders, acquired syndromes causing hyperostosis, and metabolic diseases typical of animals in captivity, are discussed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: This study aims to describe the computed tomography (CT) and magnetic resonance (MR) imaging appearance of maxillofacial lesions in renal osteodystrophy., Patients and Methods: We retrospectively reviewed the CT and MR imaging of maxillofacial region in 9 patients (6 females and 3 males with mean age of 31 yr) with renal osteodystrophy. They presented with facial swelling (n = 6), facial disfigurement (n = 2), and oral cavity mass (n = 1). They underwent CT and MR imaging of the maxillofacial region., Results: Brown tumors (n = 6) were seen in the mandible (n = 4) and maxilla (n = 2). They appeared as mixed lytic and sclerotic (n = 4) and sclerotic (n = 2) lesions at CT. The lesions appeared as hypointense at T1-weighted images and of mixed signal intensity at T2-weighted images with intense contrast enhancement (n = 6). Uremic leontiasis ossea (n = 2) appeared at CT as diffuse hyperostosis with protruded maxilla and obliterated sinus. At MR imaging, there was expansion of the maxilla with obliteration of the maxillary sinuses and protrusion of the mandible. The lesion exhibited low signal intensity at T1-weighed images. At T2-weighted images, the lesion showed low signal intensity with small hyperintense lesions. Dystrophic calcification (n = 2) was seen in the parotid and the check., Conclusion: We concluded that CT and MR imaging are helpful for diagnosis and treatment planning of maxillofacial lesions of patients with renal osteodystrophy.

Although spine injuries are not always detectable on postmortem computed tomography (PMCT), spinal hyperostosis, an important risk factor for spine injury, is relatively easily detectable on PMCT. We therefore examined the utility of the detection of spinal hyperostosis on PMCT as an indicator of spine injury. Full-body PMCT images of 88 autopsy cases with a bruise on the face or forehead but no identifiable skull fracture were reviewed prior to autopsy for the identification and classification of spinal hyperostosis. Spine injuries were observed in 56.0% of cases with spinal hyperostosis and 1.6% of cases without spinal hyperostosis. Among the cases with spinal hyperostosis, spine injuries were observed in 66.7% of cases at stage 2 or 3 and in 88.9% of cases at stage 3. Spine injuries were diagnosed on PMCT in 33.3% of cases prior to autopsy. A significant association was found between spinal hyperostosis and presence of spine injury that cannot be detected on PMCT, indicating that the identification of spinal hyperostosis on PMCT may assist in detecting spine injuries. This finding suggests that investigation of the presence of spine injury based on the identification of spinal hyperostosis on PMCT may assist in determining the correct cause of death by autopsy., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)