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.

Clinical Characteristics and Prognostic Analysis of Osteolytic and Hyperostosis Sphenoid Orbital Meningiomas: A Single-Center Experience.

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.

A biological approach to adult sex differences in skeletal indicators of childhood stress.

OBJECTIVES: In previous work examining the etiology of cribra orbitalia (CO) and porotic hyperostosis (PH) in a contemporary juvenile mortality sample, we noted that males had higher odds of having CO lesions than females. Here, we examine potential reasons for this pattern in greater detail. Four non-mutually exclusive mechanisms could explain the observed sex differences: (1) sex-biased mortality; (2) sexual dimorphism in immune responses; (3) sexual dimorphism in bone turnover; or (4) sexual dimorphism in marrow conversion. SUBJECTS AND METHODS: The sample consists of postmortem computed tomography scans and autopsy reports, field reports, and limited medical records of 488 individuals from New Mexico (203 females; 285 males) aged between 0.5 and 15 years. We used Kaplan-Meier survival analysis, predicted probabilities, and odds ratios to test each mechanism. RESULTS: Males do not have lower survival probabilities than females, and we find no indications of sex differences in immune response. Overall, males have a higher probability of having CO or PH lesions than females. CONCLUSIONS: All results indicate that lesion formation in juveniles is influenced by some combination of sex differences in the pace of red-yellow conversion of the bone marrow and bone turnover. The preponderance of males with CO and PH likely speaks to the potential for heightened osteoblastic activity in males. We find no support for the hypotheses that sex biases in mortality or immune responses impacted lesion frequency in this sample. Sex differences in biological processes experienced by children may affect lesion formation and lesion expression in later life.

Pharmacological Management of Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis Syndrome Syndrome: A Proposal of a Treatment Algorithm.

ABSTRACT: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic disease with marked clinical and radiological heterogeneity. It is characterized by a combination of dermatological and osteoarticular manifestations. The treatment of SAPHO syndrome is not yet codified. It includes several therapeutic options such as anti-inflammatory drugs, bisphosphonates, antibiotics, conventional disease-modifying antirheumatic drugs, and biological treatment.This article aims to provide an updated review of the different pharmacological options for SAPHO syndrome. We also propose a therapeutic algorithm for the management of this disease.

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.

Looking for new anabolic treatment from rare diseases of bone formation.

Bone remodelling is a complex mechanism regulated by osteoclasts and osteoblasts and perturbation of this process leads to the onset of diseases, which may be characterised by altered bone erosion or formation. In this review, we will describe some bone formation-related disorders as sclerosteosis, van Buchem disease, hypophosphatasia and Camurati-Engelmann disease. In the past decades, the research focused on these rare disorders offered the opportunity to understand important pathways regulating bone formation. Thus, the identification of the molecular defects behind the etiopathology of these diseases will open the way for new therapeutic approaches applicable also to the management of more common bone diseases including osteoporosis.

Protruding Meningioma of the Forehead With Extensive Hyperostosis Mimicking Skull Osteoma.

Meningioma is the most common intracranial benign tumor in adults. Hyperostosis accompanies about 4.5% of meningiomas. The authors report a rare case of hyperostotic meningioma that may have been misdiagnosed as giant osteoma.A 42-year male visited our clinic due to an egg-sized, hard mass on his left forehead. The mass suspected to be giant osteoma was about 4.2 × 4.0 cm sized, hard, non-movable, and non-tender. But based on radiologic findings, the mass was diagnosed as meningioma with extensive hyperostosis.Without neurologic symptoms, the diagnosis of meningioma associated with hyperostosis can be challenging and be misdiagnosed as fibrous dysplasia and osteoma by simple examination without enhanced CT and MRI.Therefore, although osseous lesions are strongly suspected to be osteomas, surgeons should consider other diagnoses, and if necessary, use contrast enhanced CT or MRI to differentiate these bony lesions.

Fluorescence-guided resection in bone and soft tissue infiltrating meningiomas.

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.

Large dural-based mass with bony hyperostosis in a 16-year-old male: IgG4-related disease mimicking lymphoplasmacyte-rich meningioma.

BACKGROUND: IgG4-related disease is an autoimmune process that presents with tumefactive lesions characterized by storiform fibrosis, a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells, obliterative phlebitis, and often elevated serum IgG4 levels. Central nervous system IgG4-related disease is very rare and usually occurs in the form of hypertrophic pachymeningitis or hypophysitis. Presentation as a large solitary meningioma-like mass with overlying hyperostosis in a young adult has not been reported before. CASE SUMMARY: A 16-year-old male presented with focal seizures for 5 months. Imaging showed a large, extra-axial, and contrast-enhancing mass lesion in the left frontoparietal region with focal calvarial thickening. Histopathology revealed a fibrosclerotic lesion involving dura with a polymorphic infiltrate of plasma cells, mature lymphocytes, histiocytes, and occasional eosinophils. Immunohistochemical workup excluded the possibilities of meningioma, lymphoproliferative neoplasms, and histiocytic lesions. Majority of plasma cells were IgG4+ rendering a diagnosis of IgG4-related disease. Further serological and imaging workup did not reveal any evidence of systemic involvement. His serum IgG4 levels were normal. Considering a gross total resection of the lesion, no further treatment was given and the patient has been asymptomatic since. CONCLUSION: IgG4-related lesions of the CNS are under-recognized and accurate diagnosis, especially in those with isolated CNS disease and normal serum IgG4 levels, necessitates robust histopathological and laboratory workup to exclude mimics. They may occur as large dural masses with hyperostosis and differentiation from lymphoplasmacyte-rich meningiomas, in particular, can be challenging. While steroids are the mainstay of treatment in IgG4-related disease, surgical resection may be curative in solitary lesions presenting with compressive symptoms.

Prospective 5-year study with 96 short curved Fitmore™ hip stems shows a high incidence of cortical hypertrophy with no clinical relevance.

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.

Rapid degradation of progressive ankylosis protein (ANKH) in craniometaphyseal dysplasia.

Mutations in the progressive ankylosis protein (NP_473368, human ANKH) cause craniometaphyseal dysplasia (CMD), characterized by progressive thickening of craniofacial bones and widened metaphyses in long bones. The pathogenesis of CMD remains largely unknown, and treatment for CMD is limited to surgical intervention. We have reported that knock-in mice (AnkKI/KI) carrying a F377del mutation in ANK (NM_020332, mouse ANK) replicate many features of CMD. Interestingly, ablation of the Ank gene in AnkKO/KO mice also leads to several CMD-like phenotypes. Mutations causing CMD led to decreased steady-state levels of ANK/ANKH protein due to rapid degradation. While wild type (wt) ANK was mostly associated with plasma membranes, endoplasmic reticulum (ER), Golgi apparatus and lysosomes, CMD-linked mutant ANK was aberrantly localized in cytoplasm. Inhibitors of proteasomal degradation significantly restored levels of overexpressed mutant ANK, whereas endogenous CMD-mutant ANK/ANKH levels were more strongly increased by inhibitors of lysosomal degradation. However, these inhibitors do not correct the mislocalization of mutant ANK. Co-expressing wt and CMD-mutant ANK in cells showed that CMD-mutant ANK does not negatively affect wt ANK expression and localization, and vice versa. In conclusion, our finding that CMD mutant ANK/ANKH protein is short-lived and mislocalized in cells may be part of the CMD pathogenesis.

[Parkinson's disease associated with SAPHO syndrome: a case report].

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.

Transorbital endoscopic eyelid approach for resection of sphenoorbital meningiomas with predominant hyperostosis: report of 2 cases.

Sphenoorbital meningiomas (SOMs) are slow-growing tumors that originate from the sphenoidal wing and are associated with visual deterioration, extrinsic ocular movement disorders, and proptosis caused by hyperostosis of the lateral wall of the orbit. In some cases, the intracranial component is quite small or "en plaque," and the majority of the symptoms arise from adjacent hyperostosis. Craniotomy has traditionally been the standard of care, but new minimally invasive multiportal endoscopic approaches offer an alternative. In the current study, the authors to present their experience with the transorbital endoscopic eyelid approach for the treatment of 2 patients with SOMs and sphenoid wing hyperostosis. Clinical and radiological data for patients with SOMs who underwent a transorbital endoscopic eyelid approach were retrospectively reviewed. Surgical technique and clinical and radiographic outcomes were analyzed. The authors report the cases of 2 patients with SOMs and proptosis due to sphenoid wing hyperostosis. One patient underwent prior craniotomy to debulk the intracranial portion of the tumor, and the other had a minimal intracranial component. Both patients were discharged 2 days after surgery. MR images and CT scans demonstrated a large debulking of the hyperostotic bone. Postoperative measurement of the proptosis with the aid of an exophthalmometer demonstrated significant reduction of the proptosis in one of the cases. Persistence of intraconal tumor in the orbital apex limited the efficacy of the procedure in the other case. A review of the literature revealed 1 publication with 3 reports of the transorbital eyelid approach for SOMs. No measure of relief of proptosis after this surgery had been previously reported. The transorbital endoscopic approach, combined with endonasal decompression of the medial orbit, may be a useful minimally invasive alternative to craniotomy in a subset of SOMs with a predominantly hyperostotic orbital wall and minimal intracranial bulky or merely en plaque disease. In these cases, relief of proptosis and optic nerve compression are the primary goals of surgery, rather than gross-total resection, which may have high morbidity or be unachievable. In cases with significant residual intraconal tumor, orbital bone removal alone may not be sufficient to reduce proptosis.

Prevalence of cribra orbitalia in Pacopampa during the formative period in Peru.

Cribra orbitalia is characterized by an aggregation of small apertures in the orbital roof in response to marrow hypertrophy. This pathological change is indicative of biological stress during youth. We examined the prevalence of this lesion in Pacopampa, a ceremonial center of the formative period, located in the northern highlands of Peru. Using this evaluation of cribra orbitalia, we reconstructed aspects of the population's health and nutritional status during the formation of Andean civilization. We examined 41 orbits of 27 adult individuals (13 males, 14 females) and recorded the macroscopic presence or absence of cribra orbitalia. The presence or absence of cribra orbitalia was the same bilaterally for all 14 individuals having both orbits preserved. The pathology was present in two of the 13 males (15.4%), one of the 14 (7.1%) females, and three of 27 individuals (11.1%) for both sexes combined. There was no difference in the frequency between sexes. The prevalence of cribra orbitalia was found to be lower in Pacopampa than in the comparative data of coastal populations. It is reasonable to assume that the increase in social complexity in Pacopampa was probably unrelated to the decline in overall health of the people.

The effects of knee immobilization on marrow adipocyte hyperplasia and hypertrophy at the proximal rat tibia epiphysis.

Marrow adipose deposition is observed during aging and in association with extended periods of immobility. The objective of this study was to determine the contribution of adipocyte hypertrophy and hyperplasia to bone marrow fat deposition induced by immobilization of the rat knee joint for 2, 4, 16 or 32 weeks. Histomorphometric analyses compared immobilized to sham-operated proximal tibia from age and gender matched rats to assess the contribution of aging and duration of immobilization on the number and size of marrow adipocytes. Results indicated that marrow adipose tissue increased with the duration of immobilization and was significant larger at 16 weeks compared to the sham-operated group (0.09956±0.13276mm2 vs 0.01990±0.01100mm2, p=0.047). The marrow adipose tissue was characterized by hyperplasia of adipocytes with a smaller average size after 2 and 4 weeks of immobilization (at 2 weeks hyperplasia: 68.86±33.62 vs 43.57±24.47 adipocytes/mm2, p=0.048; at 4 weeks hypotrophy: 0.00036±0.00019 vs 0.00046±0.00023mm2, p=0.027), and by adipocyte hypertrophy after 16 weeks of immobilization (0.00083±0.00049 vs 0.00046±0.00028mm2, p=0.027) compared to sham-operated. Both immobilized and sham-operated groups showed marrow adipose conversion with age; immobilized (p=0.008; sham: p=0.003). Overall, fat deposition in the bone marrow of the proximal rat tibia epiphysis and induced by knee joint immobilization was characterized by hyperplasia of small adipocytes in the early phase and by adipocyte hypertrophy in the later phase. Mediators of marrow fat deposition after immobilization and preventive countermeasures need to be investigated.

Frontal Hyperostosis in the Patients of Craniosynostosis After Cranial Distraction Osteogenesis.

BACKGROUND: Conventional fronto-orbital advancement and distraction osteogenesis (DOG) have been used to treat craniosynostosis, both of which are considered effective. During the authors' practice, a phenomenon of frontal hyperostosis has been observed in the patients of craniosynostosis after DOG, which has yet to be reported in the literature. The purpose of this study is trying to identify the factors related to the phenomenon. MATERIALS AND METHODS: From 1997 to 2010, all patients of craniosynostosis undergoing DOG were reviewed. The patient's age at operation, consolidation period, numbers of distractor, distance of distraction, and duration from removal of the distractors to identification of the phenomenon on computed tomography were recorded. The phenomenon was considered positive when the hyperostosis appeared on the frontal bone, where it was neither the osteotomy site nor the previous position of distractor. RESULTS: A total of 61 patients were included in this study, including 26 syndromic and 35 nonsyndromic patients. Two syndromic and 6 nonsyndromic patients had the phenomenon. There was no statistical difference between the patients with and without the phenomenon in comparison with the age, number of the distractor, consolidation period, and the distance of distraction. CONCLUSION: Frontal hyperostosis happened in some patients of craniosynostosis after DOG. Although no significant difference was demonstrated, the incidence of hyperostosis was higher in nonsyndromic patients and the patients of hyperostosis had shorter distance of distraction in both syndromic and nonsyndromic groups. Although the definite cause was unknown, we should pay attention to the phenomenon after distraction.

Overgrowth of costochondral graft in temporomandibular joint ankylosis reconstruction: A retrospective study.

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.

Bacterial Osteomyelitis or Nonbacterial Osteitis in Children: A Study Involving the German Surveillance Unit for Rare Diseases in Childhood.

BACKGROUND: Although bacterial osteomyelitis (BO) is a commonly recognized diagnosis in pediatrics, it is often difficult to distinguish from nonbacterial osteitis (NBO). The goal of our study was to distinguish between the 2 disease entities and better define NBO. METHODS: Using the German Surveillance Unit for Rare Diseases in Childhood (Erhebungseinheit für Seltene Paediatrische Erkrankungen in Deutschland), this prospective study during a 5-year period captured 657 patients at first diagnosis of either BO (n = 378) or NBO (n = 279) while analyzing epidemiologic, clinical and radiologic data. RESULTS: BO was reported in 1.2 per 100,000 children with a higher prevalence in younger male patients (58%), and NBO was reported in 0.45 per 100,000 children. BO patients tended to present with fevers (68%), elevated inflammation markers (82%) and local swelling (62%) but a shorter course of symptoms than NBO patients. NBO patients presented in good general health (86%) and were more likely to have multifocal lesions (66%). Staphylococcus aureus was the most prominent pathogen (83%), with only one methicillin-resistant S. aureus reported. Complications ranged from arthritis adjacent to the lesion to hyperostosis and vertebral fractures. CONCLUSIONS: BO and NBO can be distinguished based on symptoms, associated diseases and inflammation markers. NBO should always be considered in pediatric patients presenting with bone lesions and pain, especially in young female patients presenting with good general health, minimal inflammation markers and multifocal lesions in the vertebrae, clavicle and sternum.