What are the initial lab workup and diagnostic steps for osteomyelitis?

Osteomyelitis Laboratory Workup

Start with plain radiographs, ESR, and CRP as your initial workup, followed by blood cultures before antibiotics, and proceed to MRI with contrast if diagnosis remains uncertain—then obtain bone biopsy for definitive microbiological diagnosis when needed. 1, 2, 3

Initial Laboratory Studies

• Obtain ESR and CRP as first-line inflammatory markers in all suspected cases, as these are the most useful initial tests 1, 3
• ESR >60 mm/hour or CRP >3.2 mg/dL combined with clinical findings (ulcer depth >3 mm) helps differentiate osteomyelitis from cellulitis 4
• Procalcitonin (PCT) may be helpful when clinical examination is diagnostically equivocal, though it is not routinely required 1, 2, 3
• Obtain two sets of aerobic and anaerobic blood cultures before starting antibiotics to identify hematogenous sources 1, 2
• White blood cell count does NOT influence the likelihood of osteomyelitis and should not be relied upon for diagnosis 4

Important Caveat About Inflammatory Markers

• Normal ESR and CRP do not rule out osteomyelitis—they are non-specific and can be normal in culture-negative, fungal, or TB osteomyelitis 3, 5
• Inflammatory marker levels are influenced by the infecting organism: Staphylococcus aureus and antibiotic-resistant organisms (MRSA, VRE) demonstrate higher CRP and ESR than culture-negative or non-pyogenic organisms 5
• Fever is often absent and does not correlate with osteomyelitis diagnosis 5

Imaging Algorithm

Step 1: Plain Radiographs (Always First)

• Obtain plain radiographs of the affected area in all cases of suspected osteomyelitis as the initial imaging test 4, 1, 2, 3
• Look for cortical erosion, periosteal reaction, mixed lucency and sclerosis, bone destruction, and trabecular coarsening 4, 2
• Radiographs may be normal in early acute osteomyelitis (<14 days) and only show soft tissue swelling 4
• If initial radiographs show classic changes suggestive of osteomyelitis and there is little likelihood of noninfectious osteoarthropathy, treat for presumptive osteomyelitis after obtaining bone cultures 4

Step 2: MRI with Contrast (Gold Standard)

• MRI with and without contrast is the preferred advanced imaging modality when diagnosis remains uncertain after radiographs, with 97% sensitivity, 93% specificity, and 94% accuracy 1, 2, 3
• Characteristic MRI findings include decreased T1-weighted bone marrow signal with increased signal on fluid-sensitive sequences 1
• A normal marrow signal on MRI reliably excludes infection with 100% negative predictive value 1, 2
• MRI is superior for detecting soft tissue involvement, abscesses, fistulae, and extent of bone involvement 2

Alternative Imaging When MRI Unavailable or Contraindicated

• Consider white blood cell-labeled radionuclide scan, SPECT/CT, or FDG-PET/CT when MRI is not available or contraindicated 4, 1
• FDG-PET has 91% accuracy for chronic osteomyelitis and may be particularly useful when hardware is present 1

Microbiological Diagnosis (Definitive)

Bone Biopsy Indications

Obtain bone samples for culture (either intraoperatively or percutaneously) in the following situations: 4, 1, 2

• Patient or provider prefers definitive diagnosis to justify early surgery versus prolonged treatment 4
• Cultures suggest high risk of antibiotic-resistant organisms 4
• Progressive bony deterioration or persistently elevated inflammatory markers during therapy 4
• Failure to respond to empiric antibiotic therapy 4
• Clinical and imaging evaluations yield uncertain diagnosis 1
• Desire to use antibiotics with high potential for selecting resistant organisms (rifampin, fluoroquinolones) 4

Bone Biopsy Technique

• Intraoperative excisional biopsy during debridement is preferred over core needle biopsy because osteomyelitis can be focal 2, 3
• Percutaneous biopsy should be done under fluoroscopic or CT guidance, traversing uninvolved skin if possible 4
• Obtain 2-3 specimens if possible: at least one for culture and another for histological analysis 4
• Bone cultures have 76-100% sensitivity but only 8-67% specificity; combining with histopathology is recommended for definitive diagnosis 2, 3
• Predictors of positive bone cultures include presence of an open wound and aspiration of fluid at time of biopsy 6

Critical Pitfall: Avoid Soft Tissue Cultures for Osteomyelitis

• Do NOT use results of soft tissue or sinus tract specimens for selecting antibiotic therapy for osteomyelitis, as they do not accurately reflect bone culture results 4
• Soft tissue swabs may be falsely positive due to contamination by wound-colonizing flora or skin commensals 4

Special Considerations for Diabetic Foot Osteomyelitis

Clinical Assessment

• Perform probe-to-bone (PTB) test with a sterile blunt metal probe: in low-risk patients, a negative test largely rules out osteomyelitis; in high-risk patients, a positive test is largely diagnostic 4
• Suspect osteomyelitis when an ulcer does not heal after at least 6 weeks of appropriate wound care and off-loading (in patients with adequate blood supply) 4
• Ulcer area >2 cm² and exposed bone increase likelihood of osteomyelitis 4
• Independent risk factors include wounds extending to bone/joint, previous wound history, and recurrent/multiple wounds 4

Diagnostic Approach

• Use a combination of probe-to-bone test, plain X-rays, and inflammatory markers (ESR, CRP, or PCT) as initial diagnostic studies 1
• If initial radiographs are negative, treat for soft-tissue infection for ~2 weeks, then repeat radiographs 2-4 weeks later if suspicion persists 4
• Consider bone biopsy for most mid- or hindfoot lesions, as these are more difficult to treat and more often lead to high-level amputation 4

Vertebral Osteomyelitis Specific Workup

• Spine MRI is strongly recommended for suspected vertebral osteomyelitis 1
• Clinical presentation is typically nonspecific (back pain), and fever is often absent 5