The molecular pathophysiology of chronic non-bacterial osteomyelitis (CNO)-a systematic review.
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SUBMITTER: Hofmann SR
PROVIDER: S-EPMC5500598 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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The molecular pathophysiology of chronic non-bacterial osteomyelitis (CNO)-a systematic review.
Hofmann Sigrun Ruth SR Kapplusch Franz F Mäbert Katrin K Hedrich Christian Michael CM
Molecular and cellular pediatrics 20170706 1
Chronic non-bacterial osteomyelitis (CNO) belongs to the growing spectrum of autoinflammatory diseases and primarily affects the skeletal system. Peak onset ranges between 7 and 12 years of age. The clinical spectrum of CNO covers sometimes asymptomatic inflammation of single bones at the one end and chronically active or recurrent multifocal osteitis at the other.Despite the intense scientific efforts, the exact molecular mechanisms of CNO remain unknown. Recent data suggest CNO as a geneticall ...[more]
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Project description:(1) Background: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease of finally unknown etiology, which can occur alone or related with syndromes (chronic recurrent multifocal osteomyelitis-CRMO; synovitis, acne, pustulosis, hyperostosis and osteitis syndrome-SAPHO). The involvement of the mandible is rather rare. (2) Methods: We carried out a systematic literature search on CNO with mandibular involvement, according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines, considering the different synonyms for CNO, with a special focus on therapy. (3) Results: Finally, only four studies could be included. A total of 36 patients were treated in these studies-therefore, at most, only tendencies could be identified. The therapy in the included works was inconsistent. Various therapies could alleviate the symptoms of the disease. A complete remission could only rarely be observed and is also to be viewed against the background of the fluctuating character of the disease. The success of one-off interventions is unlikely overall, and the need for long-term therapies seems to be indicated. Non-steroidal anti-inflammatory drugs (NSAIDs) were not part of any effective therapy. Surgical therapy should not be the first choice. (4) Conclusions: In summary, no evidence-based therapy recommendation can be given today. For the future, systematic clinical trials on therapy for CNO are desirable.
| S-EPMC7084792 | biostudies-literature
Project description:Chronic nonbacterial osteomyelitis (CNO) is an inflammatory bone disorder that most frequently affects children and adolescents. Chronic recurrent multifocal osteomyelitis (CRMO) is a severe form of CNO, usually characterized by symmetrical inflammatory bone lesions and its waxing and waning character. Sometimes severe and chronic pain can significantly affect the quality of life and psychosocial development of individuals affected. In the absence of prospectively tested and widely accepted diagnostic criteria or disease biomarkers, CNO remains a diagnosis of exclusion, and infections, malignancy and other differentials require consideration (1). The pathophysiology of CNO is not fully understood, but imbalanced cytokine expression and increased inflammasome activation in monocytes from CNO patients contribute to a pro-inflammatory phenotype that contributes to bone inflammation (2). Currently, no medications are licensed for the use in CNO. Most patients show at least some response to nonsteroidal anti-inflammatory drugs, others require more aggressive treatment that can include corticosteroids, cytokine-blocking agents and/or bisphosphonates (3). While under the care of an experienced team and sufficient treatment, the prognosis is good, but some patients will develop sequalae which can include vertebral compression fractures (1).
| S-EPMC8040271 | biostudies-literature
Project description:Chronic nonbacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO) is a non-bacterial osteitis of yet unknown origin. Secondary to the absence of both high-titer autoantibodies and autoreactive T lymphocytes, and the association with other autoimmune diseases, it was recently reclassified as an autoinflammatory disorder of the musculoskeletal system. Since its etiology is largely unknown, the diagnosis is based on clinical criteria, and treatment is empiric and not always successful. In this paper, we summarize recent advances in the understanding of possible etiopathogenetic mechanisms in CNO.
| S-EPMC3364585 | biostudies-literature
Project description:BackgroundFBLIM1 gene has been recently demonstrated to be involved in the pathogenesis of bone sterile inflammation. The aim of the study is to evaluate the prevalence of FBLIM1 gene variants in a cohort of 80 Italian patients with Chronic Non-bacterial Osteomyelitis (CNO).MethodsThe coding regions of FBLIM1 gene were sequenced in a cohort of 80 patients with CNO using DNA extracted from blood lymphocytes, and PCR products were sequenced. Only rare (global MAF < 2%), coding variants detected were considered. Clinical evaluation of patients with rare variants and those without was performed. Fisher's exact test was used to compare categorical and ordinal data, and Student's t-test was used to analyze continuous data.ResultsEighteen out of 80 patients (~ 22%) presented at least one rare coding variant in FBLIM1. Eight patients presented a variant never associated before with CNO. All patients presented classical features of CNO and no statistical difference between patients with presence of FBLMI1 variants and those without were found in terms of clinical manifestation, treatment, and outcome.ConclusionConsidering the high frequency of rare variants in our CNO cohort, our data seem to confirm a possible role of FBLIM1 in the pathogenesis of CNO suggesting that CNO is a disorder of chronic inflammation and imbalanced bone remodeling.
| S-EPMC7350626 | biostudies-literature
Project description:ObjectivesChronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named sternocostoclavicular hyperostosis (SCCH) and mainly occurs in adults. Literature on CNO/SCCH is scattered and lacks diagnostic and therapeutic consensus.MethodsSystematic review and meta-analysis aiming to characterize clinical presentation and therapeutic modalities applied in adult CNO/SCCH patients. Untransformed numerical data and double-arcsine transformed proportional data were pooled in a random effects model in R-4.0.5; proportions were reported with 95% CI.ResultsForty studies were included, containing data on 2030 and 642 patients for aim 1 and 2, respectively. A female predisposition (67%, 95% CI 60, 73) and major diagnostic delay (5 years 95% CI 3, 7) were noted. Clinical presentation included chest pain (89%, 95% CI 79, 96) and swelling (79%, 95% CI 62, 91). Patients suffered from pustulosis palmoplantaris (53%, 95% CI 37, 68), arthritis (24%, 95% CI 11, 39) and acne (8%, 95% CI 4, 13). Inflammatory markers were inconsistently elevated. Autoantibody and HLA-B27 prevalence was normal, and histopathology unspecific. Increased isotope uptake (99%, 95% CI 96, 100) was a consistent imaging finding. Among manifold treatments, pamidronate and biologicals yielded good response in 83%, 95% CI 60, 98 and 56%, 95% CI 26, 85, respectively.ConclusionCNO/SCCH literature proves heterogeneous regarding diagnostics and treatment. Timely diagnosis is challenging and mainly follows from increased isotope uptake on nuclear examination. Biopsies, autoantibodies and HLA status are non-contributory, and biochemical inflammation only variably detected. Based on reported data, bisphosphonates and biologicals seem reasonably effective, but due to limitations in design and heterogeneity between studies the precise magnitude of their effect is uncertain. Fundamentally, international consensus seems imperative to advance clinical care for CNO/SCCH.
| S-EPMC9891421 | biostudies-literature
Project description:BACKGROUND:Despite advances in surgery, the treatment of chronic osteomyelitis remains complex and is often associated with a significant financial burden to healthcare systems. The aim of this systematic review was to identify the different single-stage procedures that have been used to treat adult chronic osteomyelitis and to evaluate their effectiveness. METHODS:Ovid Medline and Embase databases were searched for articles on the treatment of chronic osteomyelitis over the last 20 years. A total of 3511 journal abstracts were screened by 3 independent reviewers. Following exclusion of paediatric subjects, animal models, non-bacterial osteomyelitis and patients undergoing multiple surgical procedures, we identified 13 studies reported in English with a minimum follow-up period of 12 months. Data extraction and quality assessment were performed for all studies. Non-recurrence was defined as resolution of pain without recurrence of sinuses or need for a second procedure to treat infection within the described follow-up period. RESULTS:A total of 505 patients with chronic osteomyelitis underwent attempted single-stage procedures. Following debridement, a range of techniques have been described to eliminate residual dead space including biologic and non-biologic approaches. These include musculocutaneous flaps, insertion of S53P4 glass beads or packing with antibiotic-loaded ceramic or calcium-sulphate pellets. The average follow-up ranged from 12 to 110 months. The most common organism isolated was Staphylococcus aureus (35.2%). Non-recurrence ranged from 0 to 100%. Debridement alone was statistically significantly inferior to approaches that included dead space management (54.5% versus 90% non-recurrence). Biologic and non-biologic approaches to dead space management were comparable (89.8% versus 94.2% non-recurrence). CONCLUSION:A wide range of single-stage procedures have been performed for the treatment of chronic osteomyelitis. In general, studies were small and observational with various reporting deficiencies. No one dead space management technique appears to be superior, but debridement alone that leaves residual dead space should be avoided.
| S-EPMC6883574 | biostudies-literature
Project description:Background: Osteomyelitis is an inflammatory process characterized by progressive bone destruction. Moreover, chronic bacterial osteomyelitis is regarded as a difficult-to-treat clinical entity due to its long-standing course and frequent infection recurrence. However, the role of genetic factors in the occurrence and development of bacterial osteomyelitis is poorly understood. Methods: We performed a systematic review to assess the frequency of individual alleles and genotypes of single-nucleotide polymorphisms (SNPs) among patients with bacterial osteomyelitis and healthy people to identify whether the SNPs are associated with the risk of developing bacterial osteomyelitis. Then, gene ontology and Kyoto Encyclopedia of Gene and Genomes analyses were performed to identify the potential biological effects of these genes on the pathogenesis of bacterial osteomyelitis. Result: Fourteen eligible studies containing 25 genes were analyzed. In this review, we discovered that the SNPs in IL1B, IL6, IL4, IL10, IL12B, IL1A, IFNG, TNF, PTGS2, CTSG, vitamin D receptor (VDR), MMP1, PLAT, and BAX increased the risk of bacterial osteomyelitis, whereas those in IL1RN and TLR2 could protect against osteomyelitis. The bioinformatic analysis indicated that these osteomyelitis-related genes were mainly enriched in inflammatory reaction pathways, suggesting that inflammation plays a vital role in the development of bacterial osteomyelitis. Furthermore, functional notation for 25 SNPs in 17 significant genes was performed using the RegulomeDB and NCBI databases. Four SNPs (rs1143627, rs16944, rs2430561, and rs2070874) had smaller scores from regulome analysis, implying significant biological function. Conclusion: We systematically summarized several SNPs linked to bacterial osteomyelitis and discovered that these gene polymorphisms could be a genetic factor for bacterial osteomyelitis. Moreover, further large-scale cohort studies are needed to enhance our comprehensive understanding of the development of osteomyelitis to provide earlier individualized preventions and interventions for patients with osteomyelitis in clinical practice.
| S-EPMC8248359 | biostudies-literature
Project description:ObjectivesChronic non-bacterial osteomyelitis (CNO) is a rare polygenic autoinflammatory bone disease. We aimed to characterize the clinical manifestations and gene variants of Chinese adult patients with CNO.MethodsBy reviewing data of all CNO patients being diagnosed and followed up at the Center for Adult Autoinflammation Diseases, Department of Rheumatology, Peking Union Medical College Hospital, clinical and genetic features of these patients were evaluated and concluded.ResultsThe median age of disease onset was 19 (6-64) years old, and adult-onset was observed in 6 (60%) patients. The mean time of diagnosis delay was 92 ± 78 months. The common symptoms were bone pain (10, 100%), fever (9, 90%), and arthritis (6, 60%). In total, there were 54 skeletal lesions, and each patient had no less than 2 lesions. The most frequently affected sites included lower limbs (20.5%), mandible, vertebrae and pelvis (17.5%, separately). Variants of 4 genes were detected in our study including COL1A1, PSTPIP1, LRP5 and CLCN7. In seven patients who were treated with combination therapy containing tumor necrosis factor (TNF) α inhibitors, five (55.6%) had a complete response and 2 (44.4%) had a partial response.ConclusionThis is the first and largest case series of CNO in the Chinese adult patients. Four novel genetic mutations potentially associated with CNO were identified. Notably, CNO should be considered in the differential diagnosis of adult patients with long disease course and recurrent multifocal osteomyelitis of unknown cause, and these patients might benefit from combination therapy containing TNFα inhibitors.
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Project description:Fungal osteomyelitis is considered a rare disease, and the published literature mainly comprises case reports, case series and narrative reviews. A systematic review was undertaken to provide a practice-based global perspective on this disease, focusing on epidemiology and treatment strategies. We searched MEDLINE, EMBASE and Cochrane Library between the 3rd and 8th of March 2023 using a predefined search string. We included studies with at least one patient with a diagnosis of fungal osteomyelitis published before the 1st of January 2023. We included all study designs except for reviews, and we excluded non-English languages and grey literature. After exclusion, 678 studies, mostly case reports, were included. Descriptive analysis was performed on 1072 patients. The most common aetiological agent was Aspergillus (26.5%), followed by Candida (20.7%) and Mucor (16.8%), and the bones most frequently involved were the vertebrae. We described the characteristics of patients divided by site of infection, and we found that diabetes mellitus, disseminated fungal infection, surgery and local lesion were major risk factors. We also successfully associated duration of treatment with outcome. We provided a general overview of this rare disease, and we highlighted the need for high-quality investigations on the subject.
| S-EPMC10383745 | biostudies-literature
Project description:Bacterial chondronecrosis with osteomyelitis (BCO) is recognized as an important cause of lameness in commercial broiler chickens (meat-type chickens). Relatively little is known about the microbial communities associated with BCO. This study was conducted to increase our understanding of the microbial factors associated with BCO using a culture-independent approach. Using Illumina sequencing of the hyper-variable region V6 in the 16S rRNA gene, we characterized the bacterial communities in 97 femoral or tibial heads from normal and lame broilers carefully selected to represent diverse variations in age, line, lesion type, floor type, clinical status and bone type. Our in-depth survey based on 14 million assembled sequence reads revealed that complex bacterial communities exist in all samples, including macroscopically normal bones from clinically healthy birds. Overall, Proteobacteria (mean 90.9%) comprised the most common phylum, followed by Firmicutes (6.1%) and Actinobacteria (2.6%), accounting for more than 99% of all reads. Statistical analyses demonstrated that there are differences in bacterial communities in different types of bones (femur vs. tibia), lesion types (macroscopically normal femora or tibiae vs. those with pathognomonic BCO lesions), and among individual birds. This analysis also showed that BCO samples overrepresented genera Staphylococcus, whose species have been frequently isolated in BCO samples in previous studies. Rarefaction analysis demonstrated the general tendency that increased severities of BCO lesions were associated with reduced species diversity in both femoral and tibial samples when compared to macroscopically normal samples. These observations suggest that certain bacterial subgroups are preferentially selected in association with the development of BCO lesions. Understanding the microbial species associated with BCO will identify opportunities for understanding and modulating the pathogenesis of this form of lameness in broilers.
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