The diagnostic value of cytokines for the discrimination of vertebral osteomyelitis and degenerative diseases of the spine.

Vertebral osteomyelitis (VO) is a primary infection of the endplates of the vertebral bodies with secondary infection of the adjacent intervertebral discs. Diagnosis is often delayed due to unspecific symptoms and a lack of specific infection markers. In this prospective study, we determined the suitability of 27 cytokines for the discrimination of VO and degenerative diseases of the spine and compared its diagnostic potential in relation to the C-reactive protein (CRP), which is widely used as a non-specific inflammation marker in clinical diagnostics. The patients included in this study underwent surgical stabilization of the lumbar and/or thoracic spine with removal of 1 or more affected intervertebral discs, as therapy for VO (n = 16) or for erosive osteochondrosis (EO, control group, n = 20). We evaluated the cytokine and CRP concentrations before (pre-OP = -20-0d where 0 means the day of surgery) and after surgery (post-OP) on days 3-5, 6-11, 40-56, and 63-142. Compared to the control patients pre-OP, a significantly higher elevation of the 4 cytokines IL-6, IL-8, IL-12 (p70), and VEGF as well as CRP were found in the VO patients, showing an area under the curve > 0.80 pre-OP. No significant differences were observed between VO patients with high and low virulent bacteria with respect to all 5 elevated biomarkers. This is the first prospective study in which a broad spectrum of 27 cytokines was analysed via multiplex assay using sera from patients with and without VO. Our results show that, in addition to CRP, 4 different cytokines were significantly altered in VO but not control patients. The results implicate that these candidate cytokines may be used in a multiplex assay for discrimination between VO and degenerative diseases of the spine.

The diagnostic value of soluble urokinase-type plasminogen activator receptor (suPAR) for the discrimination of vertebral osteomyelitis and degenerative diseases of the spine.

BACKGROUND: There is still a challenge in discriminating between vertebral osteomyelitis and degenerative diseases of the spine. To this end, we determined the suitability of soluble urokinase-type plasminogen activator receptor (suPAR) and compared the diagnostic potential of suPAR to CRP. METHODS: Patients underwent surgical stabilization of the lumbar and/or thoracic spine with removal of one or more affected intervertebral discs, as therapy for vertebral osteomyelitis (n = 16) or for erosive osteochondrosis (control group, n = 20). In this prospective study, we evaluated the suPAR and CRP levels before (pre-OP) and after surgery (post-OP) on days 3-5, 6-11, 40-56, and 63-142. RESULTS: The suPAR levels in vertebral osteomyelitis patients were significantly higher than those from controls pre-OP, 3-5 days post-OP, and 6-11 days post-OP. Significantly higher CRP levels were observed in the vertebral osteomyelitis group than in the controls pre-OP and 6-11 days post-OP. Levels of suPAR and CRP correlated positively in all patients in the pre-OP period: r = 0.63 (95% CI: 0.37-0.79), p < 0.0001. The values for the area under the receiver operating characteristics curve (AUC) for pre-OP and the overall model post-OP were 0.88 (95% CI: 0.76-1.00) and 0.84 (95% CI: 0.71-0.97) for suPAR, 0.93 (95% CI: 0.85-1.00) and 0.77 (95% CI: 0.62-0.93) for CRP, and 0.98 (95% CI: 0.96-1.00) and 0.91 (95% CI: 0.82-1.00) for the combination of suPAR and CRP. The AUC for suPAR pre-OP revealed an optimum cut-off value, sensitivity, specificity, NPV, and PPV of 2.96 ng/mL, 0.69, 1.00, 0.80, and 1.00, respectively. For CRP, these values were 11.58 mg/L, 0.88, 0.90, 0.90, and 0.88, respectively. CONCLUSION: The present results show that CRP is more sensitive than suPAR whereas suPAR is more specific than CRP. Moreso, our study demonstrated that improvement in the diagnostic power for discrimination of vertebral osteomyelitis and degenerative diseases of the spine can be achieved by a combination of both suPAR and CRP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02554227, posted Sept. 18, 2015, and updated Aug. 13, 2019.