Nonbacterial and bacterial osteomyelitis in children: a case-control retrospective study.

Purpose: Osteomyelitis is a group of bone infectious (bacterial osteomyeilitis-BO) and noninfectious inflammatory diseases (nonbacterial osteomyelitis-NBO) with similar clinical, radiology, and laboratory features. Many patients with NBO are misdiagnosed as BO and receive unnecessary antibiotics and surgery. Our study aimed to compare clinical and laboratory features of NBO and BO in children, to define key discriminative criteria, and to create an NBO diagnostic score (NBODS). Methods: The retrospective multicenter cohort study included clinical, laboratory, and instrumental information about histologically confirmed NBO (n = 91) and BO (n = 31). The variables allowed us to differentiate both conditions used to construct and validate the NBO DS. Results: The main differences between NBO and BO are as follows: onset age-7.3 (2.5; 10.6) vs. 10.5 (6.5; 12.7) years (p = 0.03), frequency of fever (34.1% vs. 90.6%, p = 0.0000001), symptomatic arthritis (67% vs. 28.1%, p = 0.0001), monofocal involvement (28.6% vs. 100%, p = 0.0000001), spine (32% vs. 6%, p = 0.004), femur (41% vs. 13%, p = 0.004), foot bones (40% vs. 13%, p = 0.005), clavicula (11% vs. 0%, p = 0.05), and sternum (11% vs. 0%, p = 0.039) involvement. The following four criteria are included in the NBO DS: CRP ≤ 55 mg/l (56 points), multifocal involvement (27 points), femur involvement (17 points), and neutrophil bands ≤ 220 cell/µl (15 points). The sum > 17 points allowed to differentiate NBO from BO with a sensitivity of 89.0% and a specificity of 96.9%. Conclusion: The diagnostic criteria may help discriminate NBO and BO and avoid excessive antibacterial treatment and surgery.

Cytokine profile in patients with chronic non-bacterial osteomyelitis, juvenile idiopathic arthritis, and insulin-dependent diabetes mellitus.

OBJECTIVES: Our study aimed to evaluate the cytokine levels in pediatric chronic non-bacterial osteomyelitis (CNO) patients and compare these with other immune-mediated diseases and healthy controls. METHODS: In this prospective study, we included 42 children with CNO, 28 patients with non-systemic juvenile idiopathic arthritis (JIA), 17 children with insulin-dependent diabetes mellitus (IDDM), and 30 healthy age-matched controls. In each of the CNO patients and comparison groups, the levels of 14-3-3-η protein, S100A8/A9 protein, interleukin-4 (IL-4), interleukin-17 (IL-17), interleukin-18 (IL-18), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) were measured by ELISA assay. RESULTS: All studied cytokines in the CNO patients were significantly higher than controls, and IDDM, 14-3-3-η protein, IL-18, IL-4, IL-17, IL-1ß, and TNF-α were less than in JIA patients. In the discriminant analysis, ESR, 14-3-3 protein, S100A8/A9, IL-18, IL-4, and TNF-α can discriminate CNO from JIA, and 14-3-3 protein, S100A8/A9, IL-18, IL-17, IL-4, and TNF-α can distinguish CNO from other diseases and HC. CONCLUSION: The increased level of pro-inflammatory cytokines confirms the role of monocyte-driven inflammation in CNO patients. Cytokines may prove valuable as biomarkers and potential therapeutic targets for CNO.

How nonbacterial osteomyelitis could be discriminated from tuberculosis in the early stages: the simple algorithm.

Chronic nonbacterial osteomyelitis (CNО) and tuberculous osteomyelitis (TBO) are both primarily chronic inflammatory bone diseases with similar clinical and radiological findings, but entirely different in aetiology, pathogenesis, treatment, and outcomes. Our study aimed to evaluate the clinical and laboratory features which could discriminate the CNO and TBO. The study included 124 patients-91 with CNO and 33 with TBO. All patients underwent routine blood tests: WBC, platelets, ESR, C-reactive protein, haemoglobin, and imaging. The ability of each variable to discriminate CNO from TBO was evaluated with sensitivity and specificity analysis, AUC-ROC analysis, and calculating the odds ratio. Patients with TBO had less number of bone foci (p = 0.0000001), onset age (p = 0.00001), rarely articular involvement (p = 0.01), lower haemoglobin level (p = 0.02), higher incidence of TBO in the male subjects (p = 0.002), and higher leukocyte bands (p = 0.0000001). TBO is rarely characterized by spine (p = 0.0009), foot (p = 0.01), and clavicula (p = 0.047) involvement. The diagnostic rule: criteria allowing to differentiate NBO from TBO are negative bone microbiota tests (sensitivity-100.0%, specificity-100.0%) or major discriminative criteria or clavicula involvement alone (sensitivity-11.0%, specificity-100.0%) and at least four from the five additional criteria: number of foci > 1.0 (p = 0.00002), WBC ≤ 11.0 (p = 0.004), neutrophil bands ≤ 120.0 × 106/l (p = 0.002), lymphocytes ≤ 52% (p = 0.0005), and CRP > 0.2 mg/l (p = 0.003). All patients with monofocal CNO required bone biopsy with microbiology assessment. The created provisional criteria may help to discriminate TBO and CNO and should be used only with other known diagnostic tools. Key Points • Nonbacterial osteomyelitis and tuberculous osteomyelitis are both primarily chronic inflammatory bone diseases with similar presentations. • Nonbacterial osteomyelitis and tuberculous osteomyelitis may be associated with other immune-mediated diseases. • Only bone biopsy can confirm and discriminate both conditions. All patients with monofocal CNO required bone biopsy with microbiology assessment.

The peculiarities and treatment outcomes of the spinal form of chronic non-bacterial osteomyelitis in children: a retrospective cohort study.

Chronic non-bacterial osteomyelitis (CNO) is a group of immune-mediated diseases which appears in bone inflammation, destruction and some orthopaedic consequences, especially in the cases of spinal involvement. This study is to compare characteristics and treatment outcomes of CNO patients with spinal involvement. The retrospective cohort study included data from 91 pediatric patients with CNO. The diagnosis is based on Jannson's criteria with morphological confirmation (nonspecific chronic inflammation). Spine involvement detected by X-ray, computed tomography, magnetic resonance imaging, and bone scan in 29 (31.9%) patients. No differences in the family history, concomitant immune-mediated diseases between spinal (SpCNO) and peripheral (pCNO) forms of CNO have been revealed. Only 5 (10.2%) SpCNO patients (10.2%) had monofocal monovertebral involvement. The main risk factors of spinal involvement were female sex: RR = 2.0 (1.1; 3.9), sensitivity (Se) = 0.66, specificity (Sp) = 0.6; multifocal involvement: RR = 2.1 (0.9; 5.0), Se = 0.83, Sp = 0.37; no foot bones involvement: RR = 3.1 (1.3; 7.5), Se = 0.83, Sp = 0.5; sternum involvement RR = 2.3 (1.3; 4.1), Se = 0.24, Sp = 0.94. In the linear regression analysis only female sex (p = 0.005), multifocal involvement (p = 0.000001) and absence of foot bones involvement (p = 0.000001) were independent risk factors of spinal involvement (p = 0.000001). The response rate on bisphosphonates and tumor necrosis factor-a inhibitors was 90.9% and 66.7%, consequently. Only 4/29 (13.8%) SpCNO patients underwent surgery due to severe spinal instability or deformities. The spinal involvement is frequent in CNO and could be crucial for choosing a treatment strategy. Bisphosphonates and TNFa-inhibitors could be effective treatment options for severe SpCNO.

Multilevel spinal reconstruction in pediatric patients under 4 years old with non-congenital pathology (10-year single-center cohort study).

PURPOSE: To evaluate the influence of anterior fusion option on the short- and long-time outcomes on multilevel spinal reconstructions in young children. METHODS: Forty-five patients aged under 4 years old (2 years 2 months ± 11 months in average) underwent spinal reconstruction due to tuberculosis spondylitis (35), pyogenic spondylitis (9) and spinal tumors (1) complicated by angular kyphosis exceeded 20° (49.2° ± 14.3° in average). All lesions involved two or more spinal motion segments. Clinical and radiographic data were compared in two groups depended on the types of anterior fusion: titanium mesh cage with bone graft (TMC + BG) (19 patients) and cortical BG only (26). The average follow-up was 5 years 10 months ± 2 years 8 months (min = 3 years; max = 12 years). RESULTS: The deformity correction was similar in groups. The operation time and blood loss were less in TMC + BG group (p = 0.001) as a times for anterior bone block formation (p < 0.001) and posterior instrumentation removal (p = 0.003). Ten late post-op complications registered include disease's recurrence (1), pseudoarthrosis (6), deformity progression (1) and graft resorption (1). The complication rate was less in TMC + BG than in BG group: two and eight cases consequently, p = 0.024. CONCLUSIONS: Multilevel spinal reconstruction in early aged patients is safe and effective procedure. The anterior fusion by TMC with bone autograft has advantages of reducing blood loss, operation time, time for anterior block formation and complications rate compared with bone autograft only. These slides can be retrieved under Electronic Supplementary Material.