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

Jan Simon Scharrenberg, Ayla Yagdiran, Julia Brinkmann, Maik Brune, Jan Siewe, Norma Jung, Esther Mahabir, Jan Simon Scharrenberg, Ayla Yagdiran, Julia Brinkmann, Maik Brune, Jan Siewe, Norma Jung, Esther Mahabir

Abstract

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.

Keywords: Bacterial infection; Biomarker; Diagnostics; Soluble urokinase-type plasminogen activator receptor (suPAR); Vertebral osteomyelitis.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
suPAR serum levels (a) and CRP plasma levels (b) in vertebral osteomyelitis (dark gray bars) and control patients (light gray bars). Pre-OP, before surgery; post-OP, after surgery. The absolute suPAR concentration (ng/mL) and CRP concentration (mg/L) are indicated on the Y-axis. Box-and-whiskers plot; data points, open circles; maximum, endpoint of upper whisker; minimum, endpoint of lower whisker; third quartile (75th percentile), upper edge of the box; first quartile (25th percentile), lower edge of the box; median (50th percentile), line inside the box; mean, black diamond; data points beyond the whiskers, outliers. Results are expressed as mean ± SEM. Significant differences in concentrations are marked as follows: *p < 0.05, **p < 0.01
Fig. 2
Fig. 2
Odds ratios and 95% CI of the univariate and sex-adjusted logistic regression of patient status (vertebral osteomyelitis vs. control patients) with respect to suPAR (a) and CRP (b) each stratified by the interval pre-OP, post-OP, and all post-OP intervals combined (overall post-OP)
Fig. 3
Fig. 3
ROC curves for sex-adjusted logistic regression analyses of patient status with respect to suPAR, CRP, and the combination of suPAR and CRP; logistic models stratified by the interval pre-OP and all post-OP intervals combined (overall post-OP); AUC and 95% CI for pre-OP and for overall post-OP are 0.88 (95% CI: 0.76–1.00) and 0.84 (95% CI: 0.71–0.97) for suPAR (a, b), 0.93 (95% CI: 0.85–1.00) and 0.77 (95% CI: 0.62–0.93) for CRP (c, d), 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 (e, f), respectively

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