Nonbacterial Osteomyelitis Research Articles

Treatment Response and Longterm Outcomes in Children with Chronic Nonbacterial Osteomyelitis.

The autoinflammatory bone disorder chronic nonbacterial osteomyelitis (CNO) covers a wide clinical spectrum, ranging from mild self-limited presentations to chronically active or recurrent courses, which are then referred to as chronic recurrent multifocal osteomyelitis (CRMO). Little is known about treatment options and longterm outcomes. We investigated treatment responses and outcomes in children with CNO. A retrospective chart review was conducted in a tertiary referral center, covering 2004-2015. Disease activity was measured at 0, 3, 6, 12, and 24 months after treatment initiation, and at the last recorded visit. Fifty-six patients with CNO were identified; 44 had multifocal CNO. Fifty percent of patients relapsed after a median of 2.4 years, and as few as 40% remained relapse-free after 5 years. Nonsteroidal antiinflammatory drugs were used as first-line treatment in 55 patients, inducing remission after 3 months in all individuals with relapse rates of 50% after 2 years. Further treatment included corticosteroids (n = 23), tumor necrosis factor-α (TNF-α) inhibitors (n = 7), and bisphosphonates (n = 8). While 47% of patients with CNO relapsed within 1 year after corticosteroid therapy, favorable outcomes were achieved with TNF-α inhibitors or bisphosphonates (pamidronate). CNO is a chronic disease with favorable outcomes within the first year, but high relapse rates in longterm followup. Particularly, patients with CRMO with long-lasting, uncontrolled inflammation were at risk for the development of arthritis. Our findings underscore the importance of a timely diagnosis and treatment initiation. Prospective studies are warranted to establish evidence-based diagnostic and therapeutic approaches to CNO.

An Update on the Pathogenesis and Treatment of Chronic Recurrent Multifocal Osteomyelitis in Children.

Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic non-bacterial osteomyelitis (CNO), is a rare inflammatory disorder that primarily affects children. It is characterized by pain, local bone expansion, and radiological findings suggestive of osteomyelitis, usually at multiple sites. CRMO predominantly affects the metaphyses of long bones, but involvement of the clavicle or mandible are suggestive of the diagnosis. CRMO is a diagnosis of exclusion, and its pathogenesis remains unknown. Differential diagnosis includes infection, malignancies, benign bone tumors, metabolic disorders, and other autoinflammatory disorders. Biopsy of the bone lesion is not often required but could be necessary in unclear cases, especially for differentiation from bone neoplasia. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment. Alternative therapies have been used, including corticosteroids, methotrexate, bisphosphonates, and tumor necrosis factor (TNF)-α inhibitors. No guidelines have been established regarding diagnosis and treatment options. This manuscript gives an overview of the most recent findings on the pathogenesis of CRMO and clinical approaches for patients with the condition.

Treatment Advances in Chronic Non-Bacterial Osteomyelitis and Other Autoinflammatory Bone Conditions

Chronic non-bacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is an autoinflammatory bone disorder that primarily affects children. CNO mainly affects long bones in the lower extremities, vertebral bodies, clavicle, mandible, and pelvic bones. No laboratory biomarker has been shown reliable for clinical monitoring yet. Imaging especially whole-body MRI with STIR images has become the gold standard of monitoring disease because of its sensitivity to detect active lesions. In children with suspected CNO, regional MRI at minimum is recommended to determine the presence of bone edema and adjacent soft tissue inflammation and/or periosteal reaction. Basic laboratory workups are usually performed by referring physicians to screen for malignancy and infectious osteomyelitis. When a child has CNO-associated conditions such as psoriasis, inflammatory bowel disease, or multiple CNO lesions in characteristic sites, a bone biopsy may be postponed. However, in children with a unifocal lesion other than clavicle or ill appearance, an MRI-guided bone biopsy with bacterial, fungal, and mycobacterial cultures as well as pathology review is strongly recommended to exclude alternative diagnoses. Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the first-line treatment. However, non-responders and children with frequent relapses require other treatments such as short-term glucocorticoids, disease-modifying anti-rheumatic drugs (DMARDs), TNF-α inhibiters, and/or bisphosphonates. In children with associated arthritis without sacroiliitis, DMARDs may be considered for both conditions. In children with sacroiliitis and CNO, TNF-α inhibiters are preferred. When active spinal lesions are present, bisphosphonate may be chosen as first-line treatment or used in combination with other agents. Repeated MRI is recommended to determine the response to treatment because pain relief can occur despite persistent bone inflammation. Long-term follow-up is recommended as some patients continue to have ongoing disease activity into adulthood.

Physicians' Perspectives on the Diagnosis and Treatment of Chronic Nonbacterial Osteomyelitis.

Background/Purpose. Understanding the practices of pediatric rheumatologists in diagnosing and treating chronic nonbacterial osteomyelitis (CNO) can provide important information to guide the development of consensus treatment plans. The objectives of this study were to determine physicians' approaches to (1) diagnosing and monitoring CNO, (2) ordering a bone biopsy, and (3) making treatment decisions. Methods. A survey was distributed among members of the Childhood Arthritis and Rheumatology Research Alliance using a web-based questionnaire. Results. 121 of 277 (41%) attending physician members completed the survey. Plain radiographs (89%) were most commonly used followed by regional MRI (78%), bone scintigraphy (43%), and whole-body MRI (36%). The top three reasons for performing a biopsy were constitutional findings (66%), unifocal bone lesions (64%), and nocturnal bone pain (45%). Nearly all responders (95%) prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) as initial therapy. For patients who failed NSAID treatment, methotrexate (67%), tumor necrosis factor inhibitors (65%), and bisphosphonates (46%) were the next most commonly used treatments. The presence of a spinal lesion increased the use of bisphosphonate treatment. Conclusion. The diagnostic approach and disease activity monitoring for CNO varied among surveyed physicians. Our survey findings provided important background for the development of consensus treatment plans for CNO.

Clinical and genetic association, radiological findings and response to biological therapy in seven children from Qatar with non-bacterial osteomyelitis.

We aim to report the clinical manifestations, genetic testing results, magnetic resonance imaging (MRI) findings and biologics used in the management of non-bacterial osteomyelitis in our center. We conducted a retrospective review of medical records. A previously proposed classification was implemented as follows: chronic recurrent multifocal osteomyelitis (CRMO), chronic non-bacterial osteomyelitis (CNBO) and acute non-bacterial osteomyelitis. Four females and three males with a median age at presentation of 6 years (6 months-14 years) presented with arthralgia (7/7), back pain (4/7), arthritis (4/7) and bone pain (2/7). Six patients had CRMO and one patient had CNBO. Genetic testing revealed an apparent homozygote p.S734L LPIN2 mutation in two siblings, a heterozygote p.M694V MEFV mutation in one patient with familial Mediterranean fever and heterozygote p.Q219H PSTPIPI variant of unknown significance in one patient. The most common lesions on MRI involved the tibia (6/7), talar bones (5/7), fibula (4/7) and sacroiliac joints (4/7). Three patients received infliximab. Two are in remission after 2 and 5 years, and the third was advanced after 5 years to canakinumab. Two other patients received canakinumab first. One patient with Majeed syndrome and dyserythropoietic anemia exhibited evidence of improvement, and one had partial improvement and was then treated with infliximab. Non-bacterial osteomyelitis may coexist with other autoinflammatory diseases. MRI remains a favorable diagnostic tool and genetic testing may have a limited role in selected cases. Infliximab and canakinumab are associated with variable outcomes, and 6-week or less dosing intervals for both medications may be more effective.

Unexpectedly high incidences of chronic non-bacterial as compared to bacterial osteomyelitis in children.

Historically, osteomyelitis was considered an infectious disorder. More recently, inflammatory mechanisms were recognized causing a significant proportion of pediatric osteomyelitis. This study was to compare characteristics of children with chronic non-bacterial (CNO) and bacterial osteomyelitis (BOM). A chart review of osteomyelitis patients from the departments of pediatrics, pediatric surgery, orthopedic surgery, and oral and maxillofacial surgery was conducted in a tertiary referral center, covering the years 2004-2014. Institutional incidences of CNO (n=49) and BOM (n=56) were comparable. Differentiation between CNO and BOM based on clinical or laboratory findings was mostly impossible. However, children with BOM more frequently presented with local inflammatory signs (47 vs. 68%, p=0.040), fever (12 vs. 38%, p=0.003), and abscesses (0 vs. 39%, p<0.001). Peripheral arthritis (14 vs. 0%, p<0.001), inflammatory bowel disease (10 vs. 2%, p=ns), and hyperostosis (29 vs. 4%, p=0.001) were more common in CNO. Whole-body MRI was performed in 76% of CNO patients, unveiling multifocal lesions in 80% (CRMO). Though considered a rare disorder, institutional incidences of CNO were comparable to BOM, and the discrimination between CNO and BOM solely based on clinical aspects was mostly impossible. This is of special interest, since a correct and timely diagnosis is of utmost importance for long-term outcomes in both disorders. Whole-body MRIs should be considered in chronic osteomyelitis to (1) detect clinically inapparent lesions in CNO and (2) indirectly exclude (usually unifocal) chronic bacterial infections. Prospective studies are warranted to establish evidence-based diagnostic and therapeutic approaches to CNO.

Vertebral form of non-bacterial osteomyelitis: clinical and laboratory features and treatment characteristics

To analyze the efficacy of different treatment regimens. Material and Methods . Retrospective two-center cohort of 54 children with NBO, including 18 patients with vertebral lesions was studied. The level of evidence is 3. Results . Vertebral form of the non-bacterial osteomyelitis is characterized by high frequency of multifocal bone lesions. The features of clinical and X-ray manifestations of the vertebral form of NBO, its diagnosis and medical treatment are presented. First of all NBO should be differentiated from infectious (tuberculosis) and neoplastic lesions of the skeleton. Non-steroid anti-inflammatory drugs are not effective for the relief of pain in the NBO vertebral form, preference should be given to bisphosphonates and TNF-a inhibitors. Indications and volume of surgical techniques for diagnosis and treatment of this pathology are specified. Conclusion . Management of patients with the vertebral form of NBO should be interdisciplinary and carried out with the assistance of doctors of various specialties - pediatricians, rheumatologists, orthopedists, surgeons, phthisiatrician, etc.

Chronic Nonbacterial Osteomyelitis: Pathophysiological Concepts and Current Treatment Strategies.

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder, covering a clinical spectrum with asymptomatic inflammation of single bones at the one end, and chronic recurrent multifocal osteomyelitis (CRMO) at the other end. The exact molecular pathophysiology of CNO remains largely unknown. Provided familial clusters and the association with inflammatory disorders of the skin and intestine suggest a genetic predisposition. Recently, profound dysregulation of cytokine responses was demonstrated in CRMO. Failure to produce antiinflammatory cytokines interleukin (IL)-10 and IL-19 contributes to activation of inflammasomes and subsequent IL-1β release. In IL-10-deficient and in CNO-prone chronic multifocal osteomyelitis mice, IL-1β was linked to bone inflammation. Further, alterations to the gut microbiome were suggested in contributing to IL-1β release from innate immune cells in mice, offering an interesting target in the search for molecular mechanisms in CNO. Here, we summarize clinical presentation and treatment options in CNO/CRMO, current pathophysiological concepts, available mouse models, and promising future scientific directions.

Non-bacterial chronic osteomyelitis: experience in a tertiary hospital

Abstract Introduction Non-bacterial chronic osteomyelitis (NBCO) is an autoinflammatory disease that presents with recurrent bouts of bone inflammation in the absence of microbiological isolation. It is a diagnosis of exclusion. Its treatment was classically based on the use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, although nowadays bisphosphonates or anti-tumour necrosis factor-α (anti-TNF) drugs are frequently used with good results. The objective of the study is to describe our experience in the diagnosis and treatment of patients with NBCO. Patients and methods Retrospective chart review of patients with NBCO followed up in a tertiary centre between 2008 and 2015. Results A total of 7 patients with NBCO were recorded. Four were female and the median age was 10 years (IQR 2). The most common complaint was pain that interfered with sleep in 5 of the patients. Six patients had multifocal lesions at diagnosis. Bone biopsy demonstrated neutrophilic or lymphocytic infiltration and sclerosis in 6 patients. Four patients received antibiotics and NSAIDs without clinical response. Five received a short course of prednisone with an adequate control of symptoms, but only one of them maintained remission after corticosteroid suspension. Five patients received bisphosphonates with disease remission in 3 of them. The other 2 showed an inadequate response to pamidronate and were started on anti-TNF therapy (etanercept, infliximab or adalimumab), remaining asymptomatic at present. Conclusions Our series, although limited, confirms the effectiveness and safety of bisphosphonate and anti-TNF therapy for children with NBCO.

Pediatric Chronic Nonbacterial Osteomyelitis of the Jaw: Clinical, Radiographic, and Histopathologic Features

Chronic nonbacterial osteomyelitis (CNO) is a focal sterile inflammatory osteitis in children that most commonly develops in the long bones, but can occur in any bone. The disease course is variable, ranging from acute and self-resolving isolated lesions to chronic recurrent multifocal osteomyelitis (CRMO), which is frequently associated with extraosseous inflammatory disease. The purpose of this study was to present our clinical experience with CNO of the mandible in children. The specific aims were to 1) document the clinical characteristics, radiographic findings, and histologic features of CNO and 2) determine the percentage of our sample with multifocal disease (CRMO). This is a retrospective case series of patients with mandibular CNO. To be included, patients had to have a mandibular lesion radiographically consistent with osteomyelitis without infection, onset before aged 18years, and complete records. Medical records were reviewed for history, clinical features, imaging, and pathology. Descriptive data were summarized. The sample included 22 patients (13 female and 9 male patients) with disease onset at a mean age of 9.05 ± 2.4years. On presentation, all patients reported mandibular pain and swelling, and 45% had trismus. All had clinical and/or radiographic findings of multifocal intraosseous disease and/or extraosseous inflammatory lesions. Of the patients, 12 (54%) had a documented family history of autoimmune or autoinflammatory disease and 15 (68%) had elevated erythrocyte sedimentation rates during a flare. Computed tomography scans typically showed expansion of the affected mandible with sclerosis of the medullary space, small foci of poorly defined lytic destruction with a lamellated periosteal reaction, and swollen muscles of mastication. Four distinct histologic features were noted including parallel and interconnected osteoid seams, atypical osteoid, areas of woven bone and hypocellular fibroblastic stroma resembling fibrous dysplasia, and patchy nodular fibrosis. Pediatric CNO of the mandible has characteristic radiographic and pathologic features and is usually found as one of multiple disease foci in CRMO rather than as an isolated lesion.

Chronic nonbacterial osteomyelitis may be associated with renal disease and bisphosphonates are a good option for the majority of patients.

The aim of this Italian study was to describe the clinical features, treatment options and outcomes of a cohort of patients with chronic nonbacterial osteomyelitis (CNO). This was a retrospective cohort study. Laboratory data, diagnostic imaging, histological features and clinical course are reported. We enrolled 47 patients diagnosed with CNO. Bone pain was the leading symptom, and multifocal disease was present in 87% of the patients. The majority of the bone lesions were located in the appendicular skeleton (58%). Extraosseous manifestations were present in 34% of the patients, and renal involvement was detected in four patients. Inflammatory indices were increased in 80%, and bone x-rays were negative in 15% of the patients. Nonsteroidal anti-inflammatory drugs (NSAIDs) were the first therapy for all patients, achieving clinical remission in 27%. A good response to NSAIDs was significantly associated with a better prognosis. Bisphosphonates were used in 26 patients, with remission in 73%. Only six patients (13%), all with spine involvement, developed sequelae. We found a possible association between CNO and renal disease. Bisphosphonates were more likely to lead to clinical remission when NSAIDs and corticosteroids had failed. Vertebral localisation was the only risk factor for potential sequelae.

Serum biomarkers for the diagnosis and monitoring of chronic recurrent multifocal osteomyelitis (CRMO).

Chronic recurrent multifocal osteomyelitis (CRMO), the most severe form of chronic nonbacterial osteomyelitis, is an autoinflammatory bone disorder. A timely diagnosis and treatment initiation is complicated by the absence of widely accepted diagnostic criteria and an incomplete pathophysiological understanding. The aim of this study was to determine biomarkers for the diagnosis and follow-up of CRMO. Serum of 56 CRMO patients was collected at the time of diagnosis. As controls, sera from treatment-naïve age-matched patients with Crohn's disease (N=62) or JIA (N=28) as well as healthy individuals (N=62) were collected. Multiplex analysis of 25 inflammation markers was performed. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U tests, canonical discriminant analysis, and mixed model variance analysis. Mostly monocyte-derived serum proteins were detectable and differed significantly between groups: IL-1RA, IL-2R, IL-6, IL-12, eotaxin, MCP-1, MIP-1b, RANTES. Multicomponent discriminant analysis allowed for the definition of algorithms differentiating between CRMO, Crohn's disease, and healthy controls. Persistently high levels of MCP-1, IL-12, sIL-2R correlated with incomplete remission in follow-up samples from CRMO patients. Discrimination algorithms allow differentiation between patients with CRMO or Crohn's disease, and healthy individuals. IL-12, MCP-1, and sIL-2R can act as markers for treatment response. Though confirmation of our findings in larger multiethnical cohorts is warranted, they may prove valuable to differentiate between otherwise healthy individuals or Crohn's disease patients with "bone pain" and CRMO patients. The elevation of mainly monocyte-derived pro-inflammatory serum proteins supports the hypothesis of pro-inflammatory monocyte/macrophages driving inflammation in CRMO.

Chronic Non-Bacterial («Sterile») Osteomyelitis in the Practice of Pediatric Rheumatologist, the Contemporary Diagnostic and Treatment Approaches: Literature Review and Own Data Analysis

The article presents the current data on the pathogenesis, features of clinical manifestations, and diagnostics of different variants of chronic non-bacterial («sterile») osteomyelitis (CNO). The inherited forms of the disease, such as syndromes of deficiency of the interleukin-1 receptor antagonist (DIRA), sterile pyarthrosis with pyoderma gangrenosum and acne (PAPA-syndrome), dyserythropoietic anemia with chronic non-bacterial osteomyelitis (Majeed-syndrome) are described. The pathogenesis of CNO and related diseases is based on hyperproduction of proinflammatory cytokines, particularly of interleukin-1 β and tumor necrosis factor- α . Based on the literature data and our own observations, the recommendations for diagnostics and treatment of CNO are presented.

Syndromes with chronic non-bacterial osteomyelitis in the spine.

Chronic non-bacterial osteomyelitis (CNO) has been known for over of 40 years. It is an underrecognized entity due to the low number of described cases and poor propagation awareness of the problem. Chronic non-bacterial osteomyelitis is usually confused with infectious spondylodiscitis or malignant lesions, both primary and metastatic. Failing to consider CNO as one of possible lesions of the spine among an array of differential diagnoses may lead to a prolonged ineffective treatment increasing treatment-related morbidity. In this paper the authors describe these two syndromes, with a possible autoimmune background – chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO syndrome – that include CNO being among the manifestations. The authors present the spinal symptomatology of CNO for both syndromes published so far to help spine clinicians organize the information for better usage in everyday clinical practice.

Whole-Body Diffusion-Weighted Imaging in Chronic Recurrent Multifocal Osteomyelitis in Children.

ObjectiveChronic recurrent multifocal osteomyelitis/ chronic non-bacterial osteomyelitis (CRMO/ CNO) is a rare auto-inflammatory disease and typically manifests in terms of musculoskeletal pain. Because of a high frequency of musculoskeletal disorders in children/ adolescents, it can be quite challenging to distinguish CRMO/ CNO from nonspecific musculosketetal pain or from malignancies. The purpose of this study was to evaluate the visibility of CRMO lesions in a whole-body diffusion-weighted imaging (WB-DWI) technique and its potential clinical value to better characterize MR-visible lesions.Material and MethodsWhole-body imaging at 3T was performed in 16 patients (average: 13 years) with confirmed CRMO. The protocol included 2D Short Tau Inversion Recovery (STIR) imaging in coronal and axial orientation as well as diffusion-weighted imaging in axial orientation. Visibility of lesions in DWI and STIR was evaluated by two readers in consensus. The apparent diffusion coefficient (ADC) was measured for every lesion and corresponding reference locations.ResultsA total of 33 lesions (on average 2 per patient) visible in STIR and DWI images (b = 800 s/mm2 and ADC maps) were included, predominantly located in the long bones. With a mean value of 1283 mm2/s in lesions, the ADC was significantly higher than in corresponding reference regions (782 mm2/s). By calculating the ratio (lesion to reference), 82% of all lesions showed a relative signal increase of 10% or higher and 76% (25 lesions) showed a signal increase of more than 15%. The median relative signal increase was 69%.ConclusionThis study shows that WB-DWI can be reliably performed in children at 3T and predominantly, the ADC values were substantially elevated in CRMO lesions. WB-DWI in conjunction with clinical data is seen as a promising technique to distinguish benign inflammatory processes (in terms of increased ADC values) from particular malignancies.

DIFFERENTIATED APPROACH TO NON-BACTERIAL OSTEOMYELITIS TREATMENT IN CHILDREN: THE RETROSPECTIVE STUDY RESULTS

Differentiated Approach to Non-Bacterial Osteomyelitis Treatment in Children: the Retrospective Study Results Background. Low efficacy of the therapy of children with non-bacterial osteomyelitis remains a topical problem of modern pediatrics and rheumatology. Objective: Our aim was to assess the efficacy and safety of non-bacterial osteomyelitis treatment in children. Methods. A retrospective study of the case records of children with non-bacterial osteomyelitis has been carried out. The therapy efficacy (remission) was assessed by the following criteria: absence of fever, pain, clinically active lesions, laboratory disease activity. Laboratory and radiological methods were carried out during diagnosis of the pathological process, and subsequently every 3–6–12 months to assess disease activity depending on the initial injury extent of the skeleton. Clinical activity assessment was carried out by means of a visual analogue scale. Results. We analyzed treatment results of 52 children (68 therapy courses) with non-bacterial osteomyelitis. Nonsteroidal anti-inflammatory drugs were administered to 19 patients, sulfasalazine — to 7, methotrexate — to 9, pamidronic acid — to 18, inhibitors of tumour necrosis factor (TNF) α — to 15. Remission was achieved in 10 (53%) 4 (57%) 4 (44%), 16 (89%), and 11 (73%) patients (p = 0.001), respectively. Adverse events during treatment occurred in 21 (40%) children. No serious adverse events were reported. Conclusion. The efficacy of different regimens has been shown. It was found that pamidronic acid drug and TNF inhibitors were the most effective in treating children with non-bacterial osteomyelitis.

Cronic non-bacterial osteomyelitis (CNO) in a cohort of pediatric patients: clinical, biological and radiological response to treatment with Anakinra

Chronic nonbacterial osteomyelitis (CNO) is the most common autoinflammatory bone disorder in childhood (1). Diagnostic information is provided by TC-99 bone scintigraphy (BS) and/or whole body MRI. Non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, bisphosphonates and tumour necrosis factor inhibitors have been used until now with variable response (2).

Serum biomarkers for the diagnosis of chronic recurrent multifocal osteomyelitis (CRMO)

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder mostly affecting children and adolescents. Chronic recurrent multifocal osteomyelitis (CRMO) is the most severe form of CNO. It is characterized by recurring episodes of bone inflammation that can last for years and may cause chronic pain, pathological fractures, and disability. Despite recent advances in targeting disease mechanisms, the exact pathophysiology of CNO/CRMO remains unknown. Diagnosis of CNO can be challenging, because symptoms tend to be mild and highly variable, and is further complicated by the absence of widely accepted diagnostic criteria and disease biomarkers.

Comparison of different treatment approaches in chronic non-bacterial osteomyelitis.

Chronic non-bacterial osteomyelitis (CNO) is a heterogenous group of immune-mediated inflammatory bone diseases, which often co-exist with other rheumatic diseases. There are no approved treatments for CNO, except non-steroid anti-inflammatory drugs (NSAID). The efficacy of methotrexate (MTX), sulfasalazine, pamidronate (PAM), anti-IL1 and TNFα-inhibitors was shown in different reports, but there are some concerns about safety of pamidronate due to long-term accumulation and persistation in bone. The aim of our study was to compare the efficacy of non-randomized different treatment approaches in pediatric patient cohort with CNO.

Pediatric chronic non-bacterial osteomyelitis in Goteborg, Sweden

Chronic non-bacterial osteomyelitis (CNO) is today included among the autoinflammatory bone diseases. An alternative term in the literature is chronic recurrent multifocal osteomyelitis (CRMO). The etiology of the autoinflammatory bone diseases is unknown except for a few extremely rare monogenic diseases.