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.

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

Chronic non-bacterial osteomyelitis (CNO) is a chronic inflammatory bone disease which usually manifests in children and adolescents. There are a few data about pathogenesis and treatment. The aim of the study to compare the efficacy of different treatment approaches in pediatric CNO cohort patient. Fifty two children (25 boys and 27 girls) with CNO with average age at the onset of the disease 8.4 years (5.4; 11.0), number of foci - 3.0 (2.0; 6.0, incl. multifocal cases in 80.8%). Non-steroid anti-inflammatory drugs (NSAID) was the first-line treatment for non-vertebral cases, as well as pamidronate (PAM) for vertebral involvement. Second-line treatment includes sulfasalazine (SSZ), methotrexate (MTX), PAM and tumor necrosis factor-α inhibitors (TNFα-inh). We evaluated the dynamics of pain, patient's and physician's (MDVAS) assessment with visual-analog scale (VAS) and ability to each medication to achieve remission of CNO activity. According to the NSAID, MTX, SSZ, PAM and TNFα-inh groups the following data were registered: patient's VAS: - 14.2% (p = 0.05), - 50.0% (p = 0.04), - 23.1 (p = 0.89), - 83.3% (p = 0.0001), - 73.6% (p = 0.0007); painVAS: - 21.9% (p = 0.01), - 18.6% (p = 0.13), + 36.4 (p = 0.89), - 79.7% (p = 0.00016), - 74.1%, (p = 0.0015); MDVAS: - 13.8% (p = 0.13); - 56.4% (p = 0.09), + 30.8% (p = 0.89), - 74.7%, (p = 0.0001), - 82.1 (p = 0.0015) respectively. The ability of each treatment strategy to achieve the CNO remission was 52.6%, 44.4%, 57,1%, 88.8% and 73.3%, respectively (log-rank test, p = 0.001). The efficacy of treatment approaches for CNO depended on the severity of the disease. NSAID, methotrexate, and sulfasalazine were effective in forms without spine involvement, but pamidronate and TNF-a inhibitors were useful in vertebral forms of CNO. Pamidronate and TNF-a inhibitors more extensively suppressed CNO activity. The randomized controlled trials for assessment of the efficacy and safety of these medications is mandatory to confirm these results.