What is the probability of osteomyelitis with negative Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)?

Probability of Osteomyelitis with Negative ESR and CRP

The probability of osteomyelitis with both negative ESR and CRP is very low, making it unlikely that osteomyelitis is present when both inflammatory markers are normal. 1, 2

Diagnostic Value of ESR and CRP in Osteomyelitis

• ESR and CRP are important inflammatory markers used in the diagnosis of osteomyelitis, but they are considered suggestive rather than confirmatory criteria 1
• When both ESR and CRP are negative, infection is unlikely, providing a high negative predictive value 1, 2
• According to the IWGDF/IDSA guidelines, markedly elevated serum inflammatory markers, especially ESR, are suggestive of osteomyelitis in suspected cases 1
• Individual serum inflammatory markers alone are only suggestive and not conclusive for fracture-related infection 1

Specific Cutoff Values and Diagnostic Accuracy

• An ESR <30 mm/h indicates a low likelihood of osteomyelitis 3
• ESR values ≥60 mm/h have a sensitivity of 74% and specificity of 56% for osteomyelitis 3
• CRP values >7.9 mg/dL have a sensitivity of 49% and specificity of 80% for osteomyelitis 3
• The combination of elevated ESR (>60 mm/hr) plus CRP ≥80 mg/L has a high positive predictive value for diabetic foot osteomyelitis 1, 2
• In diabetic foot infections, the best cutoff points were found to be ESR ≥49 mm/hour (sensitivity 74.6%, specificity 57.7%) and CRP ≥35 mg/liter (sensitivity 76%, specificity 54.9%) 4

Interpretation in Clinical Context

• ESR and CRP should be interpreted alongside clinical assessment rather than used in isolation 2
• A secondary rise after initial decrease or an unexplained consistent elevation over time should increase suspicion of infection 1
• When the diagnosis of osteomyelitis remains in doubt despite clinical assessment and plain X-rays, inflammatory markers can provide additional information 1
• Neither plain X-ray, inflammatory biomarkers (ESR, CRP), nor probe-to-bone tests can on their own reliably rule in or rule out the diagnosis of diabetic foot osteomyelitis 1

Limitations and Considerations

• ESR and CRP have limited specificity and cannot differentiate bacterial infections from non-infectious causes of inflammation 2
• CRP can be elevated after surgery but generally returns to baseline values within 2 months after surgery 1
• The diagnostic accuracy of serum inflammatory markers in chronic/late-onset fracture-related infection was reviewed, but studies focusing on patients with acute/early infection are currently lacking 1
• Interpretation of inflammatory markers can be difficult when underlying inflammatory arthropathy is present 1

Clinical Application

• When both ESR and CRP are negative, clinicians can be reasonably confident in excluding osteomyelitis, especially in the absence of other clinical signs 1, 2
• In cases where clinical suspicion remains high despite negative inflammatory markers, advanced imaging such as MRI should be considered 1
• MRI has a 100% negative predictive value for excluding osteomyelitis; a normal marrow signal reliably excludes infection 1
• Serial measurements of inflammatory markers are recommended to monitor treatment response, particularly after 4 weeks of therapy 2, 5
• ESR values ≥20 mm/h are independently associated with osteomyelitis recurrence and should be used to guide the duration of antibiotic treatment 6

In conclusion, while negative ESR and CRP values significantly decrease the likelihood of osteomyelitis, they should be interpreted within the clinical context and in conjunction with other diagnostic methods, particularly when clinical suspicion is high.